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Objective: Psoriatic arthritis (PsA) is chronic disease that compromises multiple domains and might be associated with progressive joint damage, increased mortality, functional limitation, and considerably impaired quality of life. Our objective was to generate evidence-based recommendations on the management of PsA in Pan American League of Associations for Rheumatology (PANLAR) countries., Methods: We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach to adapt the 2019 recommendations of the European Alliance of Associations for Rheumatology. A working group consisting of rheumatologists from various countries in Latin America identified relevant topics for the treatment of PsA in the region. The methodology team updated the evidence and synthesized the information used to generate the final recommendations. These were then discussed and defined by a panel of 31 rheumatologists from 15 countries., Results: Theses guidelines report 15 recommendations addressing therapeutic targets, use of antiinflammatory agents and corticosteroids, treatment with disease-modifying antirheumatic drugs (conventional synthetic, biologic, and targeted synthetic), therapeutic failure, optimization of biologic therapy, nonpharmacological interventions, assessment tools, and follow-up of patients with PsA., Conclusion: Here we present a set of recommendations to guide decision making in the treatment of PsA in Latin America, based on the best evidence available, considering resources, medical expertise, and the patient's values and preferences. The successful implementation of these recommendations should be based on clinical practice conditions, healthcare settings in each country, and a tailored evaluation of patients., (Copyright © 2024 by the Journal of Rheumatology.)

Axial spondyloarthritis (axSpA) comprises a spectrum of chronic inflammatory manifestations affecting the axial skeleton and represents a challenge for diagnosis and treatment. Our objective was to generate a set of evidence-based recommendations for the management of axSpA for physicians, health professionals, rheumatologists and policy decision makers in Pan American League of Associations for Rheumatology (PANLAR) countries. Grading of Recommendations, Assessment, Development and Evaluation-ADOLOPMENT methodology was used to adapt existing recommendations after performing an independent systematic search and synthesis of the literature to update the evidence. A working group consisting of rheumatologists, epidemiologists and patient representatives from countries within the Americas prioritized 13 topics relevant to the context of these countries for the management of axSpA. This Evidence-Based Guideline article reports 13 recommendations addressing therapeutic targets, the use of NSAIDs and glucocorticoids, treatment with DMARDs (including conventional synthetic, biologic and targeted synthetic DMARDs), therapeutic failure, optimization of the use of biologic DMARDs, the use of drugs for extra-musculoskeletal manifestations of axSpA, non-pharmacological interventions and the follow-up of patients with axSpA., (© 2023. Springer Nature Limited.)

Background: Our aim was to compare the efficacy of rituximab, tocilizumab, and abatacept in individuals with rheumatoid arthritis (RA) refractory to treatments with MTX or TNFi agents., Methods: We searched 6 databases until January 2023 for phase 2-4 RCTs evaluating patients with RA refractory to MTX or TNFi therapy treated with rituximab, abatacept, and tocilizumab (intervention arm) compared to controls. Study data were independently assessed by two investigators. The primary outcome was considered as achieving ACR70 response., Results: The meta-analysis included 19 RCTs, with 7,835 patients and a mean study duration of 1.2 years. Hazard ratios for achieving an ACR70 response at six months were not different among the bDMARDs, however, we found high heterogeneity. Three factors showing a critical imbalance among the bDMARD classes were identified: baseline HAQ score, study duration, and frequency of TNFi treatment in control arm. Multivariate meta-regression adjusted to these three factors were conducted for the relative risk (RR) for ACR70. Thus, heterogeneity was attenuated (I2 = 24%) and the explanatory power of the model increased (R2 = 85%). In this model, rituximab did not modify the chance of achieving an ACR70 response compared to abatacept (RR = 1.773, 95%CI 0.113-10.21, p = 0.765). In contrast, abatacept was associated with RR = 2.217 (95%CI 1.554-3.161, p < 0.001) for ACR70 compared to tocilizumab., Conclusion: We found high heterogeneity among studies comparing rituximab, abatacept, and tocilizumab. On multivariate metaregressions, if the conditions of the RCTs were similar, we estimate that abatacept could increase the chance of reaching an ACR70 response by 2.2-fold compared to tocilizumab., (© 2023. The Author(s).)

