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array:22 [ "pii" => "S2173574322001666" "issn" => "21735743" "doi" => "10.1016/j.reumae.2021.12.004" "estado" => "S300" "fechaPublicacion" => "2022-12-01" "aid" => "1585" "copyrightAnyo" => "2022" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Reumatol Clin. 2022;18:567-73" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "en" => array:18 [ "pii" => "S1699258X21002783" "issn" => "1699258X" "doi" => "10.1016/j.reuma.2021.12.001" "estado" => "S300" "fechaPublicacion" => "2022-12-01" "aid" => "1585" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Reumatol Clin. 2022;18:567-73" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Effectiveness and safety of tocilizumab in monotherapy in biologic-naïve and non-naïve patients with rheumatoid arthritis in a real-world setting" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "567" "paginaFinal" => "573" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eficacia y seguridad de tocilizumab en monoterapia en pacientes con artritis reumatoide naive y no naive a biológicos en un entorno del mundo real" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1890 "Ancho" => 2341 "Tamanyo" => 298892 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flowchart of patients included in the study_2.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Sara Marsal Barril, Mª Auxiliadora Martin-Martinez, Francisco Javier Blanco-Garcia, Antonio Fernández-Nebro, Rosario García de Vicuña, Jesús Tornero-Molina, Fernando Sánchez-Alonso, Marta Novella-Navarro, Alejandro Escudero-Contreras, Juan José Alegre-Sancho, Ana Urruticoechea-Arana, Maria Sagrario Bustabad-Reyes, Pilar Trenor-Larraz, Trinidad Pérez-Sandoval, Maria Isabel Tevar-Sánchez, Jesús T. 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Sánchez-Costa, Enrique Raya-Álvarez" "autores" => array:17 [ 0 => array:3 [ "nombre" => "Sara" "apellidos" => "Marsal Barril" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "Mª Auxiliadora" "apellidos" => "Martin-Martinez" "email" => array:1 [ 0 => "xily_mm@yahoo.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Francisco Javier" "apellidos" => "Blanco-Garcia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Antonio" "apellidos" => "Fernández-Nebro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Rosario" "apellidos" => "García de Vicuña" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "Jesús" "apellidos" => "Tornero-Molina" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] ] ] 6 => array:3 [ "nombre" => "Fernando" "apellidos" => "Sánchez-Alonso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 7 => array:3 [ "nombre" => "Marta" "apellidos" => "Novella-Navarro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 8 => array:3 [ "nombre" => "Alejandro" "apellidos" => "Escudero-Contreras" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] ] ] 9 => array:3 [ "nombre" => "Juan José" "apellidos" => "Alegre-Sancho" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 10 => array:3 [ "nombre" => "Ana" "apellidos" => "Urruticoechea-Arana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] ] ] 11 => array:3 [ "nombre" => "Maria Sagrario" "apellidos" => "Bustabad-Reyes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">l</span>" "identificador" => "aff0060" ] ] ] 12 => array:3 [ "nombre" => "Pilar" "apellidos" => "Trenor-Larraz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">m</span>" "identificador" => "aff0065" ] ] ] 13 => array:3 [ "nombre" => "Trinidad" "apellidos" => "Pérez-Sandoval" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">n</span>" "identificador" => "aff0070" ] ] ] 14 => array:3 [ "nombre" => "Maria Isabel" "apellidos" => "Tevar-Sánchez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">o</span>" "identificador" => "aff0075" ] ] ] 15 => array:3 [ "nombre" => "Jesús T." "apellidos" => "Sánchez-Costa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 16 => array:3 [ "nombre" => "Enrique" "apellidos" => "Raya-Álvarez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">p</span>" "identificador" => "aff0080" ] ] ] ] "afiliaciones" => array:16 [ 0 => array:3 [ "entidad" => "Rheumatology Department, Hospital Universitario Vall d’Hebron, Passeig de la Vall d’Hebron, 119, 129, 08035 Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Research Unit of Spanish Society of Rheumatology, Calle Marqués del Duero, 5 Primero A, 28001 Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Rheumatology Department, Complejo Hospitalario Universitario A Coruña, As Xubias, 84, 15006 A Coruña, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Rheumatology Department, Biomedical Research Institute of Málaga (IBIMA), Hospital Universitario Regional de Málaga, Av. de Carlos Haya, 84, 29010 Málaga, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Rheumatology Department, Hospital Universitario La Princesa, Calle de Diego de León, 62, 28006, Madrid, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Rheumatology Department, Hospital Universitario de Guadalajara, Calle Donante de Sangre, S/N, 19002 Guadalajara, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Medicine and Medical Specialties Departament, University of Alcalá, Campus Universitario - C/ 19, Av. de Madrid, Km 33,600, 28871 Alcalá de Henares, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Rheumatology Department, Hospital Universitario de Torrejón, Calle Mateo Inurria, s/n, 28850 Torrejón de Ardoz, Madrid, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Rheumatology