BMJ Open. 2024 Jul 20;14(7):e081787.doi: 10.1136/bmjopen-2023-081787.

Robert D Little ^1 2, Jo McKenzie ³, Ashish Srinivasan ^4 5, Patrick Hilley ⁴, Robert B Gilmore ^6 7, Desmond Chee ⁸, Manjeet Sandhu ⁸, Daniel Saitta ⁹, Elizabeth Chow ^5 9, Lena Thin ^10 11, Gareth J Walker ^12 13, Gregory T Moore ^2 8, Kate Lynch ^14 15, Jane Andrews ^14 15, Yoon K An ^6 7, Robert V Bryant ^15 16, Susan J Connor ^17 18, Mayur Garg ^5 19, Emily K Wright ^5 20, Georgina Hold ²¹, Jonathan P Segal ^5 22, Alex Boussioutas ^3 2, Peter De Cruz ^4 5, Mark G Ward ^3 2, Miles P Sparrow ^3 2

Author information

¹Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia r.little@alfred.org.au.

²Monash University, Faculty of Medicine Nursing and Health Sciences, Clayton, Victoria, Australia.

³Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia.

⁴Department of Gastroenterology, Austin Health, Melbourne, Victoria, Australia.

⁵Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne Melbourne Medical School, Melbourne, Victoria, Australia.

⁶Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, Queensland, Australia.

⁷Mater Research Institute-UQ, South Brisbane, Queensland, Australia.

⁸Gastroenterology Department, Monash Health, Melbourne, Victoria, Australia.

⁹Department of Gastroenterology, Western Health, Melbourne, Victoria, Australia.

¹⁰Department of Gastroenterology, Fiona Stanley Hospital, Perth, Western Australia, Australia.

¹¹Department of Internal Medicine, The University of Western Australia Faculty of Medicine Dentistry and Health Sciences, Perth, Western Australia, Australia.

¹²Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.

¹³Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

¹⁴Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.

¹⁵School of Medicine, The University of Adelaide Faculty of Health and Medical Sciences, Adelaide, South Australia, Australia.

¹⁶Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia.

¹⁷Department of Gastroenterology, Liverpool Hospital, Sydney, New South Wales, Australia.

¹⁸South West Sydney Clinical Campuses, University of New South Wales Medicine & Health, Sydney, New South Wales, Australia.

¹⁹Department of Gastroenterology, Northern Health, Melbourne, Victoria, Australia.

²⁰Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.

²¹Microbiome Research Centre, University of New South Wales, Sydney, New South Wales, Australia.

²²Department of Gastroenterology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Abstract

Introduction: A substantial proportion of patients with inflammatory bowel disease (IBD) on intravenous infliximab require dose intensification. Accessing additional intravenous infliximab is labour-intensive and expensive, depending on insurance and pharmaceutical reimbursement. Observational data suggest that subcutaneous infliximab may offer a convenient and safe alternative to maintain disease remission in patients requiring dose-intensified infliximab. A prospective, controlled trial is required to confirm that subcutaneous infliximab is as effective as dose-intensified intravenous infliximab, to identify predictors of disease flare and to establish the role of subcutaneous infliximab therapeutic drug monitoring.

Methods and analysis: The DISCUS-IBD trial is an investigator-initiated, prospective, multicentre, randomised, open-label non-inferiority study comparing the rate of disease flares in participants randomised to continue dose-intensified intravenous infliximab to those switched to subcutaneous infliximab after 48 weeks. Participants are adult patients with IBD in sustained corticosteroid-free remission on any regimen of dose-intensified infliximab up to a maximum of 10 mg/kg 4-weekly intravenously. Participants allocated to intravenous infliximab will continue infliximab at the same dose-intensified regimen they were receiving at study enrolment. Subcutaneous infliximab dosing will be stratified by prior intravenous infliximab dosing. Clinical (Harvey-Bradshaw Index, partial Mayo score), biochemical (C reactive protein, faecal calprotectin), pharmacokinetic (drug-level±antidrug antibodies) and qualitative data are collected 12-weekly until study conclusion at week 48. 13 sites across Australia will participate in recruitment to reach a calculated sample size of 120 participants.

Ethics and dissemination: Multisite ethics approval was obtained from the Health District Human Research Ethics Committee (HREC) at The Alfred Hospital under a National Mutual Acceptance (NMA) agreement (HREC/90559/Alfred-2022; Local Reference: Project 618/22, version 1.6, 2 March 2023). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. DISCUS-IBD was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) prior to commencing recruitment.

Trial registration number: ACTRN12622001458729.