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"documento" => "simple-article" "crossmark" => 1 "subdocumento" => "edi" "cita" => "Med Clin. 2023;161:530-2" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Medicine in times of artificial intelligence" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "530" "paginaFinal" => "532" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La medicina en tiempos de inteligencia artificial" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ramón Pujol Farriols, Joan Guanyabens Calvet" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Ramón" "apellidos" => "Pujol Farriols" ] 1 => array:2 [ "nombre" => "Joan" "apellidos" => "Guanyabens Calvet" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020623005119?idApp=UINPBA00004N" "url" => "/23870206/0000016100000012/v2_202401260944/S2387020623005119/v2_202401260944/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Rheumatoid arthritis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "533" "paginaFinal" => "542" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Federico Díaz-González, María V. Hernández-Hernández" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Federico" "apellidos" => "Díaz-González" "email" => array:1 [ 0 => "federico.diaz.gonzalez@gmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "María V." "apellidos" => "Hernández-Hernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitario de Canarias, Tenerife, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Medicina Interna, Dermatología y Psiquiatría, Universidad de La Laguna, San Cristóbal de La Laguna, Tenerife, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Instituto Universitario de Tecnologías Biomédicas (ITB), Universidad de La Laguna, San Cristóbal de La Laguna, Tenerife, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Artritis reumatoide" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3438 "Ancho" => 2925 "Tamanyo" => 567385 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0085" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm for rheumatoid arthritis according to the Spanish Society of Rheumatology.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">DMARDs: disease-modifying antirheumatic drugs; csDMARD: conventional synthetic DMARD; tsDMARD: targeted synthetic DMARD; MTX: methotrexate.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis (RA) is a multisystem, immune-mediated chronic inflammatory disease of unknown aetiology that affects at least twice as many women as men. Its presentation is heterogeneous, and the current view of its aetiopathogenesis assumes that genetic and environmental factors are involved in its development.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> RA predominantly affects synovial (articular cavity) joints, leading to joint destruction and progressive disability. As a multisystem disease, it has extra-articular manifestations involving other organs such as the lung, cardiovascular system and even the eyes. Patients with RA have a shorter life expectancy mainly due to increased cardiovascular risk and lung involvement,<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> although infections, tumours or iatrogenesis may also play a role in this increased risk. Cohort studies have allowed the identification of genetic markers and antibodies potentially implicated in the development of RA and associated with poor prognosis.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> Anti-cyclic citrullinated peptide antibodies, also called anti-citrullinated protein antibodies (ACPA), have been shown to be highly specific for the disease (95%), although with lower sensitivity (53%–71%),<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a> with their levels being associated with more aggressive disease.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The updating of classification criteria<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> has made earlier diagnosis of RA possible. This, together with the use of combined indices<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11–14</span></a> and the application of therapeutic algorithms proposed by scientific societies<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15–17</span></a> have allowed a more objective assessment of disease activity, reducing variability in RA treatment, which has contributed to improving prognosis. Currently, we have disease-modifying antirheumatic drugs (DMARDs) such as conventional synthetics (csDMARD), represented by methotrexate, and targeted drugs, which include biologics (bDMARD) and targeted synthetics (tsDMARD). The most recommended treatment strategy is currently the so-called treat-to-target (T2T) strategy,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> which aims to achieve early and sustained clinical remission or low activity, aiming to halt radiological progression and the development of systemic complications. However, despite major advances in the management of RA, cure is still not possible and a proportion of patients fail to achieve remission or low disease activity. These patients constitute a definite therapeutic challenge for the clinician.</p><p id="par0015" class="elsevierStylePara elsevierViewall">This review aims to present the latest data on the epidemiology, genetics, pathophysiology, clinical evaluation, diagnostic approach and therapeutic management of RA.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Prevalence</span><p id="par0020" class="elsevierStylePara elsevierViewall">Its prevalence ranges from 0.5% to 1% in Caucasian populations.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The highest reported prevalence is in the Native American population and appears to be exceptional in black African populations and in certain Chinese groups. In Spain, the EPISER 16 study has determined that RA has a prevalence of 0.82% (95% confidence interval [CI] 0.59%–1.15 %) in the population over 20 years of age.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> RA is two to three times more common in women than in men at younger ages, but from the fifth decade of life onwards the disease frequency distribution becomes equal between the sexes.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Risk factors</span><p id="par0025" class="elsevierStylePara elsevierViewall">Although the cause of RA is still unknown, several genetic and environmental risk factors for RA have been identified.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Studies in monozygotic and dizygotic twins have shown disease concordance rates of 15% and 4%, respectively,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> highlighting that genetic load is probably not the most important risk factor for the development of the disease. In genetic studies, RA is strongly linked to haplotypes containing the HLA-DR4 and HLADR1 major histocompatibility complex (MHC) class II antigens. This association was identified in a short amino acid sequence between 67 and 74 of the third hypervariable region of the HLA-DRß1 gene called the “shared epitope”.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> These MHC genes are related not only to disease onset, but also to disease progression and severity.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Whole genome sequencing has revealed a large number of risk <span class="elsevierStyleItalic">loci</span> associated with RA, although less strongly than MHC class II haplotypes. Most of them are not unique to RA, but are also associated with other autoimmune diseases, such as the protein tyrosine phosphatase PTPN22. Antibody-independent predisposing genetic variants (HLA-DRB1, PTPN22, BLK, ANKRD55 and IL6ST), associated with seropositive RA (AFF3, CD28 and TNFAIP3) and seronegative RA (PRL and NFIA) have been identified.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23,24</span></a> Of the environmental factors, smoking has shown the strongest association with RA, with smokers showing a twofold increased risk of developing RA.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> The development and severity of RA has also been linked to alterations in oral and gut microbiota. The presence of periodontal disease, caused by agents such as <span class="elsevierStyleItalic">Porphyromonas gingivalis</span> and <span class="elsevierStyleItalic">Aggregatibacter actinomycetemcomitans,</span> has been linked to the development of RA and the severity of joint damage.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,27</span></a> Evidence on the timing of disease development suggests that the presence of the shared epitope and smoking act at different stages of RA development: smoking confers risk of ACPA and symptom development, while the shared epitope appears to be more related to the development of inflammatory joint symptoms.