Differential efficacy of interleukin-23 pathway inhibitors in ulcerative colitis according to disease extent: a systematic review and meta-analysis of randomized trials
Avneet Kaur, Anjul Verma, Timothy Chan, James Evans, Idan GorenBackground
Interleukin-23 (IL-23) pathway inhibitors have demonstrated efficacy for moderate-to-severe ulcerative colitis. However, whether treatment response differs according to baseline disease extent remains unclear.
Methods
We searched MEDLINE, EMBASE, and CENTRAL from January 2015 through August 2026 for randomized placebo-controlled trials evaluating IL-23 pathway inhibitors in ulcerative colitis. Clinical remission during induction and maintenance therapy was pooled using Mantel–Haenszel fixed-effect models for limited versus extensive disease. Treatment-by-disease-extent interaction was evaluated using within-trial ratios of risk ratios (RRRs).
Results
Five randomized placebo-controlled trial programs were included, four contributed extent-stratified induction data, and three contributed maintenance data. During induction, IL-23 inhibitors increased clinical remission in limited disease [risk ratio: 2.58, 95% confidence interval (CI): 1.94–3.43] and extensive disease (risk ratio: 2.25, 95% CI: 1.62–3.13), with no significant interaction (RRR: 0.80, 95% CI: 0.51–1.24,
Conclusion
IL-23 pathway inhibition is effective across disease extents in ulcerative colitis. Disease extent did not modify treatment efficacy during induction, whereas a greater relative treatment effect was observed in extensive disease during maintenance.