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Prognostic biomarkers to identify patients likely to develop severe Crohn's disease: a systematic review

Halligan, S; Boone, D; Archer, L; Ahmad, T; Bloom, S; Rodriguez-Justo, M; Taylor, SA; (2021) Prognostic biomarkers to identify patients likely to develop severe Crohn's disease: a systematic review. Health Technology Assessment , 25 (45) 1-+. 10.3310/hta25450. Green open access

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Abstract

Background: Identification of biomarkers that predict severe Crohn’s disease is an urgent unmet research need, but existing research is piecemeal and haphazard. Objective: To identify biomarkers that are potentially able to predict the development of subsequent severe Crohn’s disease. Design: This was a prognostic systematic review with meta-analysis reserved for those potential predictors with sufficient existing research (defined as five or more primary studies). Data sources: PubMed and EMBASE searched from inception to 1 January 2016, updated to 1 January 2018. Review methods: Eligible studies were studies that compared biomarkers in patients who did or did not subsequently develop severe Crohn’s disease. We excluded biomarkers that had insufficient research evidence. A clinician and two statisticians independently extracted data relating to predictors, severe disease definitions, event numbers and outcomes, including odds/hazard ratios. We assessed risk of bias. We searched for associations with subsequent severe disease rather than precise estimates of strength. A random-effects meta-analysis was performed separately for odds ratios. Results: In total, 29,950 abstracts yielded just 71 individual studies, reporting 56 non-overlapping cohorts. Five clinical biomarkers (Montreal behaviour, age, disease duration, disease location and smoking), two serological biomarkers (anti-Saccharomyces cerevisiae antibodies and anti-flagellin antibodies) and one genetic biomarker (nucleotide-binding oligomerisation domain-containing protein 2) displayed statistically significant prognostic potential. Overall, the strongest association with subsequent severe disease was identified for Montreal B2 and B3 categories (odds ratio 4.09 and 6.25, respectively). Limitations: Definitions of severe disease varied widely, and some studies confounded diagnosis and prognosis. Risk of bias was rated as ‘high’ in 92% of studies overall. Some biomarkers that are used regularly in daily practice, for example C-reactive protein, were studied too infrequently for meta-analysis. Conclusions: Research for individual biomarkers to predict severe Crohn’s disease is scant, heterogeneous and at a high risk of bias. Despite a large amount of potential research, we encountered relatively few biomarkers with data sufficient for meta-analysis, identifying only eight biomarkers with potential predictive capability. Future work: We will use existing data sets to develop and then validate a predictive model based on the potential predictors identified by this systematic review. Contingent on the outcome of that research, a prospective external validation may prove clinically desirable.

Type: Article
Title: Prognostic biomarkers to identify patients likely to develop severe Crohn's disease: a systematic review
Open access status: An open access version is available from UCL Discovery
DOI: 10.3310/hta25450
Publisher version: https://doi.org/10.3310/hta25450
Language: English
Additional information: © Queen’s Printer and Controller of HMSO 2021. This work was produced by Halligan et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Department of Imaging
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/10130922
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