Department, Hospital Universitario Reina Sofia, Córdoba. Av. Menéndez Pidal, s/n, 14004, Córdoba, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Rheumatology Department, Hospital Universitario Doctor Peset, Valencia, Av. de Gaspar Aguilar, 90, 46017 Valencia, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Rheumatology Department, Hospital Can Misses, Carrer de Corona, s/n, 07800 Ibiza, Islas Baleares, Spain" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Rheumatology Department, Hospital Universitario de Canarias, Carretera Cuesta Taco, 0, 38320 Santa Cruz de Tenerife, Islas Canarias, Spain" "etiqueta" => "l" "identificador" => "aff0060" ] 12 => array:3 [ "entidad" => "Rheumatology Department, Hospital Clínico Universitario de Valencia, Av. de Blasco Ibáñez, 17, 46010 Valencia, Spain" "etiqueta" => "m" "identificador" => "aff0065" ] 13 => array:3 [ "entidad" => "Rheumatoloy Department, Complejo Asistencial Universitario de León, Calle Altos de nava, s/n, 24001 León, Spain" "etiqueta" => "n" "identificador" => "aff0070" ] 14 => array:3 [ "entidad" => "Rheumatoloy Department, Hospital Vega Baja, Ctra. Orihuela – Almoradí S/N, 03314 San Bartolomé, Orihuela, Spain" "etiqueta" => "o" "identificador" => "aff0075" ] 15 => array:3 [ "entidad" => "Rheumatoloy Department<span class="elsevierStyleSup">,</span> Hospital Universitario San Cecilio, Av. de la Investigación, s/n, 18016 Granada, Spain" "etiqueta" => "p" "identificador" => "aff0080" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Eficacia y seguridad de tocilizumab en monoterapia en pacientes con artritis reumatoide naive y no naive a biológicos en un entorno del mundo real" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 926 "Ancho" => 1508 "Tamanyo" => 96994 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Mean variation in DAS28 ESR.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease, characterized by chronic inflammation of joints with a significant impact on patients’ quality of life, physically, socially, psychologically and economically.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The disease-modifying antirheumatic drugs (DMARDs) and biological agents against inflammatory cytokines have dramatically changed the managements of patients with RA and nowadays it is recommended to treat patients to achieve clinical remission.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">3,4</span></a> Methotrexate (MTX) is still the anchor drug for RA treatment.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">5</span></a> However, a high proportion of patients may not respond adequately, present side effects<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a> or poor tolerability, regardless of the dose,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">7</span></a> requiring additional o different therapy. Recent clinical trials have shown that treatment with anti-TNF biologics, with or without MTX, can lead to clinical remission in around 50% of patients; however the remaining half of the patients need to switch to other medications.<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Tocilizumab (TCZ), a biological agent targeting the IL-6 receptor has been approved for use in patients with RA.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a> TCZ can be used in combination with MTX or in monotherapy, and has been proven to be beneficial in decreasing disease activity, preventing structural damage and improving function in RA patients in multiple randomized clinical trials (RCT).<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a> It appears that TCZ present a better safety profile when used in monotherapy that in combination with MTX.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Data from previous RCT have proved efficacy and safety of TCZ and additional data from cohorts have confirmed this results in real world. However, additional analysis to evaluate the effectiveness of TCZ in patients in which MTX can not be prescribed due to intolerance, side effects, or adherence problems may be of interest. To the best of our knowledge, there is no reports evaluating TCZ effectiveness and safety in this specific population. Our objective is to evaluate the effectiveness and safety of TCZ in monotherapy in biologic naïve RA patients versus patients with previous biologic exposure.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">MOZART (non-controlled clinical trial to evaluate the effectiveness of TCZ in patients with moderate to severe RA and in candidates for a biologic in monotherapy) (EudraCT: 2013-004051-20, and ClinicalTrials.gov: NCT02087696). This is a 32-week prospective non-controlled multicenter study to assess the effectiveness and safety of intravenous (iv) TCZ monotherapy in MTX-intolerant RA patients with moderate-severe activity.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients</span><p id="par0030" class="elsevierStylePara elsevierViewall">All RA patients included in this study fulfilled the ACR classification criteria. Patients recruited from 20 rheumatology units in Spain between June 2014 and November 2016 were consecutively registered into this study and were followed during 24 weeks. Inclusion criteria were: moderate to severe RA (DAS28<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>3.2), inadequate clinical response to a stable dose of synthetic DMARDs or failure to respond to one or two biologics for a period ≥8 weeks, oral glucocorticoids (GCs) ≤10<span class="elsevierStyleHsp" style=""></span>mg prednisone or equivalent with a stable dose for at least one month prior to TCZ treatment.