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

Abstract

Summary Background The suitability of disease activity indices has been challenged, with growing interest in objective measures of inflammation. Aim To undertake a systematic review of efficacy and safety outcomes in placebo‐controlled randomised controlled trials (RCTs) of patients with Crohn's disease. Methods MEDLINE, 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). Results One 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. Conclusions Trial 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.

Composite outcomes in observational studies of Crohn’s disease: a systematic review and meta-analysis

“…To the best of our knowledge, this report represents the first systematic review and meta-analysis of outcomes in observational studies of CD. The data presented here complement previous reports that also focused on CD outcomes but were restricted to randomized clinical trials (RCTs), 58 , 59 which were specifically excluded from our analysis. In fact, those reports explicitly state the need to consider nonrandomized controlled trials and observational studies in addition to RCTs to get a fuller picture of outcome reporting in CD.…”

Heterogeneity in outcome assessment for inflammatory bowel disease in routine clinical practice: a mixed-methods study in a sample of English hospitals

“…19 Poor standardisation in practice may partly reflect a current lack of consensus on the most suitable CLIN-ROs and PROs for clinical trials. [5][6][7] It is noteworthy in the case of IBD that explicit recommendations for 'minimum' clinical outcome sets are largely lacking from specialist guidelines of the American College of Gastroenterology, 30 31 European Crohn's and Colitis Organisation 32 and British Society of Gastroenterology. 25 Standards for outcome assessment are not covered by current UK and US quality standards.…”

“…4 However, the precise choice of index has varied across trials. [5][6][7] Furthermore, it is recognised that the requirement for objective test results makes such instruments impractical for routine use at every clinical encounter. Several international efforts are seeking better consensus on standardisation of outcome assessment for comparative effectiveness research, including development of core outcome sets (COSs).…”

“…The first sets were based on symptoms pairs from the relevant PRO-2 (stool frequency and abdominal pain for CD; stool frequency and rectal bleeding for UC (or IBD-U)). The second sets were focused on the items from traditional disease activity indices used in clinical trials, [5][6][7][8] observational studies, 22 registries 23 and clinical audits. 19 For CD, we selected the CDAI and HBI, and for UC we identified the Mayo Score and SCCAI.…”

“…This reference list enabled us to count the number of 'relevant' IBD outcomes covered in each consultation. In addition to symptom pairs and the items from activity indices, we added discrete outcomes from other clinician-reported outcomes (CLIN-ROs) or patient-reported outcomes (PROs) based on existing systematic reviews of outcomes used in clinical trials [5][6][7] and from guidelines for clinical practice. 15 24 25 Life impact outcomes were classified using a standardised outcome taxonomy proposed by the Core Outcome Measures in Effectiveness Trials collaboration.…”