Systematic review: outcomes and adverse events from randomised trials in Crohn's disease.

Heather Catt,Dyfrig Hughes,Jamie J Kirkham,Keith Bodger

doi:10.1111/apt.15174

Abstract

SummaryBackgroundThe suitability of disease activity indices has been challenged, with growing interest in objective measures of inflammation.AimTo undertake a systematic review of efficacy and safety outcomes in placebo‐controlled randomised controlled trials (RCTs) of patients with Crohn's disease.MethodsMEDLINE, EMBASE, CINAHL and Cochrane Library were searched until November 2015, for RCTs of adult Crohn's disease patients treated with medical or surgical therapies. Data on efficacy and safety outcomes, end‐point definitions, and measurement instruments were extracted and stratified by publication date (pre‐2009 and 2009 onwards).ResultsOne hundred and eighty‐one RCTs (110 induction and 71 maintenance) were identified, including 23 850 patients. About 92.3% reported clinical efficacy endpoints. The Crohn's Disease Activity Index (CDAI) dominated, defining clinical response or remission in 63.5% of trials (35 definitions of response or remission). CDAI < 150 was the commonest endpoint, but reporting reduced between periods (46.4%‐41.1%), whilst use of CDAI100 increased (16.8%‐30.4%). Fistula studies most commonly reported fistula closure (9, 90.0%). Reporting of biomarker, endoscopy and histology endpoints increased overall (33.3%‐40.6%, 14.4%‐30.4% and 3.2%‐12.5%, respectively), but were heterogeneous and rarely reported in fistula trials. Patient‐reported outcome measures were reported in 41.4% of trials and safety endpoints in 35.4%. Many of the common adverse events relate to disease exacerbation or treatment failure.ConclusionsTrial endpoints vary across studies, over time and are distinct in fistula studies. Despite growth in reporting of objective measures of inflammation and in patient‐reported outcome measures, there is a lack of standardisation. This confirms the need for a core outcome set for comparative effectiveness research in Crohn's disease.

Highlights

Defining the key outcomes of therapeutic interventions and the best way to measure those outcomes is essential for clinical and regulatory decision‐making
MEDLINE, EMBASE, CINAHL and Cochrane Library were searched until November 2015, for randomised controlled trials (RCTs) of adult Crohn's disease patients treated with medical or surgical therapies
Patient‐reported outcome measures were reported in 41.4% of trials and safety endpoints in 35.4%

Summary

Introduction

Defining the key outcomes of therapeutic interventions and the best way to measure those outcomes is essential for clinical and regulatory decision‐making. Due to the complexity of Crohn's disease and the multitude of treatments, a number of different outcomes and outcome measures have been reported in clinical trials including symptom scores, composite disease activity indices and quality of life questionnaires.[1,2] Decision‐making relies on the availability of good information on the unintended effects (harms) from treatments. Future trial design and core outcome set development for Crohn's disease would benefit from a systematic synthesis of outcome reporting across published clinical trials, incorporating statistical testing and consideration of adverse events

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