Dose-dependent efficacy and safety of Filgotinib in moderate to severe Crohn's disease: a grade-assessed systematic review and meta-analysis of randomized controlled trials.

Background: Crohn's disease is a chronic inflammatory condition that can relapse and can impact any part of the digestive tract. Janus kinase (JAK) inhibitors, like Filgotinib, have surfaced as a promising treatment option. This meta-analysis evaluates its dose-dependent effects (100 mg or 200 mg) in moderate-to-severe cases.

Methods: A comprehensive search was conducted in PubMed, CENTRAL, Web of Science, Scopus, and EMBASE up to March 2025. Risk ratio (RR) was used for dichotomous outcomes, with 95% confidence intervals (CI).

Prospero id: CRD420251032985.

Results: Four RCTs with 1681 patients were included. Filgotinib 200 mg compared to placebo had a higher rate of mucosal remission at 24 to 58 weeks (wk) (14.9% vs 6%, RR = 2.51, 95% CI [1.06:5.95], P = 0.0370), two-item patient'sreported outcome (PRO2) clinical remission at 10 wk (35.7% vs 22.5%, RR = 1.48, 95% CI [1.21:1.81], P = 0.0002), and Crohn's Disease Activity Index (CDAI) clinical remission at 10 wk (33.4% vs 17.8%, RR = 1.77, 95% CI [1.42:2.21], P < 0.0001). However, there was no significant difference between Filgotinib 100 mg and placebo in rates of CDAI clinical remission at 10 wk (P = 0.7490) and mucosal remission at 24 to 58 wk (P = 0.5850). In both doses, there was no significant difference in total treatment adverse events (TEAEs) at 20 to 58 wk (P = 0.4576, P = 0.2354) and serious TEAEs at 20 to 58 wk (P = 0.992, P = 0.2354).

Conclusions: Filgotinib 200 mg demonstrated superior short-term clinical benefits and medium-term mucosal remission compared to placebo in moderate-to-severe CD. However, Filgotinib 100 mg showed no significant efficacy. Both doses have acceptable safety profiles, necessitating further long-term multicenter RCTs.