EFFECTIVENESS AND SAFETY OF SELECTIVE IL-12/23 RECEPTOR ANTAGONISTS IN MODERATE TO SEVERE ULCERATIVE COLITIS: A SYSTEMATIC REVIEW, META-ANALYSIS AND TRIAL SEQUENTIAL ANALYSIS.

BACKGROUND AND

OBJECTIVE

Selective IL-12/23p40 receptor antagonists (IL-12/23RA) show promise for treating moderate to severe ulcerative colitis (UC), but their efficacy and safety are not fully understood.

Objective

This systematic review and meta-analysis assess the effectiveness and safety of IL-12/23RA in UC.

METHODS

A systematic search of PubMed, Embase, Cochrane, and ClinicalTrials.gov was performed in December 2024. Randomized controlled trials (RCTs) comparing IL-12/23RA to placebo in moderate to severe UC were included. Outcomes included clinical and endoscopic remission, response rates, and adverse events (AEs). Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were pooled using a random-effects model.

RESULTS

Nine RCTs (3,808 patients in the induction phase; 1,734 in the maintenance phase) were analyzed. IL-12/23RA enhanced clinical remission (induction: RR 2.63; 95%CI 2.05-3.36; maintenance: RR 1.99; 95%CI 1.63-2.44; all P<0.01) and endoscopic remission (induction: RR 2.36; 95%CI 1.70-2.20; maintenance: RR 1.96; 95%CI 1.63-2.37; all P<0.01). IL-12/23RA reduced serious AE in the induction phase (RR 0.40; 95%CI 0.27-0.69; P<0.01), while there was no difference during maintenance (RR 0.75; 95%CI 0.31-1.84; P=0.53). No differences were observed in overall AEs or specific AEs like headache or nasopharyngitis. Trial sequential analysis confirmed sufficient sample size for clinical endpoints.

CONCLUSIONS

IL-12/23RA showed superior effectiveness and similar safety when compared to placebo in moderate to severe UC.