Differential efficacy of interleukin-23 pathway inhibitors in ulcerative colitis according to disease extent: a systematic review and meta-analysis of randomized trials.

BACKGROUND: 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, P = 0.31). During maintenance, treatment was effective in limited disease (risk ratio: 1.56, 95% CI: 1.28-1.89) and extensive disease (risk ratio: 3.42, 95% CI: 2.45-4.77), with significant interaction (RRR: 2.16, 95% CI: 1.47-3.19, P < 0.001). Sensitivity analyses restricted to selective IL-23p19 inhibitors yielded consistent results. 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.