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    "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 &#40;RA&#41; is a chronic&#44; debilitating disease characterized by synovial inflammation and joint erosion&#46; In Mexico&#44; RA has an estimated prevalence rate of 1&#46;6&#37;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a> and its prevalence among the working population represents a significant economic burden&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> As tuberculosis is endemic to Mexico&#44; the global practice of screening for tuberculosis prior to initiating biologic disease-modifying antirheumatic drugs &#40;bDMARDs&#41; is particularly important in Mexico&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a> In Mexico&#44; RA is most commonly treated with conventional synthetic DMARDs &#40;csDMARDs&#41; and non-steroidal anti-inflammatory drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">4</span></a> Only 6&#37; of patients are treated with bDMARDs&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">4</span></a> Mexican College of Rheumatology &#40;CMR&#41; guidelines<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a> recommend csDMARD therapy immediately following RA diagnosis&#44; with methotrexate as first choice&#44; unless contraindicated&#46; For patients with an inadequate response to csDMARDs&#44; treatment with tumor necrosis factor inhibitors &#40;TNFi&#41; is suggested&#59; tofacitinib is recommended following failed biologic treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Globally 30&#8211;40&#37; of patients do not respond to csDMARDs&#44; and 20&#8211;30&#37; of patients treated with bDMARDs still have active disease&#44;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a> highlighting the need for alternative therapies to address issues of tolerability and inadequate response&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA&#46; The efficacy and safety of tofacitinib as monotherapy or in combination with csDMARDs have been reported in global Phase 3<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">6&#8211;11</span></a> and long-term extension &#40;LTE&#41;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> studies and in the overall Latin American &#40;LA&#41; subpopulation&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Here we assessed tofacitinib efficacy and safety in Mexican patients with RA from global Phase 3 and LTE studies&#46;</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">Patients</span><p id="par0025" class="elsevierStylePara elsevierViewall">This analysis included data from Mexican patients who participated in four Phase 3 studies &#40;ORAL Scan&#44; A3921044<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">10</span></a>&#59; ORAL Solo&#44; A3921045<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a>&#59; Oral Sync&#44; A3921046<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a>&#59; and ORAL Standard&#44; A3921064<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">11</span></a>&#41;&#44; and one LTE study &#40;ORAL Sequel&#44; A3921024<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a>&#41; of tofacitinib for the treatment of RA&#46; Mexican patients who participated in the Phase 2 and 3 index studies and who also rolled-over into the LTE study were included in the LTE population&#46; Data from the overall study populations were reported previously&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#44;8&#44;10&#8211;12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Detailed patient inclusion criteria were reported previously&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#44;8&#44;10&#8211;12</span></a> Patients were &#8805;18-years-old with active RA based on the American College of Rheumatology &#40;ACR&#41; 1987 criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a> Key exclusion criteria included&#58; serious chronic or recurrent infections&#59; evidence of active or inadequately treated latent <span class="elsevierStyleItalic">Mycobacterium tuberculosis&#59;</span> history of recurrent herpes zoster &#40;HZ&#41;&#44; disseminated HZ or herpes simplex&#59; hepatitis B or C&#59; human immunodeficiency virus or other opportunistic infections&#59; history of lymphoproliferative disorder&#59; malignancy except adequately-treated or excised non-metastatic basal or squamous cell skin cancer or cervical carcinoma in situ&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study design and treatments</span><p id="par0035" class="elsevierStylePara elsevierViewall">The Phase 3 studies were double-blind&#44; randomized controlled studies lasting 6&#8211;24 months&#46; Patients had a previous inadequate response to methotrexate &#40;ORAL Scan and ORAL Standard&#41; or &#8805;1 bDMARD or csDMARD &#40;ORAL Sync and ORAL Solo&#41;&#46; Patients received tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg twice daily &#40;BID&#41;&#44; or placebo&#44; as monotherapy &#40;ORAL Solo&#41;&#44; or in combination with background methotrexate &#40;ORAL Standard and ORAL Scan&#41;&#44; or csDMARDs &#40;ORAL Sync&#41;&#46; ORAL Standard included an active-control arm of adalimumab 40<span class="elsevierStyleHsp" style=""></span>mg administered subcutaneously once every two weeks&#46; Data from adalimumab-treated patients are not presented due to limited sample size&#46; In ORAL Sync&#44; ORAL Standard and ORAL Scan&#44; patients receiving placebo not responding at Month 3 &#40;&#8805;20&#37; reduction from baseline in swollen and tender joint counts&#41; were advanced blindly to tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg BID&#59; at Month 6&#44; all remaining placebo patients were advanced to tofacitinib&#46; In ORAL Solo&#44; all patients receiving placebo advanced to tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg BID at Month 3&#46; Efficacy data from patients advanced to tofacitinib are not presented&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">ORAL Sequel is an ongoing &#40;study database was not locked as of April 2014 data cut-off&#59; some values may change for the final locked database&#41;&#44; open-label LTE study that enrolled patients who participated in qualifying Phase 2&#44; or Phase 3 tofacitinib index studies&#46; Patients initiated the LTE study with tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg BID&#46; Tofacitinib and concomitant RA medication dose adjustments were permitted for reasons of safety or inadequate response at the investigator&#39;s discretion&#46; Baseline values for the LTE study were those of the index studies for patients enrolling in the LTE within 14 days following the index study&#59; for all others&#44; baseline was the start of the LTE&#46; For this analysis&#44; patients were analyzed in tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID dose groups based on average total daily dose &#40;TDD&#59; sum of doses received divided by number of days a dose was received&#41; in the LTE study&#46; The 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID