Shaping rheumatoid arthritis treatment: Clinical and demographic drivers of tsDMARDs versus bDMARDs prescription post-EMA pronouncement on JAK inhibitors. Insights from the AMBI-RA study

Objectives: To evaluate the clinical-demographic drivers of treatment choice among targeted synthetic (ts-) and biologic (b-) disease-modifying anti-rheumatic drugs (DMARDs) and therapeutic outcomes in a cohort of patients with rheumatoid arthritis (RA) before and after the European Medicines Agency (EMA) pronouncement on Janus Kinase Inhibitors (JAKis) in January 2023. Methods: This single-center, ambidirectional study enrolled patients with RA who were initiating a new course of b/tsDMARDs. Retrospective (2019-2022) and prospective cohorts (2023-2024) were compared, and disease activity and treatment response (achievement of remission or low disease activity) were evaluated at 3 and 6-month follow-up. Results: The study analyzed 539 treatment courses (300 retrospective, 239 prospective) in 380 patients. Following the EMA guidelines, tumor necrosis factor-α inhibitors (TNFis) became the predominant bDMARD (from 32% to 41.4%), whilst JAKis prescriptions declined, particularly in the first-line settings (from 18% to 4.1%). The risk factors proposed by the EMA did not significantly prevent treatment with JAKis. However, we observed that a benefit associated with the first-line treatment in terms of target achievement (adjusted OR for non-response retrospective cohort 0.30, 95%CI 0.14-0.62) was mitigated in the prospective phase (OR 0.82, 95%CI 0.33-2.07). Conclusion: The 2023 EMA pronouncement on JAKis led to a shift in prescription patterns, promoting TNFis versus JAKis. The decline in JAKis prescription did not appear to be driven by EMA-identified baseline risk factors, suggesting a generalized, categorical change. This channeling may have compromised the appropriateness of treatment choices, diminishing effectiveness in the prospective cohort, particularly for first-line therapies.