</p><p id="par0035" class="elsevierStylePara elsevierViewall">RA patients were enrolled if had intolerance, contraindication or lack of adherence to MTX. The intolerance to MTX was evaluated using the UKU Side Effects Rating Scale.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">13</span></a> Lack of adherence to MTX was evaluated using the Morisky Green Levine Test.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a> Patients were excluded if presented a hepatitis C virus infection, active diverticulitis, latent tuberculosis (positive PPD or suspicious chest X-ray), women pregnant or breastfeeding. Additional information regarding selection criteria are available in the Supplementary Material section (<a class="elsevierStyleCrossRef" href="#sec0070">Table 1S</a>).</p><p id="par0040" class="elsevierStylePara elsevierViewall">Enrolled patients, who had MTX stopped 4 weeks before the baseline visit, were scheduled for eight visits (weeks 0, 4, 8, 12, 16, 20, 24, and a visit at week 32 to evaluate safety).</p><p id="par0045" class="elsevierStylePara elsevierViewall">All enrolled patients were offered to initiate open-label iv treatment with TCZ 8<span class="elsevierStyleHsp" style=""></span>mg/kg in monotherapy per protocol every 4 weeks for 6 months from June 2014 to April 2017. Patients who presented abnormal laboratory parameters (liver enzymes, absolute neutrophil counts and/or platelet counts) during treatment with TCZ, had their doses adjusted in accordance with the TCZ drug information sheet.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Demographic data, including date of diagnosis, comorbidities, current and previous treatments for RA were collected from the medical charts. The following parameters were evaluated at 0, 4, 8, 12, 24 and 32 weeks: tender joint count (TJC) 28, swollen joint count (SJC) 28, patient's global assessment (Pt-GA) of disease activity, physician's global assessment (Ph-GA) of disease activity, ESR, CRP, Health Assessment Questionnaire (HAQ), Short Form 36 Health Survey (SF-36), and fatigue by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Disease activity was assessed by the Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI) and the Simple Disease Activity Index (SDAI), which were calculated according to their formula.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The primary endpoint was the EULAR response after 24 weeks of TCZ treatment. The EULAR response criteria classify patients as good, moderate, or non-responders using the individual amount of change determined by the DAS28-ESR and the DAS28-ESR value (low, moderate, or high) and can also be applied using the DAS28-ESR (<a class="elsevierStyleCrossRef" href="#sec0070">Table 2S, Supplementary Material</a>).<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">15,16</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Secondary endpoints were: (1) effectiveness of TCZ after 24 weeks according to the American College of Rheumatology 20%, 50%, and 70% improvement (ACR 20/50/70) criteria; (2) to compare response to TCZ in monotherapy according to previous treatment with biologics; and (3) to assess the safety of TCZ by adverse events reported by patients or recorded by researchers.</p><p id="par0065" class="elsevierStylePara elsevierViewall">This study was developed in accordance with the protocol and guidelines of Good Clinical Practice and was carried out following the principles outlined in the Helsinki Declaration (v.2013). The study protocol was approved by the Ethics Committee for Clinical Research of the Hospital University Vall d’Hebron, Barcelona, Spain (Approval number: ID-RTF010). All patients provided written informed consent to participate in the study and to publish the data obtained.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">In order to obtain an estimation whereby 78% of patients achieved a moderate or good EULAR response, with 10% accuracy and a 95% confidence interval, it was necessary to include 109 patients in the study. By assuming a loss rate of 10%, the total number of recruited patients needed to achieve the primary objective was 122. When 93 patients were recruited, the statistic power to reach 78% of a good or moderate EULAR response was 0.76, at which point the scientific committee halted further inclusion. A flow chart of patient inclusion is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">To evaluate one of the secondary objectives, patients were stratified into two cohorts: cohort A, patients naïve to biologics (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>50); and cohort B, patients who previously received 1 or 2 biologics for RA treatment (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>43).</p><p id="par0080" class="elsevierStylePara elsevierViewall">An analysis of frequency of qualitative and quantitative variables was performed. Qualitative variables were expressed in percentage and absolute values, and quantitative variables were expressed as a means plus standard deviation.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Effectiveness of TCZ treatment in monotherapy was assessed based on the percentage of patients who achieved moderate and good EULAR responses after 24 weeks of treatment.</p><p id="par0090" class="elsevierStylePara elsevierViewall">An intention-to-treat analysis was conducted. If a patient terminated treatment before week 24, he/she was evaluated as a responder or non-responder according to the results obtained from the last registered visit.