Buhl Sine Schnoor, Steenholdt Casper, Brynskov Jørn, Thomsen Ole Østergaard, Bendtzen Klaus, Ainsworth Mark Andrew
Department of Gastroenterology, Herlev Hospital, Herlev, Denmark.
Institute for Inflammation Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
BMJ Open. 2014 Dec 18;4(12):e005887. doi: 10.1136/bmjopen-2014-005887.
Infliximab (IFX), a monoclonal chimeric antibody against tumour necrosis factor (TNF) α, is effective for induction and maintenance of remission in moderate to severe Crohn's disease. Discontinuation of IFX maintenance therapy in patients in remission should be considered in order to reduce the potential long-term side effects and lower costs.
This is a prospective, double-blind, randomised, placebo-controlled, multicentre study of patients with luminal Crohn's disease who have been treated with IFX for at least 1 year and are in sustained complete clinical, biochemical and endoscopic remission (ie, Crohn's Disease Activity Index (CDAI) score <150, complete mucosal healing and biochemical markers of inflammation within the normal range). These patients are randomised to receive placebo infusions or continue IFX maintenance therapy. The primary end point is the proportion of patients in maintained remission after 48 weeks (def. CDAI <150).
It is estimated that the knowledge gained about how to optimally handle patients with Crohn's disease in complete long-term sustained remission on IFX is proportionate to the risks and inconveniences related to participation in this study. Prolonged exposure to IFX may cause severe side effects and increased risk of malignancies. Conversely, IFX discontinuation should not unnecessarily create a high risk of relapse. Thus, empirical evidence is needed concerning the safety of discontinuing IFX once a patient exhibits sustained remission. Study results will be published in an English language scientific medical journal. The study is approved by the Danish Medicines Agency (EudraCT-number: 2012-002702-51) and the Regional Ethics Committee of Region Hovedstaden Denmark (Approval-number: H-4-2012-099). The project is reported to the Danish Data Protection Agency (ID-number: 2007-58-0015/HEH.750.89-27), registered at Clinicaltrials.gov, and monitored by independent GCP units for the University of Copenhagen, Odense and Aarhus. The current approved protocol is V.3.2, dated 1 June 2014.
英夫利昔单抗（IFX）是一种抗肿瘤坏死因子（TNF）α的单克隆嵌合抗体，对中重度克罗恩病的诱导缓解和维持缓解均有效。为降低潜在的长期副作用并降低成本，应考虑对处于缓解期的患者停用IFX维持治疗。
这是一项前瞻性、双盲、随机、安慰剂对照、多中心研究，研究对象为接受IFX治疗至少1年且处于持续完全临床、生化和内镜缓解状态（即克罗恩病活动指数（CDAI）评分<150、完全黏膜愈合且炎症生化标志物在正常范围内）的肠腔型克罗恩病患者。这些患者被随机分为接受安慰剂输注或继续IFX维持治疗。主要终点是48周后维持缓解的患者比例（定义为CDAI<150）。
据估计，关于如何最佳处理在IFX治疗下实现长期完全持续缓解的克罗恩病患者所获得的知识，与参与本研究相关的风险和不便程度相当。长期使用IFX可能会导致严重副作用并增加患恶性肿瘤的风险。相反，停用IFX不应不必要地造成高复发风险。因此，需要有关患者出现持续缓解后停用IFX安全性的经验证据。研究结果将发表在英文科学医学期刊上。本研究已获得丹麦药品管理局（欧洲临床试验注册号：2012 - 002702 - 51）和丹麦首都大区地区伦理委员会（批准号：H - 4 - 2012 - 099）的批准。该项目已向丹麦数据保护局报告（身份识别号：2007 - 58 - 0015/HEH.750.89 - 27），在Clinicaltrials.gov注册，并由哥本哈根大学、欧登塞大学和奥胡斯大学的独立GCP单位进行监测。当前批准的方案为V.3.2，日期为2014年6月1日。