Background: AVERT-2 (a phase IIIb, two-stage study) evaluated abatacept + methotrexate versus methotrexate alone, in methotrexate-naive, anti-citrullinated protein antibody-positive patients with early (≤ 6 months), active RA. This subanalysis investigated whether individual patients who achieved the week 24 Simplified Disease Activity Index (SDAI) remission primary endpoint could sustain remission to 1 year and then maintain it following changes in therapy., Methods: During the 56-week induction period (IP), patients were randomized to weekly subcutaneous abatacept 125 mg + methotrexate or abatacept placebo + methotrexate. Patients completing the IP who achieved SDAI remission (≤ 3.3) at weeks 40 and 52 entered a 48-week de-escalation (DE) period. Patients treated with abatacept + methotrexate were re-randomized to continue weekly abatacept + methotrexate, or de-escalate and then withdraw abatacept (after 24 weeks), or receive abatacept monotherapy. Proportions of patients achieving sustained SDAI and Boolean remission, and Disease Activity Score in 28 joints using C-reactive protein (DAS28 [CRP]) < 2.6, were assessed. For patients achieving early sustained SDAI remission at weeks 24/40/52, flow between disease activity categories and individual trajectories was evaluated; flow was also evaluated for later remitters (weeks 40/52 but not week 24)., Results: Among patients treated with abatacept + methotrexate (n/N = 451/752) at IP week 24, 22% achieved SDAI remission, 17% achieved Boolean remission, and 42% achieved DAS28 (CRP) < 2.6; of these, 56%, 58%, and 74%, respectively, sustained a response throughout IP weeks 40/52. Among patients with a sustained response at IP weeks 24/40/52, 82% (14/17) on weekly abatacept + methotrexate, 81% (13/16) on abatacept monotherapy, 63% (12/19) who de-escalated/withdrew abatacept, and 65% (11/17) on abatacept placebo + methotrexate were in SDAI remission at end of the DE period; rates were higher than for later remitters in all arms except abatacept placebo + methotrexate., Conclusions: A high proportion of individual patients achieving clinical endpoints at IP week 24 with abatacept + methotrexate sustained their responses through week 52. Of patients achieving early and sustained SDAI remission through 52 weeks, numerically more maintained remission during the DE period if weekly abatacept treatment continued., Trial Registration: NCT02504268 (ClinicalTrials.gov), registered July 21, 2015., (© 2023. Crown.)

Objective: To compare achievement of Disease Activity Index in Psoriatic Arthritis (DAPSA) remission (REM)/low disease activity (LDA) with very low disease activity (VLDA)/minimal disease activity (MDA) targets in tofacitinib-treated patients with psoriatic arthritis (PsA)., Methods: In this post hoc analysis, data were pooled from two phase 3 studies (6 months' [NCT01882439] and 12 months' [NCT01877668] duration) of patients with PsA receiving tofacitinib 5 or 10 mg twice daily. Cut-offs for DAPSA targets: ≤4 for clinical REM and >4-≤14 for LDA. VLDA and MDA were defined as meeting 7 or ≥5, respectively, of 7 criteria. An ordered logistic regression model was performed to evaluate associations between baseline characteristics and achievement of DAPSA targets as well as VLDA/MDA at month 3. Agreement between achieving DAPSA and VLDA/MDA targets at months 1-6 was assessed via kappa tests. Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) scores (month 6), modified Total Sharp Score (mTSS) and proportion of radiographic non-progressors (mTSS ≤0.5) at month 12 (NCT01877668 only) were compared across DAPSA and VLDA/MDA targets., Results: Increased disease activity at baseline was associated with reduced likelihood of achieving DAPSA-REM/DAPSA-LDA or VLDA/MDA at month 3. There was moderate agreement (kappa values 0.41-0.60) between DAPSA-REM and VLDA, and DAPSA-LDA and MDA, from months 1 to 6, although over half of patients achieving DAPSA-REM and over two thirds of patients achieving DAPSA-LDA, respectively, were not captured by VLDA and MDA. Achieving DAPSA-REM/DAPSA-LDA or VLDA/MDA was associated with improved HAQ-DI and SF-36 PCS scores at month 6, and slightly reduced radiographic progression at month 12., Conclusion: This analysis of data from tofacitinib-treated patients with PsA demonstrated moderate agreement between the DAPSA and VLDA/MDA composite instruments. In agreement with previous studies, VLDA and MDA may be more difficult to achieve than DAPSA-REM and DAPSA-LDA, respectively. However, the clinical and prognostic relevance of this finding should be determined. These data support DAPSA and VLDA/MDA as useful tools for evaluating disease activity and treatment response in PsA., Clinicaltrials: GOV: NCT01882439; NCT01877668., Competing Interests: Declaration of Competing Interest EES has received grants/contracts from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Genzyme, Janssen, Novartis and Pfizer Inc (to institution); has received consulting fees from AbbVie, Eli Lilly and Janssen; and has received other remuneration from AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis and Pfizer Inc. GC has received grants/contracts from Pfizer Inc (to institution); has received consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Pfizer Inc and Sandoz; and has received other remuneration from AbbVie, Amgen, Bristol-Myers Squibb, Janssen