</p><p id="par0095" class="elsevierStylePara elsevierViewall">To assess the effectiveness of reducing the DAS28-ESR, the median score at baseline was compared to that at week 24 using the two-sided Student <span class="elsevierStyleItalic">t</span>-test for related samples. In order to evaluate whether patients in cohorts A and B could obtain different effectiveness results, an ANCOVA was performed.</p><p id="par0100" class="elsevierStylePara elsevierViewall">All patients receiving at least one TCZ dose were included in the safety analysis. A description of the AEs recorded throughout the study period was performed.</p><p id="par0105" class="elsevierStylePara elsevierViewall">IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. was used to conduct the statistical analyses.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Baseline characteristics of patient population</span><p id="par0110" class="elsevierStylePara elsevierViewall">A total of 93 were enrolled of whom 84 were eligible for the effectiveness analysis. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the sociodemographic characteristics of the patients. The mean age of patients included was 54.4 years (SD: 12.8) with 83.3% of the participants being women. 46 (54.8%) patients were naïve to biological. Patients naïve to biologics were older than those previously treated with these compounds (57.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.5 vs 51.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.4 years), albeit with shorter disease durations (6.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.6 vs 13.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.5 years). Among the patients included, 77 (91.7%) were intolerant to MTX, 4 (4.8%) had contraindications to this drug and 1 (1.2%) showed a lack of adherence to MTX. The DAS28 at the entrance to the study was 5.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.1, with no differences between biologic naive and non-naive patients. Other RA activity indexes such as CDAI or SDAI, the counts of tender and swollen joints, acute phase reactants or functional capacity as assessed by HAQ did not reveal any differences between biologic naïve and non-naïve patients. Most patients (78.6%) had been receiving corticosteroids treatment at doses lower than 10<span class="elsevierStyleHsp" style=""></span>mg/day of Prednisone or equivalent. The previous use of biologics and disease activity at study enrollment did not influence the percentage of patients with intolerance, contraindications or lack of adherence.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Effectiveness</span><p id="par0115" class="elsevierStylePara elsevierViewall">Ninety-three point eight percent of the patients analyzed had a good or moderate EULAR response. When stratifying by previous biologics treatment, a numerically higher percentage of naive patients showed a response (95.5%) compared to those with prior biologics use (91.7%) (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.53). When analyzing effectivenes according to moderate or good response, most patients showed a moderate response (<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>). This was true when analyzed either globally (92.5%) or separately by the previous use or non-use of biologics (93.2% vs 91.7%) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows the mean variation in DAS28-ESR throughout the study with respect to baseline, which proved similar between patients naïve to biologics and those previously treated with biologics. An analysis has been carried out to evaluate the effectiveness of Tocilizumab, separating the results of the response variables by weeks to differentiate patients naïve to biological therapy versus patients who received prior treatment with biological therapy and where it can also be seen that naive patients had in every week a higher percentage of patients with EULAR response (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). Fifty-eight point five percent of the naïve to biological patients reached remission and thirty-eight point 2 percent of the patients with previous biological therapy (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). The rates of ACR response criteria are available in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. TCZ was discontinued in 11 patients due to inefficacy and in the <a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a> also shows the causes of withdrawals of the patients and the mean time until leaving the study.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Safety</span><p id="par0120" class="elsevierStylePara elsevierViewall">A total 89 AEs were recorded in a total of 50 patients. Eighty-six percent were non-serious and occurred mainly in biologic naïve patients. Fourteen serious AEs (SAEs) were recorded during the study; these corresponded to 6 patients, with 8 of them being drug-related SAEs. Four of these 6 patients discontinued TCZ due to serious adverse drug reactions. Three patients presented RA reactivation characterized by musculoskeletal pain and peripheral joint swelling, type IV hypersensitivity reaction, syncope, colonic abscess, rash, diverticular perforation, myelopathy, spinal stenosis, spinal osteoarthritis, vocal cord paresis, lower extremity fracture, and/or spontaneous miscarriage (<a class="elsevierStyleCrossRef" href="#tbl0030">Table 6</a>). No opportunistic infections, deaths, neoplasms or major adverse cardiovascular events (MACE) were reported during the study.