Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the ‘JAK-pot’ study)


In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept.

The authors of this article, led by Dr Kim Lauper at the Rheumatology Division of the Geneva University Hospitals (HUG), compared treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population.

Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the ‘JAK-pot’ collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. The authors used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi.

Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97).

While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

Full article:

Aymon R, Mongin D, Bergstra SA, et al. Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the ‘JAK-pot’ study). Annals of the Rheumatic Diseases Published Online First: 08 December 2023. doi: 10.1136/ard-2023-224670

Why is it important?

Rheumatoid arthritis (RA) is a long-lasting autoimmune disease that triggers joint inflammation and causes joint pain, stiffness and joint deformities. Treatment of RA focuses on reducing inflammation, preserving joint function and improving quality of life. This study aimed to analyse and compare the safety and tolerability of second-line treatments used in RA: JAK inhibitors (JAKi). The study, which involved 17 registries and more than 46,000 treatments, found that there was no overall increase in treatment discontinuation due to adverse events with JAKi. Tofacitinib (JAKi) had a higher discontinuation rate, especially in patients aged 65 years and older, suggesting variable safety profiles among JAK inhibitors and for higher-risk patients. Further research is needed, but these findings can already inform clinical decision-making and policy guidelines for second-line treatment in RA, drawing attention to the importance of individual patient characteristics, including age and cardiovascular risk factors, when considering treatment with JAKi.

26 Jan 2024