Switching of monoclonal antibodies against the calcitonin gene-related peptide or its receptor in migraine. Results from a Spanish Cohort

array:21 ["pii" => "S2667049624000255" "issn" => "26670496" "doi" => "10.1016/j.neurop.2024.100168" "estado" => "S250" "fechaPublicacion" => "2024-10-01" "aid" => "100168" "copyright" => "Sociedad Española de Neurología" "copyrightAnyo" => "2024" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:17 [ "pii" => "S2667049624000243" "issn" => "26670496" "doi" => "10.1016/j.neurop.2024.100167" "estado" => "S250" "fechaPublicacion" => "2024-10-01" "aid" => "100167" "copyright" => "Sociedad Española de Neurología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Sensitivity and specificity of the ocular movements test (HINTS) in the detection of central acute vestibular syndrome" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Sensibilidad y especificidad de la prueba de movimientos oculares (HINTS) en la detección del síndrome vestibular Agudo central" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1875 "Ancho" => 1715 "Tamanyo" => 144593 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Results of the distribution of causal diagnoses of central acute vestibular syndrome." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Issa Layka, Mostafa Ibrahim, Ahmed Issa" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Issa" "apellidos" => "Layka" ] 1 => array:2 [ "nombre" => "Mostafa" "apellidos" => "Ibrahim" ] 2 => array:2 [ "nombre" => "Ahmed" "apellidos" => "Issa" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2667049624000243?idApp=UINPBA00004N" "url" => "/26670496/0000000400000004/v7_202410041010/S2667049624000243/v7_202410041010/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Switching of monoclonal antibodies against the calcitonin gene-related peptide or its receptor in migraine. Results from a Spanish Cohort" "tieneTextoCompleto" => true "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "J. Arzalluz-Luque, M. Millán Vázquez, R. Lamas Pérez, N. Sánchez Rodríguez, P. Gómez López, F.J. Gómez Fernández, J. Viguera Romero, C. Jurado Cobo, M. Fernández Recio, C. González Oria" "autores" => array:10 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Arzalluz-Luque" "email" => array:1 [ 0 => "joaquin.arzalluz.sspa@juntadeandalucia.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cr0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Millán Vázquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "af0005" ] ] ] 2 => array:3 [ "nombre" => "R." "apellidos" => "Lamas Pérez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "af0005" ] ] ] 3 => array:3 [ "nombre" => "N." "apellidos" => "Sánchez Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "af0005" ] ] ] 4 => array:3 [ "nombre" => "P." "apellidos" => "Gómez López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "af0005" ] ] ] 5 => array:3 [ "nombre" => "F.J." "apellidos" => "Gómez Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "af0005" ] ] ] 6 => array:3 [ "nombre" => "J." "apellidos" => "Viguera Romero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "af0010" ] ] ] 7 => array:3 [ "nombre" => "C." "apellidos" => "Jurado Cobo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "af0015" ] ] ] 8 => array:3 [ "nombre" => "M." "apellidos" => "Fernández Recio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "af0020" ] ] ] 9 => array:3 [ "nombre" => "C." "apellidos" => "González Oria" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "af0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Unidad de Cefaleas, Servicio de Neurología, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, 41013 Sevilla, Spain" "etiqueta" => "a" "identificador" => "af0005" ] 1 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario Virgen Macarena, Av. Dr. Fedriani, 3, 41009 Sevilla, Spain" "etiqueta" => "b" "identificador" => "af0010" ] 2 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario Reina Sofía, Av. Menendez Pidal, s/n, 14004 Córdoba, Spain" "etiqueta" => "c" "identificador" => "af0015" ] 3 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario Virgen de Valme, Ctra. de Cádiz Km. 548,9, 41014 Sevilla, Spain" "etiqueta" => "d" "identificador" => "af0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Unidad de Cefaleas, Servicio de Neurología, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n., 41013 Sevilla, Spain." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Experiencia del switch de anticuerpos monoclonales frente al péptido relacionado con el gen de la calcitonina o su receptor en migraña. Resultados de una cohorte española" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2723 "Ancho" => 2764 "Tamanyo" => 363894 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Switch information. Initial (A) and switch (B) CGRP–mAbs are represented in this figure. Tables show distribution of initial CGRP–mAb, switch CGRP–mAb, and a summary of switches performed. CGRP–mAb: Calcitonin gene related-peptide monoclonal antibody." ] ] ] "textoCompleto" => "BackgroundMigraine is a common primary headache disorder, affecting more than 4.5 million people in Spain, where its prevalence is 12% for episodic migraine (EM) and 2% for chronic migraine (CM).<a class="elsevierStyleCrossRef" href="#bb0005">1</a> It is considered one of the most disabling diseases by the World Health Organization<a class="elsevierStyleCrossRef" href="#bb0010">2</a>,<a class="elsevierStyleCrossRef" href="#bb0015">3</a> and it is the second most disabling disease worldwide after low back pain.<a class="elsevierStyleCrossRef" href="#bb0020">4</a> According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), migraine is defined as recurrent headaches lasting 4–72 h, of variable intensity, usually described as pulsating and unilateral, accompanied by nausea/vomiting, photophobia, and phonophobia.<a class="elsevierStyleCrossRef" href="#bb0025">5</a> Regarding monthly headache days (MHD), it is classified in 2 major types: CM when ≥15 MHD for >3 months, requiring at least 8 days with migraine features, and EM when <15 MHD.<a class="elsevierStyleCrossRef" href="#bb0025">5</a> This disease includes not only headache but also disabling prodromal and postdromal symptoms and migraine aura. The association with other comorbidities has been stated, mostly neurological and psychiatric disorders.<a class="elsevierStyleCrossRef" href="#bb0030">6</a>Recent advances in the understanding of migraine pathophysiology outlined the importance of neuronal circuits including cortical and subcortical structures and the relevant role of the calcitonin gene-related peptide (CGRP) pathway in modulation of central pain circuits and in the triggering of migraine.<a class="elsevierStyleCrossRef" href="#bb0035">7</a> Similarly, CGRP antagonist proved to abort and prevent migraine attacks.<a class="elsevierStyleCrossRef" href="#bb0035">7</a> These findings ultimately led to the development of monoclonal antibodies (mAbs) targeting CGRP ligand (galcanezumab, fremanezumab, and eptinezumab) or its receptor (erenumab). CGRP-mAbs proved to be effective, safe, and well tolerated for preventing migraine attacks.<a class="elsevierStyleCrossRefs" href="#bb0040">8–11</a> Indeed, real-world evidence (RWE) studies, generally involving a more refractory population, confirmed efficacy, tolerability, and safety outcomes.<a class="elsevierStyleCrossRef" href="#bb0060">12</a>,<a class="elsevierStyleCrossRef" href="#bb0065">13</a> To date, comparative head-to-head trials of CGRP–mAbs are lacking.Nevertheless, the response may vary in real clinical practice. Actually, RWE shows that up to 30% of patients discontinued CGRP–mAbs, mostly due to lack of benefit.<a class="elsevierStyleCrossRef" href="#bb0070">14</a> In addition, a recent multicenter prospective study of migraine patients treated with anti-CGRP–mAbs showed that around 40%–45% of patients did not achieve ≥50% response rate (RR) at week 24 of follow-up.<a class="elsevierStyleCrossRef" href="#bb0075">15</a> Same results were found in previous prospective studies after 3 and 6 months of follow-up.<a class="elsevierStyleCrossRef" href="#bb0060">12</a>,<a class="elsevierStyleCrossRef" href="#bb0065">13</a> Interestingly, some non-responders might achieve a more effective response when switching to a different mAb, regarding monthly migraine days (MMD) reduction, improvement of quality of life parameters, and reduction of acute migraine medication use.<a class="elsevierStyleCrossRef" href="#bb0080">16</a> Due to diverse therapeutic targets (CGRP ligand vs receptor), it is reasonable to question whether different action mechanisms may play a relevant role in the variability of efficacy found among patients. However, evidence regarding switch is lacking and clinical practice guidelines have not provided recommendations in this regard.<a class="elsevierStyleCrossRef" href="#bb0085">17</a> The aim of this study was to evaluate whether switching CGRP–mAb is associated with clinical improvement in terms of effectiveness and tolerability outcomes.MethodsAn observational, longitudinal, retrospective, and multicenter study was conducted between January 2018 and June 2022. We included patients diagnosed with migraine according to ICHD-3 criteria, with or without aura, aged at least 18 years, who were treated with CGRP–mAbs and switched mAb for any reason: lack of effiectiveness or lack of tolerability. Lack of effectiveness was considered when the reduction in MHD after the period with the first mAb was <30% and lack of tolerability when adverse events (AEs) having a life impact occurred. There was no wash-out period before switching mAbs. All patients were evaluated before switch (after the period of treatment with first mAb, considered baseline) and then reevaluated 3 months after switching, when effectiveness and tolerability outcomes were assessed. No concomitant prophylactic medications were added or changed during this period, only discontinued at the request of patients.Follow-up was performed at headache monographic neurology consultations. Electronic medical records were used to collect demographic data and clinical variables at baseline and after switching, including headache frequency (MHD and MMD), severity (measured by a 1–10 visual analogue scale [VAS]), use of acute and preventive migraine medication, disability, and anxiety-depression surveys. Medication overuse was considered if used ≥10 days per month for triptans and ≥15 days for non-steroidal anti-inflammatory drugs (NSAIDs). Disability questionnaires were those regularly used for headache: Migraine Disability Assessment Scale (MIDAS) and Headache Impact Test-6 (HIT6). Anxiety and depression surveys were Hospital Anxiety and Depression-Anxiety and Hospital Anxiety and Depression-Depression. Tolerability in terms of reported AEs, the reason for discontinuation of first mAb (lack of effectiveness/lack of tolerability) and switch information were recorded.The primary outcome of the study was to determine RR (<30%, 30%–50%, ≥50%) of MHD. Secondary outcomes included measures of effectiveness (absolute changes in frequency of MHD/MMD, headache severity, disability scores, and use of acute migraine medication) and tolerability of switch. We analyzed other effectiveness outcomes such as mean reduction in VAS score and percentage of patients with VAS score reduction of at least 1 point. In addition, clinical variables of effectiveness were compared before and 3 months after switch. Differences in tolerability and reported AEs were also recorded. Lastly, we compared RR of MHD of switches performed to mAbs with same target to those performed to mAbs with different target (CGRP receptor vs ligand).Descriptive statistics were developed. Categorical variables were reported as frequencies and percentages, and quantitative variables were expressed as measures of central tendency and dispersion. Median and interquartile range (IQR) were used for variables with asymmetric and abnormal distributions. Bivariate analysis was then performed. Normality tests were used, which defined non-parametric statistical hypothesis tests. In order to analyze matched samples before and after switching mAb, Wilcoxon test was chosen. Differences in RR between switches to same and different class were studied with Mann–Whitney U test. Results were analyzed with the SPSS 28.0.1.0. statistical package and R software. Results considered statistically significant when p<.05.We conducted this study according to the declaration of Helsinki. The local ethics committee approved the study (1720-N-22). All patients received written and verbal information.ResultsOur study included 90 patients. Baseline demographics and clinical characteristics prior to switch are summarized in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>. Of the 90 patients included, 75 (83.3%) were women. The mean age of the cohort at baseline was 45.9±11 years and the mean duration of migraine was 29.2±12.4 years. Diagnosis were CM in 72 patients (80%) and EM in 18 patients (20%), including 75 (83.3%) without aura and 15 (16.7%) with aura. Time under first mAb prior to switch was 10.4±4.9 months. The median MHD was 20 (IQR: 15–29) days. Among headache days, patients had a median MMD of 15 (IQR: 12–20). The median VAS was 8 (IQR: 7–8). Regarding concomitant treatment, median monthly days of NSAIDs use was 9 (IQR: 4–13) and median monthly days of triptans use was 6 (IQR: 2–10). NSAIDs overuse happened in 15/84 (17.9%) and triptans overuse in 18/73 (24.7%). Forty-four patients (48.9%) received concomitant oral prophylaxis, and 9 (10%) received regular onabotulinumtoxinA at the same time.<elsevierMultimedia ident="t0005"></elsevierMultimedia>Switch information is summarized in <a class="elsevierStyleCrossRef" href="#f0005">Fig. 1</a>. Initial mAbs were erenumab in 59 patients (65.6%), galcanezumab in 29 (32.2%), and fremanezumab in 2 (2.2%). After discontinuation, all 90 patients switched to a different CGRP–mAb and the main switches were: 38 (42.2%) erenumab–galcanezumab, 21 (23.3%) erenumab–fremanezumab, and 20 (22.2%) galcanezumab–erenumab. Two consecutive switches were reported in 6 patients. After switch, 5/9 (55.6%) were still receiving onabotulinumtoxinA and 35/44 (79.5%) had stable oral preventive medication. The remaining patients discontinuated the concomitant treatment during the study at their request. The reasons for switch were lack of effectiveness in 50 patients (55.6%) and lack of tolerability due to AEs in 40 patients (44.4%). The most common AEs were constipation in 16 (40%) patients and flu-like syndrome in 16 (40%) patients. Other AEs were injection site related symptoms in 5 (5.6%), hair loss in 2 (2.2%) and weight gain in 1 (1.1%).<elsevierMultimedia ident="f0005"></elsevierMultimedia>Regarding effectiveness outcomes of switch, 30%–50% RR was achieved in 10 patients (11.1%) and ≥50% was seen in 32 patients (35.6%), whereas <30% RR was observed in 48 patients (53.3%) (<a class="elsevierStyleCrossRef" href="#f0010">Fig. 2</a>). The mean VAS score reduction was 0.24±1.83 (range of reduction from −7 to +6) and VAS score reduction of ≥1 was reported in 29 patients (32.2%). Assessment of clinical characteristics before and after switch is shown in <a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>. This analysis showed a significant reduction in MHD and MMD after switch (<a class="elsevierStyleCrossRef" href="#f0015">Fig. 3</a>). Median MHD with the first CGRP-mAb was 20 (IQR: 15–29) vs 13 (IQR: 7–23) after switch (p<.001). Median MMD was 15 (IQR: 12–20) before vs 10 (IQR: 7–16) after switch (p<.001). No significant differences were found in headache severity, acute medication days, or disability, anxiety or depression scores.<elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0015"></elsevierMultimedia>Most of the patients switched to a mAb with different mechanism of action: 79 (87.8%). In this group, RR were: 42 patients (53.2%) <30%, 10 (12.7%) 30%–50%, and 27 (34.2%) ≥50%. Eleven patients (12.2%) switched to a mAb with similar mechanism of action; in this group, 6 patients had RR <30% and 5 patients ≥50%. RR were compared between both groups and no significant differences were found. The group who switched to a different class mAb and to a same class mAb showed a mean reduction of 23.61% (SD ±45.67) and 30.78% (SD ±41.2) in MHD, respectively, whereas the overall cohort had a 24.4% mean reduction in MHD after switch. In <a class="elsevierStyleCrossRef" href="#f0020">Fig. 4</a>, the distribution of reduction of MHD among groups is displayed.<elsevierMultimedia ident="f0020"></elsevierMultimedia>As for tolerability after switch, 38 patients (42.2%) experienced AEs. The distribution of AEs after switch was: constipation 17 (44.7%), flu-like syndrome 13 (34.2%), injection site-related symptoms 6 (15.8%), hair loss 1 (2.6%), and weight gain 1 (2.6%). A comparative graph of tolerability before and after switch is shown in <a class="elsevierStyleCrossRef" href="#f0025">Fig. 5</a>. In the group of patients who discontinued the first mAb due to AEs (<a class="elsevierStyleCrossRef" href="#f0030">Fig. 6</a>), 50% (20/40) improved tolerability with resolution of the AEs that motivated discontinuation. The 20 patients who still had AEs described: constipation 12 (60%), flu-like syndrome 4 (20%%), injection site-related symptoms 3 (15%), and hair loss 1 (5%).<elsevierMultimedia ident="f0025"></elsevierMultimedia><elsevierMultimedia ident="f0030"></elsevierMultimedia>DiscussionThis RWE study shows that migraine refractory patients who discontinue anti-CGRP mAbs (including non-responders and those with intolerance) may benefit from switching to another mAb, mainly in terms of effectiveness. We report absolute significant reductions in median MHD and MMD compared to baseline. In addition, a ≥50% RR occurred in more than one-third of the patients and a ≥30% RR was observed in 36.7% of the patients. Although the proportion of AEs was similar after switching, we report an improvement in tolerability in those patients whose switch was motivated by lack of tolerability with the first treatment. In fact, resolution of the AEs that prompted the switch was observed in half of the patients in this group.In previous literature about switch, the first mAb is usually erenumab and switch is mostly to galcanezumab or fremanezumab<a class="elsevierStyleCrossRefs" href="#bb0090">18–20</a> when ineffectiveness of erenumab is stated. This is similar to our study and is probably due to the earlier approval of erenumab. In general, there is a lack of consensus on the definition of first CGRP mAb ineffectiveness. In most cases, RR of MHD is the main outcome when assessing switch.<a class="elsevierStyleCrossRef" href="#bb0105">21</a> Although there is a general tendency to consider lack of efficacy when <30% reduction in headache frequency is achieved,<a class="elsevierStyleCrossRef" href="#bb0095">19</a>,<a class="elsevierStyleCrossRef" href="#bb0110">22</a> most studies are retrospective and influenced by different clinical practice protocols. Given the retrospective and multicenter nature of our study, the same limitations may apply, but based on previous literature, lack of effectiveness was considered when at least 30% reduction in MHD was not achieved. However, what is considered effective may differ among patients depending on the impact on their quality of life and their previous clinical situation. Thus, <30% MHD reduction may represent effectiveness in some refractory patients. In addition, effectiveness definitions should include not only headache frequency but also additional clinical parameters, such as severity, use of abortive treatments, or impact on quality of life. Interestingly, a recent retrospective study defined ineffectiveness for the first mAb by combining several variables simultaneously,<a class="elsevierStyleCrossRef" href="#bb0115">23</a> including reduction in headache days, disability scores, and abortive medication use. These new strategies provide guidance for future work in establishing consistent definitions of switching outcomes.Limited real-world data are available regarding the effectiveness of switching, including case series and retrospective studies. No interventional clinical trial has evaluated the effect of switching to another anti-CGRP mAb. A retrospective real-world study of 78 switching patients reported that approximately one-third of erenumab non-responders had a ≥30% RR of MHD at 3 months after switching to galcanezumab/fremanezumab.