</p><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">In this multicenter non-controlled clinical trial, a higher percentage of patients with RA with moderate to high disease activity and non-tolerant or with contraindication to MTX showed a better response to TCZ in monotherapy when they did not have a previous treatment with biological, although these findings did not reach statistical significance. Although some studies in which TCZ was used in combination with MTX achieved a higher rate of response than TCZ in monotherapy,<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">17,18</span></a> other reports have shown no clinically relevant superiority of adding TCZ to MTX when patients have not completed response to MTX over switching to TCZ in monotherapy.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">19</span></a> Our results are in line with these findings concerning effectiveness, both according to EULAR and ACR response.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">19–23</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Effectiveness proved to be similar between patients with 1 or 2 previous biologics or in whom TCZ was the first-line biologic. These findings further support the use of TCZ as a first-line option in monotherapy, although TCZ is commonly administered as a second-line choice for patients who require biologics in monotherapy in routine care. The good results obtained with TCZ are consistent with those of other studies.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Our finding may be largely explained by the similarity between baseline characteristics for both groups not only in disease activity but also in functional status. Our findings are in contrasts with other studies, in which patients without prior exposure to biologics experienced better effectiveness probably because of less severity, refractivity and lower DAS28 at study entry.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">24–26</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">In terms of safety, only nine patients withdrew treatment due to AEs, four of them presenting SAEs. Of those SAEs reported, only 8 were directly drug related, and the remaining ones were events that occurred during the study period but non related to TCZ. The most frequent AEs were infections, as previously reported in other studies.<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">27,28</span></a> These results indicate that attention must be paid to the onset of serious infections during TCZ treatment as well as with anti-TNF agents, but that the safety profile of TCZ is acceptable in clinical practice.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The main strength of our study is that represents results in routine care patients. Our study main limitation is the design as .a non-controlled interventional study. All patients received TCZ as monotherapy without any control group.</p><p id="par0150" class="elsevierStylePara elsevierViewall">In conclusion, this study demonstrates effectiveness of TCZ according to significant DAS28 improvement, with no differences between naïve and previously treated with biologics patients. The percentage of patients in remission was higher in naïve patients. Our data support that TCZ in monotherapy is a highly effective treatment choice for patients with moderate and severe RA, with better remission rates in patients with no previous therapy with biologics, in clinical practice.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">This study was funded by ROCHE Farma. The <span class="elsevierStyleGrantSponsor" id="gs1">Spanish Society of Rheumatology</span> is the sponsor of this study and has participated in the study design; in the analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The corresponding author had full access to all study data and had final responsibility for the decision to submit the manuscript for publication.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">This work was funded by Roche, which manufactures tocilizumab.</p><p id="par0165" class="elsevierStylePara elsevierViewall">S Marsal Barril has no conflicts of interest to declare.</p><p id="par0170" class="elsevierStylePara elsevierViewall">MA Martin-Martinez has no conflicts of interest to declare.</p><p id="par0175" class="elsevierStylePara elsevierViewall">FJ Blanco-Garcia has no conflicts of interest to declare.</p><p id="par0180" class="elsevierStylePara elsevierViewall">A Fernandez Nebro has acted as a consultant for Roche and Sanofi.</p><p id="par0185" class="elsevierStylePara elsevierViewall">R Garcia-Vicuña has recieved personal fees from Biogen, Lilly, Pfizer, Roche, Sandoz and Sanofi; grants from Abbvie, BMS, Lilly, MSD, Roche, Sandoz, Sanofi.</p><p id="par0190" class="elsevierStylePara elsevierViewall">J Tornero-Molina has acted as a consultant for Gebro, Lilly, Pfizer and Roche.</p><p id="par0195" class="elsevierStylePara elsevierViewall">F Sánchez-Alonso has no conflicts of interest to declare.</p><p id="par0200" class="elsevierStylePara elsevierViewall">M Novella-Navarro declares grants from Janssen, UCB Pharma, Novartis, Lilly, Menarini, Grunhental, Nordic, Pfizer, Gebro.</p><p id="par0205" class="elsevierStylePara elsevierViewall">A Escudero-Contreras has no conflicts of interest to declare.</p><p id="par0210" class="elsevierStylePara elsevierViewall">JJ Alegre-Sancho has no conflicts of interest to declare.