Clin Rheumatol. 2026 Jun 4. doi: 10.1007/s10067-026-08175-y. Online ahead of print.
ABSTRACT
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.
PMID:42240789 | DOI:10.1007/s10067-026-08175-y