The Risks of Placebo in IBD Drug Trials

Placebo use in trials of therapies for inflammatory bowel disease (IBD) is associated with a higher likelihood of significant worsening of disease and serious adverse events compared to active treatment, authors of a meta-analysis reported in The Lancet Gastroenterology & Hepatology.

The study aimed to examine the risks associated with receiving placebo in randomized, placebo-controlled trials of licensed biologics and small molecules for inducing remission in patients with moderately to severely active ulcerative colitis and Crohn's disease. A systematic review was conducted across multiple databases, identifying 47 eligible trials involving 20,987 patients (14,267 on active drugs and 6,720 on placebo). The study focused on comparing adverse events between the 2 groups over a treatment period of at least 4 weeks.

The analysis revealed that while the overall risk of treatment-emergent adverse events was similar between the active drug and placebo groups (53.7% vs. 55.9%), the placebo group experienced significantly higher risks of worsening IBD activity (8.5% vs. 4.2%), withdrawal due to adverse events, serious adverse events, serious infections, serious worsening of IBD activity, and venous thromboembolic events (VTEs). The relative risk (RR) for worsening IBD activity with placebo was 0.48, with similar reductions in the risk of other serious adverse events for patients receiving active treatment. Numbers needed to treat with active drug to prevent these adverse outcomes ranged from 23 for worsening IBD activity to 452 for VTEs.

The investigators recommended that alternative trial designs be explored to lessen the risks these complications among participants.

Reference
Din S, Segal J, Blackwell J, Gros B, Black CJ, Ford AC. Harms with placebo in trials of biological therapies and small molecules as induction therapy in inflammatory bowel disease: A systematic review and meta-analysis. Lancet Gastroenterol Hepatol. Published online September 19, 2024. doi:10.1016/S2468-1253(24)00264-4