</p><p id="par0215" class="elsevierStylePara elsevierViewall">A Urruticoechea-Arana has no conflicts of interest to declare.</p><p id="par0220" class="elsevierStylePara elsevierViewall">MS Bustabad-Reyes has no conflicts of interest to declare.</p><p id="par0225" class="elsevierStylePara elsevierViewall">P Trenor-Larraz has no conflicts of interest to declare.</p><p id="par0230" class="elsevierStylePara elsevierViewall">T Perez-Sandoval has no conflicts of interest to declare.</p><p id="par0235" class="elsevierStylePara elsevierViewall">MI Tevar-Sánchez has no conflicts of interest to declare.</p><p id="par0240" class="elsevierStylePara elsevierViewall">JT Sánchez-Costa has no conflicts of interest to declare.</p><p id="par0245" class="elsevierStylePara elsevierViewall">E Raya declares grants from Abbvie, Amgen, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1806261" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1578411" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1806260" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1578412" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Patients" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Baseline characteristics of patient population" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Effectiveness" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Safety" ] ] ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "xack637339" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-06-18" "fechaAceptado" => "2021-12-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1578411" "palabras" => array:5 [ 0 => "Rheumatoid arthritis" 1 => "Tocilizumab" 2 => "Remission" 3 => "Methotrexate" 4 => "Biologic therapy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1578412" "palabras" => array:5 [ 0 => "Artritis reumatoide" 1 => "Tocilizumab" 2 => "Remisión" 3 => "Metotrexato" 4 => "Terapia biológica" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate the effectiveness and safety of tocilizumab (TCZ) monotherapy in biologic-naïve patients with rheumatoid arthritis (RA) versus patients with previous biologic exposure in a real-world setting.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Non-controlled clinical-trial, 32-week prospective multicenter study including RA patients with moderate-severe disease activity starting TCZ in monotherapy who had a prior inadequate response or were intolerant to methotrexate (MTX). Effectiveness according to EULAR response evaluated at 24-week and safety at 32-weekwere assessed.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Of the 93 were enrolled of whom 84 (90%) were eligible for the effectiveness analysis. Biologic-naïve patients (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>46, 54.8%) were younger (51.5 versus 57.9) with shorter disease duration (6.4 versus 13.3) but presented similar comorbidities in comparison with non-naïve patients. DAS28 remission was achieved in a higher percentage in the group of patients with prior biological treatment. 89 adverse events (AE) were recorded in 50 patients, most of them non-serious AE (non-SAE) (86.3%).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In a real world setting, TCZ exhibit similar effectiveness and safety in monotherapy in patients with RA regardless previous exposure to other biologic therapies. This study provides additional and valuable real-world findings on the use of TCZ in patients with RA.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la efectividad y seguridad de la monoterapia con tocilizumab (TCZ) en pacientes con artritis reumatoide (AR) sin tratamiento biológico en comparación con pacientes con exposición previa a biológico en un entorno real.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Ensayo clínico no controlado, estudio multicéntrico prospectivo de 32 semanas que incluyó pacientes con AR con actividad de la enfermedad moderada-grave que comenzaron con TCZ en monoterapia y que tuvieron una respuesta inadecuada previa o fueron intolerantes al metotrexato. La eficacia de acuerdo con la respuesta EULAR fue evaluada a las 24 semanas y la seguridad a las 32 semanas.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De los 93 pacientes seleccionados, 84 (90%) fueron elegibles para el análisis de efectividad. Los pacientes sin tratamiento biológico previo (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>46, 54,8%) eran más jóvenes (51,5 frente a 57,9 años), con una duración más corta de la enfermedad (6,4 frente a 13,3 años), pero presentaban comorbilidades similares en comparación con los pacientes con tratamiento previo. La remisión de DAS28 se logró en un mayor porcentaje en el grupo de pacientes con tratamiento biológico previo. Se registraron 89 eventos adversos en 50 pacientes, la mayoría de ellos no graves (86,3%).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En un entorno del mundo real, TCZ exhibe una eficacia y seguridad similares en monoterapia en pacientes con AR, independientemente de la exposición previa a otras terapias biológicas. Este estudio proporciona hallazgos adicionales y valiosos en el contexto del mundo real sobre el uso de TCZ en pacientes con AR.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0260" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0070" ] ] ] ] "multimedia" => array:9 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1890 "Ancho" => 2341 "Tamanyo" => 298892 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flowchart of patients included in the study_2.