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Analysis of medication persistence and reasons for discontinuation of treatment with teriflunomide and dimethyl fumarate in a hospital series of patients with multiple sclerosis
Análisis de la persistencia y de las causas de abandono del tratamiento con teriflunomida y dimetilfumarato en una serie hospitalaria de pacientes con esclerosis múltiple
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García Estévez, L. Cid Conde, A. Juanatey García" "autores" => array:3 [ 0 => array:4 [ "nombre" => "D.A." "apellidos" => "García Estévez" "email" => array:1 [ 0 => "Daniel.apolinar.garcia.estevez@sergas.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">2</span>" "identificador" => "af0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cr0005" ] ] ] 1 => array:3 [ "nombre" => "L." "apellidos" => "Cid Conde" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">3</span>" "identificador" => "af0015" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Juanatey García" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "af0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">2</span>" "identificador" => "af0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Neurología. Complexo hospitalario Universitario de Ourense." "etiqueta" => "1" "identificador" => "af0005" ] 1 => array:3 [ "entidad" => "Grupo de Neurociencias Clínica. Instituto de Investigaciones Sanitarias Galicia Sur (IIS Galicia Sur). SERGAS-UVIGO." "etiqueta" => "2" "identificador" => "af0010" ] 2 => array:3 [ "entidad" => "Servicio de Farmacia. Complexo hospitalario Universitario de Ourense." "etiqueta" => "3" "identificador" => "af0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cr0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "<span class="elsevierStyleBold">Análisis de la persistencia y de las causas de abandono del tratamiento con teriflunomida y dimetilfumarato en una serie hospitalaria de pacientes con esclerosis múltiple</span>" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2219 "Ancho" => 2264 "Tamanyo" => 238341 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier survival curve.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0015" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Dear Editor:</span></p><p id="p0020" class="elsevierStylePara elsevierViewall">Medication persistence is defined as the time of continuous therapy, from initiation of treatment to its discontinuation.<a class="elsevierStyleCrossRef" href="#bb0005"><span class="elsevierStyleSup">1</span></a> Factors conditioning medication persistence include treatment effectiveness, complexity of dosage, adverse effects, impact on patient lifestyle, patient motivation, quality of the information provided by the healthcare staff on the condition, and need for treatment after onset.<a class="elsevierStyleCrossRef" href="#bb0010"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0015"><span class="elsevierStyleSup">3</span></a> Lack of adherence to and persistence of treatments prescribed by healthcare professionals translates into reduced treatment effectiveness and increased healthcare costs.</p><p id="p0025" class="elsevierStylePara elsevierViewall">Several studies using data from medical records and databases have assessed the persistence of treatments in multiple sclerosis (MS), and generally conclude that oral treatments are more persistent than injectable treatments.<a class="elsevierStyleCrossRef" href="#bb0020"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0025"><span class="elsevierStyleSup">5</span></a> These real-world studies also report lower persistence than that described in clinical trials, undoubtedly due to differences between our patients and those included in clinical trials; persistence is largely influenced by the presence of various comorbidities in real-life patients.</p><p id="p0030" class="elsevierStylePara elsevierViewall">The aim of our study was to determine the persistence of first-line oral treatments for MS, teriflunomide (TERI) or dimethyl fumarate (DMF), and the reasons for discontinuation in a hospital series. The study was approved by the research ethics committee of the Galicia-Sur Health Research Institute.</p><p id="p0035" class="elsevierStylePara elsevierViewall">We requested that our hospital’s pharmacy department provide access to the registry of patients who started treatment with TERI or DMF for MS between 1 June 2015 and 31 October 2021. We identified 125 patients who started treatment with TERI and 77 patients with DMF. The baseline characteristics of each group are shown in <a class="elsevierStyleCrossRef" href="#t0005">Table 1</a>. Statistical analysis was performed using the SPSS statistics software. <span class="elsevierStyleItalic">P</span>-values < .05 were considered statistically significant. Medication persistence was estimated using Kaplan-Meier survival curves, which were compared with the Mantel-Cox test (log rank test).</p><elsevierMultimedia ident="t0005"></elsevierMultimedia><p id="p5015" class="elsevierStylePara elsevierViewall">Of the patients receiving TERI, 39 (31.2%) discontinued treatment; disease activity (relapse, radiological activity, or progression) was the reason for discontinuation in 21.6% of cases, and adverse reactions in 8%. Of the patients receiving DMF, 29 (37.7%) discontinued treatment; the reason for discontinuation was clinical/radiological activity in 7.8% of cases and adverse reactions in 26%. The difference in the reasons for discontinuation between groups was statistically significant (<span class="elsevierStyleItalic">P</span> < .01), with disease activity being the most frequent reason in the TERI group and presence of adverse reactions being more common in the DMF group. <a class="elsevierStyleCrossRef" href="#f0005">Fig. 1</a> shows the Kaplan-Meier survival curve analysing medication persistence with TERI and DMF. At 60 months, persistence in the TERI group (61%) is slightly higher than in the DMF group (55%), but the difference was not statistically significant (<span class="elsevierStyleItalic">P</span> = .13). One limitation of this real-world study is that the 2 treatment groups presented different baseline characteristics.