How to Lower Placebo Effects in Crohn’s Disease Trials

A Almradi et al. J Crohns Colitis 2021. Clinical, endoscopic and safety placebo rates in induction and maintenance trials of Crohn’s disease: Meta-analysis of Randomised controlled trials

The authors searched MEDLINE, EMBASE and CENTRAL from inception to March 2021. Eligible studies were placebo-controlled trials of pharmacological interventions for CD

Key findings:

  • In 125 studies (91 induction, 46 maintenance), placebo clinical remission and response rates for induction studies were 18% [95% confidence interval (CI) 16-21%], and 32% (95%CI 29-35%), respectively, and for maintenance studies were 28% (95%CI 23-34%) and 30% (95%CI 24-37%), respectively 
  • Endoscopic remission and response rates (for placebo) in induction studies were 8% (95%CI 4–18%), and 16% (95%CI 11–23%), respectively
  • Trials enrolling patients with prior biologic exposure, longer disease duration and higher CD activity index scores were associated with lower placebo clinical remission rates
  • Increased duration of follow-up, more follow-up visits and a greater proportion of patients with colonic disease distribution were associated with higher clinical placebo rates

My take: These studies show fairly high placebo responses and thus they reinforce the need for well-designed trials with objective endpoints.

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