BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

5 A Nasonova Research Institute of Rheumatology A S Loginov Moscow Clinical Scientific Center Moscow Russian Federation

Austrian registry for Biologics Biosimilars und targeted synthetic DMARDs in the treatment of rheumatic diseases BioReg Vienna Austria

Biostatistics and Medical Informatics Research Group Department of Public Health Vrije Universiteit Brussel Brussel Belgium

Center for Rheumatic Diseases University of Bucharest Bucuresti Romania

Center for treatment of Rheumatic and Musculoskeletal Diseases Diakonhjemmet Hospital Oslo Norway

Centre for Epidemiology Versus Arthritis The University of Manchester Manchester UK

Department of Rheumatology and University of Ljubljana Faculty of Medicine University Medical Centre Ljubljana Ljubljana Ljubljana Slovenia

DiMePRe J Rheumatology Unit University of Bari Bari Puglia Italy

Division of Medicine ROB FIN Helsinki University and Helsinki University Hospital Helsinki Finland

Division of Rheumatology Firat University Faculty of Medicine Elazig Turkey

Division of Rheumatology Geneva University Hospitals Geneve Switzerland

Institut de recherche en Rhumatologie CHUM Montreal Quebec Canada

Manchester University NHS Foundation Trust NIHR Manchester Biomedical Research Centre Manchester UK

Programme Area Epidemiology DRFZ Berlin Germany

Rheumatology DANBIO Aalborg University Hospital Aalborg North Denmark Region Denmark

Rheumatology Division Geneva University Hospitals Geneve Switzerland

Rheumatology Hospital Clinico Universitario Santiago de Compostela Spain

Rheumatology Institute of Rheumatology Praha Czech Republic

Rheumatology Leiden University Medical Center Leiden The Netherlands

Rheumatology Marmara University School of Medicine Istanbul Turkey

Rheumatology Research Unit Instituto de Medicina Molecular Faculdade de Medicina de Lisboa Lisbon Portugal

Rheumatology Tel Aviv University Tel Aviv Israel

Skeletal Biology and Engineering research Center KU Leuven Leuven Flanders Belgium

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$a Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study) / $c R. Aymon, D. Mongin, SA. Bergstra, D. Choquette, C. Codreanu, D. De Cock, L. Dreyer, O. Elkayam, D. Huschek, KL. Hyrich, F. Iannone, N. Inanc, L. Kearsley-Fleet, SS. Koca, TK. Kvien, BF. Leeb, G. Lukina, DC. Nordström, K. Pavelka, M. Pombo-Suarez, A. Rodrigues, Z. Rotar, A. Strangfeld, P. Verschueren, R. Westermann, J. Zavada, DS. Courvoisier, A. Finckh, K. Lauper

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$a BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

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