Rethinking the dose: A Bayesian meta-analysis of infliximab intensification in acute severe ulcerative colitis

Area of Science:

• Gastroenterology
• Clinical Pharmacology
• Biostatistics

Background:

• The optimal dosing strategy for infliximab (IFX) in acute severe ulcerative colitis (ASUC) is not well-established.
• Evidence comparing standard-dose vs. intensified-dose IFX in ASUC is mixed.
• Uncertainty exists regarding the superior efficacy of intensified IFX in achieving remission.

Purpose of the Study:

• To compare the efficacy of standard-dose versus intensified-dose infliximab (IFX) in patients with acute severe ulcerative colitis (ASUC).
• To integrate prior evidence using a Bayesian framework to quantify uncertainty in IFX dosing strategies.
• To analyze data from retrospective cohorts and the PREDICT-UC trial.

Main Methods:

• A systematic literature search was conducted from inception to December 2024.
• A two-step meta-analysis was performed: frequentist analysis of retrospective cohorts, followed by a Bayesian approach incorporating the PREDICT-UC trial.
• A Bayesian binomial regression model was applied using historical trials of standard-dose IFX as the reference.

Main Results:

• Frequentist analysis included 10 retrospective cohort studies (530 standard-dose, 406 intensified-dose patients).
• The estimated 3-month colectomy rate for standard-dose IFX was 27%.
• In the PREDICT-UC trial, intensified IFX dosing (10 mg/kg) showed a 6% colectomy rate, compared to 15% for rescue-dose (5 mg/kg) and credibly lower than standard-dose IFX.

Conclusions:

• Bayesian meta-analysis integrating observational and trial data suggests intensified IFX dosing reduces early colectomy in ASUC.
• Findings support the need for prospective trials to confirm the benefit of intensified IFX.
• Further research should focus on identifying patient subgroups that benefit most and refining individualized dosing algorithms.