dose groups were defined as TDD &#60;15<span class="elsevierStyleHsp" style=""></span>mg&#47;day and TDD &#8805;15<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; respectively&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">All studies were conducted in compliance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice Guidelines&#44; and were approved by the Institutional Review Boards and&#47;or Independent Ethics Committees at each of the investigational centers participating in the study&#46; All patients provided written informed consent&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Efficacy and safety endpoints</span><p id="par0050" class="elsevierStylePara elsevierViewall">Efficacy was assessed by ACR20&#44; ACR50&#44; and ACR70 response rates and mean changes from baseline in Disease Activity Score &#40;erythrocyte sedimentation rate&#41; &#40;DAS28-4&#91;ESR&#93;&#41; and Health Assessment Questionnaire-Disability Index &#40;HAQ-DI&#41; score&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Safety endpoints included type&#44; severity&#44; and frequency of adverse events &#40;AE&#41; and changes in clinical laboratory parameters&#46; Incidence rates &#40;IR&#59; patients with events&#47;100 patient-years&#41; were determined for serious AEs &#40;SAE&#41;&#59; discontinuations due to AEs&#59; serious infection events &#40;SIEs&#41;&#59; opportunistic infections &#40;excluding tuberculosis&#41;&#59; tuberculosis&#59; HZ &#40;all and serious&#41;&#59; malignancies &#40;excluding non-melanoma skin cancer &#91;NMSC&#93;&#41;&#59; lymphoma&#47;lymphoproliferative disorders&#59; major adverse cardiac events &#40;MACE&#41;&#59; and all-cause mortality &#40;within 30 days of last dose of study drug&#41;&#46; Malignancy events were adjudicated by &#8805;2 independent&#44; board-certified pathologists&#46; MACE was adjudicated by a blinded&#44; independent external committee for all Phase 3 studies&#44; and for all events after February 2009 in the LTE study&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analyses</span><p id="par0060" class="elsevierStylePara elsevierViewall">Efficacy and safety data reported were observed case with no imputation for missing values&#44; and were for the full analysis set &#40;all patients randomized who received &#8805;1 dose of study treatment&#41;&#46; Efficacy data up to Month 12 were pooled for Phase 3 studies &#40;efficacy data up to Month 12 of the 2-year ORAL Scan study were included here&#41;&#46; Efficacy is reported up to Month 36 for the LTE study due to limited sample size post-Month 36&#46; All available safety data are presented &#40;Phase 3&#58; up to Month 24 &#91;except for laboratory data where data post-Month 12 were not included due to limited sample size&#93;&#59; LTE&#58; up to Month 72&#41;&#46; Descriptive and summary statistics are presented&#59; no formal testing was conducted for differences between treatment groups&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">IRs were calculated based on the number of unique patients with events&#44; with exposure censored at the time of the event for patients with the AE&#44; or at time of discontinuation or data cut-off for all other patients&#46; 95&#37; confidence intervals &#40;CI&#41; were calculated using Exact Poisson adjusted for exposure&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Patients</span><p id="par0070" class="elsevierStylePara elsevierViewall">119 Mexican patients were randomized across the Phase 3 studies &#40;tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&#59; tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&#59; placebo advanced to tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#59; placebo advanced to tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&#41;&#46; 33 &#40;89&#46;2&#37;&#41;&#44; 53 &#40;96&#46;4&#37;&#41;&#44; 13 &#40;92&#46;9&#37;&#41;&#44; and 11 &#40;84&#46;6&#37;&#41; patients completed the Phase 3 studies&#44; respectively&#46; In the LTE study&#44; 212 Mexican patients were enrolled &#40;tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>86&#59; tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; <span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>126&#41;&#58; 111 &#40;52&#46;4&#37;&#41; from qualifying Phase 3 index studies and 101 &#40;47&#46;6&#37;&#41; from qualifying Phase 2 index studies&#46; Baseline demographics were generally similar across treatment groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#59; mean age ranged from 43&#46;7 to 47&#46;0 years&#59; the majority of patients &#40;89&#46;2&#8211;98&#46;2&#37;&#41; were female&#44; and mean disease duration at baseline in Phase 3 studies ranged from 7&#46;1 to 10&#46;2 years&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Efficacy</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Phase 3 studies</span><p id="par0075" class="elsevierStylePara elsevierViewall">Numerically more patients who received tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg BID achieved ACR20&#44; ACR50&#44; and ACR70 versus placebo-treated patients at Month 3 and Month 6 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; For ACR20 and ACR50&#44; improvements versus placebo-treated patients were numerically greater at Month 1&#46; The proportion of patients achieving ACR responses was generally sustained over 12 months&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Mean changes from baseline in DAS28-4&#40;ESR&#41; were numerically greater with tofacitinib versus placebo at Month 3 and Month 6 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>A&#41;&#46; Improvements in DAS28-4&#40;ESR&#41; were sustained with tofacitinib treatment up to Month 12&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Numerically greater mean improvements from baseline HAQ-DI were seen with both doses of tofacitinib versus placebo at Months 1&#44; 3&#44; and 6 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>B&#41;&#46; Improvements in HAQ-DI were sustained up to Month 12 with tofacitinib&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">LTE study</span><p id="par0090" class="elsevierStylePara elsevierViewall">ACR response rates at Month 1 of the LTE study were maintained up to Month 36 &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41; with both tofacitinib doses&#46; ACR response rates were initially numerically greater for tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID versus tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#46; After Month 9 in the LTE&#44; ACR20&#44; and ACR50 response rates were generally similar between tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups&#46; ACR70 response rates were generally higher with tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID versus tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID up to Month 36&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">Mean improvements from baseline in DAS28-4&#40;ESR&#41; observed at Month 1 of the LTE study were sustained with both tofacitinib doses