and Pfizer Inc. PN has received consulting fees and other remuneration from AbbVie, Bristol-Myers Squibb, Eli Lilly, Gilead/Galapagos, Janssen, Novartis, Pfizer Inc and UCB. JSS has received grants/contracts from AbbVie, Astro, AstraZeneca, Eli Lilly, Janssen, Merck Sharpe & Dohme, Pfizer Inc and Roche (to institution); and has received consulting fees and other remuneration from AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Eli Lilly, Gilead, ILTOO Pharma, Janssen, Merck Sharpe & Dohme, Novartis-Sandoz, Pfizer Inc, R-Pharm, Roche, Samsung, Sanofi and UCB. PJM has received grants/contracts from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun and UCB; has received consultancy fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Sun and UCB; and has received other remuneration from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB. ERS has received grants or contracts from AbbVie and Janssen; and has received consulting fees and other remuneration from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sandoz and UCB. CH, RM and DPdeL are employees and stockholders of Pfizer Inc. AES was an employee of Syneos Health, who were paid contractors to Pfizer Inc in the development of this manuscript., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To characterise infections in patients with rheumatoid arthritis (RA) in ORAL Surveillance., Methods: In this open-label, randomised controlled trial, patients with RA aged≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg two times per day or a tumour necrosis factor inhibitor (TNFi). Incidence rates (IRs; patients with first events/100 patient-years) and hazard ratios (HRs) were calculated for infections, overall and by age (50-<65 years; ≥65 years). Probabilities of infections were obtained (Kaplan-Meier estimates). Cox modelling identified infection risk factors., Results: IRs/HRs for all infections, serious infection events (SIEs) and non-serious infections (NSIs) were higher with tofacitinib (10>5 mg two times per day) versus TNFi. For SIEs, HR (95% CI) for tofacitinib 5 and 10 mg two times per day versus TNFi, respectively, were 1.17 (0.92 to 1.50) and 1.48 (1.17 to 1.87). Increased IRs/HRs for all infections and SIEs with tofacitinib 10 mg two times per day versus TNFi were more pronounced in patients aged≥65 vs 50-<65 years. SIE probability increased from month 18 and before month 6 with tofacitinib 5 and 10 mg two times per day versus TNFi, respectively. NSI probability increased before month 6 with both tofacitinib doses versus TNFi. Across treatments, the most predictive risk factors for SIEs were increasing age, baseline opioid use, history of chronic lung disease and time-dependent oral corticosteroid use, and, for NSIs, female sex, history of chronic lung disease/infections, past smoking and time-dependent Disease Activity Score in 28 joints, C-reactive protein., Conclusions: Infections were higher with tofacitinib versus TNFi. Findings may inform future treatment decisions., Trial Registration Number: NCT02092467., Competing Interests: Competing interests: A-RB has acted as a consultant for AbbVie, Akros, Alfasigma, Amgen, Biogen, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Roche and UCB, has received speaker fees or honoraria from AbbVie, Alfasigma, Amgen, Angelini, AstraZeneca, Berlin-Chemie, Bristol-Myers Squibb, MSD, Novartis, Pfizer, Roche, Sandoz, Teva, UCB and Zentiva, and has been a principal investigator in studies sponsored by Akros, AstraZeneca, Bristol-Myers Squibb, GSK, MSD, Novartis, Pfizer, Roche and UCB. GC has received grants and/or research support from AbbVie, Amgen, Eli Lilly, Gema Pharma, Genzyme, Novartis, Pfizer and Sanofi-Genzyme, and has acted as a consultant for AbbVie, Amgen, Eli Lilly, Gema Pharma, Genzyme, Novartis, Pfizer and Sanofi-Genzyme. VP-R is an employee of Instituto Nacional de Ciencias Médicas y Nutrición and is a principal investigator in studies sponsored by Bristol-Myers Squibb and Pfizer.DLB is a member of the advisory board for: AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; Board of Directors: AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; Chair: Inaugural Chair, American Heart Association Quality Oversight Committee; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; DLB/Brigham and Women's Hospital do not receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Takeda. He served as a member of the Steering Committee for ORAL Surveillance, with funding from Pfizer paid to Brigham and Women’s Hospital. CAC, DG and ABS are employees and stockholders of Pfizer. A-SC is an employee of Pfizer. GS is an employee of Syneos Health, who were paid contractors to Pfizer in the development of this manuscript. JEP has received grants and/or research support from Bristol-Myers Squibb, Roche, Seattle Genetics and UCB, and has acted as a consultant for AbbVie, Actelion, Amgen, Bayer, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi and UCB. HS-K has acted as a consultant for, and been an advisor or review panel member for, AbbVie, Eli Lilly, Galapagos, MSD, Pfizer and UCB., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the adherence to treatment with Tofacitinib in patients with Rheumatoid Arthritis (RA) using two versions of the self-questionnaire Compliance Questionnaire Rheumatology, CQR19 and CQR5, to determine the variables associated with adherence