Impact of Baseline Disease Activity and Trial Duration on Efficacy of Biologics in Active Crohn’s Disease: Meta-analysis

Abstract Background Timings of assessment of efficacy and criteria used to define Crohn’s disease (CD) activity at baseline may affect therapeutic gain of active drug over placebo in induction of remission trials in CD, but these issues have not been assessed systematically. We examined these issues in a meta-analysis. Methods We searched the literature to June 2022 for randomized controlled trials of biologics vs placebo in active CD. We extracted clinical remission and response rates according to criteria used to define CD activity and time point of assessment, pooling them in a meta-analysis for all patients according to previous biologic exposure. We calculated the number needed to treat (NNT), with a 95% confidence interval (CI) to assess therapeutic gain of active drug over placebo according to these characteristics of trial design. Results We identified 20 induction of remission trials (6754 patients). Rates of clinical remission were highest (42.6% with active drug vs 21.0% with placebo) and NNT lowest (5; 95% CI, 3-7.5) in trials using clinical and endoscopic activity to define active CD. Rates of remission were lower (26.5% with active drug, vs 18.6% with placebo) and NNT highest (12; 95% CI, 6-61) in trials using clinical activity alone. Results were similar according to previous biologic exposure. Time point of assessment seemed to have less of an effect, although the NNT was lowest in trials assessing remission rates at 9 to 12 weeks (NNT = 5.5; 95% CI, 4-8). Again, results were similar according to previous biologic exposure. Conclusions Both the criteria used to define CD activity at study entry and the time point used to confirm efficacy may be important in maximizing therapeutic gain of active drug over placebo.