JAK Inhibitors for Crohn's Disease: A Systematic Review and Dose-Response Network Meta-Analysis of Efficacy and...

Crohn's disease has limited effective treatments, and direct comparative data for Janus kinase (JAK) inhibitors are scarce. We conducted a dose-dependent network meta-analysis of randomized controlled trials in adults, searching PubMed, Cochrane Library, Scopus, and Web of Science through February 17, 2025. A Bayesian dose-response model (Emax) was implemented with the MBNMA package in R, estimating risk ratios (RRs) with 95% credible intervals, and risk of bias was assessed with RoB 2. Nine trials (n = 4838) evaluated upadacitinib, tofacitinib, and filgotinib across multiple doses. Upadacitinib 45 mg once daily achieved the greatest improvement in CDAI remission versus placebo (RR 1.8, 95% CrI 1.1-3.0). SUCRA rankings placed upadacitinib highest for overall clinical remission, CDAI mean change, and CDAI remission. Meta-regression showed higher doses were associated with higher remission rates (p = 0.041). Dose-response parameters indicated upadacitinib had a higher Emax and lower ED50 than comparators, suggesting greater efficacy and potency. Serious adverse events were more frequent with JAK inhibitors versus placebo (RR 1.61, 95% CI 1.15-2.25; p = 0.0082), with increases in sepsis, cardiovascular events, and elevated liver enzymes (p < 0.05). Adverse event risk differed by agent (p = 0.0008); upadacitinib increased overall adverse events versus placebo (RR 1.19, 95% CI 1.07-1.33) and serious infections (RR 5.39, 95% CI 2.98-9.74). JAK inhibitors improve clinical outcomes in Crohn's disease, with upadacitinib showing the most consistent efficacy, but safety risks warrant careful monitoring and head-to-head, long-term studies.