IL-23p19 Antagonists vs Ustekinumab for Treatment of Crohn's Disease: A Meta-Analysis of Randomized Controlled Trials
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.035 | 0.064 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.027 | 0.055 |
| Bibliometrics | 0.007 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.005 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".