<a class="elsevierStyleCrossRef" href="#bb0095">19</a> Previous small case reports demonstrated clinically meaningful reductions in MMD and headache intensity.<a class="elsevierStyleCrossRef" href="#bb0090">18</a>,<a class="elsevierStyleCrossRef" href="#bb0100">20</a>,<a class="elsevierStyleCrossRef" href="#bb0120">24</a>,<a class="elsevierStyleCrossRef" href="#bb0125">25</a> Another recent retrospective cohort study with 22 patients and several variables as main outcomes reported that nearly 50% of patients achieved ≥30% RR in MHD, but also sustained reductions over time in abortive medication use and MIDAS/HIT-6 score at 3-month follow-up.<a class="elsevierStyleCrossRef" href="#bb0115">23</a> In this regard, our results provide additional evidence for switch as a beneficial tool for migraine refractory patients, as we report ≥50% RR of MHD in more than one-third of patients at 3-month follow-up. Although this improvement in effectiveness can be considered discrete (with about half of the patients improving <30%), it should not be underestimated due to the refractoriness of our population. RWE studies tend to enroll more refractory patients than clinical trials,<a class="elsevierStyleCrossRef" href="#bb0130">26</a> and this can greatly influence effectiveness results. In fact, refractoriness is one of the main characteristics of our cohort, since failure of three previous prophylactic treatments is required to meet the financial conditions of CGRP mAbs in Spain, and our patients also had undergone a mAb discontinuation. In addition to the aforementioned improvement in RR, we also found significant reductions in median MHD (20 vs 13 days) and MMD (15 vs 10 days). Similarly, a subgroup analysis of the Finesse study shows that MMD decreased from 13.6 at baseline to 7.2 at month 3, and this decrease was greater in CM than in EM.<a class="elsevierStyleCrossRef" href="#bb0080">16</a> In any case, the fact that an improvement in headache frequency was observed in a refractory cohort suggests that these data can be considered representative of the real-world population and can therefore be extrapolated to clinical practice.Other effectiveness outcomes have also been evaluated in studies. Significant reductions in disability scores (MIDAS and HIT-6) and acute migraine medication have been reported at 3 months after switching.<a class="elsevierStyleCrossRef" href="#bb0080">16</a>,<a class="elsevierStyleCrossRef" href="#bb0115">23</a> It is important to emphasize that most studies focus on headache frequency<a class="elsevierStyleCrossRef" href="#bb0105">21</a>,<a class="elsevierStyleCrossRef" href="#bb0135">27</a> and do not always include other clinical parameters such as disability and anxiety/depression scores, which can be very illustrative of the impact on daily life. This may be due to the difficulty in interpreting their subjective component and the time required to complete these questionnaires. However, disability and mood disorders are important clinical factors to consider when assessing patients with refractory migraine. They were included in our study, but no significant differences were found after switching. This needs further analysis with larger cohorts.Most switch analyses focus on non-responders to prior CGRP mAbs. Therefore, given the global paucity of information on switching due to lack of tolerability, the data reported in our cohort may be relevant. Tolerability rates of current RWE are variable.<a class="elsevierStyleCrossRef" href="#bb0070">14</a>,<a class="elsevierStyleCrossRef" href="#bb0140">28</a> As for AEs, their distribution was unchanged after switching in our cohort and was also consistent with the distribution in previous studies.<a class="elsevierStyleCrossRef" href="#bb0110">22</a>,<a class="elsevierStyleCrossRef" href="#bb0135">27</a>,<a class="elsevierStyleCrossRef" href="#bb0140">28</a> Interestingly, although it was only subjectively assessed and no formal questionnaires were administered, tolerability improved in 50% of patients whose switch was motivated by AEs in our study. It may be reasonable to consider the possibility that safety profiles may be heterogeneous among CGRP-mAbs, even more given that it is unknown how their variable targets may have an impact on efficacy and tolerability. Further research in this area may have future implications so that switching may become a therapeutic strategy not only to improve efficacy but also to address tolerability issues.As aforementioned, the different mechanisms of action of anti-CGRP mAbs may differentially affect effectiveness, safety, and tolerability in migraine patients. Therefore, it is reasonable to ask whether patients who did not respond to one anti-CGRP pathway mAb class might benefit from switching to the other class. However, in our series, no differences in RR were found between patients who switched to a mAb with a different mechanism of action. This is largely influenced by the size of our cohort and the asymmetry of the switches we report. Most patients switched from a CGRP receptor-targeting mAb to another CGRP ligand-binding mAb, with the consequent challenge of stating differences in this setting.The main limitations of this study are the retrospective design and the lack of longer follow-up after switching, which was limited to 3 months. Longer follow-up from this event would provide long-term effectiveness and tolerability data, which would be of interest to evaluate the benefits of switching. These data would also provide a more accurate picture compared to real-world practice, where discontinuation is usually considered after at least 6–12 months of treatment with a mAb.<a class="elsevierStyleCrossRef" href="#bb0085">17</a> Therefore, we highlight the current need to perform prospective studies that can assess the long-term outcome of switching after at least 6 months.Although there is currently a growing body of evidence on benefits of switch, we believe our study provides additional supportive data and highlights future research directions and needs. Nevertheless, there is a lack of prospective studies with larger cohorts and longer follow-up periods. Determining the specific group of patients who could truly benefit from switching in terms of effectiveness and tolerability would be one of the major challenges in the future perspective of CGRP-mAb research.ConclusionThis RWE cohort study suggests that some migraine refractory patients may benefit from switching to another mAb after discontinuation, particularly in terms of reduction of MHD. Partial improvement in AEs is also reported in patients who discontinued due to lack of tolerability. In our experience, switching may be an individualized treatment strategy in refractory patients. However, larger studies with long-term follow-up are needed to reach conclusive results. Our findings add new information to the current evidence on CGRP-mAbs switching and encourage future research in this area.FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.Patient consentAll patients received written and verbal information.Ethical considerationsWe conducted this study according to the declaration of Helsinki. The local ethics committee approved the study (1720-N-22)." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres2261940" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "as0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "as0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "as0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1888363" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2261939" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "as0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "as0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "as0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1888362" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "s0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "s0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "s0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "s0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "s0025" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "s0030" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "s0035" "titulo" => "Patient consent" ] 11 => array:2 [ "identificador" => "s0040" "titulo" => "Ethical considerations" ] 12 => array:2 [ "identificador" => "xack779312" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-12-26" "fechaAceptado" => "2024-04-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1888363" "palabras" => array:5 [ 0 => "Migraine" 1 => "Switch" 2 => "CGRP" 3 => "Monoclonal antibodies" 4 => "Real-world evidence" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1888362" "palabras" => array:5 [ 0 => "Migraña" 1 => "switch" 2 => "CGRP" 3 => "anticuerpos monoclonales" 4 => "experiencia en vida real" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "BackgroundSwitching between calcitonin gene-related peptide (CGRP) and monoclonal antibodies (mAbs) may be a beneficial strategy after discontinuation. The aim of this study was to evaluate switching outcomes of effectiveness/tolerability. MethodsRetrospective multicentric study of migraine patients who switched to another CGRP–mAb due to lack of tolerability or effectiveness (defined as <30% reduction of monthly headache days [MHD]). Assessment was performed before and 3 months after switch. The main outcome was the response rate of MHD. Secondary outcomes included other effectiveness/tolerability measures. Results90patients were included: 75(83.3%) women, 72(80%) chronic, and 18(20%) episodic migraine. Mean age was 45.9±11 years and mean duration of migraine was 29.2±12.4 years. Mean time under first mAb prior to switch was 10.4±4.9 months. Most frequent switches were erenumab-galcanezumab 38 (42.2%) and erenumab–fremanezumab 21 (23.3%). Lack of effectiveness (50/90, 55.6%) or tolerability (40/90, 44.4%) provoked switching. Most common adverse events (AEs) leading to discontinuation were constipation and flu-like syndrome in 16 (40%) patients each. Response rate (RR) of MHD 30%–50% occurred in 10 patients (11.1%), ≥50% in 32 (35.6%) and <30% in 48 (53.3%) patients. Significant reduction was proved after switch in MHD (20 [IQR:15–29] vs 13 [IQR:7–23]; p<.001) and monthly migraine days (15 [IQR:12–20] vs 10 [IQR:7–16]; p<.001). After switching, 38 (42.2%) experienced AEs, but tolerability improved in 50% of patients who discontinued due to lack of tolerability. RR compared between switches to different CGRP-mAb classes showed no differences. ConclusionSwitching may become an individualized strategy in migraine refractory patients who discontinue CGRP–mAbs due to lack of effectiveness/tolerability. In this study, supportive data are provided to the growing evidence of switch and future needs are highlighted." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "as0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "as0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "as0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónEl switch entre anticuerpos monoclonales (AMCs) frente al CGRP podría suponer una estrategia eficaz tras la discontinuación. El objetivo fue evaluar los resultados de efectividad/tolerabilidad del switch. MétodosEstudio retrospectivo multicéntrico incluyendo pacientes con migraña que realizaron switch a otro AMC-anti-CGRP debido a falta de tolerabilidad o efectividad (<30% reducción días cefalea mensual[DCM]). Fueron evaluados previamente y tres meses tras switch. La variable principal fue la tasa de respuesta en DCM. Los objetivos secundarios incluyeron otras medidas de efectividad/tolerabilidad. ResultadosSe incluyeron 90pacientes: 75(83.3%) mujeres, 72(80%) con migraña crónica y 18(20%) episódica. La edad media fue 45.9 ± 11años, la duración media de migraña 29.2 ± 12.4años. El tiempo medio con el primer AMC fue 10.4 ± 4.9meses. Los switch más frecuentes fueron erenumab-galcanezumab 38(42.2%) y erenumab-fremanezumab 21(23.3%). La falta de efectividad (50/90, 55.6%) o tolerabilidad (40/90, 44.4%) causaron el switch. Los efectos adversos(EAs) más frecuentes fueron estreñimiento y síndrome pseudogripal en 16(40%) respectivamente. La reducción de DCM fue 30–50% en 10 pacientes(11.1%), ≥50% en 32(35.6%) y < 30% en 48(53.3%). Se demostró una reducción significativa de DCM tras el switch (20[IQR:15–29] vs 13[IQR:7–23];p < 0,001) y DMM (15[IQR:12–20] vs 10[IQR:7–16];p < 0,001). Tras el switch, 38 pacientes(42.2%) experimentaron EAs, pero la tolerabilidad mejoró en 50% de pacientes que discontinuaron por ello. La reducción DCM comparada entre AMC con distinta diana(CGRP vs. ligando) no mostró diferencias. ConclusiónEl switch podría suponer una estrategia terapéutica en pacientes refractarios tras discontinuación de AMC anti-CGRP por falta de efectividad/tolerabilidad. Este estudio aporta evidencia adicional del switch y plantea nuevas necesidades y futuras investigaciones." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "as0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "as0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "as0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "as0040" "titulo" => "Conclusión" ] ] ] ] "multimedia" => array:8 [ 0 => array:8 [ "identificador" => "f0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2723 "Ancho" => 2764 "Tamanyo" => 363894 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Switch information. Initial (A) and switch (B) CGRP–mAbs are represented in this figure. Tables show distribution of initial CGRP–mAb, switch CGRP–mAb, and a summary of switches performed. CGRP–mAb: Calcitonin gene related-peptide monoclonal antibody." ] ] 1 => array:8 [ "identificador" => "f0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1208 "Ancho" => 2188 "Tamanyo" => 88047 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "RR of MHD after switch to a different anti-CGRP mAb. CGRP: calcitonin gene-related peptide, mAb: monoclonal antibody, MHD: monthly headache days, RR: response rate." ] ] 2 => array:8 [ "identificador" => "f0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1280 "Ancho" => 2372 "Tamanyo" => 111003 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "MHD and MMD evolution before and after switch. MHD: monthly headache days, MMD: monthly migraine days. *Statistical significance p<.001." ] ] 3 => array:8 [ "identificador" => "f0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1354 "Ancho" => 2396 "Tamanyo" => 133459 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Reduction in MHD after switch in different groups. No statistical differences were found between switches to same vs different class. MHD: monthly headache days." ] ] 4 => array:8 [ "identificador" => "f0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1202 "Ancho" => 2368 "Tamanyo" => 131398 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0025" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Tolerability before and after switch. AEs distribution is shown before and after switch in absolute numbers. AEs: adverse events." ] ] 5 => array:8 [ "identificador" => "f0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 827 "Ancho" => 2368 "Tamanyo" => 81425 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0030" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "AEs among patients who discontinuated first mAb because of lack of tolerability and their distribution. In 50% (20/40) of patients, there was a resolution of the AE that motivated discontinuation. The distribution of AEs among patients who still had lack of tolerability is shown. AEs: adverse events, mAb: monoclonal antibody." ] ] 6 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0035" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "HAD-A: Hospital Anxiety and Depression-Anxiety, HAD-D: Hospital Anxiety and Depression-Depression, HIT-6: headache impact test-6, IQR: interquartile range, mAb: monoclonal antibody, m: months, MHD: monthly headache days, MIDAS: migraine disability assessment scale, MMD: monthly migraine days, NSAIDs: non-steroidal anti-inflammatory drugs, SD: standard deviation, VAS: visual analogue scale, y: years." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n=90 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Female sex, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 (83.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.9±11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diagnosis</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic migraine, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72 (80) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Episodic migraine, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 (20) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aura, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (16.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Duration of migraine (y), mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29.2±12.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Time under first mAb prior to switch (m), mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.4±4.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MHD, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (15–29) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MMD, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (12–20) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VAS, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (7–8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute monthly NSAIDs use (days), median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (4–13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute monthly triptans use (days), median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (2–10) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NSAIDs overuse, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15/84 (17.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Triptans overuse, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18/73 (24.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oral preventive treatment, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (48.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">OnabotulinumtoxinA, n (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (10) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MIDAS, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (30–92) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIT-6, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 (63–70) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HAD-A, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (10–21) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HAD-D, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.5 (7–8) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3678840.