BACKGROUND: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. METHODS: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. RESULTS: We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. CONCLUSION: The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.

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

BioReg Vienna Austria

Centre for Epidemiology versus Arthritis Centre for Musculoskeletal Research Faculty of Biology Medicine and Health University of Manchester Manchester Academic Health Science Centre Manchester UK

Charité University Medicine Berlin Germany

DANBIO Glostrup Denmark

Department of Development and Regeneration KU Leuven Leuven Belgium

Department of Rheumatology biorx si University Medical Centre Ljubljana Slovenia

Department of Rheumatology Sackler Faculty of Medicine Tel Aviv University Sourasky Medical Center Tel Aviv Israel

Departments of Clinical Medicine and Rheumatology Aarhus University and Aarhus University Hospital Aalborg Denmark

Departments of Medicine and Rheumatology ROB FIN Helsinki University Hospital and Helsinki University Helsinki Finland

Division of Rheumatology and Research Diakonhjemmet Hospital Oslo Norway

Division of Rheumatology Department of Internal Medicine and Department of Medicine Faculty of Medicine Geneva University Hospitals Geneva Switzerland

Division of Rheumatology Department of Internal Medicine and Department of Medicine Faculty of Medicine Geneva University Hospitals Geneve Switzerland

Division of Rheumatology KU Leuven University Hospitals Leuven Belgium

Division of Rheumatology School of Medicine Marmara University Istanbul Turkey

Epidemiology Unit German Rheumatism Research Center Berlin Germany

Faculty of Medicine University of Ljubljana Ljubljana Slovenia

GISEA DETO Rheumatology Unit University of Bari Bari Italy

Institut de recherche en rhumatologie de Montréal Montreal Quebec Canada

NIHR Manchester Biomedical Research Centre Manchester University NHS Foundation Trust Manchester Academic Health Science Centre Manchester UK

Private Office Hollabrunn Austria

Rheumatology Department Charles University Prag Czech Republic

Rheumatology Department Hospital Garcia de Orta on behalf of Reuma pt Almada Portugal

Rheumatology Leiden University Medical Center Leiden The Netherlands

Rheumatology Service Hospital Clinico Universitario Santiago de Compostela Spain

Rheumatology University of Medicine and Pharmacy Center of Rheumatic Diseases Bucharest Romania

Ann Rheum Dis. 2024 Jan 2;83(1):e1. doi: 10.1136/ard-2022-222586corr1. PubMed

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Does Concomitant Use of Methotrexate with JAK Inhibition Confer Benefit for Cardiovascular Outcomes? A Commentary

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study)