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 926 "Ancho" => 1508 "Tamanyo" => 96994 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Mean variation in DAS28 ESR.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">All variables are recorded at the time of inclusion in the study. Categorical variables are expressed as number (<span class="elsevierStyleItalic">n</span>) and percentages (%); SD: standard deviation. BMI: body mass index; CDAI: Clinical disease activity index; CRP: C-Reactive Protein; DAS28-ESR: Disease Activity Score using 28 joints-erythrocyte sedimentation rate; DMARD: Disease-modifying antirheumatic drugs; FACIT-F: Functional Assessment of Chronic Illness Therapy-Fatigue; GC: glucocorticoids; HAQ (0-3): Health Assessment Questionnaire; MTX: Methotrexate; NSAID: non-steroidal anti-inflammatory drugs; SDAI: Simple disease activity index; SF36: Short Form-36.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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">Variables \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">Total (84) \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"><span class="elsevierStyleItalic">Sex, female, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70 (83.3) \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"><span class="elsevierStyleItalic">Age (years), mean (SD)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.4 (12.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Age by group (years)</span></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"><span class="elsevierStyleHsp" style=""></span>Naive patients, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.5 (12.4) \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"><span class="elsevierStyleHsp" style=""></span>Non naive patient, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57.9 (12.5) \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"><span class="elsevierStyleHsp" style=""></span>Disease duration, years, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.5 (9.7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Disease duration by group (years)</span></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"><span class="elsevierStyleHsp" style=""></span>Naive patients, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.4 (6.6) \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"><span class="elsevierStyleHsp" style=""></span>Non naive patient, mean (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.3 (11.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">N. previous synthetic DMARDs</span></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"><span class="elsevierStyleHsp" style=""></span>0 <span class="elsevierStyleItalic">n</span> (%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 (2.4) \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"><span class="elsevierStyleHsp" style=""></span>1 <span class="elsevierStyleItalic">n</span> (%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 (17.9) \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"><span class="elsevierStyleHsp" style=""></span>>1 <span class="elsevierStyleItalic">n</span> (%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 (79.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></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"><span class="elsevierStyleItalic">Naive patients, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 (54.8) \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"><span class="elsevierStyleItalic">DAS28-ESR, mean (SD)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.5 (1.1) \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"><span class="elsevierStyleItalic">CDAI, mean (SD)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.9 (11.1) \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"><span class="elsevierStyleItalic">SDAI, mean (SD)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36.2 (17.1) \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"><span class="elsevierStyleItalic">SF36 (0–100), mean (SD))</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90.7 (6.8) \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"><span class="elsevierStyleItalic">FACTI-F, mean (SD)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.5 (9.7) \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"><span class="elsevierStyleItalic">CRP, mg/L, mean (SD)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.2 (17.1) \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"><span class="elsevierStyleItalic">ESR, mm/1</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">st</span></span><span class="elsevierStyleItalic">hour, mean (SD)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.4 (29.1) \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"><span class="elsevierStyleItalic">HAQ, mean (SD)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.8 (0.7) \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"><span class="elsevierStyleItalic">Hypertension, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (34.5) \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"><span class="elsevierStyleItalic">Diabetes, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 (7.1) \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"><span class="elsevierStyleItalic">Dyslipidemia, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 (22.6) \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"><span