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic and clinical characteristics of the overall cohort prior to switch." ] ] 7 => array:8 [ "identificador" => "t0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0040" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "HAD-A: Hospital Anxiety and Depression-Anxiety, HAD-D: Hospital Anxiety and Depression-Depression, HIT-6: headache impact test-6, IQR: interquartile range, MHD: monthly headache days, MIDAS: migraine disability assessment scale, MMD: monthly migraine days, NSAIDs: non-steroidal anti-inflammatory drugs, VAS: visual analogue scale." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Before switch \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">After switch \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MHD, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 (15–29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 (7–23) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MMD, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (12–20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (7–16) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VAS score, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (7–8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.5 (7–8.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute monthly NSAIDs use (days), median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (4–13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (3–12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute monthly triptans use (days), median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (2–10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (3–9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MIDAS, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (30–92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (25.5–90) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HIT-6 score, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 (63–70) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65 (61–68) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HAD-A, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (10–21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.5 (9–21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HAD-D, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.5 (7–8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.5 (2–9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3678839.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Statistical analysis of efficacy outcomes before and after switch." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "One-year prevalence of migraine in Spain: a nationwide population-based survey" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "J. Matías-Guiu" 1 => "J. Porta-Etessam" 2 => "V. Mateos" 3 => "S. Díaz-Insa" 4 => "A. Lopez-Gil" 5 => "C. Fernández" 6 => "Scientific Committee of the PALM Program" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0333102410382794" "Revista" => array:6 [ "tituloSerie" => "Cephalalgia" "fecha" => "2011 Mar" "volumen" => "31" "numero" => "4" "paginaInicial" => "463" "paginaFinal" => "470" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "GBD 2016 Disease and Injury Incidence and Prevalence Collaborators" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(17)32154-2" "Revista" => array:7 [ "tituloSerie" => "Lancet" "fecha" => "2017 Sep 16" "volumen" => "390" "numero" => "10100" "paginaInicial" => "1211" "paginaFinal" => "1259" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28919117" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bb0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "GBD 2016 Headache Collaborators" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1474-4422(18)30322-3" "Revista" => array:7 [ "tituloSerie" => "Lancet Neurol" "fecha" => "2018 Nov" "volumen" => "17" "numero" => "11" "paginaInicial" => "954" "paginaFinal" => "976" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30353868" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bb0020" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Migraine: epidemiology, burden, and comorbidity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.C. Burch" 1 => "D.C. Buse" 2 => "R.B. Lipton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ncl.2019.06.001" "Revista" => array:7 [ "tituloSerie" => "Neurol Clin" "fecha" => "2019 Nov" "volumen" => "37" "numero" => "4" "paginaInicial" => "631" "paginaFinal" => "649" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31563224" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bb0025" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The International Classification of Headache Disorders, 3rd edition" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Headache Classification Committee of the International Headache Society (IHS)" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0333102417738202" "Revista" => array:7 [ "tituloSerie" => "Cephalalgia" "fecha" => "2018 Jan" "volumen" => "38" "numero" => "1" "paginaInicial" => "1" "paginaFinal" => "211" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30185059" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bb0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neurological and psychiatric comorbidities of migraine: concepts and future perspectives" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Pelzer" 1 => "I. de Boer" 2 => "A.M.J.M. van den Maagdenberg" 3 => "G.M. Terwindt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/03331024231180564" "Revista" => array:4 [ "tituloSerie" => "Cephalalgia" "fecha" => "2023 Jun" "volumen" => "43" "numero" => "6" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bb0035" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CGRP and its receptors provide new insights into migraine pathophysiology" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T.W. Ho" 1 => "L. Edvinsson" 2 => "P.J. Goadsby" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrneurol.2010.127" "Revista" => array:7 [ "tituloSerie" => "Nat Rev Neurol" "fecha" => "2010 Oct" "volumen" => "6" "numero" => "10" "paginaInicial" => "573" "paginaFinal" => "582" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20820195" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bb0040" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Tepper" 1 => "M. Ashina" 2 => "U. Reuter" 3 => "J.L. Brandes" 4 => "D. Doležil" 5 => "S. Silberstein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1474-4422(17)30083-2" "Revista" => array:7 [ "tituloSerie" => "Lancet Neurol" "fecha" => "2017 Jun" "volumen" => "16" "numero" => "6" "paginaInicial" => "425" "paginaFinal" => "434" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28460892" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bb0045" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.C. Detke" 1 => "P.J. Goadsby" 2 => "S. Wang" 3 => "D.I. Friedman" 4 => "K.J. Selzler" 5 => "S.K. Aurora" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1212/WNL.0000000000006640" "Revista" => array:7 [ "tituloSerie" => "Neurology" "fecha" => "2018 Dec 11" "volumen" => "91" "numero" => "24" "paginaInicial" => "e2211" "paginaFinal" => "e2221" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30446596" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bb0050" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of fremanezumab compared with placebo for prevention of episodic migraine: a randomized clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.W. Dodick" 1 => "S.D. Silberstein" 2 => "M.E. Bigal" 3 => "P.P. Yeung" 4 => "P.J. Goadsby" 5 => "T. Blankenbiller" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2018.4853" "Revista" => array:7 [ "tituloSerie" => "JAMA" "fecha" => "2018 May 15" "volumen" => "319" "numero" => "19" "paginaInicial" => "1999" "paginaFinal" => "2008" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29800211" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bb0055" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Eptinezumab in episodic migraine: a randomized, double-blind, placebo-controlled study (PROMISE-1)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Ashina" 1 => "J. Saper" 2 => "R. Cady" 3 => "B.A. Schaeffler" 4 => "D.M. Biondi" 5 => "J. Hirman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0333102420905132" "Revista" => array:7 [ "tituloSerie" => "Cephalalgia" "fecha" => "2020 Mar" "volumen" => "40" "numero" => "3" "paginaInicial" => "241" "paginaFinal" => "254" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32075406" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bb0060" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Erenumab in the prevention of high-frequency episodic and chronic migraine: Erenumab in Real Life in Italy (EARLY), the first Italian multicenter, prospective real-life study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Barbanti" 1 => "C. Aurilia" 2 => "G. Egeo" 3 => "L. Fofi" 4 => "S. Cevoli" 5 => "B. Colombo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/head.14032" "Revista" => array:7 [ "tituloSerie" => "Headache" "fecha" => "2021 Feb" "volumen" => "61" "numero" => "2" "paginaInicial" => "363" "paginaFinal" => "372" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33337544" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bb0065" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse: real-life effectiveness and predictors of response at 6months" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E. Caronna" 1 => "V.J. Gallardo" 2 => "A. Alpuente" 3 => "M. Torres-Ferrus" 4 => "P. Pozo-Rosich" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s10194-021-01328-1" "Revista" => array:6 [ "tituloSerie" => "J Headache Pain" "fecha" => "2021 Oct 7" "volumen" => "22" "numero" => "1" "paginaInicial" => "120" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34620085" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bb0070" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Real-world effectiveness and tolerability of erenumab: a retrospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Kanaan" 1 => "G. Hettie" 2 => "E. Loder" 3 => "R. Burch" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0333102420946725" "Revista" => array:7 [ "tituloSerie" => "Cephalalgia" "fecha" => "2020 Nov" "volumen" => "40" "numero" => "13" "paginaInicial" => "1511" "paginaFinal" => "1522" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32791922" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bb0075" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predictors of response to anti-CGRP monoclonal antibodies: a 24-week, multicenter, prospective study on 864 migraine patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "P. Barbanti" 1 => "G. Egeo" 2 => "C. Aurilia" 3 => "C. Altamura" 4 => "F. d'Onofrio" 5 => "C. Finocchi" 6 => "Italian Migraine Registry study group" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s10194-022-01498-6" "Revista" => array:7 [ "tituloSerie" => "J Headache Pain" "fecha" => "2022 Nov 1" "volumen" => "23" "numero" => "1" "paginaInicial" => "138" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36316648" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0140673622012144" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bb0080" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: a subgroup analysis of the Finesse Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Straube" 1 => "G. Broessner" 2 => "C. Gaul" 3 => "X. Hamann" 4 => "J. Hipp" 5 => "T. Kraya" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s10194-023-01593-2" "Revista" => array:5 [ "tituloSerie" => "J Headache Pain" "fecha" => "2023 May 23" "volumen" => "24" "numero" => "1" "paginaInicial" => "59" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bb0085" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Sacco" 1 => "F.M. Amin" 2 => "M. Ashina" 3 => "L. Bendtsen" 4 => "C.I. Deligianni" 5 => "R. Gil-Gouveia" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s10194-022-01431-x" "Revista" => array:6 [ "tituloSerie" => "J Headache Pain" "fecha" => "2022 Jun 11" "volumen" => "23" "numero" => "1" "paginaInicial" => "67" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35690723" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bb0090" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early experiences in switching between monoclonal antibodies in patients with nonresponsive migraine in Spain: a case series" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "I. Patier Ruiz" 1 => "J. Sánchez-Rubio Ferrández" 2 => "A. Cárcamo Fonfría" 3 => "T. Molina García" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000518899" "Revista" => array:8 [ "tituloSerie" => "Eur Neurol" "fecha" => "2022" "volumen" => "85" "numero" => "2" "paginaInicial" => "132" "paginaFinal" => "135" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34510038" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0213911120300935" "estado" => "S300" "issn" => "02139111" ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bb0095" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of antibody switch in non-responders to a CGRP receptor antibody treatment in migraine: a multi-center retrospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.H. Overeem" 1 => "A. Peikert" 2 => "M.D. Hofacker" 3 => "K. Kamm" 4 => "R. Ruscheweyh" 5 => "A. Gendolla" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/03331024211048765" "Revista" => array:7 [ "tituloSerie" => "Cephalalgia" "fecha" => "2022 Apr" "volumen" => "42" "numero" => "4–5" "paginaInicial" => "291" "paginaFinal" => "301" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34644203" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bb0100" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-responders to treatment with antibodies to the CGRP-receptor may profit from a switch of antibody class" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Ziegeler" 1 => "A. May" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/head.13729" "Revista" => array:7 [ "tituloSerie" => "Headache" "fecha" => "2020 Feb" "volumen" => "60" "numero" => "2" "paginaInicial" => "469" "paginaFinal" => "470" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31872439" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bb0105" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Monoclonal antibodies against CGRP (R): non-responders and switchers: real world data from an austrian case series" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Kaltseis" 1 => "V. Filippi" 2 => "F. Frank" 3 => "C. Eckhardt" 4 => "A. Schiefecker" 5 => "G. Broessner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12883-023-03203-9" "Revista" => array:6 [ "tituloSerie" => "BMC Neurol" "fecha" => "2023 Apr 28" "volumen" => "23" "numero" => "1" "paginaInicial" => "174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37118682" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bb0110" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term effect of switching from an anti-CGRP receptor to an anti-CGRP ligand antibody in treatment-refractory chronic migraine: a prospective real-world analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Lambru" 1 => "V. Caponnetto" 2 => "B. Hill" 3 => "S. Ratti" 4 => "S. Sacco" 5 => "M. Murphy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s13311-023-01394-0" "Revista" => array:7 [ "tituloSerie" => "Neurotherapeutics" "fecha" => "2023 Sep" "volumen" => "20" "numero" => "5" "paginaInicial" => "1284" "paginaFinal" => "1293" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37430146" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bb0115" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Switching anti-CGRP(R) monoclonal antibodies in multi-assessed non-responder patients and implications for ineffectiveness criteria: a retrospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.F. Iannone" 1 => "A. Burgalassi" 2 => "G. Vigani" 3 => "G. Tabasso" 4 => "F. De Cesaris" 5 => "A. Chiarugi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/03331024231160519" "Revista" => array:4 [ "tituloSerie" => "Cephalalgia" "fecha" => "2023 Apr" "volumen" => "43" "numero" => "4" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bb0120" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Failure of monoclonal antibodies against CGRP or its receptor does not imply lack of efficacy of other drugs from the same class" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Porta-Etessam" 1 => "N. González-García" 2 => "Á.L. Guerrero" 3 => "D. García-Azorín" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.nrleng.2020.10.008" "Revista" => array:6 [ "tituloSerie" => "Neurologia (Engl Ed)" "fecha" => "2021 Oct" "volumen" => "36" "numero" => "8" "paginaInicial" => "638" "paginaFinal" => "640" ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bb0125" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Switching of monoclonal antibodies against calcitonin gene-related peptide in chronic migraine in clinical practice: a case series" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.D.P. Briceño-Casado" 1 => "M.D. Gil-Sierra" 2 => "B. De-La-Calle-Riaguas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ejhpharm-2021-002946" "Revista" => array:6 [ "tituloSerie" => "Eur J Hosp Pharm" "fecha" => "2023 Jul" "volumen" => "30" "numero" => "4" "paginaInicial" => "e19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36220334" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bb0130" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Real-world long-term efficacy and safety of erenumab in adults with chronic migraine: a 52-week, single-center, prospective, observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.K. Cullum" 1 => "T.P. Do" 2 => "M. Ashina" 3 => "L. Bendtsen" 4 => "S.S. Hugger" 5 => "A. Iljazi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s10194-022-01433-9" "Revista" => array:6 [ "tituloSerie" => "J Headache Pain" "fecha" => "2022 Jun 2" "volumen" => "23" "numero" => "1" "paginaInicial" => "61" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35655137" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bb0135" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Switching between anti-calcitonin gene-related peptide monoclonal antibodies: a comparison of monthly and quarterly dosing" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Ihara" 1 => "S. Ohtani" 2 => "N. Watanabe" 3 => "N. Takahashi" 4 => "N. Miyazaki" 5 => "R. Takemura" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jns.2023.120811" "Revista" => array:3 [ "tituloSerie" => "J Neurol Sci" "fecha" => "2023 Oct 15" "volumen" => "453" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bb0140" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Monoclonal antibodies against calcitonin gene-related peptide for migraine prophylaxis: a systematic review of real-world data" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A.R. Pavelic" 1 => "C. Wöber" 2 => "F. Riederer" 3 => "K. Zebenholzer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/cells12010143" "Revista" => array:5 [ "tituloSerie" => "Cells" "fecha" => "2022 Dec 29" "volumen" => "12" "numero" => "1" "paginaInicial" => "143" ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack779312" "titulo" => "Acknowledgments" "texto" => "The authors acknowledge Fundación Pública Andaluza para la Gestión de la Investigación en Salud (FISEVI) of Hospital Universitario Virgen del Rocío for statistical and methodological support on this manuscript." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/26670496/0000000400000004/v7_202410041010/S2667049624000255/v7_202410041010/en/main.assets" "Apartado" => array:4 [ "identificador" => "91827" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/26670496/0000000400000004/v7_202410041010/S2667049624000255/v7_202410041010/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2667049624000255?idApp=UINPBA00004N"]

