Switching from Dose-Intensified intravenous to SubCutaneoUS infliximab in Inflammatory Bowel Disease (DISCUS-IBD): protocol for a multicentre randomised controlled trial

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

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.

Keywords: Adult gastroenterology; Clinical trials; Inflammatory bowel disease.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Administration, Intravenous
  • Adult
  • Australia
  • Drug Monitoring / methods
  • Female
  • Gastrointestinal Agents* / administration & dosage
  • Gastrointestinal Agents* / therapeutic use
  • Humans
  • Inflammatory Bowel Diseases* / drug therapy
  • Infliximab* / administration & dosage
  • Infliximab* / pharmacokinetics
  • Infliximab* / therapeutic use
  • Injections, Subcutaneous
  • Male
  • Multicenter Studies as Topic
  • Prospective Studies

Substances

  • Gastrointestinal Agents
  • Infliximab