Real-world efficacy and safety profile of four JAK inhibitors in rheumatoid arthritis: a French single-center observational study.

OBJECTIVE

To evaluate real-world treatment maintenance, effectiveness, and safety of Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA), and to assess changes in prescribing patterns following the October 2022 PRAC recommendations.

METHODS

This retrospective single-center study included all consecutive RA patients initiating a first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) between April 2018 and November 2023. The primary endpoint was treatment maintenance (Kaplan-Meier). Secondary outcomes included changes in DAS28-CRP and DAS28 at 6 and 12 months and reasons for treatment discontinuation. Patients initiating JAKi before versus after PRAC were compared.

RESULTS

Among 120 patients (85% women, mean age 57 ± 14 years, mean disease duration 19 ± 12 years, mean follow-up of 21 ± 16 months), overall treatment maintenance was 73% at 12 months, 62% at 24 months, and 57% at 36 months. Baricitinib showed the highest long-term persistence, whereas filgotinib demonstrated excellent 12-month survival in younger, low-risk patients. All JAKi significantly improved disease activity, with reductions in DAS28-CRP of -1.57 ± 1.26 at 6 months and -1.13 ± 1.63 at 12 months. Forty-nine discontinuations occurred (57% inefficacy, 35% intolerance) after a mean follow-up of 15 ± 15 months. Serious adverse events included three pulmonary embolisms and one myocardial infarction, all in high-risk patients before PRAC. No major cardiovascular events, venous thromboembolism, or malignancies occurred after PRAC recommendations.

CONCLUSION

JAKi demonstrated effectiveness and acceptable long-term persistence. Safety outcomes were strongly influenced by baseline cardiovascular risk, underscoring the need for careful patient selection following PRAC guidance. Key Points • In routine care, all four JAK inhibitors demonstrated clinically meaningful effectiveness despite long-standing, severe and comorbid rheumatoid arthritis. • Treatment persistence differed across JAK inhibitors, but observed differences were largely driven by patient profiles and prescribing context rather than clear drug-related effects. • Implementation of PRAC recommendations in October 2022 markedly modified patient selection, with exclusion of high cardiovascular and thromboembolic risk profiles. • Serious cardiovascular and thromboembolic events occurred exclusively in high-risk patients treated before PRAC recommendations.