up to Month 36 &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>A&#41;&#46; Improvement in DAS28-4&#40;ESR&#41; was numerically greater with tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID versus tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID at all time points&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">Patients treated with tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID had similar improvements from baseline in HAQ-DI at Month 1 of the LTE study that were generally sustained to Month 36 &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>B&#41;&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Safety</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Phase 3 studies</span><p id="par0105" class="elsevierStylePara elsevierViewall">Up to Month 3&#44; 29&#46;7&#37; of patients had AEs with tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; 21&#46;8&#37; with tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; and 18&#46;5&#37; with placebo &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#59; infections occurred in 16&#46;2&#37; and 9&#46;1&#37; of patients receiving tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID and tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; respectively&#44; versus 7&#46;4&#37; with placebo&#46; During Months 3&#8211;6&#44; 4&#46;5&#37; and 4&#46;7&#37; of patients treated with tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; respectively&#44; had AEs&#46; Post-Month 6&#44; 24&#46;2&#37; and 13&#46;7&#37; of patients treated with tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID had AEs&#44; respectively&#46; The most frequently occurring AEs by treatment period are listed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; There was one pregnancy during the Phase 3 studies &#40;tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID group&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">SAEs occurred in two patients &#40;5&#46;4&#37;&#41; receiving tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID &#40;one event was treatment-related &#91;investigator-determined&#93;&#41;&#59; three patients &#40;5&#46;5&#37;&#41; receiving tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID &#40;five separate events&#44; two treatment-related&#41;&#59; and two patients &#40;14&#46;3&#37;&#41; from the placebo to tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID treatment sequence &#40;three separate events&#44; two treatment-unrelated events during placebo treatment phase&#44; one treatment-related during active treatment&#41;&#46; Discontinuation due to AEs was infrequent for all treatment groups during all three time periods in Phase 3 studies &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; There were no SIEs&#44; tuberculosis&#44; malignancies or adjudicated cardiovascular events&#46; There were three patients with HZ&#59; two &#40;3&#46;6&#37;&#41; with tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID and one &#40;3&#46;7&#37;&#41; with placebo&#46; No Mexican patients died during Phase 3 studies&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">There was a slight increase from baseline in hemoglobin with tofacitinib treatment up to Month 12&#44; and slight decreases from baseline in neutrophil and lymphocyte counts &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>A&#8211;C&#41;&#46; 31&#44; 41&#44; 12&#44; and nine patients in the tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; placebo to tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#44; and placebo to tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID sequences&#44; respectively&#44; had confirmed lymphopenia &#40;two sequential absolute lymphocyte counts &#60;2000<span class="elsevierStyleHsp" style=""></span>cells&#47;mm<span class="elsevierStyleSup">3</span>&#41; during the 12-month Phase 3 study period&#59; none had SIEs within 30 days of the lowest lymphocyte cell count&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">LTE study</span><p id="par0120" class="elsevierStylePara elsevierViewall">Up to Month 72 of the LTE study&#44; AEs occurred in 91&#46;9&#37; and 81&#46;0&#37; of patients receiving tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">The most frequently occurring AEs in either dose group were urinary tract infection&#44; upper respiratory tract infection&#44; and nasopharyngitis &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Infections occurred in 74&#46;4&#37; and 57&#46;9&#37; of patients receiving tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; respectively&#46; There was one pregnancy in the tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID group&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Three Mexican patients died during the LTE study &#40;without 30-day rule&#41;&#58; two patients receiving tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#59; and one receiving tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#46; Causes of death were&#58; hepatic failure and sepsis&#59; and respiratory failure and chronic obstructive pulmonary disease for patients treated with tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID&#59; and synovial sarcoma and metastases to lung for the patient receiving tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg BID&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">In the LTE study&#44; mean increases from baseline in hemoglobin levels and mean decreases from baseline in neutrophil count were observed with both doses of tofacitinib&#44; and were stable with longer treatment duration &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>D and E&#41;&#46; Mean lymphocyte count increased up to Month 1&#44; returned to baseline levels by Month 3&#44; and gradually decreased thereafter &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>F&#41;&#46; Of the 80 and 115 patients with confirmed lymphopenia in the tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID groups&#44; respectively&#44; none had SIEs within 30 days of the lowest lymphocyte cell count&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">IRs and 95&#37; CIs for SAEs&#44; discontinuations due to AEs&#44; and other events of special interest are presented in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46; IRs for all safety events of special interest were generally similar between tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; with overlapping CIs &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; However&#44; tofacitinib exposure for the two groups was low&#46; There were no opportunistic infections &#40;excluding tuberculosis&#41; or MACE in either treatment group&#46; There were two cases of tuberculosis in the tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID group&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0145" class="elsevierStylePara elsevierViewall">In this analysis of Mexican patients from the tofacitinib global RA program&#44; tofacitinib reduced the signs and symptoms of RA and improved physical