Abstract
INTRODUCTION: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing interleukin (IL)-23p19 antagonists with ustekinumab, stratified by prior biologic exposure, in patients with moderate-to-severe Crohn's disease (CD). METHODS: Through a systematic review through August 17, 2024, we identified phase 2 and 3 RCTs comparing IL-23p19 antagonists vs ustekinumab in adults with moderate-to-severe CD. The primary outcome was achieving clinical remission at ∼1 year, and secondary outcomes were achieving endoscopic remission and serious adverse events. We performed subgroup analyses based on prior exposure to biologic therapy, primarily tumor necrosis factor antagonists. Certainty of evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: We included 5 head-to-head RCTs with a treat-through design (n = 2,506), of which 1 was conducted exclusively in patients with prior tumor necrosis factor antagonist exposure. On meta-analysis, patients treated with IL-23p19 inhibitors may be more likely to achieve clinical remission (relative risk [RR], 1.18 95% confidence interval [CI] 1.02-1.36) (low certainty of evidence) and endoscopic remission (RR 1.53, 95% CI 1.07-2.20) compared with ustekinumab. On subgroup analysis, IL-23p19 antagonists are probably more efficacious than ustekinumab in patients with prior biologic exposure (clinical remission: RR 1.31, 95% CI 1.16-1.48; endoscopic remission: RR 1.61, 95% CI 1.27-2.05) (moderate to high certainty), but not in biologic-naive patients (clinical remission: RR 0.99, 95% CI 0.90-1.08; endoscopic remission: RR 1.16, 95% CI 0.82-1.65). IL-23p19 antagonists may be associated with a lower risk of serious adverse events as compared with ustekinumab (RR 0.79, 95% CI 0.61-1.02). DISCUSSION: IL-23p19 antagonists are probably more efficacious and safer than ustekinumab in patients with moderate-to-severe CD in patients with prior biologic exposure, but not in biologic-naive patients.