How to Minimize Placebo Response and Remission Rates

In the current volume of Inflammatory Bowel Diseases, Wong et al1 presents the results of a post hoc analysis of individual patient data from 3 placebo-controlled clinical trial programs (GEMINI-2,UNITI-1/2, and CLASSIC-1) investigating efficacy of vedolizumab, ustekinumab, and adalimumab in ­moderate to severe Crohn’s disease (CD). In contrast to the numerous previously published meta-analyses of clinical drug trials focusing on the efficacy of the “verum” arm, the present study is focusing on the effect of the placebo, in particular factors that may affect the size of the placebo response. Understanding what may drive placebo response is interesting, as it may pave the way for designing more efficacious clinical studies (ie, studies that require fewer participants in order to demonstrate efficacy), potentially reducing the cost of clinical drug development and the cost of other clinically relevant studies aiming at demonstrating efficacy of interventions. As such, the authors should be complemented for their initiative. The study demonstrates that placebo response rates (defined as patients having a reduction in CDAI (Crohn’s Disease Activity Index) score of greater than or equal to 100 points) are influenced by baseline factors such as isolated ileal disease and duration of disease less than 1 year (univariate analysis), both of which were associated with high placebo response rate. However, in the multivariate analysis, only disease duration below 1 year retained statistical significance. When evaluating remission rates, the univariate analyses suggested that low disease activity (CRP [C-recative Protein] <5 mg/L, albumin >40 g/L) and short disease duration (less than 5 years) were associated with a high chance of achieving remission even when treated with placebo. However, in the multivariate analysis, only disease duration (less than 5 years) maintained statistical significance.