function&#44; when administered as monotherapy or in combination with csDMARDs up to 12 Months in Phase 3&#44; and up to 36 Months in the LTE study&#46; Although formal statistical comparisons were not conducted&#44; tofacitinib efficacy in Mexican patients was generally consistent with that observed in the global<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#44;8&#44;10&#8211;12</span></a> and LA<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> Phase 3 and LTE analyses&#59; however&#44; a greater proportion of Mexican patients were female and Mexican patients were typically younger&#46; The small sample sizes in the subpopulations precluded statistical comparison between treatment groups and formal conclusions being drawn regarding the efficacy and safety of tofacitinib&#46; These factors should be considered in interpreting outcomes&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The safety profile of tofacitinib in Mexican patients was generally similar with respect to the Phase 3 and LTE global<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7&#44;8&#44;10&#8211;12</span></a> and LA analyses&#44;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> including low and comparable IRs of opportunistic infections &#40;excluding tuberculosis&#41;&#44; tuberculosis&#44; malignancies &#40;excluding NMSC&#41;&#44; and MACE in LTE study analyses&#46; As in the global LTE study&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> there were increases in hemoglobin levels and decreases in absolute neutrophil and lymphocyte counts in the Mexican LTE study population&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Patients with RA have a greater risk of infections&#44; including tuberculosis&#44; that increases with use of immunosuppressive agents and bDMARDs&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">15</span></a> In LA&#44; registry data on the use of bDMARDs<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">16&#44;17</span></a> also indicated increased risk of infections and tuberculosis with therapy&#46; In this analysis&#44; no SIEs or tuberculosis occurred during Phase 3 studies and there were no opportunistic infections and only two cases of tuberculosis reported during the LTE study&#46; However&#44; it should be acknowledged that the Mexican subpopulation is small&#44; and patients participating in tofacitinib Phase 3 and LTE studies were screened for active or latent tuberculosis&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">In the global RA program&#44; IRs for HZ were generally higher with tofacitinib versus placebo and bDMARDs<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">18</span></a>&#59; the overall HZ risk was particularly increased in Japanese and Korean patients&#46; The IRs &#40;unique patients with events&#47;100 patient-years&#41; of HZ in Mexican tofacitinib-treated patients in the LTE analysis presented here were numerically lower with tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID and similar with 10<span class="elsevierStyleHsp" style=""></span>mg BID compared with the global LTE analysis &#40;4&#46;2 &#91;95&#37; CI 3&#46;5&#44; 5&#46;0&#93; and 4&#46;5 &#91;3&#46;8&#44; 5&#46;4&#93; for tofacitinib 5 and 10<span class="elsevierStyleHsp" style=""></span>mg BID&#44; respectively&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> but higher than those reported in analyses of registry data for bDMARD-treated patients with RA in the UK<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> &#40;1&#46;6 events&#47;100 patient-years&#41;&#44; US<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> &#40;1&#46;2 events&#47;100 patient-years&#41; and Germany<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> &#40;1&#46;1 events&#47;100 patient-years&#41;&#46; In interpreting the rate of HZ observed in these analyses&#44; it should be noted that patients with history of recurrent HZ&#44; disseminated HZ or herpes simplex were not permitted to be enrolled in these studies&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">In light of CMR recommendations&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a> tofacitinib&#39;s oral administration route may be of benefit in reducing the number of clinic visits required by patients&#46; Moreover&#44; unlike bDMARDs&#44; which are administered via injection and with which patients may lose response owing to acquired drug resistance&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a> tofacitinib is an oral small molecule therapy and patients with RA may prefer treatment in the form of a tablet over injectable therapies&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">23</span></a> Accordingly&#44; tofacitinib offers an alternative for Mexican patients with RA who failed treatment with csDMARDs&#46; A further potential benefit of a small molecule therapy for RA in the Mexican healthcare setting may be a reduction in administrative costs owing to fewer required patient visits to the clinic and independence from temperature-controlled supply chains&#46; However&#44; an evaluation of the pharmacoeconomic impact of tofacitinib for RA therapy was not included in this study&#44; and additional studies should be performed to assess this&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Compared to the tofacitinib global study population&#44; the number of patients&#44; tofacitinib exposure and treatment duration were lower in these subpopulation analyses which may explain the lower rates of long-latency AEs such as MACE and malignancies&#46; Interpretation of the Phase 3 data in this analysis was limited by pooling of data from studies with different patient populations&#44; study designs&#44; and methodologies&#46; Fewer patients were enrolled in the placebo groups of Phase 3 studies and consequently patient exposure was lower&#46; In interpreting the Phase 3 efficacy analyses&#44; it should also be noted that patients remaining in the placebo group at Month 6 were those from ORAL Scan&#44; Sync&#44; and Standard who had at least 20&#37; improvement in both tender&#47;painful and swollen joint counts at Month 3 and this may explain the relatively high response rate observed for some efficacy endpoints &#40;e&#46;g&#46; ACR20&#47;50&#41; in the placebo group at Month 6&#46; Interpretation of the data from the LTE study was limited by its observational nature&#46; Furthermore&#44; the tolerability and efficacy of tofacitinib have already been demonstrated in patients enrolling in the LTE study through their index study participation&#46; Dose adjustments were also permitted in the LTE&#44; limiting comparison between tofacitinib doses&#46; Nonetheless&#44; due scarce long-term real-life data&#44; LTE data and real-world data studies<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a> are important in evaluating tofacitinib in the Mexican subpopulation&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg BID and 10<span class="elsevierStyleHsp" style=""></span>mg BID showed improvement in efficacy endpoints which were sustained with