S1491 Effect of Intensified Dosing and Accelerated Scheduling Induction Regimens of Infliximab Therapy on Early and Late Incidence of Colectomy in Acute Severe Ulcerative Colitis: A Bayesian Hierarchal Network Meta-Analysis

Introduction: Infliximab (IFX) is a key rescue therapy for acute severe ulcerative colitis (ASUC). However, extremely high tumor necrosis factor (TNF)-α levels and compromised mucosal integrity in ASUC create a “sink effect,” reducing IFX efficacy at standard doses. To overcome this, intensified dosing strategies, either by increasing dose or shortening intervals, have been proposed. Given the limited high-quality evidence for such regimens, this network meta-analysis (NMA) combines data from RCTs and observational studies (OS), adjusting for bias using a Bayesian hierarchical model (Schmitz et al., 2013). Methods: Three databases and 4 trial registries were searched. IFX regimens were classified as: IFX5-STS (5 mg/kg, standard schedule at weeks 0, 2, 6), IFX5-ACS (5 mg/kg, accelerated—3 doses within 4 weeks), IFX10-STS (10 mg/kg, standard schedule), and IFX10-ACS (10 mg/kg, accelerated schedule) A 3-level Bayesian hierarchical NMA accounting for bias due to OS was used. Treatment efficacy was ranked using SUCRA values and rankograms. Results: A total of 1 RCT and 20 OS were included. Early colectomy (EC), defined as colectomy within 3 months of IFX induction, was not significantly reduced by any regimen when compared to others. The IFX5-STS regimen had the highest probability of reducing EC (SUCRA = 78.27%), followed by IFX10-STS (SUCRA = 51.5%). Late colectomy (LC), defined as colectomy within 12 months, was significantly reduced only by the IFX10-STS regimen as compared to other regimens. IFX10-STS also ranked highest for preventing LC (SUCRA = 97.34%), followed by IFX5-STS (SUCRA = 58.31%). Meta-regression showed that covariates like age group, steroid refractoriness, and intensified maintenance therapy did not significantly influence the results. Conclusion: This analysis suggests only IFX10-STS significantly reduces late colectomy risk in ASUC patients. Accelerated regimens (IFX5-ACS and IFX10-ACS) showed no significant benefit in reducing EC or LC rates. Although some guidelines, like the British Society of Gastroenterology, recommend accelerated dosing in patients with high CRP and albumin, this NMA does not support their efficacy. A key limitation is the heterogeneity among studies in defining “accelerated” regimens, leading to broad classification criteria. Future high-quality RCTs are needed to clarify the effectiveness of these variant IFX regimens.