TOPLINE:

In adults with rheumatoid arthritis (RA) starting their first JAK inhibitor, treatment was effective and had an acceptable long-term persistence in routine practice. Fewer serious adverse events were reported after following the October 2022 Pharmacovigilance Risk Assessment Committee (PRAC) recommendations to restrict use in higher‑risk patients.

METHODOLOGY:

• Researchers conducted a retrospective observational cohort study to evaluate the real-world effectiveness, treatment maintenance, and safety of four JAK inhibitors in patients with RA and to assess how prescribing patterns changed after PRAC recommendations.
• They included 120 adults with RA (mean age, 57 years; 85% women; mean disease duration, 19 years) who started their first JAK inhibitor at a French tertiary centre between April 2018 and November 2023 and were followed up through October 2025.
• Participants received one of four JAK inhibitors: tofacitinib, baricitinib, upadacitinib, or filgotinib, selected by their treating rheumatologist.
• The primary outcome was treatment maintenance assessed at 12, 24, and 36 months, and reasons for discontinuations were identified. Secondary outcomes included changes in the disease activity score in 28 joints (DAS28), DAS28 using C-reactive protein (DAS28‑CRP), and other patient‑reported measures at 6 and 12 months.
• Researchers also compared outcomes before and after October 2022 PRAC safety recommendation guidance.

TAKEAWAY:

• JAK inhibitors showed drug survival rates of 73% at 12 months, 62% at 24 months, and 57% at 36 months, with a median survival of 47 months. Baricitinib demonstrated the highest long-term maintenance (median survival, 48 months), and filgotinib achieved the highest 12-month survival (92%).
• All four JAK inhibitors were associated with improved disease activity, with mean DAS28-CRP reductions of 1.57 points at 6 months and 1.13 points at 12 months (P < .001 for both). Most drugs were linked to improvements in DAS28, joint counts, pain, fatigue, and patient global assessment.
• A total of 49 patients (41%) discontinued treatment — 57% because of inefficacy and 35% because of intolerance. Discontinuation rates were lower after PRAC implementation than before it (17% vs 48%).
• No major cardiovascular events, venous thromboembolism, or new malignancies were reported after PRAC implementation, whereas three pulmonary embolisms and one myocardial infarction occurred before PRAC implementation in patients with risk factors.

IN PRACTICE:

"High-risk cardiovascular and thromboembolic events occurred exclusively in older and comorbid patients treated before PRAC restrictions, supporting an individualized approach to JAKi [JAK inhibitor] selection integrating inflammatory severity, age and cardiovascular risk profile," the authors wrote.

SOURCE:

This study was led by Salomé Abdellaoui, Hôpital Cochin, AP-HP Centre Université Paris Cité, Paris, France. It was published online on June 04, 2026, in Clinical Rheumatology.

LIMITATIONS:

The retrospective single-centre design may have limited the generalisability of the findings. The shorter follow-up period for filgotinib limited long-term comparisons across JAK inhibitors. Adverse events were recorded only when they led to treatment discontinuation.

DISCLOSURES:

This study did not receive any funding.One author disclosed receiving honoraria and research grants from multiple pharmaceutical and biopharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.