long-term therapy up to 36 months post-index study&#46; The safety profile of tofacitinib in Mexican patients with RA was consistent with that of the LA and global populations&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Key messages</span><p id="par0180" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Sustained efficacy in reducing signs and symptoms of RA was observed up to 36 months in Mexican patients treated with tofacitinib in the LTE study&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall">The safety profile of tofacitinib in the Mexican subpopulation was consistent with that observed in the global and overall Latin American Phase 3 and LTE study populations&#46;</p></li></ul></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Ethical responsibilities</span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Protection of human and animal subjects</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Confidentiality of data</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Right to privacy and informed consent</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conflict of interest</span><p id="par0210" class="elsevierStylePara elsevierViewall">R Burgos-Vargas has received research grants&#44; consultancy fees&#44; and&#47;or speakers&#8217; fees from AbbVie&#44; Janssen&#44; Lilly&#44; Novartis&#44; Pfizer Inc&#46;&#44; and UCB&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">MH Cardiel has received research grants&#44; consultancy fees&#44; and speakers&#8217; fees from AbbVie&#44; Astellas&#44; Astra Zeneca&#44; Bristol-Myers Squibb&#44; Infinity&#44; Janssen&#44; Lilly&#44; Merck-Serono&#44; Pfizer Inc&#44; Roche&#44; and UCB&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">D Xibill&#233; has received consultancy fees from Pfizer Inc&#46; and payment for clinical studies from AstraZeneca&#44; Bristol-Myers Squibb&#44; Janssen&#44; Pfizer Inc&#46;&#44; and UCB&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">C Pacheco-Tena has received payment for clinical studies&#44; consultancy fees&#44; or speaker fees from AstraZeneca&#44; Bristol-Myers Squibb&#44; GlaxoSmithKline&#44; Janssen&#44; Lilly&#44; Merck-Serono&#44; Novo Nordisk&#44; Pfizer Inc&#44; Roche&#44; Sanofi&#44; UCB&#44; and Vertex&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">V Pascual-Ramos has nothing to disclose&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">C Abud-Mendoza has received consultancy fees and speaker fees from Bristol-Myers Squibb&#44; Pfizer Inc&#44; and Roche and speaker fees from Merck-Serono and UCB&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">EY Mahgoub&#44; H Fan&#44; R Rojo&#44; and K Santana are employees and shareholders of Pfizer Inc&#46; MU Rahman and EG Garc&#237;a were employees and shareholders of Pfizer Inc at the time the analyses were conducted&#46;</p></span></span>"
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    "fechaRecibido" => "2016-12-05"
    "fechaAceptado" => "2017-04-12"
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            0 => "Efficacy"
            1 => "Janus kinase"
            2 => "Mexico"
            3 => "Rheumatoid arthritis"
            4 => "Safety"
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            0 => "Eficacia"
            1 => "Quinasa Janus"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis &#40;RA&#41;&#46; We characterized efficacy and safety of tofacitinib in Mexican patients from RA Phase 3 and long-term extension &#40;LTE&#41; studies&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Data from Mexican patients with RA and an inadequate response to disease-modifying antirheumatic drugs &#40;DMARDs&#41; were taken from four Phase 3 studies &#40;pooled across studies&#41; and one open-label LTE study of tofacitinib&#46; Patients received tofacitinib 5 or 10<span class="elsevierStyleHsp" style=""></span>mg twice daily&#44; adalimumab &#40;one Phase 3 study&#41; or placebo &#40;four Phase 3 studies&#41; as monotherapy or in combination with conventional synthetic DMARDs&#46; Efficacy up to Month 12 &#40;Phase 3&#41; and Month 36 &#40;LTE&#41; was assessed by American College of Rheumatology 20&#47;50&#47;70 response rates&#44; Disease Activity Score &#40;erythrocyte sedimentation rate&#41;&#44; and Health Assessment Questionnaire-Disability Index&#46; Safety&#44; including incidence rates &#40;IRs&#59; patients with events&#47;100 patient-years&#41; for adverse events &#40;AEs&#41; of special interest&#44; was assessed throughout the studies&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">119 and 212 Mexican patients were included in the Phase 3 and LTE analyses&#44; respectively&#46; Tofacitinib-treated patients in Phase 3 had numerically greater improvements in efficacy responses versus placebo at Month 3&#46; Efficacy was sustained in Phase 3 and LTE studies&#46; IRs for AEs of special interest were similar to those with tofacitinib in the global and Latin American RA populations&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In Mexican patients from the tofacitinib global RA program&#44; tofacitinib efficacy was demonstrated up to Month 12 in Phase 3 studies and Month 36 in the LTE study&#44; with a safety profile consistent with tofacitinib global population&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Tofacitinib es un inhibidor de la cinasa Janus para el tratamiento de la artritis reumatoide &#40;AR&#41;&#46; Se evaluaron la eficacia y la seguridad de tofacitinib en pacientes mexicanos a partir de los estudios fase 3 y de extensi&#243;n a largo plazo &#40;ELP&#41; de AR&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Datos de pacientes mexicanos con AR y respuesta inadecuada a f&#225;rmacos antirreum&#225;ticos modificadores de la enfermedad &#40;FARME&#41; fueron tomados de 4 estudios fase 3 y de un estudio abierto de ELP de tofacitinib&#46; Los pacientes recibieron tofacitinib 5 o 10<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a&#44; adalimumab &#40;en un estudio fase 3&#41; o placebo &#40;en 4 estudios fase 3&#41; como monoterapia o en combinaci&#243;n con FARME sint&#233;tico convencional&#46; Se evalu&#243; la eficacia al mes 12 &#40;fase 3&#41; y al mes 36 &#40;ELP&#41; por medio de las tasas de respuesta del Colegio Americano de Reumatolog&#237;a 20&#47;50&#47;70&#44; el puntaje de actividad de la enfermedad &#40;DAS&#41; 28-4&#44; velocidad de sedimentaci&#243;n globular y el &#237;ndice de discapacidad del cuestionario de evaluaci&#243;n de la salud &#40;HAQ-DI&#41;&#46; Se evalu&#243; la seguridad a trav&#233;s de los estudios&#44; incluyendo tasas de incidencia &#40;IR&#59; pacientes con evento&#47;100 pacientes-a&#241;o&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Ciento diecinueve y 212 pacientes mexicanos fueron incluidos en el an&#225;lisis de los estudios fase 3 y de extensi&#243;n a largo plazo&#44; respectivamente&#46; Pacientes tratados con tofacitinib en los estudios fase 3&#44; num&#233;ricamente&#44; tuvieron una mayor mejor&#237;a en las respuestas de eficacia