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Gender is another risk factor, as women are more predisposed to develop RA. Although the hormonal role is not yet well defined, it must have some influence, as the disease has an earlier onset in women and although during pregnancy they often go into remission, flare-ups are common after childbirth.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Aetiopathogenesis</span><p id="par0035" class="elsevierStylePara elsevierViewall">There is strong experimental evidence that the onset of RA is a T-cell-mediated, antigen-specific process with the synovial membrane as the primary target. However, it is not known whether the arthritogenic antigen is one or several and whether it is the same or varies between individuals. It is speculated that this could be an exogenous antigen, probably viral in nature, or an endogenous protein.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Histologically, the RA synovial membrane is characterised by: 1) hyperplasia of the synoviocyte layer, predominantly at the expense of fibroblast-like synoviocytes (FLS), which changes from being one to three cells thick to one that may be 50−100 cells deep; 2) increased vascularisation and; 3) presence of an inflammatory cell infiltrate, mainly CD4+ T-cells. These changes transform the synovium into a granulation tissue that invades the bone and cartilage, called <span class="elsevierStyleItalic">pannus</span>. The histological appearance of the synovium in RA is not specific, as it is seen in other inflammatory arthritis.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding the cellular component, CD4+ T-cells constitute the majority of infiltrating cells in the rheumatoid synovium showing an activated phenotype, often organised in lymphoid aggregates in the subintimal zone (below the synoviocyte layer). A prevalence of Th1 and Th17 cells is observed, with Th2 and regulatory T-cell (Tregs) deficiency<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>. B-lymphocytes are also present in the synovium, clustering in the centre of the lymphoid follicles surrounded by T-cells. B-cells can differentiate into plasma cells and produce rheumatoid factor (RF) under the influence of T-cells and cytokines such as IL-6 or B-lymphocyte stimulator (BLyS). Activated macrophages and dendritic cells are also found in the rheumatoid synovium, which in addition to their primary role as antigen presenting cells (APCs)<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> may be involved in the perpetuation of synovitis.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> In RA, FLS display an aggressive phenotype by producing matrix metalloproteinases (MMPs) that confer on the <span class="elsevierStyleItalic">pannus</span> the invasive capacity responsible for the joint erosion that characterises advanced RA. FLS also have additional pro-inflammatory effects through the production of IL-6 and granulocyte macrophage colony-stimulating factor (GM-CSF) that activate B and T-cells, chemotactic factors such as CCL2 and IL-8 (CXCL8), which recruit myeloid cells, or receptor activator of nuclear factor kappa-B ligand (RANKL), which promotes osteoclast formation.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The role of cytokines in the pathogenesis of RA has been demonstrated by the efficacy of therapies targeting TNF-α and IL-6.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31,32</span></a> TNF-α mainly produced by monocytes/macrophages is a potent stimulator of synovial fibroblasts, which release MMPs (collagenases and stromelysin), enzymes responsible for joint tissue destruction in RA.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">RF and ACPA are two autoantibodies closely related to RA that have been extensively studied for their potential pathogenic role. In the case of RF, the evidence seems to suggest that it is indeed a surrogate marker of B-cell activation.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However, ample evidence supports the role of ACPAs in RA pathogenesis essentially as enhancers of inflammation.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> From a practical point of view, the determination of both autoantibodies is useful for the diagnosis of the disease<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and their presence at high titres is associated with more aggressive disease and worse prognosis.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> RA patients who do not have these autoantibodies are referred to as seronegative RA (referring to the absence of RF), and while it appears that radiological progression of RF and ACPA negative RAs tends to be reduced,<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> the absence of these autoantibodies may delay diagnosis and, consequently, the initiation of treatment, which can sometimes be associated with more aggressive disease.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Pathogenic model of rheumatoid arthritis</span><p id="par0060" class="elsevierStylePara elsevierViewall">The prevailing pathogenic model of RA today proposes that the onset of RA requires an environmental component responsible for the sustained activation of innate immunity.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> This process can last for many years, fostering a state of autoimmunity which gradually increases until some as yet unknown process, euphemistically termed “second hit”, causes the clinical manifestations of the disease to occur.</p><p id="par0065" class="elsevierStylePara elsevierViewall">A key element in the preclinical phase of RA, also called “pre-RA”, is the induction of peptidyl arginine deiminase (PAD), an enzyme responsible for the post-translational change that converts arginine from structural proteins (collagens type I and II, fibrinogen, enolase and vimentin) into citrulline. Citrullination is not specific to RA, as it is produced during ageing, by environmental factors such as smoking<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> and by germs such as <span class="elsevierStyleItalic">P. gingivalis or A. actinomycetemcomitans</span> in the oral microbiota.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> What is characteristic of RA is the generation of antibodies against citrullinated proteins. Citrullination and other structural protein modifications (carbamylation, acetylation) generate neoepitopes with increased MHC avidity and which are more effectively presented by APCs to T-cells.</p><p id="par0070" class="elsevierStylePara elsevierViewall">In “pre-RA”, ACPAs and RF may be detected as early as 10 or more years before the onset of clinical manifestations,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> and although there is evidence that ACPAs may contribute to the onset or exacerbation of synovitis, they do not themselves cause arthritis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In “pre-RA” there may be non-specific arthralgias, with no histological alterations in the synovial membrane. It is in the “early RA” stage that arthritis occurs, and immune cell infiltration of the synovial membrane is evident. Once the inflammatory process is fully established, we speak of “established RA”. At this stage the synovium is transformed into a <span class="elsevierStyleItalic">pannus</span> with the characteristics of a locally invasive neoplasm that attacks and degrades the cartilage and adjacent subchondral bone.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Signs and symptoms</span><p id="par0075" class="elsevierStylePara elsevierViewall">There are excellent reviews on articular and extra-articular manifestations of RA,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> a detailed description of the clinical manifestations of RA is beyond the scope of this review. Briefly, the most common presenting symptoms are diffuse, symmetrical joint pain and swelling, predominantly affecting the small joints of the hands. These symptoms are often associated with prolonged (>1<span class="elsevierStyleHsp" style=""></span>h) morning stiffness and generalised asthenia. Although the disease may start as asymmetric or monoarticular, RA will eventually progress over a few weeks to months to a symmetric inflammatory arthritis that may affect the carpals, metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the hands, elbows, shoulders, hips, knees, ankles and small joints of the feet. In advanced stages, joint erosions and impingement may be seen on X-rays of joints with chronic and/or severe inflammation. If left untreated and the inflammation persists over time, typical joint deformities such as ulnar deviation of the hand or triangular foot will develop. Today, early diagnosis and aggressive initial treatment have made these RA deformities exceptional.