to Tofacitinib and to compare the performance of both questionnaires., Material and Methods: A cross-sectional study was carried out. We included patients ≥18 years old, with RA (ACR/EULAR criteria 2010) under treatment with Tofacitinib. Sociodemographic data, clinical characteristics, treatment and data on patient evaluation. All the patients completed self-questionnaires CQR19 and CQR5., Statistical Analysis: Descriptive statistics. t-Test or Mann Whitney to compare the continuous variables, Chi 2 test or Fisher's exact test for the categorical ones. Kappa concordance index. Multiple logistic regression., Results: We included 52 patients, 82.7% women, with a median (m) age of 57.7 years, disease duration m 16 years, 63.5% had comorbidities. Of the patients, 86.5% were treated with Tofacitinib (5 mg BID) and 48% received Tofacitinib as monotherapy. The median time of Tofacitinib treatment was 13 months, 42.3% suspended treatment, and only one patient permanently stopped treatment due to lack of provision. Median CQR19 was 89.5% and 84.6% had an adherence ≥ 80%. The variables significantly associated with adherence ≥ 80% were the presence of comorbidities (p = .014) and older age (p = .033). Considering the CQR5, a similar percentage of patients (82.7%) were adherents to treatment, however, the concordance with CQR19 was low. In the multivariate analysis, older age was the only variable independently associated with good adherence to treatment., Conclusions: Treatment adherence to Tofacitinib was very good for both presentations. Older age was associated with higher adherence. The agreement between the questionnaires CQR19 and CQR5 was low., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background/objective: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Interstitial lung disease (ILD) is an extra-articular manifestation of RA. We investigated incidence rates of ILD in patients with RA, receiving tofacitinib 5 or 10 mg twice daily, and identified potential risk factors for ILD., Methods: This post hoc analysis comprised a pooled analysis of patients receiving tofacitinib 5 or 10 mg twice daily or placebo from 2 phase (P)1, 10 P2, 6 P3, 1 P3b/4, and 2 long-term extension studies. Interstitial lung disease events were adjudicated as "probable" (supportive clinical evidence) or "possible" (no supportive clinical evidence) compatible adverse events. Incidence rates (patients with events per 100 patient-years) were calculated for ILD events., Results: Of 7061 patients (patient-years of exposure = 23,393.7), 42 (0.6%) had an ILD event; median time to ILD event was 1144 days. Incidence rates for ILD with both tofacitinib doses were 0.18 per 100 patient-years. Incidence rates generally remained stable over time. There were 17 of 42 serious adverse events (40.5%) of ILD; for all ILD events (serious and nonserious), 35 of 42 events (83.3%) were mild to moderate in severity. A multivariable Cox regression analysis identified age 65 years or older (hazard ratio 2.43 [95% confidence interval, 1.13-5.21]), current smokers (2.89 [1.33-6.26]), and Disease Activity Score in 28 joints-erythrocyte sedimentation rate score (1.30 [1.04-1.61]) as significant risk factors for ILD events., Conclusions: Across P1/2/3/4/long-term extension studies, incidence rates for ILD events were 0.18 following tofacitinib treatment, and ILD events were associated with known risk factors for ILD in RA., Competing Interests: This study was sponsored by Pfizer Inc. G.C. has received research grants from Novartis and Pfizer Inc. and is a speaker, advisor and/or consultant to AbbVie, Bristol-Myers Squibb, Eli Lilly, Genzyme, Janssen, Novartis, Pfizer Inc., and Roche. E.M. has received research grants from Eli Lilly, Pfizer Inc., and Roche and is a member of the speakers' bureaus for AbbVie, Bristol-Myers Squibb, Eli Lilly, Pfizer Inc., Roche, and Sanofi. M.H.C. has received research grants from Gilead, Pfizer Inc., and Roche; and is a consultant and member of the speakers' bureaus for Eli Lilly and Pfizer Inc. A.F. has received research grants from Boehringer Ingelheim and Corbus and is a consultant to Boehringer Ingelheim and Roche. A.F. is a former employee of the University of Colorado and is currently employed by Bristol-Myers Squibb. P.R. is a consultant to Pfizer Inc. S.C. is a consultant to AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Novartis, and Pfizer Inc. J.L.R., A.V.T., T.G., K.K., L.W., and D.P.L., are employees and shareholders of Pfizer Inc. S.S. is a former employee of Pfizer Inc., Capelle aan den IJssel, the Netherlands. J.K.P., H.M., and O.C. declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Enerceptan (EtaBS) has been developed as a proposed biosimilar of etanercept., Methods: This randomized, multicenter, evaluator-blinded, noninferiority study conducted in Argentina included adults with active, moderate, and severe rheumatoid arthritis with inadequate response to methotrexate. Subjects were randomly assigned to 32 weeks treatment with EtaBS (n = 99) or etanercept (n = 51) at a weekly 50-mg dose administered subcutaneously. Patients were categorized according to prior use of biologic disease-modifying antirheumatic drugs and concomitant use of steroids. The primary efficacy endpoint was ACR20 response rate at week 32. Safety, immunogenicity, and steady-state concentration of both drugs were evaluated. The