Effectiveness and Safety of Janus Kinase Inhibitors in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Real-world Studies

BACKGROUND: Janus kinase (JAK) inhibitors (JAKis) are increasingly used to treat inflammatory bowel disease (IBD), but most pivotal data come from randomized controlled trials. Real-world evidence is needed to clarify their effectiveness and safety in routine clinical practice. SUMMARY: We conducted a systematic review and meta-analysis of real-world studies reporting outcomes in IBD patients treated with JAKis (tofacitinib, upadacitinib, or filgotinib). PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to August 11, 2025. Primary outcomes were clinical response and clinical remission; secondary outcomes included steroid-free clinical remission, endoscopic and biochemical responses, and safety outcomes. 63 studies involving 8130 IBD patients were included. In ulcerative colitis (UC), pooled clinical response and remission rates were 55% and 43% for tofacitinib, 77% and 65% for upadacitinib, and 69% and 55% for filgotinib; steroid-free remission with tofacitinib approached 50% at 1 year. In Crohn's disease (CD), upadacitinib achieved clinical response and remission in around two thirds of patients. Across agents, safety profiles were acceptable: mortality was 0%; hospitalization and treatment discontinuation rates were 8% and 28% for tofacitinib, 5% and 12% for upadacitinib, and 4% and 15% for filgotinib; serious adverse events occurred in ≤8% of patients. KEY MESSAGES: Descriptive real-world data show that tofacitinib, upadacitinib, and filgotinib all provide clinically meaningful effectiveness in UC and CD, complementing evidence from randomized trials. Across real-world cohorts, JAKis have generally acceptable safety profiles, with low rates of serious adverse events and no observed drug-related mortality.