Statistics

Original article

Experiencia del switch de anticuerpos monoclonales frente al péptido relacionado con el gen de la calcitonina o su receptor en migraña. Resultados de una cohorte española

J. Arzalluz-Luquea,

Corresponding author

joaquin.arzalluz.sspa@juntadeandalucia.es

Corresponding author at: Unidad de Cefaleas, Servicio de Neurología, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n., 41013 Sevilla, Spain.

, M. Millán Vázqueza, R. Lamas Péreza, N. Sánchez Rodrígueza, P. Gómez Lópeza, F.J. Gómez Fernándeza, J. Viguera Romerob, C. Jurado Coboc, M. Fernández Reciod, C. González Oriaa

a Unidad de Cefaleas, Servicio de Neurología, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, 41013 Sevilla, Spain

b Servicio de Neurología, Hospital Universitario Virgen Macarena, Av. Dr. Fedriani, 3, 41009 Sevilla, Spain

c Servicio de Neurología, Hospital Universitario Reina Sofía, Av. Menendez Pidal, s/n, 14004 Córdoba, Spain

d Servicio de Neurología, Hospital Universitario Virgen de Valme, Ctra. de Cádiz Km. 548,9, 41014 Sevilla, Spain

Read

210

Times
was read the article

Total PDF

139

Total HTML

Share statistics

 array:21 [
  "pii" => "S2667049624000255"
  "issn" => "26670496"
  "doi" => "10.1016/j.neurop.2024.100168"
  "estado" => "S250"
  "fechaPublicacion" => "2024-10-01"
  "aid" => "100168"
  "copyright" => "Sociedad Espa&#241;ola de Neurolog&#237;a"
  "copyrightAnyo" => "2024"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemSiguiente" => array:17 [
    "pii" => "S2667049624000243"
    "issn" => "26670496"
    "doi" => "10.1016/j.neurop.2024.100167"
    "estado" => "S250"
    "fechaPublicacion" => "2024-10-01"
    "aid" => "100167"
    "copyright" => "Sociedad Espa&#241;ola de Neurolog&#237;a"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "fla"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Sensitivity and specificity of the ocular movements test &#40;HINTS&#41; in the detection of central acute vestibular syndrome"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Sensibilidad y especificidad de la prueba de movimientos oculares &#40;HINTS&#41; en la detecci&#243;n del s&#237;ndrome vestibular Agudo central"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "f0010"
          "etiqueta" => "Fig&#46; 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 1875
              "Ancho" => 1715
              "Tamanyo" => 144593
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "al0010"
              "detalle" => "Fig&#46; "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Results of the distribution of causal diagnoses of central acute vestibular syndrome&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Issa Layka, Mostafa Ibrahim, Ahmed Issa"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Issa"
              "apellidos" => "Layka"
            ]
            1 => array:2 [
              "nombre" => "Mostafa"
              "apellidos" => "Ibrahim"
            ]
            2 => array:2 [
              "nombre" => "Ahmed"
              "apellidos" => "Issa"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2667049624000243?idApp=UINPBA00004N"
    "url" => "/26670496/0000000400000004/v7_202410041010/S2667049624000243/v7_202410041010/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Switching of monoclonal antibodies against the calcitonin gene-related peptide or its receptor in migraine&#46; Results from a Spanish Cohort"
    "tieneTextoCompleto" => true
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "J&#46; Arzalluz-Luque, M&#46; Mill&#225;n V&#225;zquez, R&#46; Lamas P&#233;rez, N&#46; S&#225;nchez Rodr&#237;guez, P&#46; G&#243;mez L&#243;pez, F&#46;J&#46; G&#243;mez Fern&#225;ndez, J&#46; Viguera Romero, C&#46; Jurado Cobo, M&#46; Fern&#225;ndez Recio, C&#46; Gonz&#225;lez Oria"
        "autores" => array:10 [
          0 => array:4 [
            "nombre" => "J&#46;"
            "apellidos" => "Arzalluz-Luque"
            "email" => array:1 [
              0 => "joaquin.arzalluz.sspa@juntadeandalucia.es"
            ]
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "af0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cr0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "M&#46;"
            "apellidos" => "Mill&#225;n V&#225;zquez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "af0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "R&#46;"
            "apellidos" => "Lamas P&#233;rez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "af0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "N&#46;"
            "apellidos" => "S&#225;nchez Rodr&#237;guez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "af0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "P&#46;"
            "apellidos" => "G&#243;mez L&#243;pez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "af0005"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "F&#46;J&#46;"
            "apellidos" => "G&#243;mez Fern&#225;ndez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "af0005"
              ]
            ]
          ]
          6 => array:3 [
            "nombre" => "J&#46;"
            "apellidos" => "Viguera Romero"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "af0010"
              ]
            ]
          ]
          7 => array:3 [
            "nombre" => "C&#46;"
            "apellidos" => "Jurado Cobo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "af0015"
              ]
            ]
          ]
          8 => array:3 [
            "nombre" => "M&#46;"
            "apellidos" => "Fern&#225;ndez Recio"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "af0020"
              ]
            ]
          ]
          9 => array:3 [
            "nombre" => "C&#46;"
            "apellidos" => "Gonz&#225;lez Oria"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "af0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Unidad de Cefaleas&#44; Servicio de Neurolog&#237;a&#44; Hospital Universitario Virgen del Roc&#237;o&#44; Avenida Manuel Siurot s&#47;n&#44; 41013 Sevilla&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "af0005"
          ]
          1 => array:3 [
            "entidad" => "Servicio de Neurolog&#237;a&#44; Hospital Universitario Virgen Macarena&#44; Av&#46; Dr&#46; Fedriani&#44; 3&#44; 41009 Sevilla&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "af0010"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Neurolog&#237;a&#44; Hospital Universitario Reina Sof&#237;a&#44; Av&#46; Menendez Pidal&#44; s&#47;n&#44; 14004 C&#243;rdoba&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "af0015"
          ]
          3 => array:3 [
            "entidad" => "Servicio de Neurolog&#237;a&#44; Hospital Universitario Virgen de Valme&#44; Ctra&#46; de C&#225;diz Km&#46; 548&#44;9&#44; 41014 Sevilla&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "af0020"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cr0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author at&#58; Unidad de Cefaleas&#44; Servicio de Neurolog&#237;a&#44; Hospital Universitario Virgen del Roc&#237;o&#44; Avenida Manuel Siurot s&#47;n&#46;&#44; 41013 Sevilla&#44; Spain&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Experiencia del switch de anticuerpos monoclonales frente al p&#233;ptido relacionado con el gen de la calcitonina o su receptor en migra&#241;a&#46; Resultados de una cohorte espa&#241;ola"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "f0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2723
            "Ancho" => 2764
            "Tamanyo" => 363894
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0005"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Switch information&#46; Initial &#40;A&#41; and switch &#40;B&#41; CGRP&#8211;mAbs are represented in this figure&#46; Tables show distribution of initial CGRP&#8211;mAb&#44; switch CGRP&#8211;mAb&#44; and a summary of switches performed&#46; CGRP&#8211;mAb&#58; Calcitonin gene related-peptide monoclonal antibody&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0065">Background</span><p id="p0005" class="elsevierStylePara elsevierViewall">Migraine is a common primary headache disorder&#44; affecting more than 4&#46;5 million people in Spain&#44; where its prevalence is 12&#37; for episodic migraine &#40;EM&#41; and 2&#37; for chronic migraine &#40;CM&#41;&#46;<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> It is considered one of the most disabling diseases by the World Health Organization<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> and it is the second most disabling disease worldwide after low back pain&#46;<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a> According to the International Classification of Headache Disorders&#44; 3rd edition &#40;ICHD-3&#41;&#44; migraine is defined as recurrent headaches lasting 4&#8211;72&#8239;h&#44; of variable intensity&#44; usually described as pulsating and unilateral&#44; accompanied by nausea&#47;vomiting&#44; photophobia&#44; and phonophobia&#46;<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> Regarding monthly headache days &#40;MHD&#41;&#44; it is classified in 2 major types&#58; CM when &#8805;<span class="elsevierStyleHsp" style=""></span>15 MHD for &#62;<span class="elsevierStyleHsp" style=""></span>3&#8239;months&#44; requiring at least 8&#8239;days with migraine features&#44; and EM when &#60;<span class="elsevierStyleHsp" style=""></span>15 MHD&#46;<a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> This disease includes not only headache but also disabling prodromal and postdromal symptoms and migraine aura&#46; The association with other comorbidities has been stated&#44; mostly neurological and psychiatric disorders&#46;<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a></p><p id="p0010" class="elsevierStylePara elsevierViewall">Recent advances in the understanding of migraine pathophysiology outlined the importance of neuronal circuits including cortical and subcortical structures and the relevant role of the calcitonin gene-related peptide &#40;CGRP&#41; pathway in modulation of central pain circuits and in the triggering of migraine&#46;<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a> Similarly&#44; CGRP antagonist proved to abort and prevent migraine attacks&#46;<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a> These findings ultimately led to the development of monoclonal antibodies &#40;mAbs&#41; targeting CGRP ligand &#40;galcanezumab&#44; fremanezumab&#44; and eptinezumab&#41; or its receptor &#40;erenumab&#41;&#46; CGRP-mAbs proved to be effective&#44; safe&#44; and well tolerated for preventing migraine attacks&#46;<a class="elsevierStyleCrossRefs" href="#bb0040"><span class="elsevierStyleSup">8&#8211;11</span></a> Indeed&#44; real-world evidence &#40;RWE&#41; studies&#44; generally involving a more refractory population&#44; confirmed efficacy&#44; tolerability&#44; and safety outcomes&#46;<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> To date&#44; comparative head-to-head trials of CGRP&#8211;mAbs are lacking&#46;</p><p id="p0015" class="elsevierStylePara elsevierViewall">Nevertheless&#44; the response may vary in real clinical practice&#46; Actually&#44; RWE shows that up to 30&#37; of patients discontinued CGRP&#8211;mAbs&#44; mostly due to lack of benefit&#46;<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a> In addition&#44; a recent multicenter prospective study of migraine patients treated with anti-CGRP&#8211;mAbs showed that around 40&#37;&#8211;45&#37; of patients did not achieve &#8805;<span class="elsevierStyleHsp" style=""></span>50&#37; response rate &#40;RR&#41; at week 24 of follow-up&#46;<a class="elsevierStyleCrossRef" href="#bb0075"><span class="elsevierStyleSup">15</span></a> Same results were found in previous prospective studies after 3 and 6&#8239;months of follow-up&#46;<a class="elsevierStyleCrossRef" href="#bb0060"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0065"><span class="elsevierStyleSup">13</span></a> Interestingly&#44; some non-responders might achieve a more effective response when switching to a different mAb&#44; regarding monthly migraine days &#40;MMD&#41; reduction&#44; improvement of quality of life parameters&#44; and reduction of acute migraine medication use&#46;<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> Due to diverse therapeutic targets &#40;CGRP ligand vs receptor&#41;&#44; it is reasonable to question whether different action mechanisms may play a relevant role in the variability of efficacy found among patients&#46; However&#44; evidence regarding switch is lacking and clinical practice guidelines have not provided recommendations in this regard&#46;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> The aim of this study was to evaluate whether switching CGRP&#8211;mAb is associated with clinical improvement in terms of effectiveness and tolerability outcomes&#46;</p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0070">Methods</span><p id="p0020" class="elsevierStylePara elsevierViewall">An observational&#44; longitudinal&#44; retrospective&#44; and multicenter study was conducted between January 2018 and June 2022&#46; We included patients diagnosed with migraine according to ICHD-3 criteria&#44; with or without aura&#44; aged at least 18&#8239;years&#44; who were treated with CGRP&#8211;mAbs and switched mAb for any reason&#58; lack of effiectiveness or lack of tolerability&#46; Lack of effectiveness was considered when the reduction in MHD after the period with the first mAb was &#60;<span class="elsevierStyleHsp" style=""></span>30&#37; and lack of tolerability when adverse events &#40;AEs&#41; having a life impact occurred&#46; There was no wash-out period before switching mAbs&#46; All patients were evaluated before switch &#40;after the period of treatment with first mAb&#44; considered baseline&#41; and then reevaluated 3&#8239;months after switching&#44; when effectiveness and tolerability outcomes were assessed&#46; No concomitant prophylactic medications were added or changed during this period&#44; only discontinued at the request of patients&#46;</p><p id="p0025" class="elsevierStylePara elsevierViewall">Follow-up was performed at headache monographic neurology consultations&#46; Electronic medical records were used to collect demographic data and clinical variables at baseline and after switching&#44; including headache frequency &#40;MHD and MMD&#41;&#44; severity &#40;measured by a 1&#8211;10 visual analogue scale &#91;VAS&#93;&#41;&#44; use of acute and preventive migraine medication&#44; disability&#44; and anxiety-depression surveys&#46; Medication overuse was considered if used &#8805;<span class="elsevierStyleHsp" style=""></span>10&#8239;days per month for triptans and &#8805;<span class="elsevierStyleHsp" style=""></span>15 days for non-steroidal anti-inflammatory drugs &#40;NSAIDs&#41;&#46; Disability questionnaires were those regularly used for headache&#58; Migraine Disability Assessment Scale &#40;MIDAS&#41; and Headache Impact Test-6 &#40;HIT6&#41;&#46; Anxiety and depression surveys were Hospital Anxiety and Depression-Anxiety and Hospital Anxiety and Depression-Depression&#46; Tolerability in terms of reported AEs&#44; the reason for discontinuation of first mAb &#40;lack of effectiveness&#47;lack of tolerability&#41; and switch information were recorded&#46;</p><p id="p0030" class="elsevierStylePara elsevierViewall">The primary outcome of the study was to determine RR &#40;&#60;<span class="elsevierStyleHsp" style=""></span>30&#37;&#44; 30&#37;&#8211;50&#37;&#44; &#8805;<span class="elsevierStyleHsp" style=""></span>50&#37;&#41; of MHD&#46; Secondary outcomes included measures of effectiveness &#40;absolute changes in frequency of MHD&#47;MMD&#44; headache severity&#44; disability scores&#44; and use of acute migraine medication&#41; and tolerability of switch&#46; We analyzed other effectiveness outcomes such as mean reduction in VAS score and percentage of patients with VAS score reduction of at least 1 point&#46; In addition&#44; clinical variables of effectiveness were compared before and 3&#8239;months after switch&#46; Differences in tolerability and reported AEs were also recorded&#46; Lastly&#44; we compared RR of MHD of switches performed to mAbs with same target to those performed to mAbs with different target &#40;CGRP receptor vs ligand&#41;&#46;</p><p id="p0035" class="elsevierStylePara elsevierViewall">Descriptive statistics were developed&#46; Categorical variables were reported as frequencies and percentages&#44; and quantitative variables were expressed as measures of central tendency and dispersion&#46; Median and interquartile range &#40;IQR&#41; were used for variables with asymmetric and abnormal distributions&#46; Bivariate analysis was then performed&#46; Normality tests were used&#44; which defined non-parametric statistical hypothesis tests&#46; In order to analyze matched samples before and after switching mAb&#44; Wilcoxon