Placebo response rates in Crohn’s disease – who responds best?

Review by Prof. Eamonn Quigley (USA)

Study Summary 

Crohn’s disease is increasing in incidence worldwide and in North America and Western Europe now outstrips ulcerative colitis as the most prevalent form of inflammatory bowel disease (IBD). Over recent years a plethora of biologic agents and small molecules have appeared on the stage and offer improved outcomes for the Crohn’s patient. This study performed a meta-analysis of placebo clinical response and remission rates in 8 induction and 4 maintenance trials of what they referred to as “advanced therapies.” Overall, clinical response and remission rates for placebo were 27% and 10%, respectively, for induction therapy and 32% and 22% for maintenance therapy. Whether the individual had previously been exposed to another biologic agent did not influence placebo response rates in the induction phase, though rates were numerically higher among bio-naïve subjects in the maintenance phase. Factors associated with lower placebo remission rates included higher levels of C-reactive protein (CRP) and Crohn’s disease activity index (CDAI) at baseline; in contrast, higher albumin levels and body mass index (BMI) at baseline were associated with augmented placebo response rates. 

Commentary 

The first conclusion to be drawn from this study is that regardless of prior therapy some patients, albeit a minority, with Crohn’s disease will respond to a placebo. Whether this reflects an ebb and flow of the natural history of the disease or a clinical response to other components of the overall management process is unknown. The second conclusion to take away is that some individuals are especially likely or unlikely to respond to placebo and their inclusion in, or exclusion from, clinical trials will influence outcomes and potentially bias results in one direction or another. At an individual patient level one can ask whether it is appropriate to consider randomizing a patient who has little or no chance of responding to it to placebo. More on this issue in a forthcoming News You Can Use.

Citation

Solitano V, Hogan M, Singh S, et al. Placebo rates in Crohn’s disease randomized trials: an individual patient data meta-analysis. Gastroenterology 2025;168:344-356.

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