noninferiority margin for ACR20 was estimated at 12%., Results: In the per-protocol population, 85 subjects (92.4%) treated with EtaBS and 44 subjects (93.6%) treated with etanercept achieved ACR20 (difference, -1.2%; 95% confidence interval, -10.1% to 7.6%). Frequent adverse drug reactions occurred in 34.3% and 38% of subjects treated with EtaBS and etanercept, respectively. The most common reaction was upper respiratory tract infection. Six and 3 serious adverse events occurred in 4 and 3 subjects treated with EtaBS and etanercept, respectively. Injection site reactions occurred in 67.7% and 66.0% of subjects treated with EtaBS and etanercept, respectively. Two subjects treated with EtaBS and 1 subject treated with etanercept developed antibodies by week 32., Conclusions: Efficacy outcomes for EtaBS were noninferior to original etanercept in patients with moderate-to-severe rheumatoid arthritis with inadequate response to methotrexate. Safety and immunogenicity results were comparable between the two. This study is a major step toward improving access to biologics in Latin America., Competing Interests: I.S. received honoraria as clinical investigator from Novartis, Merck, GlaxoSmithKline, Janssen, Bristol Myers Squibb, AbbVie, Roche, Eli Lilly, Sanofi, AstraZeneca, Servier, and Gema Biotech SAU, and fees as speaker and advisor from Janssen, Bristol Myers Squibb, Eli Lilly, Genzyme, and Gema Biotech SAU. E.M. is a speaker and advisor at Sanofi, Gema Biotech SAU, AbbVie, Pfizer, Amgen, GlaxoSmithKline, Sandoz, Eli Lilly, Roche, Bristol Myers Squibb, and AstraZeneca. G.C. has received grants and/or personal fees from AbbVie, Amgen, Bristol Myers Squibb, Gema Biotech SAU, Janssen, and Pfizer. D.S. has received research grants from Roche, Sanofi-Genzyme, Bristol Myers Squibb, Galápagos, Janssen, Eli Lilly, GlaxoSmithKline, UCB, and Gema Biotech SAU; fees for conference from Roche, Bristol Myers Squibb, and AbbVie; and fees as rheumatology consultant from Bristol Myers Squibb and Roche. M.Á.C. has received personal fees from Gema Biotech SAU. E.K. has received honoraria form BRIX SDL, LATECBA SA, AbbVie Argentina, Bristol Myers Squibb, and Gema Biotech SAU. E.S. has received honoraria as a central radiological assessor from Gema Biotech SAU. E.G. has received honoraria from Biosidus SA and Gema Biotech SAU. L.C. and N.L. are connected with Gema Biotech SAU. M.A.L., R.P.H., A.S., P.T., H.V., J.V.Z., and A.F. have no conflicts of interest to declare., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate longterm drug survival (proportion of patients still receiving treatment) and discontinuation of etanercept (ETN), infliximab (IFX), adalimumab (ADA), certolizumab pegol (CZP), and golimumab (GOL) using observational data from patients with rheumatoid arthritis (RA)., Methods: Following a systematic literature review, drug survival at 12 and 12-24 months of followup was estimated by summing proportions of patients continuing treatment and dividing by number of studies. Drug survival at ≥ 36 months of followup was estimated through Metaprop., Results: There were 170 publications included. In the first-line setting, drug survival at 12 months with ETN, IFX, or ADA was 71%, 69%, and 70%, respectively, while at 12-24 months the corresponding rates were 63%, 57%, and 59%. In the second-line setting, drug survival at 12 months with ETN, IFX, or ADA was 61%, 69%, and 55%, respectively, while at 12-24 months the corresponding rates were 53%, 39%, and 43%. Drug survival at ≥ 36 months with ETN, IFX, or ADA in the first-line setting was 59% (95% CI 46-72%), 49% (95% CI 43-54%), and 51% (95% CI 41-60%), respectively, while in the second-line setting the corresponding rates were 56% (95% CI 52-61%), 48% (95% CI 40-55%), and 41% (95% CI 36-47%). Discontinuation of ETN, IFX, and ADA at 36 months of followup was 38-48%, 42-62%, and 38-59%, respectively. Data on CZP and GOL were scarce., Conclusion: After > 12 months of followup, more patients with RA receiving ETN remain on treatment compared with other tumor necrosis factor inhibitors.

Objective: Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. This study assessed the cost-effectiveness of secukinumab, an interleukin-17A inhibitor, versus other biologics in PsA from the Argentinean social security perspective., Methods: A semi-Markov model evaluated subcutaneous (sc) treatment with secukinumab 150 mg and 300 mg against other sc treatments such as adalimumab, certolizumab pegol, etanercept, golimumab, ustekinumab, and intravenous treatment infliximab in biologic-naïve (with or without moderate to severe psoriasis) and biologic-experienced PsA patients over a lifetime horizon. Response to treatments was determined using the PsA Response Criteria (PsARC) at 12 weeks. Model inputs were derived from randomized controlled trials, network meta-analyses, published literature, and other Argentinean sources. Model outcomes included quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratios. Sensitivity analyses and alternative scenarios with a higher cost option were also conducted., Results: Among biologic-naïve PsA patients without psoriasis, secukinumab 150 mg provided the highest QALYs (7.18) versus all sc biologics at the lowest cost ($3 755 678 Argentine peso), thus dominating them. Among biologic-naïve PsA patients with psoriasis and biologic-experienced PsA patients, secukinumab 300 mg provided highest QALYs (6.99 and 7.53, respectively), dominated infliximab, and was cost-effective versus other sc biologics. Deterministic sensitivity analyses indicated sensitivity of results to variation in PsARC rates, drug acquisition costs, Health Assessment Questionnaire change, and utilities. A probabilistic sensitivity analysis showed maximum net monetary benefits with both secukinumab doses. Results from an alternative scenario analysis were similar to base-case analysis., Conclusions: For both biologic-naïve and experienced PsA patients, secukinumab is either a dominant or cost-effective treatment option compared with other biologics in Argentina., (Copyright © 2019 ISPOR--The professional society for health economics and outcomes research. