Placebo Effect on the Health-related Quality of Life of Inflammatory Bowel Disease Patients: A Systematic Review With Meta-analysis.

Background and Aims: Placebo effect in health-related quality of life [HRQoL] of inflammatory bowel disease [IBD] patients has been poorly characterised. This systematic review and meta-analysis aimed to assess: i] mean improvements in IBDQ [Inflammatory Bowel Disease Questionnaire] and SF-36 [36-Item Short Form Health Survey] scores among placebo-treated IBD patients; and ii] the proportion of placebo-treated patients achieving IBDQ-defined response and remission and correspondent odds ratios [OR].

Methods: Literature search was performed using four databases. Mean differences and ORs were computed using the random-effects model. Univariate and multivariate regressions were performed to evaluate the weight of different factors on the placebo effect.

Results: From the 328 identified records 26 were included in the study, comprising 2842 placebo-treated IBD patients. Pooled mean differences on IBDQ following placebo administration were above the clinically meaningful improvement [≥16 points] in ulcerative colitis [UC] patients during the induction regimen (17.67; 95% confidence interval [CI]: 12.90, 22.44) and during maintenance in both Crohn's disease [CD] [27.60; 95% CI: 14.29, 40.91] and UC patients [27.50; 95% CI: 18.73, 36.27]. The treatment regimen was the only significant variable in multivariate analysis, with lower placebo-related IBDQ improvements during induction. Maintenance trials' inclusion criteria were also relevant. The proportions of placebo-treated patients achieving IBDQ-defined response and remission were 0.42 [95% CI: 0.49, 0.56] and 0.31 [95% CI: 0.28, 0.34], respectively, with 0.49 and 0.40 the ORs for response and remission. Significant improvements were also observed on SF-36 score.

Conclusions: Herein we prove that placebo effect on HRQoL is meaningful, providing insights about implications for clinical trials' design and interpretation and for IBD management.