Real-world evidence on JAK inhibitors in rheumatology practice: comparative safety, efficacy, and outcomes between JAK inhibitors.

OBJECTIVES

Janus kinase inhibitors (JAKinibs) are increasingly used in rheumatic diseases, yet comparative real-world data on retention, safety, and prescribing patterns remain limited. We evaluated drug survival, adverse events, and discontinuation for three JAKinibs.

METHODS

This retrospective, three-arm comparative cohort included patients with rheumatic diseases who received ≥ 1 JAKinib between May 2020 and July 2025.

RESULTS

We included 185 patients(median age 44 years, 67.0% female) with seropositive RA (n = 87), seronegative RA (n = 36), ankylosing spondylitis (n = 39), psoriatic arthritis(n = 17), and others(n = 6). Tofacitinib was prescribed in 94 patients(50.8%), baricitinib in 45 (24.3%), and upadacitinib in 69 (37.3%). Most (89.7%) received one JAKinib. Tofacitinib, baricitinib, and upadacitinib were initiated as first JAKinib in 95.7%, 86.7%, and 81.2% of cases, respectively(p = 0.012). At last follow-up, 58.9% remained on any JAKinib. Six-month survival was 81.9% for tofacitinib, 77.8% for baricitinib, and 69.6% for upadacitinib(p = 0.049); median survival was 16.5, 17, and 11 months, respectively (p < 0.001). Secondary non-response was the leading cause of discontinuation, with adverse events accounting for less than 10%.

CONCLUSION

JAKinibs showed favourable retention and safety. Treatment sequencing and early access influenced persistence; tofacitinib predominated due to early availability and prior use in biologic-naive patients, while upadacitinib was mainly prescribed after advanced therapy failure yet remained effective in refractory cases. Key Points • JAKinibs remain effective and tolerable across a range of inflammatory rheumatic diseases,regardless of prior biologic exposure or treatment line. • Upadacitinib, although often prescribed after failure of multiple advanced therapies andother JAKinibs, showed high continuation and retention rates, highlighting its role as a viablelate-line option. • Secondary unresponsiveness is the primary barrier to long-term JAKinib persistence,suggesting a need for early recognition and individualized treatment.