Adverse Events and Nocebo Effects in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Christopher Ma, Nicola R. Panaccione, Tran M. Nguyen, Leonardo Guizzetti, Claire E. Parker, Isra M. Hussein, Niels Vande Casteele, Reena Khanna, Parambir S. Dulai, Siddharth Singh, Brian G. Feagan, Vipul Jairath*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

Background and Aims: Nocebo effects, adverse outcomes occurring in patients receiving inert therapy, contribute to adverse event [AE] reporting in randomized controlled trials [RCTs]. High placebo AE rates may result in inaccurate estimation of treatment-related AEs. We estimate the pooled rate of AEs in patients randomized to placebo compared to active therapy in inflammatory bowel disease [IBD] RCTs. Methods: MEDLINE, EMBASE and CENTRAL were searched to March 1, 2017 for RCTs of conventional medical therapies for Crohn's disease [CD] or ulcerative colitis [UC]. Rates of AEs, serious AEs [SAEs], AE-related trial withdrawal, infections and worsening IBD were pooled using a random-effects model. Results: We included 124 CD [n = 26 042] and 71 UC RCTs [n = 16 798]. The pooled placebo AE rate was 70.6% (95% confidence interval [CI]: 65.3%, 75.4%) and 54.5% [47.8%, 61.1%] in CD and UC RCTs, respectively. There was no significant risk difference [RD] in AE, SAE or AE-related withdrawal rates between CD patients receiving placebo or active drug. A 1.6% [95% CI: 0.1%, 3.1%] increase in AE rates was observed among UC patients randomized to active therapy. Patients receiving active therapy had a higher risk of infection (RD 1.0% [95% CI: 0.4%, 1.7%] for CD, 2.9% [95% CI: 1.4%, 4.4%] for UC) although a lower risk of worsening CD (RD-3.2% [95% CI:-4.8%,-1.5%]) or UC (RD-3.7% [95% CI:-5.7%,-1.8%]). Conclusions: AEs are commonly reported by patients randomized to either placebo or active treatment in IBD RCTs. Clinically relevant differences in AE, SAE and AE-related withdrawal were not observed.

Original languageEnglish (US)
Pages (from-to)1201-1216
Number of pages16
JournalJournal of Crohn's and Colitis
Volume13
Issue number9
DOIs
StatePublished - Sep 1 2019
Externally publishedYes

Keywords

  • Adverse event
  • inflammatory bowel disease
  • nocebo

ASJC Scopus subject areas

  • Gastroenterology

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