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate etanercept in patients from Latin America, Central/Eastern Europe, and Asia with non-radiographic axial spondyloarthritis (nr-axSpA)., Methods: A subset analysis was performed on nr-axSpA patients from Argentina, Colombia, the Czech Republic, Hungary, Russia and Taiwan who were enrolled in EMBARK (NCT01258738). Patients received either etanercept 50 mg or placebo once weekly. The primary endpoint was proportion of patients achieving 40% improvement from baseline based on Assessment of SpondyloArthritis International Society (ASAS) criteria. Secondary endpoints included other efficacy assessments, health-related quality of life (HRQoL) and safety., Results: Of the 117 patients in this subset, 59 were treated with etanercept and 58 received placebo. At week 12, numerically greater improvements from baseline were observed for all efficacy endpoints in etanercept-treated patients compared with those receiving placebo. Statistically significant differences between the two treatment groups were observed for proportion of patients achieving ASAS40 (P = 0.0413, at week 8), ASAS5/6 (P = 0.0126), Ankylosing Spondylitis Disease Activity Score - C-reactive protein (CRP) inactive disease (P = 0.0093), Spondyloarthritis Research Consortium of Canada magnetic resonance imaging of sacroiliac joint scores (P = 0.0014), high-sensitivity CRP (P=0.032), and erythrocyte sedimentation rate (P = 0.0082). Statistically significant improvements in the etanercept-treated group compared with placebo group were observed for nocturnal back pain (P = 0.040), total back pain (P = 0.025), physician global assessment of disease (P = 0.023), and Work Productivity and Activity Impairment Questionnaire percent impairment while working (P = 0.047). Adverse events were similar between the two treatment groups., Conclusions: In this subset of patients with nr-axSpA from Latin America, Central/Eastern Europe, and Asia, treatment with etanercept, compared with placebo, resulted in improved disease symptoms and patient HRQoL. Etanercept was well tolerated., (© 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America., Methods: Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history., Results: Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (p Bonferroni < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (p Bonferroni = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment., Conclusion: Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.

Objective: To evaluate the long-term clinical and imaging efficacy of etanercept in patients with early, active nonradiographic axial spondyloarthritis (SpA)., Methods: Adult patients who satisfied the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA (but not the modified New York radiographic criteria), with symptom duration >3 months to <5 years, and who were unresponsive to ≥2 nonsteroidal antirheumatic drugs (NSAIDs) received double-blind etanercept 50 mg/week or placebo for 12 weeks, followed by open-label etanercept 50 mg/week to week 104. Clinical, magnetic resonance imaging (MRI; Spondyloarthritis Research Consortium of Canada [SPARCC] scores), and safety outcomes at 104 weeks were analyzed., Results: Of 215 randomized patients (etanercept: n = 106; placebo: n = 109), 205 entered the study (etanercept/etanercept: n = 100; placebo/etanercept: n = 105) and 169 completed the open-label period (etanercept/etanercept: n = 83; placebo/etanercept: n = 86). At week 104, 61 of 81 (75%), 49 of 81 (61%), 48 of 80 (60%), and 57 of 81 (70%) patients who received etanercept throughout the trial achieved ASAS20, ASAS40, Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease, and Bath Ankylosing Spondylitis Disease Activity Index criteria for 50% improvement (BASDAI 50) scores, respectively (observed). From baseline to week 104, continued improvements in clinical outcomes (ASDAS-C-reactive protein: -1.5 and -1.7; BASDAI: -3.3 and -3.8 [last observation carried forward]), and SPARCC MRI scores (sacroiliac joint: -6.0 and -3.4; spinal: -2.1 and -0.8 [observed]) were seen in patients receiving etanercept/etanercept and placebo/etanercept. During the study, 8% in the etanercept/etanercept group and 7% in the placebo/etanercept group had serious adverse events; no new safety signals were seen., Conclusion: Patients with early, active nonradiographic axial SpA and an inadequate response to at least 2 NSAIDs demonstrated improvement in clinical and imaging outcomes that were sustained through 104 weeks of etanercept treatment., (© 2017, American College of Rheumatology.)

