S2025 Comparative Efficacy and Tolerability of Janus Kinas Inhibitors for Moderate to Severe Crohn’s Disease—A Systematic Review and Bayesian Network Meta-Analysis

Introduction: Crohn’s disease, a chronic Inflammatory bowel disease, has limited treatments with variable efficacy and side effects. Janus kinase (JAK) inhibitors offer promise by targeting inflammatory cytokine pathways. This network meta-analysis systematically evaluates their comparative efficacy and safety in moderate-to-severe Crohn’s, incorporating the latest randomised clinical trials evidence. Methods: We conducted a thorough search on PubMed, Cochrane, Embase, Scopus and ClinicalTrials.gov. Screening used Rayyan with data extracted to Excel. Analyses was done on R 4.4.3 software, including Bayesian network meta-analysis with pooled mean differences and hazard ratios with a 95% confidence interval via random/fixed-effects models based on deviance information criteria (DIC). Surface under the cumulative ranking curve (SURCA) values ranked interventions for clinical/endoscopic remission, response, and safety outcomes. Results: A total of 12 RCTs with 25 interventions were included involving 5,129 patients. Upadacitinib 45 mg once daily OD showed significant efficacy in achieving clinical remission compared to placebo (HR: 2.47; 95% CrI: 1.51–4.10), supported by the highest SUCRA value of 0.79 and a significant MD (MD: 0.907; CrI: 0.410–1.41). For endoscopic remission, Upada 45 mg OD was also superior to placebo (HR: 5.89; CrI: 2.79–13.86), though Upada 24 mg QD had a higher SUCRA value (0.87 vs 0.38). Upada 24 mg QD showed the most favorable trend in clinical response (HR: 2.18; CrI: 0.93–5.22; SUCRA: 0.74) while Upada 45 mg OD had lower effectiveness (HR: 1.25; CrI: 0.82–1.90; SUCRA: 0.30). In endoscopic response, Upada 24 mg QD ranked highest (HR: 17.89; CrI: 2.66–340.59; SUCRA: 0.85), followed by Upada 45 mg OD (HR: 6.56; CrI: 3.14–15.07; SUCRA: 0.56). Filgotinib 200 mg OD showed the best safety for total adverse events (HR: 0.93; CrI: 0.78–1.10; SUCRA: 0.74), while Upada 45 mg OD had the lowest SUCRA (0.13). For serious AE, Upada 45 mg OD had an HR of 1.08 (CrI: 0.92–1.28) but the highest SUCRA (0.71). In GI perforation, Filgotinib 200 mg OD had HR of 0.95 (CrI: 0.18–4.65; SUCRA: 0.63) compared to Upada 45 mg OD (HR: 1.40; CrI: 0.04–106.14; SUCRA: 0.46). Conclusion: Upada 45 mg OD demonstrated superior efficacy, particularly for remission outcomes, while 24 mg QD showed favorable clinical/endoscopic remission trends. Filgotinib 200 mg OD exhibited the best safety profile with fewer adverse events.