Switch to a Second JAK Inhibitor Helpful in UC

TOPLINE:

Switching to a second-line Janus kinase (JAK) inhibitor resulted in steroid-free clinical remission in about half of the patients with active ulcerative colitis (UC) after induction; compared with filgotinib, upadacitinib as a second JAK inhibitor was independently associated with the improved outcome.

METHODOLOGY:

• Researchers conducted a retrospective observational cohort study across 28 Belgian and French centres to evaluate the effectiveness and safety of a second JAK inhibitor in patients with UC.
• They included 169 patients (median age, 34.6 years; 38% women) with active moderate to severe UC, defined as a partial Mayo score ≥ 3, between July 2019 and December 2024.
• These patients had experienced either failure or intolerance to a first JAK inhibitor (tofacitinib, filgotinib, or upadacitinib) and were treated with a second JAK inhibitor from one among the three.
• The primary outcome was steroid-free clinical remission, defined as a partial Mayo score ≤ 2 with no individual subscore above 1, after 8-14 weeks of initiating the second JAK inhibitor. The median follow-up duration was 96 days.
• Adverse events were assessed, with severe adverse events defined as events requiring hospitalisation and/or discontinuation of treatment.

TAKEAWAY:

• As a second-line treatment, 105 patients received upadacitinib, 54 received filgotinib, and 10 received tofacitinib. Treatment persistence at 6 months was estimated at 72.8% for upadacitinib, 57.2% for filgotinib, and 66.7% for tofacitinib.
• At weeks 8-14, steroid-free clinical remission was achieved in 47.9% of patients. Upadacitinib was independently associated with higher odds of steroid-free clinical remission than filgotinib (adjusted odds ratio [aOR], 3.15; 95% CI, 1.52-6.79), with no significant difference observed between filgotinib and tofacitinib.
• Factors independently associated with steroid-free clinical remission included usage of steroids at baseline (aOR, 0.24; P < .001) and ileorectal anastomosis (aOR, 0.10; P = .017).
• Adverse events occurred in 24.3% of patients, with infections and dermatologic lesions being the most common. Nine patients experienced severe adverse events; no cases of death, cancer, or major acute cardiovascular events were reported.

IN PRACTICE:

“Here we report the largest experience to date of intraclass switching of JAKi [JAK inhibitor]. We show that 47.9% of patients present a SFCR [steroid-free clinical remission] after the induction period,” the authors wrote.

SOURCE:

This study was led by Mathilde Osty, Gastroenterology Department, Hôpital Henri Mondor, APHP, Créteil, France. It was published online on May 22, 2025, in Alimentary Pharmacology & Therapeutics.

LIMITATIONS:

The sample size was small to analyse each specific sequence of the use of JAK inhibitors. The retrospective observational nature of this study resulted in the lack of information on faecal calprotectin and endoscopic outcomes, and data on long-term follow-up were also lacking.

DISCLOSURES:

This study did not receive any specific funding. Several authors reported counselling, boards, or fees and receiving lecture fees and/or consulting fees and grants from various companies, including AbbVie, Biogen, and Lilly.

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