Placebo rates in randomized clinical trials of ulcerative colitis: an individual patient data meta-analysis.

BACKGROUND AND AIMS: We assessed placebo rates and associated factors using individual patient data (IDP) from randomized clinical trials (RCTs) in ulcerative colitis (UC).

METHODS

We conducted an IPD meta-analysis using Vivli and Yale University Open Data Access data-sharing platforms. Phase 2 and 3 RCTs of advanced biologics in adults with moderate-to-severe UC published since 2010 were included. Pooled placebo rates and 95% CIs were estimated using one- and two-stage meta-analytical approaches. Significant patient-level factors (P < .05) were identified using regression analyses. Primary outcomes were clinical response and remission.

RESULTS

Data were available for 1703 patients from nine studies. For induction trials, overall placebo response and remission rates were 33% (95% CI 29%-38%) and 9% (95% CI 7%-11%). Overall placebo response and remission rates in maintenance trials were 28% (95% CI 18%-41%) and 14% (95% CI 9%-20%). A lower body mass index reduced the odds of placebo response and remission, while higher baseline albumin levels and left-sided (compared to extensive) UC increased the odds of these outcomes. A 1-point increase in the Mayo Clinic Score (MCS) and adapted MCS was associated with a 26% and 27% reduction in odds of clinical remission. For induction trials, prior biologic exposure was associated with lower odds of response and remission. Multicenter trials have lower placebo effects than single-center trials.

CONCLUSIONS

These results enable future trials to incorporate design elements that reduce placebo rates as well as a precise benchmark for expected rates in clinical trials that do not include placebo.