Comparative Efficacy of Different Targeted Therapies in Patients With Moderate-to-Severe Ulcerative Colitis: Systematic Review/Network Meta-Analysis and Mechanistic Overview.

Ongoing evaluations of targeted therapies for moderate-to-severe ulcerative colitis (UC) continue to unfold, with the emergence of novel drugs. However, head-to-head trials comparing these therapies are still lacking. The aim of this study is to investigate the therapeutic effects of targeted therapies in moderate-to-severe UC. The Cochrane Library, Web of Science, PubMed, and Embase were searched from the inception to November 12, 2024. Statistical analyses included multivariate random effects models and Bayesian modeling. Stratified and sensitivity analyses were also performed. Publication bias was assessed using funnel plots. Outcomes such as clinical response/remission, endoscopic remission, mucosal healing, quality of life, adverse events (AEs), and serious adverse events (SAEs) were used to quantify the relative therapeutic effects. Thirty-three studies (33 reported on the induction phase; 13 reported on the maintenance phase) were identified. In the induction phase, Upadacitinib 45 mg demonstrated the highest efficacy in achieving clinical remission (OR 10.03; 95% CI, 4.83-20.80), clinical response (OR 7.96; 95% CI, 3.89-16.28), and mucosal healing rate (OR 8.91; 95% CI, 3.36-23.62). Cobitolimod 250 mg was the first-ranked treatment (SUCRA, 92.67%) in Endoscopic remission. Vedolizumab 108 mg was the best dosage in reducing Adverse Events (AEs). The optimal dosage for reducing Serious Adverse Events (SAEs) was found to be Tulisokibart 1000/500 mg. During the maintenance phase, Etrasimod 2 mg/kg ranked first in clinical remission (OR 9.58; 95% CI, 2.82-32.59), and Upadacitinib 45 mg was superior in endoscopic remission. Additionally, the most effective medication for raising quality of life was Guselkumab 200 mg (OR 3.04; 95% CI, 1.70-5.40). Consequently, there is a need for further high-quality research to conclusively determine the best therapeutic option.