Meta-analysis: Factors predicting post-operative recurrence with placebo therapy in patients with Crohn's disease

Abstract

Background: The use of placebo in randomized clinical trials (PC-RCTs) is often required to evaluate drug efficacy in maintenance of Crohn's disease (CD). Aim: To determine pooled estimates of placebo rates of maintaining clinical remission and endoscopic recurrence following surgery for CD and identify factors that influenced placebo outcomes. Methods: We performed a systematic review and meta-analysis of PC-RCTs evaluating post-operative maintenance therapies for CD identified from MEDLINE from 1966 to 2005. Results: Twelve studies met our inclusion criteria. The pooled placebo rate of maintaining clinical remission was 56% (95% CI 47-64%; range 34-89%) during a median follow-up of 52 weeks (range 12-156 weeks), but significant heterogeneity existed among the studies (P < 0.001). Prior steroid therapy was the only factor found to be associated with maintaining remission (P = 0.04). The pooled placebo endoscopic recurrence rate was 58% (95% CI 51-65%; range 36-80%) during a median follow-up of 52 weeks (range 12-156 weeks), with significant heterogeneity noted (P = 0.0003). Prior surgery, concomitant small bowel and colonic disease, fistulizing phenotype, or prior immunomodulator therapy influenced endoscopic recurrence (P < 0.05). Conclusion: Placebo rates in PC-RCTs evaluating post-operative clinical and endoscopic recurrence demonstrate significant variability, which is influenced by specific study characteristics. © 2008 The Authors.