P0684 Rethinking the Dose: A Bayesian Meta-Analysis of Infliximab Intensification in Acute Severe Ulcerative Colitis

Abstract Background The optimal infliximab (IFX) dosing strategy for acute severe ulcerative colitis (ASUC) remains unclear. Though intensified IFX dosing is frequently employed, evidence supporting its efficacy has been mixed, and it is uncertain if intensified IFX more effectively captures remission than standard-dose IFX. We conducted an updated meta-analysis comparing standard- versus intensified-dose IFX in ASUC, incorporating PREDICT-UC trial data and applying a Bayesian framework to better integrate prior evidence and quantify uncertainty Methods Electronic databases were systematically searched from inception to December 2024 (PROSPERO ID:CRD42024616359). We conducted a two-step meta-analysis. First, retrospective cohort studies were assessed with a frequentist random-effects meta-analytic approach. Second, because there is only one trial (PREDICT-UC) comparing intensified vs standard IFX in ASUC we applied a Bayesian meta-analytic approach by using historical trials of standard-dose IFX in ASUC to define the posterior probability distribution, and then compared that to PREDICT-UC. Results Ten retrospective studies (530 standard-dose and 406 intensified-dose patients) were included. Bayesian analysis demonstrated a reduction in the risk for colectomy at 3 months with intensified IFX dosing. The pooled historical colectomy rate from four standard-dose RCTs was 27% (95% Credible Interval: 21%–33%). In PREDICT-UC, the colectomy rates were 15% in those who received rescue 5 mg/kg and 6% in the upfront 10 mg/kg arm, both credibly lower than the historical standard dose estimate. Conclusion Integrating observational and trial data via Bayesian methods suggests intensified IFX dosing reduces early colectomy in ASUC. These findings support prospective, adequately powered trials to confirm benefit, identify subgroups most likely to respond, and refine individualized accelerated-dosing algorithms. Conflict of interest: Dr. Goyal, Manjeet: No conflict of interest Dutta, Priayata: No conflict of interest Choy, Matthew: No conflict of interest Berinstein, Jeffrey: No conflict of interest Hassan, Syed A: No conflict of interest Sharma, Vishal: None Ahuja, Vineet: Nil Berinstein, Elliot: No conflict of interest Li Wai Suen, Christopher: Grant: I am supported by an Australian National Health and Medical Research Council (NHMRC) postgraduate scholarship. The cytokine study was carried out with support from the St Vincent’s Hospital (Melbourne) Research Endowment Fund. The PREDICT UC study was supported by a Jassen-Cilag investigator-initiated study grant. Non-financial Support: Diasorin provided reagents and research support for the calprotectin study but was not involved in the study design or writing of the abstract. Essange reagents (Netherlands) provided testing kits for the infliximab study but was not involved in the study design or writing of the abstract. Other: I have previously received educational support from Pfizer, Shire, and Ferring. Higgins, Peter: Grant: NIH, Abbvie, Eli Lilly, Pfizer Personal Fees: Consulting - Abbvie Non-financial Support: None Con, Danny: No conflict of interest De Cruz, Peter: No conflict of interest Bishu, Shrinivas: No conflict of interest