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Although RA is a multisystem disease that can affect different organs, in the context of earlier and more aggressive treatment, some of these extra-articular manifestations may have decreased in frequency.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Interstitial lung disease is the most severe extra-articular manifestation of RA, its incidence has probably increased due to improved diagnostic techniques. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the multiple extra-skeletal manifestations of RA.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Diagnosis</span><p id="par0085" class="elsevierStylePara elsevierViewall">There is no pathognomonic test for the diagnosis of RA, so diagnostic guidance is provided by classification criteria that combine clinical findings with laboratory results. The most widely accepted are those reviewed by the American College of Rheumatology (ACR) and the European League of Associations for Rheumatology (EULAR) in 2010<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). These criteria have been developed for epidemiological purposes and to homogenise the populations included in clinical trials. In the absence of better tools, these criteria are considered useful for the clinical diagnosis of RA (sensitivity 82% and specificity 61%).<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> This means that we are probably diagnosing as RA processes of different aetiology and pathogenesis, but with similar clinical manifestations, which could explain the heterogeneity of response to the drugs used for treatment.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">When faced with a patient with polyarthritis, a differential diagnosis should be made with other pathologies with similar symptoms (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Early diagnosis and referral to specialised care of patients with suspected RA is essential to initiate early treatment in order to avoid limitations in quality of life and disability. The presence of specific antibodies and the presence of synovitis on ultrasound and/or MRI can facilitate diagnosis in the early stages of the disease.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Monitoring the patient with rheumatoid arthritis</span><p id="par0095" class="elsevierStylePara elsevierViewall">The current strategy for the management of RA is based on close monitoring of disease activity, with the aim of achieving early remission or low activity. The aim is to preserve physical function in early-stage patients and to prevent progression in those with established disease. This strategy is known as T2T (<span class="elsevierStyleItalic">treat-to-target</span>) and has been adopted as the standard of care by various scientific societies such as the ACR,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> EULAR<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> or the Spanish Society of Rheumatology (SER).<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> In order to assess treatment response, it is essential to measure the variation in disease activity over time using validated methods. The most commonly used tools for this are combined indices that include physical examination, patient and/or physician assessment and acute phase reactants<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11–14</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). However, these indices have limitations as: a) they exclude joints in the counts, so that a patient with swollen joints can be considered as “in remission”; b) they may underestimate systemic inflammation because of the effect of some of biologics (anti-IL-6) on acute phase reactants; and c) concomitant pathologies such as fibromyalgia or osteoarthritis interfere with the assessment of pain using visual analogue scales.</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Imaging techniques such as MRI and especially joint ultrasound are increasingly used in the evaluation of RA. Ultrasound makes it possible to detect synovial inflammation or joint damage even when physical examination or radiography is normal, as well as assessing in a more precise way the inflammatory activity of the synovium in response to treatment.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Treatment</span><p id="par0105" class="elsevierStylePara elsevierViewall">The goal of RA treatment is to achieve remission or minimal activity as soon as possible, within what is known as the “window of opportunity”. This concept has evolved over the years from encompassing the first two years after RA diagnosis to refer to the period of three to four months after symptom onset or even to pre-clinical stages.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> It is in this period that therapeutic intervention leads to optimal results.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The treatment of RA has evolved dramatically in recent decades, mainly due to the development of new drugs. However, non-pharmacological therapy, such as regular exercise to maintain good muscular and cardiovascular fitness, continues to play an important role in the management of RA by helping to preserve the functional status of patients.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The drugs used to treat RA are divided into three classes: non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids and DMARDs, including csDMARD, bDMARD and tsDMARD. The latter two groups of DMARDs are identified as targeted therapy.</p><p id="par0120" class="elsevierStylePara elsevierViewall">NSAIDs provide partial relief of pain (main therapeutic action) and stiffness after joint rest. They do not slow the progression of the disease and should therefore always be used in conjunction with DMARDs. Their gastrointestinal and renal toxicity must be taken into account, as well as the associated risk of developing thromboembolic events, as RA patients are more prone to accelerated atherosclerosis.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Glucocorticoids are potent suppressors of the inflammatory response and have even been postulated to slow the radiological progression of RA.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> However, their dose- and time-dependent side effects are well known. Controversy remains about when and how they should be used, but it has been established that, when indicated, they should be used at the lowest dose (≤7.5<span class="elsevierStyleHsp" style=""></span>mg/day of prednisone) and for the shortest possible time.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> They are generally prescribed as bridge therapy while awaiting the effect of DMARDs. In severe refractory disease with visceral involvement or vasculitis, intravenous methylprednisolone pulses (250−1000<span class="elsevierStyleHsp" style=""></span>mg) can be used daily for one to three days. Intra-articular glucocorticoid injections (with triamcinolone acetonide or betamethasone) may be useful to suppress inflammation in isolated joints resistant to systemic treatment. They usually produce rapid relief of symptomatology and are generally safe, although no more than three to four injections per year per joint are recommended.</p><p id="par0130" class="elsevierStylePara elsevierViewall">DMARDs (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>) are slow-acting drugs that require weeks (four to eight weeks) to months (up to six in the case of hydroxychloroquine) to show a therapeutic effect and should be started as soon as the diagnosis of RA is established.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">csDMARD</span><p id="par0135" class="elsevierStylePara elsevierViewall">Methotrexate. Its mechanism of action is not well understood. It is the first-line drug of choice, as it is the csDMARD most likely to induce a long-term response.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Approximately half of the patients treated with methotrexate do not show radiographic progression, however, 30% will require the addition of a bDMARD to their treatment.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> It is generally safe, with hepatotoxicity and myelosuppression being the most serious adverse effects.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Leflunomide is a prodrug with extensive enterohepatic recirculation, giving it a very long persistence in the body. It has shown similar efficacy to methotrexate in the treatment of RA in controlled clinical trials.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> It can be used as monotherapy or in combination with methotrexate, as although it is not recommended in the label and may increase liver toxicity, this combination may be useful in certain patients.