Objective: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assessed tofacitinib efficacy and safety in the Latin American (LA) subpopulation of global Phase 3 and long-term extension (LTE) studies., Materials and Methods: Data from LA patients with RA and inadequate response to disease-modifying antirheumatic drugs (DMARDs) were pooled across five Phase 3 studies. Phase 3 patients received tofacitinib 5 or 10mg twice daily (BID), adalimumab or placebo; patients in the single LTE study received tofacitinib 5 or 10mg BID; treatments were administered alone or with conventional synthetic DMARDs. Efficacy was reported up to 12 months (Phase 3) and 36 months (LTE) by American College of Rheumatology (ACR) 20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate [ESR]) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Incidence rates (IRs; patients with event/100 patient-years) of adverse events (AEs) of special interest were reported., Results: The Phase 3 studies randomized 496 LA patients; the LTE study enrolled 756 LA patients from Phase 2 and Phase 3. In the Phase 3 studies, patients who received tofacitinib 5 and 10mg BID showed improvements vs placebo at Month 3 in ACR20 (68.9% and 75.7% vs 35.6%), ACR50 (45.8% and 49.7% vs 20.7%) and ACR70 (17.5% and 23.1% vs 6.9%) responses, mean change from baseline in HAQ-DI (-0.6 and -0.8 vs -0.3) and DAS28-4(ESR) score (-2.3 and -2.4 vs -1.4). The improvements were sustained up to Month 36 in the LTE study. In the Phase 3 studies, IRs with tofacitinib 5 and 10mg BID and placebo were 7.99, 6.57 and 9.84, respectively, for SAEs, and 3.87, 5.28 and 3.26 for discontinuation due to AEs. IRs of AEs of special interest in tofacitinib-treated LA patients were similar to the global population., Conclusion: In Phase 3 and LTE studies in LA patients with RA, tofacitinib demonstrated efficacy up to 36 months with a manageable safety profile up to 60 months, consistent with the overall tofacitinib study population., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Objective: To evaluate the efficacy and safety of etanercept (ETN) after 48 weeks in patients with early active non-radiographic axial spondyloarthritis (nr-axSpA)., Methods: Patients meeting Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA, but not modified New York radiographic criteria, received double-blind ETN 50 mg/week or placebo (PBO) for 12 weeks, then open-label ETN (ETN/ETN or PBO/ETN). Clinical, health, productivity, MRI and safety outcomes were assessed and the 48-week data are presented here., Results: 208/225 patients (92%) entered the open-label phase at week 12 (ETN, n=102; PBO, n=106). The percentage of patients achieving ASAS40 increased from 33% to 52% between weeks 12 and 48 for ETN/ETN and from 15% to 53% for PBO/ETN (within-group p value <0.001 for both). For ETN/ETN and PBO/ETN, the EuroQol 5 Dimensions utility score improved by 0.14 and 0.08, respectively, between baseline and week 12 and by 0.23 and 0.22 between baseline and week 48. Between weeks 12 and 48, MRI Spondyloarthritis Research Consortium of Canada sacroiliac joint (SIJ) scores decreased by -1.1 for ETN/ETN and by -3.0 for PBO/ETN, p<0.001 for both. Decreases in MRI SIJ inflammation and C-reactive protein correlated with several clinical outcomes at weeks 12 and 48., Conclusions: Patients with early active nr-axSpA demonstrated improvement from week 12 in clinical, health, productivity and MRI outcomes that was sustained to 48 weeks., Trial Registration Number: NCT01258738., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objectives: To compare over 2 years the safety, efficacy and radiographic outcomes of subcutaneous abatacept versus adalimumab, in combination with methotrexate (MTX), in patients with rheumatoid arthritis (RA)., Methods: AMPLE is a phase IIIb, 2-year, randomised, investigator-blinded study with a 1-year primary endpoint. Biologic-naive patients with active RA and an inadequate response to MTX were randomised to 125 mg abatacept weekly or 40 mg adalimumab bi-weekly, both with a stable dose of MTX., Results: Of 646 patients randomised, 79.2% abatacept and 74.7% adalimumab patients completed year 2. At year 2, efficacy outcomes, including radiographic, remained comparable between groups and with year 1 results. The American College Rheumatology 20, 50 and 70 responses at year 2 were 59.7%, 44.7% and 31.1% for abatacept and 60.1%, 46.6% and 29.3% for adalimumab. There were similar rates of adverse events (AEs) and serious adverse events (SAEs). More serious infections occurred with adalimumab (3.8% vs 5.8%) including two cases of tuberculosis with adalimumab. There were fewer discontinuations due to AEs (3.8% vs 9.5%), SAEs (1.6% vs 4.9%) and serious infections (0/12 vs 9/19 patients) in the abatacept group. Injection site reactions (ISRs) occurred less frequently with abatacept (4.1% vs 10.4%)., Conclusions: Through 2 years of blinded treatment in this first head-to-head study between biologic disease-modifying antirheumatic drugs in RA patients with an inadequate response to MTX, subcutaneous abatacept and adalimumab were similarly efficacious based on clinical, functional and radiographic outcomes. Overall, AE frequency was similar in both groups but there were less discontinuations due to AEs, SAEs, serious infections and fewer local ISRs with abatacept.

