Filgotinib in Moderate-to-Severe Crohn’s Disease: A Network Meta-Analysis of Efficacy and Adverse Events

<b>Background:</b> Filgotinib is an emerging Janus kinase 1 (JAK1) inhibitor being investigated for inflammatory bowel disease. This systematic review and network meta-analysis (NMA) evaluated the efficacy and safety of filgotinib in adult patients with moderate-to-severe crohn's disease. <b>Methods:</b> We systematically searched PubMed, EMBASE, and Scopus through April 2025. Randomized controlled trials evaluating filgotinib versus placebo in adults with moderate-to-severe Crohn's disease were included. Primary outcomes were clinical remission and endoscopic response. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool. A network meta-analysis was performed to integrate direct and indirect evidence, reporting risk ratios (RRs) with 95% confidence intervals (CIs). <b>Results:</b> Five randomized controlled trials (from 4 publications) met the inclusion criteria. Filgotinib 200 mg significantly improved clinical remission compared with placebo (RR: 1.75 [1.40-2.19]) and 100 mg (RR: 1.38 [1.11-1.71]), while 100 mg showed no significant difference versus placebo (RR: 1.27 [0.99-1.63]). For endoscopic response, both 200 mg (RR: 1.72 [1.09-2.69]) and 100 mg (RR: 1.65 [1.02-2.69]) demonstrated significant benefit over placebo, though no difference was observed between active doses (RR: 1.04 [0.64-1.68]; I² = 57%). In the two-item patient-reported outcome, 200 mg showed significant improvement versus placebo (RR: 1.47 [1.20-1.80]) and 100 mg (RR: 1.26 [1.02-1.55]), while 100 mg remained insignificant versus placebo (RR: 1.17 [0.93-1.46]). Neither dose increased the risk of treatment-emergent adverse events, serious adverse events, or infections compared with placebo, with consistent homogeneity across analyses. <b>Conclusions:</b> Filgotinib 200 mg demonstrated superior efficacy across clinical, endoscopic, and patient-reported outcomes compared with 100 mg and placebo, with a favorable safety profile. The 100 mg dose showed limited efficacy and no advantage over placebo. Filgotinib represents a promising oral therapeutic option, particularly for biologic-naïve patients and in maintenance therapy, while also showing potential benefit in perianal fistulising crohn's disease. Future trials should explore long-term safety and head-to-head comparisons with established biologics.