S2028 Escalating the Dosage: A Meta-Analysis Comparing Standard and Intensified Infliximab for ASUC

Introduction: The standard dosing strategy for infliximab (IFX), set at 5 mg/kg at weeks 0, 2, and 6 for treating acute severe ulcerative colitis (ASUC), remains a subject of debate. Intensified IFX dosing, which involves administering 5 mg/kg at shorter intervals, increasing the dose to 10 mg/kg, or using combinations, aims to quickly achieve therapeutic drug levels. However, evidence supporting this approach remains insufficient. Herein, we aim to evaluate the efficacy of standard vs intensified IFX induction regimens in adult ASUC patients. Methods: Electronic databases were searched from their inception until December 2024, following PRISMA guidelines. The primary outcome measured was the 3-month colectomy rate with ASUC receiving either standard or intensified IFX induction. Event rates were converted into log odds ratios (logOR) and standard errors (SE). IFX randomized controlled trials (RCTs) were utilized to determine historical pooled colectomy rates for standard IFX dosing through a random-effects model meta-analysis. A fixed-effects generalized linear model (GLM) was used to compare colectomy rates between IFX RCTs and the PREDICT-UC study. Results: Out of 2180 screened studies, 41 full-text articles were reviewed, resulting in the inclusion of 11 studies (10 retrospective studies and 1 randomized controlled trial [RCT]) to compare intensified vs standard infliximab (IFX) dosing. Among these, 4 RCTs evaluated standard dose IFX against other agents for ASUC. Given that our search identified 10 retrospective studies but only one RCT comparing standard vs intensified IFX, we employed 2 analytical approaches. Initially, we conducted a meta-analysis of the retrospective studies. Subsequently, we aggregated RCTs of standard dose IFX vs other agents in ASUC to establish a historical 3-month colectomy rate for standard dose IFX, which was then compared to the rates reported in the RCT of standard vs intensified dose IFX. The meta-analysis of retrospective studies, involving 530 patients on standard IFX and 406 on intensified IFX, showed a reduced risk of colectomy at 3 months with intensified dosing (P < 0.05). The 4 RCTs with standard IFX dosing indicated a historical 3-month colectomy rate of 28% (95% CI: 22%-34%). Conclusion: Intensified dosing of IFX serves as a protective measure against colectomy in patients with ASUC. Future prospective studies are needed to consider the integration of adaptive IFX dosing strategies.