</p><elsevierMultimedia ident="f0005"></elsevierMultimedia><p id="p0040" class="elsevierStylePara elsevierViewall">Lymphocytopaenia was the reason for discontinuation in up to 50% of patients discontinuing treatment due to adverse reactions to DMF, but was not recorded in any patient receiving TERI. This differential profile between TERI and DMF has led us to consider TERI as the ideal treatment for switching from injectable drugs to oral drugs for the convenience of patients who have remained clinically and radiologically stable, in whom safety and tolerability take priority over anti-inflammatory power due to the low level of inflammatory activity observed in these patients.<a class="elsevierStyleCrossRef" href="#bb0030"><span class="elsevierStyleSup">6</span></a> Another characteristic to be considered when switching drugs is the potential effect of TERI in slowing brain atrophy.<a class="elsevierStyleCrossRef" href="#bb0035"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0040"><span class="elsevierStyleSup">8</span></a> Likewise, patients presenting greater clinical/radiological activity may be treated with DMF, as demonstrated by propensity score studies that support the effectiveness of DMF over TERI.<a class="elsevierStyleCrossRef" href="#bb0045"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleSup">,</span><a class="elsevierStyleCrossRef" href="#bb0050"><span class="elsevierStyleSup">10</span></a></p><p id="p0045" class="elsevierStylePara elsevierViewall">Persistence is a complex concept involving effectiveness, safety, and tolerability of treatment as well as patient satisfaction, and should be considered a measure of treatment efficiency.</p><span id="s0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0005">Sources of funding</span><p id="p0050" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="l0015"><li class="elsevierStyleListItem" id="li0015"><span class="elsevierStyleLabel">-</span><p id="p0055" class="elsevierStylePara elsevierViewall">None.</p></li></ul></p></span><span id="s0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="st0010">Conflicts of interest</span><p id="p0060" class="elsevierStylePara elsevierViewall">Dr García Estévez has received fees from Sanofi in relation to product presentations (teriflunomide) and from Biogen for participating in an advisory board (dimethyl fumarate).</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "s0005" "titulo" => "Sources of funding" ] 1 => array:2 [ "identificador" => "s0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-01-22" "fechaAceptado" => "2022-01-23" "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="p0075" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="ec0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "s0015" ] ] ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "f0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2219 "Ancho" => 2264 "Tamanyo" => 238341 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier survival curve.</p>" ] ] 1 => array:8 [ "identificador" => "t0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0010" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as mean (standard deviation), unless other wise indicated.</p><p id="sp7040" class="elsevierStyleSimplePara elsevierViewall">EDSS: Expanded Disability Status Scale; MRI: magnetic resonance imaging; MS: Multiple sclerosis; NS: not significant.</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"> \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TERIFLUNOMIDE (n = 125) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">DIMETHYL FUMARATE (n = 77) \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="center" 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> \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">Sex (M/W) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34/91 \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16/71 \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="center" 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">Age at diagnosis (years) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.0 (10.8) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.3 (8.2) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< .01 \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">MS progression time from diagnosis (months) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">110.6 (102.7) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.3 (74.9) \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="center" 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">Age at treatment onset (years) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.8 (10.4) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.1 (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="center" 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">EDSS score at treatment onset \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.12 (1.72) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.54 (1.12) \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="center" 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">Previous treatment with disease-modifying drugs, 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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">85 (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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39 (50.6%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.015 \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">Treatment indication, n (%)<ul class="elsevierStyleList" id="l0005"><li class="elsevierStyleListItem" id="li0005"><span class="elsevierStyleLabel">-</span><p id="p0005" class="elsevierStylePara elsevierViewall">Disease activity<a class="elsevierStyleCrossRef" href="#tf0005"><span class="elsevierStyleSup">†</span></a></p></li></ul> \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">87 (69.6%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 (85.7%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.011 \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"><ul class="elsevierStyleList" id="l0010"><li class="elsevierStyleListItem" id="li0010"><span class="elsevierStyleLabel">-</span><p id="p0010" class="elsevierStylePara elsevierViewall">Convenience<a class="elsevierStyleCrossRef" href="#tf0010"><span class="elsevierStyleSup">‡</span></a></p></li></ul> \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 (30.4%) \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (14.3%) \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"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3399747.