Systematic Review: Outcomes and adverse events from randomised trials in Crohn's disease

BACKGROUND The suitability of disease activity indices has been challenged, with growing interest in objective measures of inflammation. AIM We undertook a systematic review of efficacy and safety outcomes in placebo-controlled randomized controlled trials (RCTs) of patients with Crohn’s disease. METHODS MEDLINE, EMBASE, CINAHL and Cochrane Library were searched to 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 was extracted and stratified by publication date (pre-2009 and 2009-onwards). RESULTS 181 RCTs (110 induction and 71 maintenance) were identified, including 23,850 patients. 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% to 41.1%), whilst CDAI100 increased (16.8% to 30.4%). Fistula studies most commonly reported fistula closure (9, 90.0%). Reporting of biomarker, endoscopy and histology end-points increased overall (33.3% to 40.6%, 14.4% to 30.4%, and 3.2% to 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. CONCLUSION Trials 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.