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Sulfasalazine was the first DMARD developed specifically to treat RA almost a century ago. Its mechanism of action in RA is unknown. It has similar efficacy to methotrexate; however, its intestinal tolerance is worse (especially in non-enteric-coated presentations). Generally speaking, it is little used in our environment for the management of RA.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Hydroxychloroquine is the drug with the lowest effectiveness profile of the csDMARD in RA. It is therefore only used as monotherapy in low-activity RA, in patients with mild undifferentiated polyarthritis or as part of triple therapy, a treatment combining methotrexate, sulfasalazine and hydroxychloroquine.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> It requires regular ophthalmological monitoring.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">bDMARD</span><p id="par0155" class="elsevierStylePara elsevierViewall">When remission or low RA activity is not achieved with csDMARD within three to six months or when patients have poor prognostic factors, initiation of treatment with bDMARD is indicated.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> These can be administered subcutaneously or intravenously (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><p id="par0160" class="elsevierStylePara elsevierViewall">Anti-TNF-α: all are complete monoclonal antibodies or fragments (certolizumab pegol), except etanercept, which is a fusion protein. Since 2014, biosimilars of infliximab, adalimumab and etanercept, which have shown similar efficacy and safety to the innovative molecules they mimic, have been available in Spain.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> Anti-TNF-α have shown better efficacy in symptom control and prevention of structural damage in combination with methotrexate or leflunomide than in monotherapy.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Anti-IL6: tocilizumab and sarilumab are indicated in RA patients with insufficient response to csDMARD and/or biologic agents. Their clinical and radiological efficacy is comparable to that of anti-TNF-α, and they have been shown to be equally effective both in monotherapy and in combination with csDMARD.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> Their mechanism of action results in a significant and rapid decrease in inflammatory reactants. It also has notable effects on systemic symptoms and, in particular, on anaemia.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Anti-CTL-4: abatacept is indicated in RA with csDMARD failure. Its efficacy is similar in monotherapy or in combination with methotrexate<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> and the presence of ACPA is associated with a better therapeutic response.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> Abatacept is one of the biologics with the best safety profile in terms of infections.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Anti-CD20: Rituximab and its biosimilars are used in patients with RA refractory to csDMARD and failure of at least one anti-TNF-α. Its effect can last for nine to 12 months after administration, although it can sometimes be maintained for up to two years after administration. Anti-CD20 is most effective in patients with positive autoantibodies (RF and/or ACPA).<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> Response is slower than with other bDMARD and should be assessed at 12–16 weeks after infusion. Repeated administrations of rituximab result in hypogammaglobulinemia which may predispose to infections.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">tsDMARD</span><p id="par0180" class="elsevierStylePara elsevierViewall">Janus kinases are a group of four intracellular proteins: JAK1, JAK2, JAK3 and Tyk2, which are involved in signalling various cytokine and growth factor receptors. Their inhibition has shown efficacy in the control of symptoms, signs and progression of RA in monotherapy or in association with methotrexate.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> As synthetic drugs, they have the advantage of oral administration and some allow dose optimisation. Recently, JAK inhibitors have undergone special safety monitoring to explain an increased risk of cardiovascular and tumour events in RA patients compared to anti-TNF-α<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a>.</p><p id="par0185" class="elsevierStylePara elsevierViewall">Scientific societies have proposed similar treatment strategies for the management of RA.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15–17</span></a><a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the treatment strategy proposed by SER in the latest guidelines for the management of RA.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The use of biosimilars has been prioritised over the use of innovative biologics in “naïve” patients for pharmacoeconomic reasons, which is undoubtedly helping to sustain the health system.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Prognosis of rheumatoid arthritis</span><p id="par0190" class="elsevierStylePara elsevierViewall">Changes in pharmacotherapy and treatment approach have improved the clinical outcomes of RA patients over the past 25 years.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> The availability of biologics since the late 1990s, a more aggressive treatment strategy in patients with earlier diagnosis and the widespread use of methotrexate have improved early mortality in RA patients.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> These improvements have decreased the need for joint surgery<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> and reduced disability in RA patients.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Factors such as functional limitation, the presence of structural damage (erosions), RF- or ACPA-positive and extra-articular manifestations have been associated with a worse prognosis in RA patients.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Long-term complications of rheumatoid arthritis</span><p id="par0200" class="elsevierStylePara elsevierViewall">The coexisting conditions that have the greatest effect on morbidity and mortality in RA are infections (especially pulmonary), interstitial lung disease, osteoporosis and cardiovascular disease.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> Their management is complex and there are updated guidelines addressing their management.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">All RA patients should be vaccinated annually against influenza and receive pneumococcal vaccination at appropriate intervals. Live vaccines should be avoided in patients receiving immunosuppressive drugs. Both physicians and their RA patients must be vigilant to avoid infections and treat them early and aggressively. It is essential to temporarily discontinue immunosuppressive therapy during infections.</p><p id="par0210" class="elsevierStylePara elsevierViewall">Between 10% and 50% of RA patients have interstitial lung involvement. Risk factors are: aggressive RA, male sex, advanced age, obesity, smoking and positive ACPA. Symptoms usually include dyspnoea and non-productive cough of insidious onset. Management requires the use of high-dose glucocorticoids and immunosuppressants.</p><p id="par0215" class="elsevierStylePara elsevierViewall">The incidence of osteoporosis doubles in RA patients, so bone density studies should be performed in all patients, especially those who are to receive glucocorticoids or have other risk factors, in order to initiate antiresorptive treatment.</p><p id="par0220" class="elsevierStylePara elsevierViewall">Cardiovascular disease accounts for most of the excess mortality associated with RA. Modifiable risk factors for atherosclerosis must be aggressively sought and treated. In particular, smoking cessation is essential, as it has also been associated with increased severity of arthritis.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ethical considerations</span><p id="par0225" class="elsevierStylePara elsevierViewall">This document has not required the use of humans and therefore no ethical considerations apply to it.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0230" class="elsevierStylePara elsevierViewall">This work has been financially supported by the Association for the support of research in Rheumatology at the <span class="elsevierStyleGrantSponsor" id="gs0005">University Hospital of the Canaries</span> (REUNINVES); and by the <span class="elsevierStyleGrantSponsor" id="gs0010">Instituto de Salud Carlos III</span> PI21/00406 to F. D-G.