en comparaci&#243;n con el placebo al mes 3&#46; La eficacia fue sostenida en los estudios fase 3 y de extensi&#243;n a largo plazo&#46; Las tasas de incidencia de los eventos adversos de especial inter&#233;s fueron similares a aquellas con tofacitinib en la poblaci&#243;n global y latinoamericana&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En pacientes mexicanos del programa global de tofacitinib en AR&#44; la eficacia de tofacitinib se demostr&#243; hasta el mes 12 en los estudios fase 3 y hasta el mes 36 en el estudio de extensi&#243;n a largo plazo&#44; con un perfil de seguridad consistente con el de la poblaci&#243;n global de los estudios de tofacitinib&#46;</p></span>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; ACR20&#44; &#40;B&#41; ACR50&#44; and &#40;C&#41; ACR70 response rates &#40;95&#37; CI&#41; by treatment sequence in the Mexican Phase 3 study population over time &#40;FAS&#44; no imputation&#41;&#46; Data in figure are replicated in tabular form in Supplementary Table 1&#46; Patients remaining in the placebo group at Month 6 were those with at least 20&#37; improvement in both tender&#47;painful and swollen joint counts at Month 3 in ORAL Scan&#44; ORAL Sync and ORAL Standard&#59; non-responders in the placebo group of these three studies and all placebo patients in ORAL Solo were advanced to tofacitinib treatment at Month 3 in a blinded fashion&#46; The analysis was conducted on observed data with no imputation&#46; The fact &#8216;responders&#8217; remained in the placebo group at Month 6 with observed data being used in the analysis may contribute to the relatively high response rates for ACR20 and ACR50 in the placebo group at Month 6&#46; ACR&#44; American College of Rheumatology&#59; BID&#44; twice daily&#59; CI&#44; confidence interval&#59; FAS&#44; full analysis set&#59; <span class="elsevierStyleItalic">N</span>&#44; number of evaluable patients at time point of interest&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Mean &#40;95&#37; CI&#41; change from baseline in DAS28-4&#40;ESR&#41; and &#40;B&#41; mean &#40;95&#37; CI&#41; change from baseline in HAQ-DI score by treatment sequence in the Mexican Phase 3 study population over time &#40;FAS&#44; no imputation&#41;&#46; Data in figure are replicated in tabular form in Supplementary Table 2&#46; Patients remaining in the placebo group at Month 6 were those with at least 20&#37; improvement in both tender&#47;painful and swollen joint counts at Month 3 in ORAL Scan&#44; ORAL Sync&#44; and ORAL Standard&#59; non-responders in the placebo group of these three studies and all placebo patients in ORAL Solo were advanced to tofacitinib treatment at Month 3 in a blinded fashion&#46; The analysis was conducted on observed data with no imputation&#46; BID&#44; twice daily&#59; CI&#44; confidence interval&#59; DAS28-4&#40;ESR&#41;&#44; Disease Activity Score &#40;erythrocyte sedimentation rate&#41;&#59; FAS&#44; full analysis set&#59; HAQ-DI&#44; Health Assessment Questionnaire-Disability Index&#59; <span class="elsevierStyleItalic">N</span>&#44; number of evaluable patients at time point of interest&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 3641
            "Ancho" => 2080
            "Tamanyo" => 340744
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; ACR20&#44; &#40;B&#41; ACR50&#44; and &#40;C&#41; ACR70 response rates &#40;95&#37; CI&#41; in the Mexican LTE study population over time &#40;FAS&#44; no imputation&#41;&#46; Data in figure are replicated in tabular form in Supplementary Table 3&#46; ACR&#44; American College of Rheumatology&#59; BID&#44; twice daily&#59; CI&#44; confidence interval&#59; FAS&#44; full analysis set&#59; LTE&#44; long-term extension&#59; <span class="elsevierStyleItalic">N</span>&#44; number of evaluable patients at time point of interest&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "fig0020"
        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr4.jpeg"
            "Alto" => 3252
            "Ancho" => 2503
            "Tamanyo" => 356063
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Mean &#40;95&#37; CI&#41; change from baseline in DAS28-4&#40;ESR&#41; and B&#41; mean &#40;95&#37; CI&#41; change from baseline in HAQ-DI score in the Mexican LTE study population over time &#40;FAS&#44; no imputation&#41;&#46; Data in figure are replicated in tabular form in Supplementary Table 4&#46; BID&#44; twice daily&#59; CI&#44; confidence interval&#59; DAS28-4&#40;ESR&#41;&#44; Disease Activity Score &#40;erythrocyte sedimentation rate&#41;&#59; FAS&#44; full analysis set&#59; HAQ-DI&#44; Health Assessment Questionnaire-Disability Index&#59; LTE&#44; long-term extension&#59; <span class="elsevierStyleItalic">N</span>&#44; number of evaluable patients at time point of interest&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "fig0025"
        "etiqueta" => "Fig&#46; 5"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr5.jpeg"
            "Alto" => 2764
            "Ancho" => 3333
            "Tamanyo" => 463694
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Mean laboratory parameters over time in the Mexican Phase 3 &#40;A&#8211;C&#41; and LTE &#40;D&#8211;F&#41; study populations&#46; &#40;A&#41; and &#40;D&#41; change from baseline in hemoglobin&#59; &#40;B&#41; and &#40;E&#41; change from baseline absolute neutrophil count&#59; C&#41; and F&#41; absolute lymphocyte count&#46; Data in figure are replicated in tabular form in Supplementary Table 5A &#40;panels A&#8211;C&#41; and Supplementary Table 5B &#40;panels D&#8211;F&#41;&#46; Data for Phase 3 is only presented up to Month 12 due to low sample size post-Month 12 BID&#44; twice daily&#59; LTE&#44; long-term extension&#59; <span class="elsevierStyleItalic">N</span>&#44; number of evaluable patients at time point of interest&#59; SE&#44; standard error&#46;</p>"
        ]
      ]
      5 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
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                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="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Phase 3 studies</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">LTE study</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>5<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>10<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Placebo<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>5<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>10<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Total exposure&#44; patient-years</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">339&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">230&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Treatment duration&#44; mean days &#40;maximum&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">310&#46;4 &#40;729&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">362&#46;4 &#40;750&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">400&#46;4 &#40;736&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1438&#46;4 &#40;2183&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">662&#46;2 &#40;1183&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age &#40;years&#41;&#44; mean &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#46;6 &#40;21&#8211;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#46;1 &#40;22&#8211;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&#46;0 &#40;23&#8211;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43&#46;7 &#40;19&#8211;77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&#46;3 &#40;23&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Female&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33 &#40;89&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54 &#40;98&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26 &#40;96&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83 &#40;96&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">118 &#40;93&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Weight &#40;kg&#41;&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&#46;3 &#40;13&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&#46;4 &#40;13&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">66&#46;9 &#40;18&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64&#46;6 &#40;14&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#46;1 &#40;12&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">BMI &#40;kg&#47;m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#41;&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;8 &#40;5&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&#46;7 &#40;5&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;0 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;9 &#40;5&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;6 &#40;5&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Duration of RA &#40;years&#41;&#44; mean &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;1 &#40;0&#46;3&#8211;37&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;2 &#40;0&#46;7&#8211;31&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;2 &#40;0&#46;8&#8211;49&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;3 &#40;0&#46;5&#8211;28&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;8 &#40;0&#46;0&#8211;37&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">DAS28-4&#40;ESR&#41;&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;5 &#40;1&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;4 &#40;1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;7 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;1 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;2 &#40;1&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">HAQ-DI&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;0&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6 &#40;0&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;4 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;4 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">CRP &#40;mg&#47;L&#41;&#44; mean &#40;SD&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">17&#46;1 &#40;13&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;1 &#40;17&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#46;1 &#40;21&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;7 &#40;1&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;5 &#40;1&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Anti-CCP-positive&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33 &#40;89&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45 &#40;81&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21 &#40;77&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;2&#46;3&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">98 &#40;77&#46;8&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#8224;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Previous glucocorticoid use&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22 &#40;59&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31 &#40;56&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13 &#40;48&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33 &#40;38&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">54 &#40;42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleItalic">Previous csDMARD use&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Methotrexate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37 &#40;100&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53 &#40;96&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26 &#40;96&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65 &#40;75&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82 &#40;65&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sulfasalazine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14 &#40;37&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;37&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;7&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;4&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Leflunomide&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;13&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;10&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;1&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;0&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chloroquine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19 &#40;51&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;45&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;40&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;8&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15 &#40;11&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Anti-CCP category data at baseline in the LTE study were missing or not collected for 82 &#40;95&#46;4&#37;&#41; and two &#40;1&#46;6&#37;&#41; patients in the 5<span class="elsevierStyleHsp" style=""></span>mg BID and 10<span class="elsevierStyleHsp" style=""></span>mg BID dose groups&#44; respectively&#46;</p> <p class="elsevierStyleNotepara" id="npar0010">BID&#44; twice daily&#59; BMI&#44; body mass index&#59; CCP&#44; cyclic citrullinated peptide&#59; CRP&#44; C-reactive protein&#59; csDMARD&#44; conventional synthetic disease-modifying antirheumatic drug&#59; DAS28-4&#40;ESR&#41;&#44; Disease Activity Score &#40;erythrocyte sedimentation rate&#41;&#59; HAQ-DI&#44; Health Assessment Questionnaire-Disability Index&#59; LTE&#44; long-term extension&#59; RA&#44; rheumatoid arthritis&#59; SD&#44; standard deviation&#46;</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">AE&#44; adverse event&#59; BID&#44; twice daily&#59; MedDRA&#44; Medical Dictionary for Regulatory Activities&#46;</p>"