test was chosen&#46; Differences in RR between switches to same and different class were studied with Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; Results were analyzed with the SPSS 28&#46;0&#46;1&#46;0&#46; statistical package and R software&#46; Results considered statistically significant when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p><p id="p0040" class="elsevierStylePara elsevierViewall">We conducted this study according to the declaration of Helsinki&#46; The local ethics committee approved the study &#40;1720-N-22&#41;&#46; All patients received written and verbal information&#46;</p></span><span id="s0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0075">Results</span><p id="p0045" class="elsevierStylePara elsevierViewall">Our study included 90 patients&#46; Baseline demographics and clinical characteristics prior to switch are summarized in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>&#46; Of the 90 patients included&#44; 75 &#40;83&#46;3&#37;&#41; were women&#46; The mean age of the cohort at baseline was 45&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#8239;years and the mean duration of migraine was 29&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;4&#8239;years&#46; Diagnosis were CM in 72 patients &#40;80&#37;&#41; and EM in 18 patients &#40;20&#37;&#41;&#44; including 75 &#40;83&#46;3&#37;&#41; without aura and 15 &#40;16&#46;7&#37;&#41; with aura&#46; Time under first mAb prior to switch was 10&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;9&#8239;months&#46; The median MHD was 20 &#40;IQR&#58; 15&#8211;29&#41; days&#46; Among headache days&#44; patients had a median MMD of 15 &#40;IQR&#58; 12&#8211;20&#41;&#46; The median VAS was 8 &#40;IQR&#58; 7&#8211;8&#41;&#46; Regarding concomitant treatment&#44; median monthly days of NSAIDs use was 9 &#40;IQR&#58; 4&#8211;13&#41; and median monthly days of triptans use was 6 &#40;IQR&#58; 2&#8211;10&#41;&#46; NSAIDs overuse happened in 15&#47;84 &#40;17&#46;9&#37;&#41; and triptans overuse in 18&#47;73 &#40;24&#46;7&#37;&#41;&#46; Forty-four patients &#40;48&#46;9&#37;&#41; received concomitant oral prophylaxis&#44; and 9 &#40;10&#37;&#41; received regular onabotulinumtoxinA at the same time&#46;</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p0050" class="elsevierStylePara elsevierViewall">Switch information is summarized in <a class="elsevierStyleCrossRef" href="#f0005">Fig&#46; 1</a>&#46; Initial mAbs were erenumab in 59 patients &#40;65&#46;6&#37;&#41;&#44; galcanezumab in 29 &#40;32&#46;2&#37;&#41;&#44; and fremanezumab in 2 &#40;2&#46;2&#37;&#41;&#46; After discontinuation&#44; all 90 patients switched to a different CGRP&#8211;mAb and the main switches were&#58; 38 &#40;42&#46;2&#37;&#41; erenumab&#8211;galcanezumab&#44; 21 &#40;23&#46;3&#37;&#41; erenumab&#8211;fremanezumab&#44; and 20 &#40;22&#46;2&#37;&#41; galcanezumab&#8211;erenumab&#46; Two consecutive switches were reported in 6 patients&#46; After switch&#44; 5&#47;9 &#40;55&#46;6&#37;&#41; were still receiving onabotulinumtoxinA and 35&#47;44 &#40;79&#46;5&#37;&#41; had stable oral preventive medication&#46; The remaining patients discontinuated the concomitant treatment during the study at their request&#46; The reasons for switch were lack of effectiveness in 50 patients &#40;55&#46;6&#37;&#41; and lack of tolerability due to AEs in 40 patients &#40;44&#46;4&#37;&#41;&#46; The most common AEs were constipation in 16 &#40;40&#37;&#41; patients and flu-like syndrome in 16 &#40;40&#37;&#41; patients&#46; Other AEs were injection site related symptoms in 5 &#40;5&#46;6&#37;&#41;&#44; hair loss in 2 &#40;2&#46;2&#37;&#41; and weight gain in 1 &#40;1&#46;1&#37;&#41;&#46;</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0055" class="elsevierStylePara elsevierViewall">Regarding effectiveness outcomes of switch&#44; 30&#37;&#8211;50&#37; RR was achieved in 10 patients &#40;11&#46;1&#37;&#41; and &#8805;<span class="elsevierStyleHsp" style=""></span>50&#37; was seen in 32 patients &#40;35&#46;6&#37;&#41;&#44; whereas &#60;<span class="elsevierStyleHsp" style=""></span>30&#37; RR was observed in 48 patients &#40;53&#46;3&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#f0010">Fig&#46; 2</a>&#41;&#46; The mean VAS score reduction was 0&#46;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;83 &#40;range of reduction from &#8722;<span class="elsevierStyleHsp" style=""></span>7 to &#43;<span class="elsevierStyleHsp" style=""></span>6&#41; and VAS score reduction of &#8805;<span class="elsevierStyleHsp" style=""></span>1 was reported in 29 patients &#40;32&#46;2&#37;&#41;&#46; Assessment of clinical characteristics before and after switch is shown in <a class="elsevierStyleCrossRef" href="#t0010">Table 2</a>&#46; This analysis showed a significant reduction in MHD and MMD after switch &#40;<a class="elsevierStyleCrossRef" href="#f0015">Fig&#46; 3</a>&#41;&#46; Median MHD with the first CGRP-mAb was 20 &#40;IQR&#58; 15&#8211;29&#41; vs 13 &#40;IQR&#58; 7&#8211;23&#41; after switch &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; Median MMD was 15 &#40;IQR&#58; 12&#8211;20&#41; before vs 10 &#40;IQR&#58; 7&#8211;16&#41; after switch &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; No significant differences were found in headache severity&#44; acute medication days&#44; or disability&#44; anxiety or depression scores&#46;</p><elsevierMultimedia ident="f0010"></elsevierMultimedia><elsevierMultimedia ident="t0010"></elsevierMultimedia><elsevierMultimedia ident="f0015"></elsevierMultimedia><p id="p0060" class="elsevierStylePara elsevierViewall">Most of the patients switched to a mAb with different mechanism of action&#58; 79 &#40;87&#46;8&#37;&#41;&#46; In this group&#44; RR were&#58; 42 patients &#40;53&#46;2&#37;&#41; &#60;<span class="elsevierStyleHsp" style=""></span>30&#37;&#44; 10 &#40;12&#46;7&#37;&#41; 30&#37;&#8211;50&#37;&#44; and 27 &#40;34&#46;2&#37;&#41; &#8805;<span class="elsevierStyleHsp" style=""></span>50&#37;&#46; Eleven patients &#40;12&#46;2&#37;&#41; switched to a mAb with similar mechanism of action&#59; in this group&#44; 6 patients had RR &#60;<span class="elsevierStyleHsp" style=""></span>30&#37; and 5 patients &#8805;<span class="elsevierStyleHsp" style=""></span>50&#37;&#46; RR were compared between both groups and no significant differences were found&#46; The group who switched to a different class mAb and to a same class mAb showed a mean reduction of 23&#46;61&#37; &#40;SD &#177;<span class="elsevierStyleHsp" style=""></span>45&#46;67&#41; and 30&#46;78&#37; &#40;SD &#177;<span class="elsevierStyleHsp" style=""></span>41&#46;2&#41; in MHD&#44; respectively&#44; whereas the overall cohort had a 24&#46;4&#37; mean reduction in MHD after switch&#46; In <a class="elsevierStyleCrossRef" href="#f0020">Fig&#46; 4</a>&#44; the distribution of reduction of MHD among groups is displayed&#46;</p><elsevierMultimedia ident="f0020"></elsevierMultimedia><p id="p0065" class="elsevierStylePara elsevierViewall">As for tolerability after switch&#44; 38 patients &#40;42&#46;2&#37;&#41; experienced AEs&#46; The distribution of AEs after switch was&#58; constipation 17 &#40;44&#46;7&#37;&#41;&#44; flu-like syndrome 13 &#40;34&#46;2&#37;&#41;&#44; injection site-related symptoms 6 &#40;15&#46;8&#37;&#41;&#44; hair loss 1 &#40;2&#46;6&#37;&#41;&#44; and weight gain 1 &#40;2&#46;6&#37;&#41;&#46; A comparative graph of tolerability before and after switch is shown in <a class="elsevierStyleCrossRef" href="#f0025">Fig&#46; 5</a>&#46; In the group of patients who discontinued the first mAb due to AEs &#40;<a class="elsevierStyleCrossRef" href="#f0030">Fig&#46; 6</a>&#41;&#44; 50&#37; &#40;20&#47;40&#41; improved tolerability with resolution of the AEs that motivated discontinuation&#46; The 20 patients who still had AEs described&#58; constipation 12 &#40;60&#37;&#41;&#44; flu-like syndrome 4 &#40;20&#37;&#37;&#41;&#44; injection site-related symptoms 3 &#40;15&#37;&#41;&#44; and hair loss 1 &#40;5&#37;&#41;&#46;</p><elsevierMultimedia ident="f0025"></elsevierMultimedia><elsevierMultimedia ident="f0030"></elsevierMultimedia></span><span id="s0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0080">Discussion</span><p id="p0070" class="elsevierStylePara elsevierViewall">This RWE study shows that migraine refractory patients who discontinue anti-CGRP mAbs &#40;including non-responders and those with intolerance&#41; may benefit from switching to another mAb&#44; mainly in terms of effectiveness&#46; We report absolute significant reductions in median MHD and MMD compared to baseline&#46; In addition&#44; a &#8805;<span class="elsevierStyleHsp" style=""></span>50&#37; RR occurred in more than one-third of the patients and a &#8805;<span class="elsevierStyleHsp" style=""></span>30&#37; RR was observed in 36&#46;7&#37; of the patients&#46; Although the proportion of AEs was similar after switching&#44; we report an improvement in tolerability in those patients whose switch was motivated by lack of tolerability with the first treatment&#46; In fact&#44; resolution of the AEs that prompted the switch was observed in half of the patients in this group&#46;</p><p id="p0075" class="elsevierStylePara elsevierViewall">In previous literature about switch&#44; the first mAb is usually erenumab and switch is mostly to galcanezumab or fremanezumab<a class="elsevierStyleCrossRefs" href="#bb0090"><span class="elsevierStyleSup">18&#8211;20</span></a> when ineffectiveness of erenumab is stated&#46; This is similar to our study and is probably due to the earlier approval of erenumab&#46; In general&#44; there is a lack of consensus on the definition of first CGRP mAb ineffectiveness&#46; In most cases&#44; RR of MHD is the main outcome when assessing switch&#46;<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a> Although there is a general tendency to consider lack of efficacy when &#60;<span class="elsevierStyleHsp" style=""></span>30&#37; reduction in headache frequency is achieved&#44;<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a> most studies are retrospective and influenced by different clinical practice protocols&#46; Given the retrospective and multicenter nature of our study&#44; the same limitations may apply&#44; but based on previous literature&#44; lack of effectiveness was considered when at least 30&#37; reduction in MHD was not achieved&#46; However&#44; what is considered effective may differ among patients depending on the impact on their quality of life and their previous clinical situation&#46; Thus&#44; &#60;<span class="elsevierStyleHsp" style=""></span>30&#37; MHD reduction may represent effectiveness in some refractory patients&#46; In addition&#44; effectiveness definitions should include not only headache frequency but also additional clinical parameters&#44; such as severity&#44; use of abortive treatments&#44; or impact on quality of life&#46; Interestingly&#44; a recent retrospective study defined ineffectiveness for the first mAb by combining several variables simultaneously&#44;<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> including reduction in headache days&#44; disability scores&#44; and abortive medication use&#46; These new strategies provide guidance for future work in establishing consistent definitions of switching outcomes&#46;</p><p id="p0080" class="elsevierStylePara elsevierViewall">Limited real-world data are available regarding the effectiveness of switching&#44; including case series and retrospective studies&#46; No interventional clinical trial has evaluated the effect of switching to another anti-CGRP mAb&#46; A retrospective real-world study of 78 switching patients reported that approximately one-third of erenumab non-responders had a &#8805;<span class="elsevierStyleHsp" style=""></span>30&#37; RR of MHD at 3&#8239;months after switching to galcanezumab&#47;fremanezumab&#46;<a class="elsevierStyleCrossRef" href="#bb0095"><span class="elsevierStyleSup">19</span></a> Previous small case reports demonstrated clinically meaningful reductions in MMD and headache intensity&#46;<a class="elsevierStyleCrossRef" href="#bb0090"><span class="elsevierStyleSup">18</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0100"><span class="elsevierStyleSup">20</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0120"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0125"><span class="elsevierStyleSup">25</span></a> Another recent retrospective cohort study with 22 patients and several variables as main outcomes reported that nearly 50&#37; of patients achieved &#8805;<span class="elsevierStyleHsp" style=""></span>30&#37; RR in MHD&#44; but also sustained reductions over time in abortive medication use and MIDAS&#47;HIT-6 score at 3-month follow-up&#46;<a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> In this regard&#44; our results provide additional evidence for switch as a beneficial tool for migraine refractory patients&#44; as we report &#8805;<span class="elsevierStyleHsp" style=""></span>50&#37; RR of MHD in more than one-third of patients at 3-month follow-up&#46; Although this improvement in effectiveness can be considered discrete &#40;with about half of the patients improving &#60;<span class="elsevierStyleHsp" style=""></span>30&#37;&#41;&#44; it should not be underestimated due to the refractoriness of our population&#46; RWE studies tend to enroll more refractory patients than clinical trials&#44;<a class="elsevierStyleCrossRef" href="#bb0130"><span class="elsevierStyleSup">26</span></a> and this can greatly influence effectiveness results&#46; In fact&#44; refractoriness is one of the main characteristics of our cohort&#44; since failure of three previous prophylactic treatments is required to meet the financial conditions of CGRP mAbs in Spain&#44; and our patients also had undergone a mAb discontinuation&#46; In addition to the aforementioned improvement in RR&#44; we also found significant reductions in median MHD &#40;20 vs 13&#8239;days&#41; and MMD &#40;15 vs 10&#8239;days&#41;&#46; Similarly&#44; a subgroup analysis of the Finesse study shows that MMD decreased from 13&#46;6 at baseline to 7&#46;2 at month 3&#44; and this decrease was greater in CM than in EM&#46;<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a> In any case&#44; the fact that an improvement in headache frequency was observed in a refractory cohort suggests that these data can be considered representative of the real-world population and can therefore be extrapolated to clinical practice&#46;</p><p id="p0085" class="elsevierStylePara elsevierViewall">Other effectiveness outcomes have also been evaluated in studies&#46; Significant reductions in disability scores &#40;MIDAS and HIT-6&#41; and acute migraine medication have been reported at 3&#8239;months after switching&#46;<a class="elsevierStyleCrossRef" href="#bb0080"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0115"><span class="elsevierStyleSup">23</span></a> It is important to emphasize that most studies focus on headache frequency<a class="elsevierStyleCrossRef" href="#bb0105"><span class="elsevierStyleSup">21</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a> and do not always include other clinical parameters such as disability and anxiety&#47;depression scores&#44; which can be very illustrative of the impact on daily life&#46; This may be due to the difficulty in interpreting their subjective component and the time required to complete these questionnaires&#46; However&#44; disability and mood disorders are important clinical factors to consider when assessing patients with refractory migraine&#46; They were included in our study&#44; but no significant differences were found after switching&#46; This needs further analysis with larger cohorts&#46;</p><p id="p0090" class="elsevierStylePara elsevierViewall">Most switch analyses focus on non-responders to prior CGRP mAbs&#46; Therefore&#44; given the global paucity of information on switching due to lack of tolerability&#44; the data reported in our cohort may be relevant&#46; Tolerability rates of current RWE are variable&#46;<a class="elsevierStyleCrossRef" href="#bb0070"><span class="elsevierStyleSup">14</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a> As for AEs&#44; their distribution was unchanged after switching in our cohort and was also consistent with the distribution in previous studies&#46;<a class="elsevierStyleCrossRef" href="#bb0110"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0135"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bb0140"><span class="elsevierStyleSup">28</span></a> Interestingly&#44; although it was only subjectively assessed and no formal questionnaires were administered&#44; tolerability improved in 50&#37; of patients whose switch was motivated by AEs in our study&#46; It may be reasonable to consider the possibility that safety profiles may be heterogeneous among CGRP-mAbs&#44; even more given that it is unknown how their variable