ABSTRACT 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.
Qtaishat et al. (Sun,) studied this question.