PDF(Pubmed)
Abstract：
BACKGROUND: 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: 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.
BACKGROUND: 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.
BACKGROUND: ACTRN12622001458729.
METHODS: 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.
BACKGROUND: 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.
BACKGROUND: ACTRN12622001458729.
摘要：
背景：接受静脉注射英夫利昔单抗治疗的炎症性肠病（IBD）患者中有相当大比例需要剂量强化。获得额外的静脉注射英夫利昔单抗是劳动密集型且昂贵的，取决于保险和药品报销。观察数据表明，皮下英夫利昔单抗可能提供一种方便且安全的替代方法，以维持需要剂量强化英夫利昔单抗的患者的疾病缓解。一个潜在的，需要进行对照试验以确认皮下英夫利昔单抗与剂量强化静脉注射英夫利昔单抗一样有效,确定疾病发作的预测因子，并建立皮下英夫利昔单抗治疗药物监测的作用。
方法：DISCUS-IBD试验由研究者发起，prospective,多中心,随机化，开放标签非劣效性研究比较48周后随机接受持续剂量强化静脉英夫利昔单抗治疗的参与者与接受皮下英夫利昔单抗治疗的参与者的疾病爆发率.参与者是IBD的成年患者，在任何剂量强化英夫利昔单抗方案下，每周4次静脉内最大剂量为10mg/kg的持续无皮质类固醇缓解。分配给静脉注射英夫利昔单抗的参与者将以他们在研究登记时接受的相同剂量强化方案继续英夫利昔单抗。皮下英夫利昔单抗给药将通过先前的静脉内英夫利昔单抗给药进行分层。临床(哈维-布拉德肖指数，部分梅奥得分)，生化(C反应蛋白，粪便钙卫蛋白)，每周12次收集药代动力学(药物水平±抗药抗体)和定性数据,直至第48周研究结束.澳大利亚的13个地点将参加招聘，以达到120名参与者的计算样本量。
背景：根据国家相互接受（NMA）协议（HREC/90559/Alfred-2022；本地参考：项目618/22，1.6版，2023年3月2日），获得了阿尔弗雷德医院卫生区人类研究伦理委员会（HREC）的批准。研究结果将在国家和国际胃肠病学会议上报告，并在同行评审的期刊上发表。在开始招募之前，DISCUS-IBD在澳大利亚和新西兰临床试验注册中心（ANZCTR）进行了前瞻性注册。
背景：ACTRN12622001458729。
方法：DISCUS-IBD试验由研究者发起，prospective,多中心,随机化，开放标签非劣效性研究比较48周后随机接受持续剂量强化静脉英夫利昔单抗治疗的参与者与接受皮下英夫利昔单抗治疗的参与者的疾病爆发率.参与者是IBD的成年患者，在任何剂量强化英夫利昔单抗方案下，每周4次静脉内最大剂量为10mg/kg的持续无皮质类固醇缓解。分配给静脉注射英夫利昔单抗的参与者将以他们在研究登记时接受的相同剂量强化方案继续英夫利昔单抗。皮下英夫利昔单抗给药将通过先前的静脉内英夫利昔单抗给药进行分层。临床(哈维-布拉德肖指数，部分梅奥得分)，生化(C反应蛋白，粪便钙卫蛋白)，每周12次收集药代动力学(药物水平±抗药抗体)和定性数据,直至第48周研究结束.澳大利亚的13个地点将参加招聘，以达到120名参与者的计算样本量。
背景：根据国家相互接受（NMA）协议（HREC/90559/Alfred-2022；本地参考：项目618/22，1.6版，2023年3月2日），获得了阿尔弗雷德医院卫生区人类研究伦理委员会（HREC）的批准。研究结果将在国家和国际胃肠病学会议上报告，并在同行评审的期刊上发表。在开始招募之前，DISCUS-IBD在澳大利亚和新西兰临床试验注册中心（ANZCTR）进行了前瞻性注册。
背景：ACTRN12622001458729。