targets may have an impact on efficacy and tolerability&#46; Further research in this area may have future implications so that switching may become a therapeutic strategy not only to improve efficacy but also to address tolerability issues&#46;</p><p id="p0095" class="elsevierStylePara elsevierViewall">As aforementioned&#44; the different mechanisms of action of anti-CGRP mAbs may differentially affect effectiveness&#44; safety&#44; and tolerability in migraine patients&#46; Therefore&#44; it is reasonable to ask whether patients who did not respond to one anti-CGRP pathway mAb class might benefit from switching to the other class&#46; However&#44; in our series&#44; no differences in RR were found between patients who switched to a mAb with a different mechanism of action&#46; This is largely influenced by the size of our cohort and the asymmetry of the switches we report&#46; Most patients switched from a CGRP receptor-targeting mAb to another CGRP ligand-binding mAb&#44; with the consequent challenge of stating differences in this setting&#46;</p><p id="p0100" class="elsevierStylePara elsevierViewall">The main limitations of this study are the retrospective design and the lack of longer follow-up after switching&#44; which was limited to 3&#8239;months&#46; Longer follow-up from this event would provide long-term effectiveness and tolerability data&#44; which would be of interest to evaluate the benefits of switching&#46; These data would also provide a more accurate picture compared to real-world practice&#44; where discontinuation is usually considered after at least 6&#8211;12&#8239;months of treatment with a mAb&#46;<a class="elsevierStyleCrossRef" href="#bb0085"><span class="elsevierStyleSup">17</span></a> Therefore&#44; we highlight the current need to perform prospective studies that can assess the long-term outcome of switching after at least 6&#8239;months&#46;</p><p id="p0105" class="elsevierStylePara elsevierViewall">Although there is currently a growing body of evidence on benefits of switch&#44; we believe our study provides additional supportive data and highlights future research directions and needs&#46; Nevertheless&#44; there is a lack of prospective studies with larger cohorts and longer follow-up periods&#46; Determining the specific group of patients who could truly benefit from switching in terms of effectiveness and tolerability would be one of the major challenges in the future perspective of CGRP-mAb research&#46;</p></span><span id="s0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0085">Conclusion</span><p id="p0110" class="elsevierStylePara elsevierViewall">This RWE cohort study suggests that some migraine refractory patients may benefit from switching to another mAb after discontinuation&#44; particularly in terms of reduction of MHD&#46; Partial improvement in AEs is also reported in patients who discontinued due to lack of tolerability&#46; In our experience&#44; switching may be an individualized treatment strategy in refractory patients&#46; However&#44; larger studies with long-term follow-up are needed to reach conclusive results&#46; Our findings add new information to the current evidence on CGRP-mAbs switching and encourage future research in this area&#46;</p></span><span id="s0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0090">Funding</span><p id="p0115" class="elsevierStylePara elsevierViewall">This research received no specific grant from any funding agency in the public&#44; commercial&#44; or not-for-profit sectors&#46;</p></span><span id="s0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0095">Patient consent</span><p id="p0120" class="elsevierStylePara elsevierViewall">All patients received written and verbal information&#46;</p></span><span id="s0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0100">Ethical considerations</span><p id="p0125" class="elsevierStylePara elsevierViewall">We conducted this study according to the declaration of Helsinki&#46; The local ethics committee approved the study &#40;1720-N-22&#41;&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:14 [
        0 => array:3 [
          "identificador" => "xres2261940"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "as0005"
              "titulo" => "Background"
            ]
            1 => array:2 [
              "identificador" => "as0010"
              "titulo" => "Methods"
            ]
            2 => array:2 [
              "identificador" => "as0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "as0020"
              "titulo" => "Conclusion"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1888363"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres2261939"
          "titulo" => "Resumen"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "as0025"
              "titulo" => "Introducci&#243;n"
            ]
            1 => array:2 [
              "identificador" => "as0030"
              "titulo" => "M&#233;todos"
            ]
            2 => array:2 [
              "identificador" => "as0035"
              "titulo" => "Resultados"
            ]
            3 => array:2 [
              "identificador" => "as0040"
              "titulo" => "Conclusi&#243;n"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1888362"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "s0005"
          "titulo" => "Background"
        ]
        5 => array:2 [
          "identificador" => "s0010"
          "titulo" => "Methods"
        ]
        6 => array:2 [
          "identificador" => "s0015"
          "titulo" => "Results"
        ]
        7 => array:2 [
          "identificador" => "s0020"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "s0025"
          "titulo" => "Conclusion"
        ]
        9 => array:2 [
          "identificador" => "s0030"
          "titulo" => "Funding"
        ]
        10 => array:2 [
          "identificador" => "s0035"
          "titulo" => "Patient consent"
        ]
        11 => array:2 [
          "identificador" => "s0040"
          "titulo" => "Ethical considerations"
        ]
        12 => array:2 [
          "identificador" => "xack779312"
          "titulo" => "Acknowledgments"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2023-12-26"
    "fechaAceptado" => "2024-04-02"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1888363"
          "palabras" => array:5 [
            0 => "Migraine"
            1 => "Switch"
            2 => "CGRP"
            3 => "Monoclonal antibodies"
            4 => "Real-world evidence"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1888362"
          "palabras" => array:5 [
            0 => "Migra&#241;a"
            1 => "switch"
            2 => "CGRP"
            3 => "anticuerpos monoclonales"
            4 => "experiencia en vida real"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Background</span><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">Switching between calcitonin gene-related peptide &#40;CGRP&#41; and monoclonal antibodies &#40;mAbs&#41; may be a beneficial strategy after discontinuation&#46; The aim of this study was to evaluate switching outcomes of effectiveness&#47;tolerability&#46;</p></span> <span id="as0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0015">Methods</span><p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">Retrospective multicentric study of migraine patients who switched to another CGRP&#8211;mAb due to lack of tolerability or effectiveness &#40;defined as &#60;<span class="elsevierStyleHsp" style=""></span>30&#37; reduction of monthly headache days &#91;MHD&#93;&#41;&#46; Assessment was performed before and 3 months after switch&#46; The main outcome was the response rate of MHD&#46; Secondary outcomes included other effectiveness&#47;tolerability measures&#46;</p></span> <span id="as0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0020">Results</span><p id="sp0055" class="elsevierStyleSimplePara elsevierViewall">90patients were included&#58; 75&#40;83&#46;3&#37;&#41; women&#44; 72&#40;80&#37;&#41; chronic&#44; and 18&#40;20&#37;&#41; episodic migraine&#46; Mean age was 45&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#8239;years and mean duration of migraine was 29&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;4&#8239;years&#46; Mean time under first mAb prior to switch was 10&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;9&#8239;months&#46; Most frequent switches were erenumab-galcanezumab 38 &#40;42&#46;2&#37;&#41; and erenumab&#8211;fremanezumab 21 &#40;23&#46;3&#37;&#41;&#46; Lack of effectiveness &#40;50&#47;90&#44; 55&#46;6&#37;&#41; or tolerability &#40;40&#47;90&#44; 44&#46;4&#37;&#41; provoked switching&#46; Most common adverse events &#40;AEs&#41; leading to discontinuation were constipation and flu-like syndrome in 16 &#40;40&#37;&#41; patients each&#46; Response rate &#40;RR&#41; of MHD 30&#37;&#8211;50&#37; occurred in 10 patients &#40;11&#46;1&#37;&#41;&#44; &#8805;<span class="elsevierStyleHsp" style=""></span>50&#37; in 32 &#40;35&#46;6&#37;&#41; and &#60;<span class="elsevierStyleHsp" style=""></span>30&#37; in 48 &#40;53&#46;3&#37;&#41; patients&#46; Significant reduction was proved after switch in MHD &#40;20 &#91;IQR&#58;15&#8211;29&#93; vs 13 &#91;IQR&#58;7&#8211;23&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; and monthly migraine days &#40;15 &#91;IQR&#58;12&#8211;20&#93; vs 10 &#91;IQR&#58;7&#8211;16&#93;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; After switching&#44; 38 &#40;42&#46;2&#37;&#41; experienced AEs&#44; but tolerability improved in 50&#37; of patients who discontinued due to lack of tolerability&#46; RR compared between switches to different CGRP-mAb classes showed no differences&#46;</p></span> <span id="as0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0025">Conclusion</span><p id="sp0060" class="elsevierStyleSimplePara elsevierViewall">Switching may become an individualized strategy in migraine refractory patients who discontinue CGRP&#8211;mAbs due to lack of effectiveness&#47;tolerability&#46; In this study&#44; supportive data are provided to the growing evidence of switch and future needs are highlighted&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "as0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "as0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "as0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "as0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="as0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0035">Introducci&#243;n</span><p id="sp0065" class="elsevierStyleSimplePara elsevierViewall">El switch entre anticuerpos monoclonales &#40;AMCs&#41; frente al CGRP podr&#237;a suponer una estrategia eficaz tras la discontinuaci&#243;n&#46; El objetivo fue evaluar los resultados de efectividad&#47;tolerabilidad del switch&#46;</p></span> <span id="as0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0040">M&#233;todos</span><p id="sp0070" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo multic&#233;ntrico incluyendo pacientes con migra&#241;a que realizaron switch a otro AMC-anti-CGRP debido a falta de tolerabilidad o efectividad &#40;&#60;<span class="elsevierStyleHsp" style=""></span>30&#37; reducci&#243;n d&#237;as cefalea mensual&#91;DCM&#93;&#41;&#46; Fueron evaluados previamente y tres meses tras switch&#46; La variable principal fue la tasa de respuesta en DCM&#46; Los objetivos secundarios incluyeron otras medidas de efectividad&#47;tolerabilidad&#46;</p></span> <span id="as0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0045">Resultados</span><p id="sp0075" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 90pacientes&#58; 75&#40;83&#46;3&#37;&#41; mujeres&#44; 72&#40;80&#37;&#41; con migra&#241;a cr&#243;nica y 18&#40;20&#37;&#41; epis&#243;dica&#46; La edad media fue 45&#46;9&#8239;&#177;&#8239;11a&#241;os&#44; la duraci&#243;n media de migra&#241;a 29&#46;2&#8239;&#177;&#8239;12&#46;4a&#241;os&#46; El tiempo medio con el primer AMC fue 10&#46;4&#8239;&#177;&#8239;4&#46;9meses&#46; Los switch m&#225;s frecuentes fueron erenumab-galcanezumab 38&#40;42&#46;2&#37;&#41; y erenumab-fremanezumab 21&#40;23&#46;3&#37;&#41;&#46; La falta de efectividad &#40;50&#47;90&#44; 55&#46;6&#37;&#41; o tolerabilidad &#40;40&#47;90&#44; 44&#46;4&#37;&#41; causaron el switch&#46; Los efectos adversos&#40;EAs&#41; m&#225;s frecuentes fueron estre&#241;imiento y s&#237;ndrome pseudogripal en 16&#40;40&#37;&#41; respectivamente&#46; La reducci&#243;n de DCM fue 30&#8211;50&#37; en 10 pacientes&#40;11&#46;1&#37;&#41;&#44; &#8805;<span class="elsevierStyleHsp" style=""></span>50&#37; en 32&#40;35&#46;6&#37;&#41; y&#8239;&#60;&#8239;30&#37; en 48&#40;53&#46;3&#37;&#41;&#46; Se demostr&#243; una reducci&#243;n significativa de DCM tras el switch &#40;20&#91;IQR&#58;15&#8211;29&#93; vs 13&#91;IQR&#58;7&#8211;23&#93;&#59;p&#8239;&#60;&#8239;0&#44;001&#41; y DMM &#40;15&#91;IQR&#58;12&#8211;20&#93; vs 10&#91;IQR&#58;7&#8211;16&#93;&#59;p&#8239;&#60;&#8239;0&#44;001&#41;&#46; Tras el switch&#44; 38 pacientes&#40;42&#46;2&#37;&#41; experimentaron EAs&#44; pero la tolerabilidad mejor&#243; en 50&#37; de pacientes que discontinuaron por ello&#46; La reducci&#243;n DCM comparada entre AMC con distinta diana&#40;CGRP vs&#46; ligando&#41; no mostr&#243; diferencias&#46;</p></span> <span id="as0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0050">Conclusi&#243;n</span><p id="sp0080" class="elsevierStyleSimplePara elsevierViewall">El switch podr&#237;a suponer una estrategia terap&#233;utica en pacientes refractarios tras discontinuaci&#243;n de AMC anti-CGRP por falta de efectividad&#47;tolerabilidad&#46; Este estudio aporta evidencia adicional del switch y plantea nuevas necesidades y futuras investigaciones&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "as0025"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "as0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "as0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "as0040"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
    "multimedia" => array:8 [
      0 => array:8 [
        "identificador" => "f0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2723
            "Ancho" => 2764
            "Tamanyo" => 363894
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0005"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Switch information&#46; Initial &#40;A&#41; and switch &#40;B&#41; CGRP&#8211;mAbs are represented in this figure&#46; Tables show distribution of initial CGRP&#8211;mAb&#44; switch CGRP&#8211;mAb&#44; and a summary of switches performed&#46; CGRP&#8211;mAb&#58; Calcitonin gene related-peptide monoclonal antibody&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "f0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1208
            "Ancho" => 2188
            "Tamanyo" => 88047
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0010"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">RR of MHD after switch to a different anti-CGRP mAb&#46; CGRP&#58; calcitonin gene-related peptide&#44; mAb&#58; monoclonal antibody&#44; MHD&#58; monthly headache days&#44; RR&#58; response rate&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "f0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1280
            "Ancho" => 2372
            "Tamanyo" => 111003
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0015"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">MHD and MMD evolution before and after switch&#46; MHD&#58; monthly headache days&#44; MMD&#58; monthly migraine days&#46; &#42;Statistical significance <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "f0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 1354
            "Ancho" => 2396
            "Tamanyo" => 133459
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0020"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">Reduction in MHD after switch in different groups&#46; No statistical differences were found between switches to same vs different class&#46; MHD&#58; monthly headache days&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "f0025"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 1202
            "Ancho" => 2368
            "Tamanyo" => 131398
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0025"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0025" class="elsevierStyleSimplePara elsevierViewall">Tolerability before and after switch&#46; AEs distribution is shown before and after switch in absolute numbers&#46; AEs&#58; adverse events&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "f0030"
        "etiqueta" => "Fig&#46; 6"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr6.jpeg"
            "Alto" => 827
            "Ancho" => 2368
            "Tamanyo" => 81425
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0030"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">AEs among patients who discontinuated first mAb because of lack of tolerability and their distribution&#46; In 50&#37; &#40;20&#47;40&#41; of patients&#44; there was a resolution of the AE that motivated discontinuation&#46; The distribution of AEs among patients who still had lack of tolerability is shown&#46; AEs&#58; adverse events&#44; mAb&#58; monoclonal antibody&#46;</p>"