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0235" class="elsevierStylePara elsevierViewall">The authors declare the following conflicts of interest:</p><p id="par0240" class="elsevierStylePara elsevierViewall">Federico Díaz-González has received consultancy fees from: Abbvie, Lilly, Pfizer, Galapagos; fees for lectures from: Janssen, Galapagos, Abbvie, Abbvie, Novartis and financial support for research projects from: Janssen, Novartis and Abbvie.</p><p id="par0245" class="elsevierStylePara elsevierViewall">Maria V. Hernández-Hernández has received fees for consultancy from: UCB; and fees for lectures from: Janssen, Galapagos, Abbvie, BMS, UCB, Novartis, Lilly, Roche and Grünenthal.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:19 [ 0 => array:3 [ "identificador" => "xres2080549" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1774932" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2080550" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1774933" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Prevalence" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Risk factors" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Aetiopathogenesis" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Pathogenic model of rheumatoid arthritis" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Signs and symptoms" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Diagnosis" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Monitoring the patient with rheumatoid arthritis" ] 12 => array:3 [ "identificador" => "sec0045" "titulo" => "Treatment" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "csDMARD" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "bDMARD" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "tsDMARD" ] ] ] 13 => array:2 [ "identificador" => "sec0065" "titulo" => "Prognosis of rheumatoid arthritis" ] 14 => array:2 [ "identificador" => "sec0070" "titulo" => "Long-term complications of rheumatoid arthritis" ] 15 => array:2 [ "identificador" => "sec0075" "titulo" => "Ethical considerations" ] 16 => array:2 [ "identificador" => "sec0080" "titulo" => "Funding" ] 17 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 18 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-04-16" "fechaAceptado" => "2023-07-12" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1774932" "palabras" => array:5 [ 0 => "Rheumatoid arthritis" 1 => "Etiopathogenesis" 2 => "Treatment" 3 => "Treat to target strategy" 4 => "Disease activity" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1774933" "palabras" => array:5 [ 0 => "Artritis reumatoide" 1 => "Etiopatogenia" 2 => "Tratamiento" 3 => "Estrategia <span class="elsevierStyleItalic">treat to target</span>" 4 => "Actividad de la enfermedad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Rheumatoid arthritis (RA) is a chronic inflammatory multisystemic disease of unknown etiology and autoimmune nature that predominantly affects peripheral joints in a symmetrical fashion. Although much progress has been made in understanding the pathophysiology of RA, its etiology remains unknown. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 play the important roles in the pathogenesis and maintenance of inflammation in RA. The presence of anti-citrullinated peptide antibodies aids in the diagnosis in patients with undifferentiated polyarthritis and is associated with a more aggressive RA. The natural history of RA causes joint deformity and disability, as well as reduced life expectancy, both due to increased cardiovascular risk, pulmonary involvement, infections, iatrogenesis or tumors. Early diagnosis and the use of targeted drugs to induce early remission have improved the RA prognosis.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">La artritis reumatoide (AR) es una enfermedad inflamatoria crónica multisistémica de etiología desconocida y de naturaleza autoinmune que afecta predominantemente a las articulaciones periféricas de forma simétrica. Aunque se ha avanzado mucho en la comprensión de su fisiopatología, su etiología sigue siendo desconocida. El factor de necrosis tumoral (TNF)-α y la interleucina (IL)-6, juegan un papel importante en la patogénesis y la perpetuación de la inflamación en la AR. La presencia de anticuerpos antipéptidos citrulinados ayuda en el diagnóstico en pacientes con poliartritis indiferenciadas y se relaciona con una evolución más agresiva de la AR. La evolución natural de la AR causa deformidad articular y discapacidad, además de una reducción de la esperanza de vida, por aumento del riesgo cardiovascular, afectación pulmonar, infecciones, iatrogenia o tumores. El diagnóstico precoz y la utilización de fármacos dirigidos que buscan la remisión temprana han mejorado sustancialmente el pronóstico de la AR.</p></span>" ] ] "multimedia" => array:6 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3438 "Ancho" => 2925 "Tamanyo" => 567385 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0085" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Treatment algorithm for rheumatoid arthritis according to the Spanish Society of Rheumatology.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">DMARDs: disease-modifying antirheumatic drugs; csDMARD: conventional synthetic DMARD; tsDMARD: targeted synthetic DMARD; MTX: methotrexate.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0090" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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=""><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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Cardiovascular \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pericarditis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pericardial effusion \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Valvulopathy \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myocarditis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Arrhythmias or conduction disturbances \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiac nodules \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Dermatological \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Vasculitis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ulcers \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lymphoedema \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drug-induced toxicoderma \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. Gastrointestinal \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Xerostomia \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastritis or peptic ulcer \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stomatitis or mucositis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. Haematological \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lymphadenopathy \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Splenomegaly \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Leukopenia \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lymphoma \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Amyloidosis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cryoglobulinemia \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lymphocytic syndrome \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5. Liver \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nodular regenerative hyperplasia \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Portal fibrosis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cirrhosis/hepatitis secondary to treatment \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6. Neurological \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Spinal cord involvement due to C1–C2 incomplete dislocation \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Peripheral nerve entrapment \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mononeuritis multiplex \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Brain nodules \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7. Ophthalmological \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dry eye (associated with secondary Sjögren’s syndrome) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Episcleritis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Scleritis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Scleromalacia \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8. Pulmonary \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pulmonary fibrosis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Interstitial lung disease \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lung nodules \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pleural effusion \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pleuritis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bronchiectasis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cryptogenic organizing pneumonia \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9. Renal \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glomerulonephritis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Proteinuria (in association with amyloidosis) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Treatment-induced kidney disease \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3444900.