Objectives: To assess patients' preferences for rheumatoid-arthritis treatments with biologic agents using a discrete-choice experiment., Methods: A discrete-choice experiment was conducted with adult rheumatoid-arthritis patients who had never been treated with biological agents from two university hospitals-public and private-in Buenos Aires, Argentina. We evaluated preferences for seven treatment attributes (with two to three levels each): effectiveness, mode of administration, frequency of administration, local and systemic adverse events, severe infections, and out-of-pocket costs.A probit regression model was used to analyze the relative importance of rheumatoid-arthritis treatment attributes. We estimated attributes' relative importance and their 95% confidence intervals., Results: Survey responses from 240 patients with rheumatoid arthritis receiving conventional disease-modifying antirheumatic drugs were included in the study. All tested biological agents' attributes significantly affected the choice of treatment. Attributes' relative importance in decreasing order was the following (mean, confidence interval 95%): cost, 0.81 (0.69-0.92); systemic adverse events, 0.66 (0.57-0.76); frequency of administration, 0.61 (0.52-0.71); efficacy, 0.42 (0.32-0.51); route of administration, 0.41 (0.30-0.52); local adverse events, 0.40 (0.31-0.49); and serious infections, 0.29 (0.22-0.37)., Conclusions: Different treatment attributes had a significant and different influence in rheumatoid-arthritis patients' choice of biological agents. This type of study can not only inform about patients' preferences but also about the trade-offs among different possible treatments or process-related attributes., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objective: There is a need for comparative studies to provide evidence-based treatment guidance for biologic agents in rheumatoid arthritis (RA). Therefore, this study was undertaken as the first head-to-head comparison of subcutaneous (SC) abatacept and SC adalimumab, both administered along with background methotrexate (MTX), for the treatment of RA., Methods: Patients with active RA who were naive to treatment with biologic agents and had an inadequate response to MTX were randomly assigned to receive 125 mg SC abatacept weekly or 40 mg SC adalimumab biweekly, both given in combination with MTX, in a 2-year study. The primary end point was treatment noninferiority, assessed according to the American College of Rheumatology 20% improvement response (ACR20) at 1 year., Results: Of the 646 patients who were randomized and treated, 86.2% receiving SC abatacept and 82% receiving SC adalimumab completed 12 months of treatment. At 1 year, 64.8% of patients in the SC abatacept group and 63.4% in the SC adalimumab group demonstrated an ACR20 response; the estimated difference between groups was 1.8% (95% confidence interval -5.6%, 9.2%), thus demonstrating the noninferiority of abatacept compared to adalimumab. All efficacy measures showed similar results and kinetics of response between treatments. The rate of radiographic nonprogression (defined as a total modified Sharp/van der Heijde score [SHS] less than or equal to the smallest detectable change) was 84.8% for SC abatacept-treated patients and 88.6% for SC adalimumab-treated patients, while the mean change from baseline in the total SHS was 0.58 and 0.38, respectively. In the SC abatacept and SC adalimumab groups, the incidence of serious adverse events (SAEs) was 10.1% and 9.1%, respectively, and the rate of serious infections was 2.2% and 2.7%, respectively. In patients treated with SC abatacept, the frequency of discontinuations due to AEs was 3.5% and discontinuations due to SAEs was 1.3%, while in patients treated with SC adalimumab, the frequencies were 6.1% and 3%, respectively. Injection site reactions occurred in 3.8% of patients receiving SC abatacept compared to 9.1% of patients receiving SC adalimumab (P=0.006)., Conclusion: The results demonstrate that SC abatacept and SC adalimumab have comparable efficacy in patients with RA, as shown by similar kinetics of response and comparable inhibition of radiographic progression over 1 year of treatment. The safety was generally similar, other than the occurrence of significantly more local injection site reactions in patients treated with SC adalimumab., (Copyright © 2013 by the American College of Rheumatology.)

Introduction: The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported outcome tool recommended for the assessment of disease activity in patients with rheumatoid arthritis (RA) in clinical practice. This analysis evaluated the long-term effect of upadacitinib vs. comparators on RAPID3 scores in patients with RA in the phase 3 SELECT clinical trial program. Methods: This post hoc analysis included data from five randomized controlled trials (RCTs) in patients receiving upadacitinib 15 mg or 30 mg once daily (QD) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The proportions of patients reporting RAPID3 remission (scores ≤ 3) were assessed at week 60. Correlations between absolute scores for RAPID3 and Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) at week 60 were assessed using Spearman correlation coefficients. Results: A total of 3117 patients were included from the SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE, and -EARLY trials. By week 60, 32–52% of methotrexate-naïve and csDMARD inadequate responder (IR) patients treated with either upadacitinib 15 mg QD or upadacitinib 30 mg QD reported RAPID3 scores consistent with remission. The proportions were slightly lower in the biologic DMARD-IR SELECT-BEYOND population (19–28%). RAPID3 scores highly correlated (Spearman correlation values ≥ 0.58) with CDAI, SDAI, and DAS28(CRP) scores through week 60 (all p < 0.001). Conclusions: Upadacitinib, as monotherapy or in combination with csDMARDs, was associated with patient-reported remission assessed by RAPID3 over 60 weeks across the SELECT RCTs in patients with RA. Trial registration: SELECT-BEYOND (NCT02706847); SELECT-NEXT (NCT02675426); SELECT-MONOTHERAPY (NCT02706951); SELECT-EARLY (NCT02706873); SELECT-COMPARE (NCT02629159). Plain Language Summary: Rheumatoid arthritis (RA) is a disease that causes inflammation of the joints. Doctors have several ways of assessing how bad a patient's disease is, and these often use a combination of signs and symptoms to develop a 'score'. One method is called RAPID3, which is a score based on an overall assessment of the disease by the patient, the level of pain, and the amount of physical disability. An advantage of RAPID3 is that it is quick and easy to use, and since it uses only patient-reported symptoms, it can be measured easily via telemedicine, without the need for an in-person consultation. In this study, we decided to look into the effect of upadacitinib, a drug used for the treatment of RA, on RAPID3 score in patients with RA. We also investigated whether RAPID3 correlates with other ways of measuring RA severity, including scores that use physician-measured factors such as number of affected joints, as this can help show whether RAPID3 is a valid and useful tool. We found that upadacitinib led to long-term improvements in RAPID3 score, and that results were the same in different studies and patient groups, including patients who had not responded well to other treatments. We also found that RAPID3 correlated well with other measures, i.e., improvements in RAPID3 happened in parallel with improvements in other scores. Overall, these results suggest that RAPID3 can be a useful tool in patients with RA. [ABSTRACT FROM AUTHOR]