        ]
      ]
      6 => array:8 [
        "identificador" => "t0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0035"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="sp6000" class="elsevierStyleSimplePara elsevierViewall">HAD-A&#58; Hospital Anxiety and Depression-Anxiety&#44; HAD-D&#58; Hospital Anxiety and Depression-Depression&#44; HIT-6&#58; headache impact test-6&#44; IQR&#58; interquartile range&#44; mAb&#58; monoclonal antibody&#44; m&#58; months&#44; MHD&#58; monthly headache days&#44; MIDAS&#58; migraine disability assessment scale&#44; MMD&#58; monthly migraine days&#44; NSAIDs&#58; non-steroidal anti-inflammatory drugs&#44; SD&#58; standard deviation&#44; VAS&#58; visual analogue scale&#44; y&#58; years&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Female sex&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">75 &#40;83&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diagnosis</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Chronic migraine&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72 &#40;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Episodic migraine&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18 &#40;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Aura&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;16&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Duration of migraine &#40;y&#41;&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Time under first mAb prior to switch &#40;m&#41;&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MHD&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;15&#8211;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MMD&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;12&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VAS&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;7&#8211;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute monthly NSAIDs use &#40;days&#41;&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;4&#8211;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute monthly triptans use &#40;days&#41;&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;2&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NSAIDs overuse&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#47;84 &#40;17&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Triptans overuse&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">18&#47;73 &#40;24&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral preventive treatment&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44 &#40;48&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OnabotulinumtoxinA&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MIDAS&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52 &#40;30&#8211;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HIT-6&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66 &#40;63&#8211;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HAD-A&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;10&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HAD-D&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5 &#40;7&#8211;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3678840.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">Demographic and clinical characteristics of the overall cohort prior to switch&#46;</p>"
        ]
      ]
      7 => array:8 [
        "identificador" => "t0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "al0040"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="sp6010" class="elsevierStyleSimplePara elsevierViewall">HAD-A&#58; Hospital Anxiety and Depression-Anxiety&#44; HAD-D&#58; Hospital Anxiety and Depression-Depression&#44; HIT-6&#58; headache impact test-6&#44; IQR&#58; interquartile range&#44; MHD&#58; monthly headache days&#44; MIDAS&#58; migraine disability assessment scale&#44; MMD&#58; monthly migraine days&#44; NSAIDs&#58; non-steroidal anti-inflammatory drugs&#44; VAS&#58; visual analogue scale&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Before switch&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">After switch&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MHD&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20 &#40;15&#8211;29&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">13 &#40;7&#8211;23&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MMD&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;12&#8211;20&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;7&#8211;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VAS score&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;7&#8211;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5 &#40;7&#8211;8&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute monthly NSAIDs use &#40;days&#41;&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;4&#8211;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;3&#8211;12&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute monthly triptans use &#40;days&#41;&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;2&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3 &#40;3&#8211;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MIDAS&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52 &#40;30&#8211;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53 &#40;25&#46;5&#8211;90&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HIT-6 score&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66 &#40;63&#8211;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65 &#40;61&#8211;68&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HAD-A&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15 &#40;10&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#46;5 &#40;9&#8211;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HAD-D&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&#46;5 &#40;7&#8211;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;5 &#40;2&#8211;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab3678839.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Statistical analysis of efficacy outcomes before and after switch&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bs0005"
          "bibliografiaReferencia" => array:28 [
            0 => array:3 [
              "identificador" => "bb0005"
              "etiqueta" => "1&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "One-year prevalence of migraine in Spain&#58; a nationwide population-based survey"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [
                            0 => "J&#46; Mat&#237;as-Guiu"
                            1 => "J&#46; Porta-Etessam"
                            2 => "V&#46; Mateos"
                            3 => "S&#46; D&#237;az-Insa"
                            4 => "A&#46; Lopez-Gil"
                            5 => "C&#46; Fern&#225;ndez"
                            6 => "Scientific Committee of the PALM Program"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0333102410382794"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cephalalgia"
                        "fecha" => "2011 Mar"
                        "volumen" => "31"
                        "numero" => "4"
                        "paginaInicial" => "463"
                        "paginaFinal" => "470"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bb0010"
              "etiqueta" => "2&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global&#44; regional&#44; and national incidence&#44; prevalence&#44; and years lived with disability for 328 diseases and injuries for 195 countries&#44; 1990&#8211;2016&#58; a systematic analysis for the Global Burden of Disease Study 2016"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "GBD 2016 Disease and Injury Incidence and Prevalence Collaborators"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(17)32154-2"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2017 Sep 16"
                        "volumen" => "390"
                        "numero" => "10100"
                        "paginaInicial" => "1211"
                        "paginaFinal" => "1259"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28919117"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bb0015"
              "etiqueta" => "3&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global&#44; regional&#44; and national burden of migraine and tension-type headache&#44; 1990&#8211;2016&#58; a systematic analysis for the Global Burden of Disease Study 2016"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "GBD 2016 Headache Collaborators"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1474-4422(18)30322-3"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet Neurol"
                        "fecha" => "2018 Nov"
                        "volumen" => "17"
                        "numero" => "11"
                        "paginaInicial" => "954"
                        "paginaFinal" => "976"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30353868"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bb0020"
              "etiqueta" => "4&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Migraine&#58; epidemiology&#44; burden&#44; and comorbidity"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;C&#46; Burch"
                            1 => "D&#46;C&#46; Buse"
                            2 => "R&#46;B&#46; Lipton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ncl.2019.06.001"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurol Clin"
                        "fecha" => "2019 Nov"
                        "volumen" => "37"
                        "numero" => "4"
                        "paginaInicial" => "631"
                        "paginaFinal" => "649"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31563224"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bb0025"
              "etiqueta" => "5&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The International Classification of Headache Disorders&#44; 3rd edition"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Headache Classification Committee of the International Headache Society &#40;IHS&#41;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0333102417738202"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cephalalgia"
                        "fecha" => "2018 Jan"
                        "volumen" => "38"
                        "numero" => "1"
                        "paginaInicial" => "1"
                        "paginaFinal" => "211"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30185059"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bb0030"
              "etiqueta" => "6&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Neurological and psychiatric comorbidities of migraine&#58; concepts and future perspectives"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "N&#46; Pelzer"
                            1 => "I&#46; de Boer"
                            2 => "A&#46;M&#46;J&#46;M&#46; van den Maagdenberg"
                            3 => "G&#46;M&#46; Terwindt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/03331024231180564"
                      "Revista" => array:4 [
                        "tituloSerie" => "Cephalalgia"
                        "fecha" => "2023 Jun"
                        "volumen" => "43"
                        "numero" => "6"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bb0035"
              "etiqueta" => "7&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CGRP and its receptors provide new insights into migraine pathophysiology"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46;W&#46; Ho"
                            1 => "L&#46; Edvinsson"
                            2 => "P&#46;J&#46; Goadsby"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrneurol.2010.127"
                      "Revista" => array:7 [
                        "tituloSerie" => "Nat Rev Neurol"
                        "fecha" => "2010 Oct"
                        "volumen" => "6"
                        "numero" => "10"
                        "paginaInicial" => "573"
                        "paginaFinal" => "582"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20820195"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bb0040"
              "etiqueta" => "8&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Safety and efficacy of erenumab for preventive treatment of chronic migraine&#58; a randomised&#44; double-blind&#44; placebo-controlled phase 2 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Tepper"
                            1 => "M&#46; Ashina"
                            2 => "U&#46; Reuter"
                            3 => "J&#46;L&#46; Brandes"
                            4 => "D&#46; Dole&#382;il"
                            5 => "S&#46; Silberstein"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1474-4422(17)30083-2"
                      "Revista" => array:7 [
                        "tituloSerie" => "Lancet Neurol"
                        "fecha" => "2017 Jun"
                        "volumen" => "16"
                        "numero" => "6"
                        "paginaInicial" => "425"
                        "paginaFinal" => "434"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28460892"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bb0045"
              "etiqueta" => "9&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Galcanezumab in chronic migraine&#58; the randomized&#44; double-blind&#44; placebo-controlled REGAIN study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46;C&#46; Detke"
                            1 => "P&#46;J&#46; Goadsby"
                            2 => "S&#46; Wang"
                            3 => "D&#46;I&#46; Friedman"
                            4 => "K&#46;J&#46; Selzler"
                            5 => "S&#46;K&#46; Aurora"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1212/WNL.0000000000006640"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurology"
                        "fecha" => "2018 Dec 11"
                        "volumen" => "91"
                        "numero" => "24"
                        "paginaInicial" => "e2211"
                        "paginaFinal" => "e2221"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30446596"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bb0050"
              "etiqueta" => "10&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of fremanezumab compared with placebo for prevention of episodic migraine&#58; a randomized clinical trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;W&#46; Dodick"
                            1 => "S&#46;D&#46; Silberstein"
                            2 => "M&#46;E&#46; Bigal"
                            3 => "P&#46;P&#46; Yeung"
                            4 => "P&#46;J&#46; Goadsby"
                            5 => "T&#46; Blankenbiller"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2018.4853"
                      "Revista" => array:7 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2018 May 15"
                        "volumen" => "319"
                        "numero" => "19"
                        "paginaInicial" => "1999"
                        "paginaFinal" => "2008"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29800211"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bb0055"
              "etiqueta" => "11&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Eptinezumab in episodic migraine&#58; a randomized&#44; double-blind&#44; placebo-controlled study &#40;PROMISE-1&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Ashina"
                            1 => "J&#46; Saper"
                            2 => "R&#46; Cady"
                            3 => "B&#46;A&#46; Schaeffler"
                            4 => "D&#46;M&#46; Biondi"
                            5 => "J&#46; Hirman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0333102420905132"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cephalalgia"
                        "fecha" => "2020 Mar"
                        "volumen" => "40"
                        "numero" => "3"
                        "paginaInicial" => "241"
                        "paginaFinal" => "254"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32075406"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bb0060"
              "etiqueta" => "12&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Erenumab in the prevention of high-frequency episodic and chronic migraine&#58; Erenumab in Real Life in Italy &#40;EARLY&#41;&#44; the first Italian multicenter&#44; prospective real-life study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Barbanti"
                            1 => "C&#46; Aurilia"
                            2 => "G&#46; Egeo"
