Safety and efficacy of different JAK inhibitors in the treatment of inflammatory bowel disease: a network meta-analysis

Targeting the Janus kinase (JAK) signaling pathway is a new way to treat inflammatory bowel disease (IBD). This network meta-analysis aimed to compare the efficacy and safety of various JAK inhibitors, including brepocitinib, filgotinib, ivarmacitinib, peficitinib, ritlecitinib, tofacitinib, and upadacitinib, in patients with IBD. The analysis included patients with both Crohn's disease (CD) and ulcerative colitis (UC). We systematically searched PubMed, Embase, the Cochrane Library, and the Web of Science for randomized controlled trials evaluating JAK inhibitors in patients with CD or UC up to 4 May 2024. A pooled analysis of UC and CD was performed. The primary outcome was clinical remission. Secondary outcomes included clinical response, endoscopic remission, endoscopic response, endoscopic improvement, adverse events (AEs), serious adverse events (SAEs), AEs leading to treatment discontinuation, and infections. Ranking was assessed using the surface under the cumulative ranking curve (SUCRA) probabilities. Ritlecitinib exhibited the highest SUCRA probabilities for clinical remission (88.7%), clinical response (86.0%), and endoscopic improvement (92.1%). Upadacitinib exhibited superiority in endoscopic remission (85.6%) and response (99.5%), demonstrating moderate efficacy in clinical response (82.2%). A safety analysis revealed comparable AE rates for most agents compared to placebo, except for upadacitinib and brepocitinib. Tofacitinib showed the lowest risk of SAEs (72.3%). Upadacitinib had the lowest discontinuation rate (81.3%). Ivarmacitinib demonstrated optimal infection safety (80.3%). Upadacitinib has the best efficacy-safety profile for IBD, while ritlecitinib's superior efficacy is offset by higher safety risks. Long-term studies are needed to confirm these results. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024595343, Identifier CRD42024595343.