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                  <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="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Up to Month 3</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Month 3&#8211;6</th><th class="td" title="table-head  " colspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post-Month 6</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>5<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>10<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Placebo<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>5<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>10<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Placebo<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>5<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>10<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Patients with AEs&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;29&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;21&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;18&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;4&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;36&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;24&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;13&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Discontinuations due to AEs&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="9" align="left" valign="top"><span class="elsevierStyleItalic">Most common AEs by MedDRA preferred term &#40;the 10 most frequently occurring AEs are listed by number of patients with events&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Gastritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;8&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;12&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Vomiting&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;8&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Upper respiratory tract infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nausea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;5&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pharyngitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Urinary tract infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;9&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Abdominal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;2&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Influenza&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;8&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;1&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nasopharyngitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;5&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;3&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tooth fracture&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0 &#40;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;3&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;5&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Summary of AEs&#44; discontinuations due to AEs&#44; and most common AEs in the Mexican Phase 3 study subpopulation by treatment period&#46;</p>"
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">AE&#44; adverse event&#59; BID&#44; twice daily&#59; HZ&#44; herpes zoster&#59; LTE&#44; long-term extension&#59; MedDRA&#44; Medical Dictionary for Regulatory Activities&#46;</p>"
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                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="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">LTE study</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>5<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>10<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Patients with AEs&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">79 &#40;91&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">102 &#40;81&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Discontinuations due to AEs&#44; n &#40;&#37;&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18 &#40;20&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;8&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleItalic">Most common AEs by MedDRA preferred term &#40;the 10 most frequently occurring AEs are listed by number of patients with events&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Upper respiratory tract infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16 &#40;18&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15 &#40;11&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Urinary tract infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19 &#40;22&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;9&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;8&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12 &#40;9&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Nasopharyngitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;2&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16 &#40;12&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pharyngitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;8&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;8&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>HZ&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;9&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diarrhea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;8&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Gastritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;5&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8 &#40;6&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pharyngotonsillitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9 &#40;10&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;2&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Fall&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7 &#40;8&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;4&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  <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="table-head  " rowspan="2" align="left" valign="top" scope="col" style="border-bottom: 2px solid black">IR&#44; patients with event&#47;100 patient-years &#40;95&#37; CI&#41;</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">LTE study</th></tr><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>5<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tofacitinib<br>10<span class="elsevierStyleHsp" style=""></span>mg BID<br><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>126&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total exposure&#44; patient-years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">339&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">230&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SAEs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;2 &#40;3&#46;8&#44; 9&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;8 &#40;2&#46;4&#44; 8&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Discontinuations due to AEs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;3 &#40;3&#46;2&#44; 8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;8 &#40;2&#46;4&#44; 8&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serious infections&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;4 &#40;1&#46;0&#44; 4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
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