TY - JOUR T1 - PRedicting Outcomes For Crohn’s dIsease using a moLecular biomarkEr (PROFILE): protocol for a multicentre, randomised, biomarker-stratified trial JF - BMJ Open JO - BMJ Open DO - 10.1136/bmjopen-2018-026767 VL - 8 IS - 12 SP - e026767 AU - Miles Parkes AU - Nurulamin M Noor AU - Francis Dowling AU - Harvey Leung AU - Simon Bond AU - Lynne Whitehead AU - Sara Upponi AU - Paul Kinnon AU - Andrew P Sandham AU - Paul A Lyons AU - Eoin F McKinney AU - Kenneth G C Smith AU - James C Lee Y1 - 2018/12/01 UR - http://bmjopen.bmj.com/content/8/12/e026767.abstract N2 - Background The course of Crohn’s disease (CD) varies substantially between individuals, but reliable prognostic markers do not exist. This hinders disease management because patients with aggressive disease are undertreated by conventional ‘step-up’ therapy (in which treatment is gradually escalated in response to refractory or relapsing disease) while those with more indolent disease would be exposed to unnecessary treatment-related toxicity if a more aggressive ‘top-down’ approach was indiscriminately used. The Predicting outcomes for Crohn’s disease using a molecular biomarker trial will assess whether a prognostic transcriptional biomarker, that we have developed and validated, can improve clinical outcomes by facilitating personalised therapy in CD. This represents the first the biomarker-stratified trial in inflammatory bowel disease.Methods and analysis This biomarker-stratified trial will compare the relative efficacy of ‘top-down’ and ‘accelerated step-up’ therapy between biomarker-defined subgroups of patients with newly diagnosed CD. 400 participants from ~50 UK centres will be recruited. Subjects within each biomarker subgroup (IBDhi or IBDlo) will be randomised (1:1) to receive one of the treatment strategies until trial completion (48 weeks). The primary outcome is the incidence of sustained surgery and steroid-free remission from the completion of induction treatment through to week 48. Secondary outcomes include mucosal healing, quality-of-life assessments and surrogate measures of disease burden including number of flares, cumulative steroid exposure, number of hospital admissions and number of Crohn’s-related surgeries (assessed hierarchically). Analyses will compare the relative benefit of the treatment strategies in each biomarker-defined subgroup, powered as an interaction analysis, to determine whether the biomarker can accurately match patients to the most appropriate therapy.Ethics and dissemination Ethical approval has been obtained and recruitment is under way at sites around the UK. Following trial completion and data analysis, the results of the trial will be submitted for publication in peer-reviewed journals and presented at international conferences.Trial registration number ISRCTN11808228; Pre-results. ER -