Effectiveness of 2nd JAKi in UC

August 11, 2025

Issue 16

Clinical Question

Is JAK inhibitor intraclass switching effective and safe in ulcerative colitis?

Editor’s Bottom Line

Failure of one JAK inhibitor does not preclude response to a second JAK inhibitor in patients with ulcerative colitis.

Reference

Osty M, Altwegg R, Serrero M, et al. Effectiveness and Safety of a Second JAK Inhibitor in Ulcerative Colitis: The J2J Multicentre Study. Aliment Pharmacol Ther. Epub ahead of print May 22, 2025. https://onlinelibrary.wiley.com

Synopsis

The multi-centre retrospective GETAID-coordinated J2J study evaluated the effectiveness and safety of a second JAK inhibitor (JAK) in patients with moderate-to-severe ulcerative colitis (UC) who had failed or were intolerant to a first JAK inhibitor (JAKi). The study included 169 UC patients from 28 Belgian and French centres who received a second-line JAKi between July 2019 and December 2024.

Among the cohort, 105 patients received upadacitinib, 54 received filgotinib and 10 received tofacitinib as second-line therapy. The majority (67.5%) had received tofacitinib as their first JAK inhibitor, while 27.2% had received filgotinib and 5.3% had received upadacitinib. Discontinuation of the first JAK inhibitor occurred due to loss of response in 57% of patients and primary failure in 39%.

The primary outcome was steroid-free clinical remission (SFCR) at weeks 8–14, defined as a partial Mayo score ≤2 with no individual sub-score >1.

During a median follow-up of 96 days, 47.9% met the primary outcome. When stratified by second-line agent, SFCR was achieved by 55.2% of second-line upadacitinib recipients, 33.3% of filgotinib patients and 50% of those who received tofacitinib as second-line JAK inhibitor. The difference in SFCR rates between upadacitinib and filgotinib patients was statistically significant (p=0.0088).

Multivariate analysis confirmed this, showing upadacitinib was independently associated with three-fold higher odds of SFCR, compared to filgotinib (Odds Ratio [OR]: 3.15; 95% Confidence Interval [CI], 1.52–6.79). Factors independently associated with poorer outcomes included steroid use at baseline (OR: 0.24; 95% CI, 0.10–0.54) and ileorectal anastomosis (OR: 0.10; 95% CI, 0.01–0.69).

Drug persistence at six months was 72.8% with upadacitinib, 57.2% with filgotinib, and 66.7% with tofacitinib. Thirty-one percent of patients discontinued treatment, with equal numbers stopping due to primary failure (40.4%) and secondary failure (40.4%).

Safety results showed 24.3% of patients experienced at least one adverse event, with the most common adverse events including infections (7.7%) and dermatological lesions (8.3%), with acne being particularly frequent in the upadacitinib group (7.6%). Nine patients (5%) required treatment discontinuation due to adverse events. Two cases of ophthalmic herpes zoster occurred in the upadacitinib group but did not lead to permanent withdrawal. There were no deaths, malignancies or major cardiovascular events reported during the study period.

Details

Study Design: Retrospective observational cohort
Funding: No funding
Allocation: Not applicable
Setting: Multicenter
Level of Evidence: 2b