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tf0005" "etiqueta" => "†" "nota" => "<p class="elsevierStyleNotepara" id="np0005">Relapses, new MRI lesion, progression.</p>" ] 1 => array:3 [ "identificador" => "tf0010" "etiqueta" => "‡" "nota" => "<p class="elsevierStyleNotepara" id="np0010">Clinically stable patient who wishes to switch from an injectable to an oral drug.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of the treatment groups.</p>" ] ] 2 => array:7 [ "identificador" => "ec0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "detalles" => array:1 [ 0 => array:3 [ "identificador" => "al0015" "detalle" => "Image " "rol" => "short" ] ] "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 228089 ] "descripcion" => array:1 [ "en" => "<p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">Supplementary material</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bb0005" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Medication compliance and persistence: terminology and definitions" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Cramer" 1 => "A. Roy" 2 => "A. Burrell" 3 => "C.J. Fairchild" 4 => "M.J. Fuldeore" 5 => "D.A. Ollendorf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1524-4733.2007.00213.x" "Revista" => array:6 [ "tituloSerie" => "Value Health" "fecha" => "2008" "volumen" => "11" "paginaInicial" => "44" "paginaFinal" => "47" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18237359" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bb0010" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of share decision making on disease-modifying drug adherence in multiple sclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Ben-Zacharia" 1 => "M. Adamson" 2 => "A. Boyd" 3 => "P. Hardeman" 4 => "J. Smrtka" 5 => "B. Walker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7224/1537-2073.2017-070" "Revista" => array:6 [ "tituloSerie" => "Int J MS Care" "fecha" => "2018" "volumen" => "20" "paginaInicial" => "287" "paginaFinal" => "297" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30568566" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bb0015" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Tintoré" 1 => "M. Alexander" 2 => "K. Costello" 3 => "M. Duddy" 4 => "D.E. Jones" 5 => "N. Law" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/PPA.S115090" "Revista" => array:6 [ "tituloSerie" => "Patient Prefer Adherence" "fecha" => "2017" "volumen" => "11" "paginaInicial" => "33" "paginaFinal" => "45" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28053511" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bb0020" "etiqueta" => "4." 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Soilu-Hänninen" 2 => "H.-M. Kuusisto" 3 => "S. Atyla" 4 => "J. Junnila" 5 => "A. Berglund" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/ane.13301" "Revista" => array:2 [ "tituloSerie" => "Acta Neurol Scand" "fecha" => "2020" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bb0030" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hematological Alterations Related to Treatment with Teriflunomide and Dimethyl Fumarate in Multiple Sclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.A. García-Estévez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3390/neurosci1010003" "Revista" => array:6 [ "tituloSerie" => "NeuroSci" "fecha" => "2020" "volumen" => "1" "numero" => "1" "paginaInicial" => "17" "paginaFinal" => "23" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bb0035" "etiqueta" => "7." 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"referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Esclerosis múltiple benigna, edad avanzada y deterioro cognitivo: ¿una tríada clínica adecuada para el tratamiento con teriflunomida?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.A. García-Estévez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.neurop.2021.05.004" "Revista" => array:5 [ "tituloSerie" => "Neurology Perspectives" "fecha" => "2021" "volumen" => "1" "paginaInicial" => "189" "paginaFinal" => "191" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bb0045" "etiqueta" => "9." 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"referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dimethyl fumarate and teriflunomide for multiple sclerosis in a real-life setting: A French retrospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Condé" 1 => "X. Moisset" 2 => "B. Pereira" 3 => "M. Zuel" 4 => "R. Colamarino" 5 => "M. Maillet-Vioud" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/ene.13839" "Revista" => array:6 [ "tituloSerie" => "Eur. J. Neurol." "fecha" => "2018" "volumen" => "26" "paginaInicial" => "460" "paginaFinal" => "467" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30320947" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/26670496/0000000200000003/v2_202312201929/S266704962200014X/v2_202312201929/en/main.assets" "Apartado" => array:4 [ "identificador" => "92880" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letter" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/26670496/0000000200000003/v2_202312201929/S266704962200014X/v2_202312201929/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S266704962200014X?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 23 | 2 | 25 |
| 2024 September | 58 | 8 | 66 |
| 2024 August | 49 | 8 | 57 |
| 2024 July | 60 | 6 | 66 |
| 2024 June | 47 | 3 | 50 |
| 2024 May | 52 | 3 | 55 |
| 2024 April | 34 | 11 | 45 |
| 2024 March | 53 | 10 | 63 |
| 2024 February | 46 | 2 | 48 |
| 2024 January | 59 | 12 | 71 |
| 2023 December | 30 | 14 | 44 |
| 2023 November | 37 | 13 | 50 |
| 2023 October | 22 | 11 | 33 |
| 2023 September | 16 | 7 | 23 |
| 2023 August | 40 | 8 | 48 |
| 2023 July | 26 | 6 | 32 |
| 2023 June | 78 | 12 | 90 |
| 2023 May | 76 | 9 | 85 |
| 2023 April | 45 | 12 | 57 |
| 2023 March | 15 | 13 | 28 |
| 2023 February | 8 | 8 | 16 |
| 2023 January | 8 | 6 | 14 |
| 2022 December | 8 | 7 | 15 |
| 2022 November | 18 | 6 | 24 |
| 2022 October | 21 | 15 | 36 |
| 2022 September | 38 | 20 | 58 |
| 2022 August | 41 | 28 | 69 |
| 2022 July | 30 | 26 | 56 |
| 2022 June | 0 | 14 | 14 |
| 2022 May | 0 | 22 | 22 |
| 2022 April | 0 | 11 | 11 |
| 2022 March | 0 | 14 | 14 |
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