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Extra-articular manifestations of rheumatoid arthritis.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0095" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">ACPA: anti-citrullinated protein antibodies; ACR/EULAR: American College of Rheumatology/European League of Associations for Rheumatology; CMC: carpometacarpal; RF: rheumatoid factor; IP: interphalangeal; PIP: distal interphalangeal; PIP: proximal interphalangeal; MCP: metacarpophalangeal; MTP: metatarsophalangeal; CRP: C-reactive protein; MRI: magnetic resonance imaging; ESR: erythrocyte sedimentation rate.</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=""><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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The classification criteria proposed by ACR/EULAR include clinical and serological variables. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The classification criteria should be applied only in case of ≥1 swollen joint. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">A score of ≥6 points is required for a definitive diagnosis of RA. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Joint involvement and distribution: 0–5 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">These variables include any swollen or painful joint (except PIP of hands and feet, 1st MTP and CMC joint) on physical examination; findings of inflammation identified by MRI or ultrasound may be used. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* 1 large joint (shoulder, elbow, hip, knee or ankle): 0 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* 2−3 large joints: 1 point. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* 1−3 small joints (MCP, PIP, 2nd-5th MTP, IP of thumb and wrist): 2 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* 4−10 small joints: 3 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* >10 joints (≥1 small joint<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>): 5 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Duration of symptoms: 0–1 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">This variable refers to the maximum duration of signs and symptoms reported by patients over any joint that is clinically affected at assessment. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* <6 weeks: 0 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* ≥6 weeks: 1 point. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serology<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>: 0–3 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* Negative RF<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a> and negative ACPA: 0 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* Weak positive RF<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> or weak positive ACPA: 2 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* Strong positive RF<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">e</span></a> or strong positive ACPA: 3 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Acute phase reactants<a class="elsevierStyleCrossRef" href="#tblfn0030"><span class="elsevierStyleSup">f</span></a>: 0–1 point. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">*Normal CRP and ESR: 0 points. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">*Elevated CRP or ESR: 1 point. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3444898.png" ] ] ] "notaPie" => array:6 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Additional small joints include the temporomandibular joint, sternoclavicular joint and others that may be affected in RA.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">If the result of the RF determination is qualitative, a positive result should be reported as a weak positive.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Equal to or less than the upper limit of the normal value for the local laboratory.</p>" ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">>1–3 times the normal value for the local laboratory.</p>" ] 4 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "e" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">>3 times the upper limit of the normal value for the local laboratory.</p>" ] 5 => array:3 [ "identificador" => "tblfn0030" "etiqueta" => "f" "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Determined according to local laboratory standards.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Classification criteria for rheumatoid arthritis (ACR/EULAR 2010).</p>" ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0100" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">ACPA: anti-citrullinated peptide antibodies; APR: acute phase reactants; Ca: cancer; MRI: magnetic resonance imaging; PsA: psoriatic arthritis; RF: rheumatoid factor.</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Disease \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Presentation \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Physical examination \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comment \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 rowgroup " rowspan="2" align="left" valign="middle">Systemic lupus erythematosus</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="middle">Polyarthritis, morning stiffness, asthenia and elevated acute phase reactants</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="middle">Arthritis and other characteristic manifestations such as Raynaud’s, malar rash, alopecia or aphthous ulcer</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Skin rashes in photoexposed areas, oral +/− genital aphthous ulcer, cytopenias, nephritis or specific serological tests. Arthritis is not usually erosive. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">An overlap syndrome (Rhupus) may occur, with erosive arthritis and positive lupus and RA serologies. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Polymyalgia rheumatica \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sudden weakness of the waist (scapular and pelvic)<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>constitutional symptoms, occasional fever. Arthritis may occur \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weakness in arms and legs \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anaemia, elevated APR, and age >50 years \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Spondyloarthropathies (axial spondylarthritis, PsA, enteropathic arthritis, reactive arthritis) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Axial skeletal involvement, asymmetric arthritis (distal interphalangeal joints of hands and/or feet). \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Limitation of axial mobility, pain in enthesis. Skin lesions, genital (balanitis circinata in reactive a. or genital psoriasis) or typical nail lesions (nail psoriasis) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Asymmetric arthritis, axial and distal involvement together with the associated underlying disease (psoriasis, inflammatory bowel disease, infection), in addition to serological markers HLAB27, B08, B38… \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other connective tissue diseases (scleroderma), myopathies, vasculitides \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Arthritis and general symptoms (fever, asthenia…) as initial manifestation \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Specific cutaneous manifestations: Raynaud’s, Gottron’s papules, vasculitic lesions, etc. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Differential diagnosis by specific systemic symptoms, analytical alterations (elevated muscle enzymes) and specific antibodies. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gout and pseudogout \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mono or oligoarticular arthritis of sudden onset, very painful, with strong localised reaction, which develops in crises. Self-healing in 7 days \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Presence of intense pain, flushing and heat in the affected joint \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diagnosis by presence of microcrystals in synovial fluid, double contour sign during acute crisis by ultrasound or calcification of cartilage in knees and/or carpals. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Arthrosis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Asymmetric polyarticular involvement. Mechanical pain. Affects load-bearing, axial joints and joints with increased use. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Joint impingement, osteophyte formation, presence of hydrarthrosis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For diagnosis: age at presentation >50 years. Radiographic findings, clinical course and absence of inflammatory markers for diagnosis. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Septic arthritis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Monoarticular, systemic symptoms (fever) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythema and localised heat, heat, severe functional impotence \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Synovial fluid culture \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RS3PE syndrome \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Symmetrical synovitis, oedema with pitting on dorsum of wrists up to metacarpophalangeal joints, (“boxing glove”-like) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Limited mobilisation of the carpus due to oedema. In addition, range limitation of shoulder motion. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative RF and ACPA. Ultrasound and MRI with tenosynovitis of the extensors of the forearms and hands, with minor amounts of flexor tenosynovitis and synovitis of the metacarpophalangeal and proximal interphalangeal joints. Association with solid tumours and haematological disorders. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tumours \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Poly-oligo-arthritis associated with constitutional symptoms or B-symptoms \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weight loss, skin lesions or toxic habits \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Careful medical history, laboratory study and chest X-ray. Depending on sex, rule out prostate or breast Ca. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3444899.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Differential diagnosis of rheumatoid arthritis.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0105" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">CDAI: <span class="elsevierStyleItalic">Clinical Disease Activity Index</span>; DAS: <span class="elsevierStyleItalic">Disease Activity Score;</span> VAS: visual analogue scale; NPJ: number of painful joints; NSJ: number of swollen joints; RAPID: <span class="elsevierStyleItalic">Routine Assessment of Patient Index Data</span>; SDAI: <span class="elsevierStyleItalic">Simplified Disease Activity Index</span>; PGA: physician global assessment; PaGA: patient global assessment.</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Scores \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Formula \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Cut-off points</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" 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="left" 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Remission \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Low activity \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Moderate activity \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">High activity \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SDAI<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NAT28<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>NAT28<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PaGA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PGA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PCR \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤3.3 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>3.3–11 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>11–26 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>26 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CDAI<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">NAT28<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>NAT28<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PaGA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PGA \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤2.8 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>2.8–10 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>10–22 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>22 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DAS<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Formula including Ritchie’s index of painful joint count (0–78), swollen joint count (0–44), PaGA, VSG and/or PCR \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤1.6 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>1.6–2.4 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>2.4–3.7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>3.7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DAS28<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Formula including count of 28 painful and swollen joints (excludes hips, knees, ankles and feet), PaGA, VSG and/or CRP \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≤2.6 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>2.6–3.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>3.1–5.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>5.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RAPID3<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Assessment of physical function according to questionnaire (0−10)<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>VAS patient pain<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PaGA \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3.1–6 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.1–12 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>12 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3444901.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Disease activity scores and cut-off points.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0110" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Ab: antibodies; ARs: adverse reactions; dis: disease; DMARD: disease-modifying antirheumatic drug; csDMARD: conventional synthetic DMARD; bDMARD: biologic DMARD; tsDMARD: targeted synthetic DMARD; g: grams; HBV: hepatitis B virus; HCV: hepatitis C virus; Ig: immunoglobulins; EMA: European Medicines Agency; IL-6: interleukin-6; i. v.: intravenous; JAK: Janus kinase: kg: kilograms; mg: milligram; Rx: X-ray; s.c.: subcutaneous; TNF: tumour necrosis factor; wk: week.</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Drug \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Type \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AR and considerations \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 rowgroup " rowspan="3" align="left" valign="middle">Methotrexate</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="middle">Dihydrofolate reductase inhibitor</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="3" align="left" valign="middle">10−25<span class="elsevierStyleHsp" style=""></span>mg/week oral or s.c., although its bioavailability increases 90% by s.c. route.</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The most common: gastrointestinal intolerance, headaches, hypertransaminasemia, oral ulcers, reversible alopecia and skin rashes. They improve with the addition of folic acid (1–3<span class="elsevierStyleHsp" style=""></span>mg/day) or leucovorin (15<span class="elsevierStyleHsp" style=""></span>mg 24<span class="elsevierStyleHsp" style=""></span>h after methotrexate) without decreasing efficacy. More serious ARs: myelosuppression and hepatotoxicity. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Avoid if liver disorders or alcohol abuse or hepatitis virus infections. In renal insufficiency and advanced age increased risk of myelotoxicity. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Teratogenic, discontinue at least 3 months before a planned pregnancy in both females and males. \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 rowgroup " rowspan="2" align="left" valign="middle">Leflunomide</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="2" align="left" valign="middle">Dihydroorotate dehydrogenase inhibitor</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="2" align="left" valign="middle">10−20<span class="elsevierStyleHsp" style=""></span>mg/day orally</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Most common: weight loss, diarrhoea (can be severe and cause hyponatraemia), reversible alopecia, pancytopenia, hypertension and peripheral neuropathy. The most serious AR, hepatotoxicity. Avoid if alcohol abuse or hepatitis virus infection. Special caution with methotrexate. Avoid administration with drugs that use the cytochrome P450 2C9 (CYP2C9) pathway (anticoagulants, rifampicin, etc.). \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">It is teratogenic. Discontinue at least 3 months before conception and washout with cholestyramine (8<span class="elsevierStyleHsp" style=""></span>g every 8<span class="elsevierStyleHsp" style=""></span>h for 11 days) is recommended. