Abstract
BackgroundIt is believed increasingly that patients with severe Crohn’s disease are best treated early with biological therapy, which may ameliorate subsequent disease course and diminish long-term complications. However, we cannot predict currently which new presentations of Crohn’s disease are destined to develop severe disease so treatment cannot be targeted to the most appropriate patients. Accordingly, via systematic review and meta-analysis we aim to identify if biomarkers of disease activity are able to predict development of severe disease.Methods/designWe will search the primary literature and conference proceedings for studies of biomarkers of all types including clinical, endoscopic, radiological, faecal, urinary, serological, genetic, and histological. Precise definition of “severe” disease is elusive so we will include sensitivity analysis to account for different definitions. We will use the CHARMS checklist to frame our question and to extract data. We will extract the study design, setting, participant characteristics, biomarker(s) investigated, and study outcomes. Bias will be assessed via the PROBAST tool. We will present the results using narrative and graphical methods. We will present the summary by meta-analysis where there are sufficient studies with reasonable homogeneity, using methods appropriate to the type of data extracted. Heterogeneity will be presented via Forest and ROC plots.DiscussionIf this systematic review and meta-analysis identifies biomarkers that appear sufficiently predictive for subsequent severe disease course, we aim to combine them in a predictive model, followed by external validation using individual patient data. A predictive model able to identify new presentations of Crohn’s disease destined to develop severe disease subsequently would have considerable clinical utility for patient management.Systematic review registrationPROSPERO CRD42016029363.Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0383-5) contains supplementary material, which is available to authorized users.
Highlights
It is believed increasingly that patients with severe Crohn’s disease are best treated early with biological therapy, which may ameliorate subsequent disease course and diminish long-term complications
If this systematic review and meta-analysis identifies biomarkers that appear sufficiently predictive for subsequent severe disease course, we aim to combine them in a predictive model, followed by external validation using individual patient data
We focused our attention on the 35 clinical trials identified, and 13 appeared potentially eligible for a systematic review
Summary
It is believed increasingly that patients with severe Crohn’s disease are best treated early with biological therapy, which may ameliorate subsequent disease course and diminish long-term complications. We cannot predict currently which new presentations of Crohn’s disease are destined to develop severe disease so treatment cannot be targeted to the most appropriate patients. Newer biological therapies appear to ameliorate ultimate disease trajectory, raising the possibility that early “top-down” treatment with these agents could “stop the disease in its tracks”. Biologicals appear incrementally more effective when used in combination with other immunomodulators such as azathioprine [2], especially when administered in a “top-down” fashion [3, 4]. Newer agents such as adalimumab are effective [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
