Stratified by baseline corticosteroid use: which advanced therapy works best for whom in ulcerative colitis?

Corticosteroids (CS) are commonly used as bridging therapy in ulcerative colitis (UC), but whether baseline CS use modifies the subsequent efficacy of advanced therapies remains unclear. With differing mechanisms across drug classes, it is uncertain whether CS impact on outcomes is consistent or drug-class-dependent.

We searched PubMed, Embase, Web of Science, and Cochrane Library for CS-stratified randomized controlled trials (RCTs) comparing active drugs with placebo in moderate-to-severe UC. After deduplication, studies were selected per predefined criteria. Bias risk was assessed with the Cochrane tool. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model; robustness was tested by leave-one-out sensitivity analyses.

Ten RCTs (7 publications, 6,286 patients) were included. Overall, CS-naïve patients showed significantly higher rates of endoscopic improvement (RR = 1.91, 95% CI: 1.33-2.74, p < 0.001, I² = 0%), symptom relief (RR = 1.63, 95% CI: 1.16-2.29, p = 0.005, I² = 0%) and clinical remission (RR = 1.50, 95% CI: 1.03-2.19, p = 0.03, I² = 0%) than CS users during induction; no significant differences were observed for other efficacy endpoints. This overall trend masked marked heterogeneity by drug class. IL-23 inhibitors exhibited a pronounced advantage in non-CS users across multiple endpoints, including clinical remission, clinical response, and endoscopic improvement. S1P modulators yielded the largest effect size for histologic-endoscopic mucosal improvement (RR = 3.04, 95% CI: 1.18-7.86, p = 0.02). No significant differences were found between groups in adverse events, serious adverse events, discontinuations, infections, acne, or CPK elevation, even with CS use up to 52 weeks.

Baseline CS status may influence the efficacy of advanced therapies in UC. IL-23 inhibitors appeared to benefit CS-naïve patients across multiple endpoints, whereas JAK inhibitors showed a numerical but nonsignificant advantage in CS-exposed patients. Short-term concomitant CS did not significantly increase adverse events, supporting the clinical acceptability of CS bridging in highly active disease. These findings support stratified reporting in future RCTs and call for prospective studies to validate these observations.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251248449, identifier, CRD420251248449.