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sulphasalazine \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mesalazine derivative \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2−3<span class="elsevierStyleHsp" style=""></span>g/day orally \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Most common gastrointestinal (in Spain, its formulation does not include enteric coating). Most serious ARs: leukopenia, granulocytopenia, and hepatotoxicity. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hydroxychloroquine \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antimalarial \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">200−400<span class="elsevierStyleHsp" style=""></span>mg/day (maximum 5<span class="elsevierStyleHsp" style=""></span>mg/kg/day) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastrointestinal toxicity is more common. They may cause ocular toxicity due to accumulation in the retina. Periodic ophthalmological control is recommended. \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 rowgroup " rowspan="6" align="left" valign="middle">Anti-TNF-α</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TNF-α inhibitors \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-Adalimumab: 40<span class="elsevierStyleHsp" style=""></span>mg/s.c./2 wk. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Upper respiratory and urinary tract infections, and increased risk of opportunistic infections. Reactivation of latent tuberculosis (screening and primary prophylaxis in case of positive Quantiferon or Mantoux with normal chest X-ray) or HBV or HCV infection (in case of infection it has to be treated) Can cause injection site reaction, paradoxical psoriasis, skin toxicity, hepatotoxicity, demyelinating diseases Contraindicated for use of live virus vaccines. \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 rowgroup " rowspan="5" align="left" valign="middle">Bind to TNF receptors or the soluble molecule, blocking its effect</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-Etanercept: 50<span class="elsevierStyleHsp" style=""></span>mg/s.c./wk. \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 " rowspan="5" align="left" valign="middle">All cross the placental barrier except certolizumab pegol, which can be administered according to the SmPC in pregnancy.</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-Certolizumab pegol: 400<span class="elsevierStyleHsp" style=""></span>mg weeks 0,2 and 4; then 200<span class="elsevierStyleHsp" style=""></span>mg/s.c./2 wk. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-Golimumab: 50<span class="elsevierStyleHsp" style=""></span>mg/s.c./4 wk. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">-Infliximab: 3<span class="elsevierStyleHsp" style=""></span>mg/kg/i.v. wk 0,2,6 and then every 8 wks \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biosimilars of adalimumab, etanercept and infliximab are currently available. \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 rowgroup " rowspan="3" align="left" valign="middle">Anti-IL6</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="3" align="left" valign="middle">Monoclonal Abs that bind to both soluble and membrane-bound IL-6 receptors (IL6-r), inhibiting their signalling</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tocilizumab: 162<span class="elsevierStyleHsp" style=""></span>mg/s.c./wk or 8<span class="elsevierStyleHsp" style=""></span>mg/kg/i.v. every 4 weeks \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 " rowspan="3" align="left" valign="middle">More common: infections and laboratory abnormalities (Dyslipidemia, neutropenia, thrombopenia and elevated transaminases). In patients with a history of diverticulosis, risk of intestinal perforation.</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sarilumab: 200<span class="elsevierStyleHsp" style=""></span>mg/s.c./2 wk. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No biosimilars on the market yet \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 rowgroup " rowspan="4" align="left" valign="middle">AntiCTL-4</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="4" align="left" valign="middle">Selective modulator of T-cell co-stimulation. Binds to CD80 and CD86 on CPA and blocks their interaction with CD28 on the T-cell, inhibiting the second signal necessary for cell activation</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Abatacept (2 routes of administration) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Upper respiratory tract and urinary tract infections Reactivation of tuberculosis or latent hepatitis \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−10<span class="elsevierStyleHsp" style=""></span>mg/kg/i.v. at weeks 0,2 and 4 and then every 4 weeks thereafter \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Haematological disturbances, skin reactions \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−125<span class="elsevierStyleHsp" style=""></span>mg/s.c./wk. \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 " rowspan="2" align="left" valign="middle">It is considered the safest in terms of infections.</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No biosimilars on the market yet \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 rowgroup " rowspan="2" align="left" valign="middle">Anti-CD20</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Human-murine chimeric monoclonal Ab directed against the CD20 surface molecule present on the B lymphocyte. Produces \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Rituximab: 1<span class="elsevierStyleHsp" style=""></span>g i.v. in weeks 0 and 2 Subsequently administer every 6−8–12 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 " rowspan="2" align="left" valign="middle">Most common ARs: infusion reactions, urinary tract or respiratory tract infections. Repeated administration causes Ig depletion, predisposing to opportunistic infections.</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">B-lymphocyte depletion \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Several biosimilars are available \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 rowgroup " rowspan="4" align="left" valign="middle">Jakinibs</td><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " rowspan="4" align="left" valign="middle">They selectively inhibit the activity of one or more of the Janus kinase family of enzymes, inhibiting the JAK-STAT signalling pathway in lymphocytes. First generation inhibit more JAK (tofacitinib is considered a pan-JAK, baricitinib inhibits JAK1 and JAK2, upadacitinib/filgotinib inhibit JAK1).</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tofacitinib: 5<span class="elsevierStyleHsp" style=""></span>mg/orally/12 h \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increased incidence of upper respiratory or urinary tract infections Increased incidence of shingles. \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Baricitinib: 2−4<span class="elsevierStyleHsp" style=""></span>mg/orally/24<span class="elsevierStyleHsp" style=""></span>h \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 " rowspan="3" align="left" valign="middle">It is recommended to avoid its use in patients ≥65 years of age with increased cardiovascular risk (smokers, with a history of cardiac or thrombotic events, with increased cholesterol, with extra-articular manifestations of RA) and patients at high risk of tumours.</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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Upadacitinib: 15<span class="elsevierStyleHsp" style=""></span>mg/orally/24<span class="elsevierStyleHsp" style=""></span>h \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Filgotinib: 100−200<span class="elsevierStyleHsp" style=""></span>mg/orally/24<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3444902.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">csDMARD, bDMARD and tsDMARD with indication for RA treatment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:60 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The etiology of rheumatoid arthritis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H.U. 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Rheumatoid arthritis
Artritis reumatoide
a Servicio de Reumatología, Hospital Universitario de Canarias, Tenerife, Spain
b Departamento de Medicina Interna, Dermatología y Psiquiatría, Universidad de La Laguna, San Cristóbal de La Laguna, Tenerife, Spain
c Instituto Universitario de Tecnologías Biomédicas (ITB), Universidad de La Laguna, San Cristóbal de La Laguna, Tenerife, Spain