Real-world assessment of the efficacy and tolerability profile of JAK inhibitors in difficult-to-treat rheumatoid arthritis

Objective: To evaluate the effectiveness and tolerability of JAK inhibitors (JAKi) in patients with difficult-to-treat rheumatoid arthritis (D2TRA) in clinical practice. Methods: We included RA patients initiating a JAKi between 2018 and 2022. Patients meeting EULAR criteria for D2TRA were compared to active non-D2TRA patients. Efficacy was evaluated at the first visit (FV) (6 months following JAKi initiation) and the last available visit (LV) up to December 2022. Results: 45 patients with D2TRA, all presenting signs of disease activity (imaging, CRP levels), were compared to 29 active non-D2TRA. DAS28 and DAS28-CRP reduction from baseline to FV was significant and similar between both groups, before and after adjusting for several factors including the number and exposure duration to previous targeted therapies. DAS28 and DAS28-CRP remained stable in both groups between FV and LV. The proportion of responders and patients achieving remission or low disease activity at FV and LV was similar in both groups. Thirty-five patients (42 %) discontinued JAKi over a mean observation period of 20 +/- 10 months, with no significant difference in discontinuation rates between groups (p = 0.36). Discontinuations due to inefficacy and side effects were evenly distributed. Frequency of infections, herpes zoster, myocardial infarctions, and venous thromboembolism was similar between groups, with a higher likelihood in patients aged >= 65 years and/or with at least one cardiovascular risk factor (30/39, 77 %). Conclusion: JAKi effectively reduced disease activity in D2TRA patients with the same extent as active nonD2TRA patients. Tolerability profiles were comparable, with outcomes largely dependent on the presence of age and/or cardiovascular risk factors. Haut du formulaire.