                            3 => "L&#46; Fofi"
                            4 => "S&#46; Cevoli"
                            5 => "B&#46; Colombo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/head.14032"
                      "Revista" => array:7 [
                        "tituloSerie" => "Headache"
                        "fecha" => "2021 Feb"
                        "volumen" => "61"
                        "numero" => "2"
                        "paginaInicial" => "363"
                        "paginaFinal" => "372"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33337544"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bb0065"
              "etiqueta" => "13&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse&#58; real-life effectiveness and predictors of response at 6<span class="elsevierStyleHsp" style=""></span>months"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "E&#46; Caronna"
                            1 => "V&#46;J&#46; Gallardo"
                            2 => "A&#46; Alpuente"
                            3 => "M&#46; Torres-Ferrus"
                            4 => "P&#46; Pozo-Rosich"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s10194-021-01328-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Headache Pain"
                        "fecha" => "2021 Oct 7"
                        "volumen" => "22"
                        "numero" => "1"
                        "paginaInicial" => "120"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34620085"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bb0070"
              "etiqueta" => "14&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Real-world effectiveness and tolerability of erenumab&#58; a retrospective cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Kanaan"
                            1 => "G&#46; Hettie"
                            2 => "E&#46; Loder"
                            3 => "R&#46; Burch"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0333102420946725"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cephalalgia"
                        "fecha" => "2020 Nov"
                        "volumen" => "40"
                        "numero" => "13"
                        "paginaInicial" => "1511"
                        "paginaFinal" => "1522"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32791922"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bb0075"
              "etiqueta" => "15&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Predictors of response to anti-CGRP monoclonal antibodies&#58; a 24-week&#44; multicenter&#44; prospective study on 864 migraine patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "P&#46; Barbanti"
                            1 => "G&#46; Egeo"
                            2 => "C&#46; Aurilia"
                            3 => "C&#46; Altamura"
                            4 => "F&#46; d&#39;Onofrio"
                            5 => "C&#46; Finocchi"
                            6 => "Italian Migraine Registry study group"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s10194-022-01498-6"
                      "Revista" => array:7 [
                        "tituloSerie" => "J Headache Pain"
                        "fecha" => "2022 Nov 1"
                        "volumen" => "23"
                        "numero" => "1"
                        "paginaInicial" => "138"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36316648"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0140673622012144"
                          "estado" => "S300"
                          "issn" => "01406736"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bb0080"
              "etiqueta" => "16&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway&#58; a subgroup analysis of the Finesse Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Straube"
                            1 => "G&#46; Broessner"
                            2 => "C&#46; Gaul"
                            3 => "X&#46; Hamann"
                            4 => "J&#46; Hipp"
                            5 => "T&#46; Kraya"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s10194-023-01593-2"
                      "Revista" => array:5 [
                        "tituloSerie" => "J Headache Pain"
                        "fecha" => "2023 May 23"
                        "volumen" => "24"
                        "numero" => "1"
                        "paginaInicial" => "59"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bb0085"
              "etiqueta" => "17&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Sacco"
                            1 => "F&#46;M&#46; Amin"
                            2 => "M&#46; Ashina"
                            3 => "L&#46; Bendtsen"
                            4 => "C&#46;I&#46; Deligianni"
                            5 => "R&#46; Gil-Gouveia"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s10194-022-01431-x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Headache Pain"
                        "fecha" => "2022 Jun 11"
                        "volumen" => "23"
                        "numero" => "1"
                        "paginaInicial" => "67"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35690723"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bb0090"
              "etiqueta" => "18&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early experiences in switching between monoclonal antibodies in patients with nonresponsive migraine in Spain&#58; a case series"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "I&#46; Patier Ruiz"
                            1 => "J&#46; S&#225;nchez-Rubio Ferr&#225;ndez"
                            2 => "A&#46; C&#225;rcamo Fonfr&#237;a"
                            3 => "T&#46; Molina Garc&#237;a"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1159/000518899"
                      "Revista" => array:8 [
                        "tituloSerie" => "Eur Neurol"
                        "fecha" => "2022"
                        "volumen" => "85"
                        "numero" => "2"
                        "paginaInicial" => "132"
                        "paginaFinal" => "135"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34510038"
                            "web" => "Medline"
                          ]
                        ]
                        "itemHostRev" => array:3 [
                          "pii" => "S0213911120300935"
                          "estado" => "S300"
                          "issn" => "02139111"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bb0095"
              "etiqueta" => "19&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of antibody switch in non-responders to a CGRP receptor antibody treatment in migraine&#58; a multi-center retrospective cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;H&#46; Overeem"
                            1 => "A&#46; Peikert"
                            2 => "M&#46;D&#46; Hofacker"
                            3 => "K&#46; Kamm"
                            4 => "R&#46; Ruscheweyh"
                            5 => "A&#46; Gendolla"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/03331024211048765"
                      "Revista" => array:7 [
                        "tituloSerie" => "Cephalalgia"
                        "fecha" => "2022 Apr"
                        "volumen" => "42"
                        "numero" => "4&#8211;5"
                        "paginaInicial" => "291"
                        "paginaFinal" => "301"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34644203"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bb0100"
              "etiqueta" => "20&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Non-responders to treatment with antibodies to the CGRP-receptor may profit from a switch of antibody class"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46; Ziegeler"
                            1 => "A&#46; May"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/head.13729"
                      "Revista" => array:7 [
                        "tituloSerie" => "Headache"
                        "fecha" => "2020 Feb"
                        "volumen" => "60"
                        "numero" => "2"
                        "paginaInicial" => "469"
                        "paginaFinal" => "470"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31872439"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bb0105"
              "etiqueta" => "21&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Monoclonal antibodies against CGRP &#40;R&#41;&#58; non-responders and switchers&#58; real world data from an austrian case series"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "K&#46; Kaltseis"
                            1 => "V&#46; Filippi"
                            2 => "F&#46; Frank"
                            3 => "C&#46; Eckhardt"
                            4 => "A&#46; Schiefecker"
                            5 => "G&#46; Broessner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12883-023-03203-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "BMC Neurol"
                        "fecha" => "2023 Apr 28"
                        "volumen" => "23"
                        "numero" => "1"
                        "paginaInicial" => "174"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37118682"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bb0110"
              "etiqueta" => "22&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Long-term effect of switching from an anti-CGRP receptor to an anti-CGRP ligand antibody in treatment-refractory chronic migraine&#58; a prospective real-world analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "G&#46; Lambru"
                            1 => "V&#46; Caponnetto"
                            2 => "B&#46; Hill"
                            3 => "S&#46; Ratti"
                            4 => "S&#46; Sacco"
                            5 => "M&#46; Murphy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s13311-023-01394-0"
                      "Revista" => array:7 [
                        "tituloSerie" => "Neurotherapeutics"
                        "fecha" => "2023 Sep"
                        "volumen" => "20"
                        "numero" => "5"
                        "paginaInicial" => "1284"
                        "paginaFinal" => "1293"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37430146"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bb0115"
              "etiqueta" => "23&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Switching anti-CGRP&#40;R&#41; monoclonal antibodies in multi-assessed non-responder patients and implications for ineffectiveness criteria&#58; a retrospective cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;F&#46; Iannone"
                            1 => "A&#46; Burgalassi"
                            2 => "G&#46; Vigani"
                            3 => "G&#46; Tabasso"
                            4 => "F&#46; De Cesaris"
                            5 => "A&#46; Chiarugi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/03331024231160519"
                      "Revista" => array:4 [
                        "tituloSerie" => "Cephalalgia"
                        "fecha" => "2023 Apr"
                        "volumen" => "43"
                        "numero" => "4"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bb0120"
              "etiqueta" => "24&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Failure of monoclonal antibodies against CGRP or its receptor does not imply lack of efficacy of other drugs from the same class"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46; Porta-Etessam"
                            1 => "N&#46; Gonz&#225;lez-Garc&#237;a"
                            2 => "&#193;&#46;L&#46; Guerrero"
                            3 => "D&#46; Garc&#237;a-Azor&#237;n"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.nrleng.2020.10.008"
                      "Revista" => array:6 [
                        "tituloSerie" => "Neurologia &#40;Engl Ed&#41;"
                        "fecha" => "2021 Oct"
                        "volumen" => "36"
                        "numero" => "8"
                        "paginaInicial" => "638"
                        "paginaFinal" => "640"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bb0125"
              "etiqueta" => "25&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Switching of monoclonal antibodies against calcitonin gene-related peptide in chronic migraine in clinical practice&#58; a case series"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;D&#46;P&#46; Brice&#241;o-Casado"
                            1 => "M&#46;D&#46; Gil-Sierra"
                            2 => "B&#46; De-La-Calle-Riaguas"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/ejhpharm-2021-002946"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Hosp Pharm"
                        "fecha" => "2023 Jul"
                        "volumen" => "30"
                        "numero" => "4"
                        "paginaInicial" => "e19"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/36220334"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bb0130"
              "etiqueta" => "26&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Real-world long-term efficacy and safety of erenumab in adults with chronic migraine&#58; a 52-week&#44; single-center&#44; prospective&#44; observational study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;K&#46; Cullum"
                            1 => "T&#46;P&#46; Do"
                            2 => "M&#46; Ashina"
                            3 => "L&#46; Bendtsen"
                            4 => "S&#46;S&#46; Hugger"
                            5 => "A&#46; Iljazi"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s10194-022-01433-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Headache Pain"
                        "fecha" => "2022 Jun 2"
                        "volumen" => "23"
                        "numero" => "1"
                        "paginaInicial" => "61"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35655137"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bb0135"
              "etiqueta" => "27&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Switching between anti-calcitonin gene-related peptide monoclonal antibodies&#58; a comparison of monthly and quarterly dosing"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Ihara"
                            1 => "S&#46; Ohtani"
                            2 => "N&#46; Watanabe"
                            3 => "N&#46; Takahashi"
                            4 => "N&#46; Miyazaki"
                            5 => "R&#46; Takemura"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jns.2023.120811"
                      "Revista" => array:3 [
                        "tituloSerie" => "J Neurol Sci"
                        "fecha" => "2023 Oct 15"
                        "volumen" => "453"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bb0140"
              "etiqueta" => "28&#46;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Monoclonal antibodies against calcitonin gene-related peptide for migraine prophylaxis&#58; a systematic review of real-world data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A&#46;R&#46; Pavelic"
                            1 => "C&#46; W&#246;ber"
                            2 => "F&#46; Riederer"
                            3 => "K&#46; Zebenholzer"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/cells12010143"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cells"
                        "fecha" => "2022 Dec 29"
                        "volumen" => "12"
                        "numero" => "1"
                        "paginaInicial" => "143"
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack779312"
        "titulo" => "Acknowledgments"
        "texto" => "<p id="p0135" class="elsevierStylePara elsevierViewall">The authors acknowledge Fundaci&#243;n P&#250;blica Andaluza para la Gesti&#243;n de la Investigaci&#243;n en Salud &#40;FISEVI&#41; of Hospital Universitario Virgen del Roc&#237;o for statistical and methodological support on this manuscript&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/26670496/0000000400000004/v7_202410041010/S2667049624000255/v7_202410041010/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "91827"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/26670496/0000000400000004/v7_202410041010/S2667049624000255/v7_202410041010/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2667049624000255?idApp=UINPBA00004N"
]

Article information

ISSN: 26670496
Original language: English

DOI:10.1016/j.neurop.2024.100168

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 October	27	14	41
2024 September	25	23	48
2024 August	74	26	100
2024 July	13	8	21

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter