Protocol for a multi-national risk-stratified randomised controlled trial in paediatric Crohn’s disease: methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or high risk for aggressive disease course

Harris, R. E. et al. (2020) Protocol for a multi-national risk-stratified randomised controlled trial in paediatric Crohn’s disease: methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or high risk for aggressive disease course. BMJ Open, 10(7), e034892. (doi: 10.1136/bmjopen-2019-034892)

Abstract

Introduction: Immunomodulators such as thiopurines (azathioprine (AZA)/6-mercaptopurine (6MP)), methotrexate (MTX) and biologics such as adalimumab (ADA) are well established for maintenance of remission within paediatric Crohn’s disease (CD). It remains unclear, however, which maintenance medication should be used first line in specific patient groups. Aims: To compare the efficacy of maintenance therapies in newly diagnosed CD based on stratification into high and low-risk groups for severe CD evolution; MTX versus AZA/6MP in low-risk and MTX versus ADA in high-risk patients. Primary end point: sustained remission at 12 months (weighted paediatric CD activity index ≤12.5 and C reactive protein ≤1.5 fold upper limit) without relapse or ongoing requirement for exclusive enteral nutrition (EEN)/steroids 12 weeks after treatment initiation. Methods and analysis: REDUCE-RISK in CD is an international multicentre open-label prospective randomised controlled trial funded by EU within the Horizon2020 framework (grant number 668023). Eligible patients (aged 6–17 years, new-onset disease receiving steroids or EEN for induction of remission for luminal ± perianal CD are stratified into low and high-risk groups based on phenotype and response to induction therapy. Participants are randomised to one of two treatment arms within their risk group: low-risk patients to weekly subcutaneous MTX or daily oral AZA/6MP, and high-risk patients to weekly subcutaneous MTX or fortnightly ADA. Patients are followed up for 12 months at prespecified intervals. Electronic case report forms are completed prospectively. The study aims to recruit 312 participants (176 low risk; 136 high risk). Ethics and dissemination: ClinicalTrials.gov Identifier: (NCT02852694), authorisation and approval from local ethics committees have been obtained prior to recruitment. Individual informed consent will be obtained prior to participation in the study. Results will be published in a peer-reviewed journal with open access.

• Item Type: Articles
• Additional Information: Funding: This work was supported as part of the PIBD-SETQuality (Paediatric Inflammatory Bowel Diseases Network for Safety, Efficacy, Treatment and Quality improvement of care) project funded by the European Commission Horizon 2020 - Research and Innovation Framework Programme (grant number 668023). ADA (Humira) is provided by AbbVie.The main study sponsor is PIBDNet. PIBDNet is the EU legal representative for the study. The specific contact for the sponsor is Frank Ruemmele (Service de Gastro-entéroloegie, Hôpital Necker Enfants Maldes, 149 rue de Sèvres, 75015 Paris, France).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Russell, Dr Richard
• Authors: Harris, R. E., Aloi, M., de Ridder, L., Croft, N. M., Koletzko, S., Levine, A., Turner, D., Veereman, G., Neyt, M., Bigot, L., Ruemmele, F. M., and Russell, R. K.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: BMJ Open
• Publisher: BMJ Publishing Group
• ISSN: 2044-6055
• ISSN (Online): 2044-6055
• Copyright Holders: Copyright © Author(s) (or their employer(s)) 2020
• First Published: First published in BMJ Open 10(7):e034892
• Publisher Policy: Reproduced under a Creative Commons license