Placebo Effect for Clinical Remission in Induction and Maintenance Treatment in Crohn's Disease: A Systematic Literature Review and Meta-Analysis

OBJECTIVES: The primary objective was to perform a systematic literature review (SLR) and meta-analysis of the placebo effect for induction and maintenance treatment in Crohn’s Disease (CD).

METHODS: PubMed and Embase were searched for English-language publications and conference abstracts published through December 1, 2022. Studies were selected for inclusion if patients were treated for Crohn’s Disease and placebo was used in at least one arm. Random-effects meta-analyses were conducted to estimate the overall treatment effect for clinical remission. Inter-study heterogeneity was assessed with Cochrane's Q and I2 tests (with significant heterogeneity indicated by P < .10 or I2 ≥ 50%).

RESULTS: A total of 4,819 records were identified, of which 34 references met the selection criteria for systematic review and meta-analysis. In the induction setting, a total of 10,744 patients were included, with 3,960 in the placebo arm. In the maintenance setting, a total of 4,879 patients were included, with 1,939 in the placebo arm. The overall treatment effect for clinical remission with placebo in the induction setting was 17% (95% CI: 14%-20%, test of theta = 0: z = 10.23, Prob > |z| = 0.0000, test of homogeneity: Q = chi2(32) = 238.78, Prob > Q = 0.0000, tau2 = 0.0077, I2 = 88.03%). The overall treatment effect for clinical remission with placebo in the maintenance setting was 24% (95% CI: 19%-29%, test of theta = 0: z = 10.23, Prob > |z| = 0.0000, test of homogeneity: Q = chi2(32) = 238.78, Prob > Q = 0.0000, tau2 = 0.0077, I2 = 88.03%).

CONCLUSIONS: The systematic literature review and meta-analysis show a placebo effect of achieving clinical remission in Crohn’s Disease. There is a need to further understand the factors driving the placebo effect in Crohn’s Disease.