class="elsevierStyleItalic">Solid neoplasms, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.2) \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"><span class="elsevierStyleItalic">Cerebrovascular accident, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (3.6) \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"><span class="elsevierStyleItalic">Lung disease, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 (3.6) \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"><span class="elsevierStyleItalic">Chronic renal failure, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (6.0) \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"><span class="elsevierStyleItalic">BMI, kg/m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">, mean (SD)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.0 (5.3) \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"><span class="elsevierStyleItalic">Extraarticular manifestations, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (10.7) \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"><span class="elsevierStyleItalic">NSAID, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45 (53.6) \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"><span class="elsevierStyleItalic">GC, n (%)</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 (78.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Baseline sociodemographic and clinical characteristics of the population included in the analysis of study.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Data are expressed as number (<span class="elsevierStyleItalic">n</span>) and percentages (%). Efficacy of Tociluzumab treatment were assessed based on EULAR response: Delta DAS28_ESR (DAS28_ESRLast visit evaluated – DAS28_ERS<span class="elsevierStyleInf">Visit1</span>). EULAR: European League Against Rheumatism; ACR: American College of Rheumatology. Remission DAS28-ESR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>2.6; Remission CDAI<span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>2.8.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "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-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Variables \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 " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Week</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value (per week)</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">4 wks \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">8 wks \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">12 wks \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">24 wks \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">4 wks \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">8 wks \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">12 wks \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">24 wks \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">No response EULAR, <span class="elsevierStyleItalic">n</span> (%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (31.3) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (15.8) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (6.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (10.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \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"><0.001 \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"><0.001 \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"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate EULAR response, <span class="elsevierStyleItalic">n</span> (%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 (68.8) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63 (82.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 (91.7) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57 (87.7) \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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><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">Good EULAR response, <span class="elsevierStyleItalic">n</span> (%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.3) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.3) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (1.4) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><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">ACR20, <span class="elsevierStyleItalic">n</span> (%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 (88.8) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 (96.1) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 (93.6) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (89.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.023 \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">0.57 \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">0.17 \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">0.033 \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">ACR50, <span class="elsevierStyleItalic">n</span> (%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 (83.8 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">70 (92.1) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67 (93.1) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">57 (87.7) \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">0.002 \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">0.11 \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">0.17 \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">0.016 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n