Abstract

Protocol for a multinational 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. 2020 Jul 1;10(7):e034892. doi: 10.1136/bmjopen-2019-034892.

Rachel E Harris 1, Marina Aloi 2, Lissy de Ridder 3, Nicholas M Croft 4, Sibylle Koletzko 5 6, Arie Levine 7, Dan Turner 8, Gigi Veereman 9 10, Mattias Neyt 11, Laetitia Bigot 12, Frank M Ruemmele 13 14, Richard K Russell 1, PIBD SETQuality consortium and PIBDnet

 
     

Author information

  • 1Department of Paediatric Gastroenterology, Royal Hospital for Children Glasgow, Glasgow, UK.
  • 2Paediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Roma, Lazio, Italy.
  • 3Paediatrics, Erasmus MC/Sophia Childrens Hospital, Rotterdam, The Netherlands l.deridder@erasmusmc.nl.
  • 4Department of Paediatric Gastroenterology, Barts and The London School of Medicine and Dentistry, London, UK.
  • 5Pediatric Gastroenterology and Hepatology, Dr. V. Hauner Children's Hospital, Munich, Germany.
  • 6Department of Pediatrics, Collegium Medicum University of Warmia and Mazury, Olsztyn, Poland.
  • 7Edith Wolfson Medical Center, Tel Aviv University, Tel Aviv, Israel.
  • 8Department of Paediatric Gastroenterology, Hebrew University of Jerusalem, Jerusalem, Israel.
  • 9Pediatric GI, UZBrussels-VUB, Brussels, Belgium.
  • 10Free University Brussels, University Hospital, Brussels, Belgium.
  • 11ME-TA Medical Evaluation and Technology Assessment, Merendree, Belgium.
  • 12PIBD-Net, Hôpital universitaire Necker-Enfants malades, Paris, Île-de-France, France.
  • 13Service de Gastroentérologie Pédiatrique, Hôpital Universitaire Necker-Enfants Malades, Paris, Île-de-France, France.
  • 14Department of Paediatric Gastroenterology, Université Paris Descartes, Paris, Île-de-France, France.

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.

Trial registration number: NCT02852694; Pre-results.

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