一项多中心随机对照试验方案，该试验旨在研究根据溃疡性结肠炎炎症负荷进行个性化戈利木单抗给药的应用：由INITIAtive小组牵头的GOAL-ARC研究（戈利木单抗剂量优化至适当水平以实现结肠炎缓解）（NCT 0268772）
Protocol for a multicentred randomised controlled trial investigating the use of personalised golimumab dosing tailored to inflammatory load in ulcerative colitis: the GOAL-ARC study (GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis) led by the INITIAtive group (NCT 0268772).
作者信息
Sheridan Juliette, Coe Carol Ann, Doran Peter, Egan Laurence, Cullen Garret, Kevans David, Leyden Jan, Galligan Marie, O'Toole Aoibhlinn, McCarthy Jane, Doherty Glen
机构信息
Centre for Colorectal Disease, St. Vincent's University Hospital, School of Medicine, UCD, Dublin, Ireland.
UCD Clinical Research Centre, UCD School of Medicine, Dublin, Ireland.
出版信息
BMJ Open Gastroenterol. 2018 Jan 11;5(1):e000174. doi: 10.1136/bmjgast-2017-000174. eCollection 2018.
INTRODUCTION
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), often leading to an impaired quality of life in affected patients. Current treatment modalities include antitumour necrosis factor (anti-TNF) monoclonal antibodies (mABs) including infliximab, adalimumab and golimumab (GLM). Several recent retrospective and prospective studies have demonstrated that fixed dosing schedules of anti-TNF agents often fails to consistently achieve adequate circulating therapeutic drug levels (DL) with consequent risk of immunogenicity treatment failure and potential risk of hospitalisation and colectomy in patients with UC.The design of GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis aims to address the impact of dose escalation of GLM immediately following induction and during the subsequent maintenance phase in response to suboptimal DL or persisting inflammatory burden as represented by raised faecal calprotectin (FCP).
AIM
The primary aim of the study is to ascertain if monitoring of FCP and DL of GLM to guide dose optimisation (during maintenance) improves rates of patient continuous clinical response and reduces disease activity in UC.
METHODS AND ANALYSIS
A randomised, multicentred two-arm trial studying the effect of dose optimisation of GLM based on FCP and DL versus treatment as per SMPC. Eligible patients will be randomised in a 1:1 ratio to 1 of 2 treatment groups and shall be treated over a period of 46 weeks.
ETHICS AND DISSEMINATION
The study protocol was approved by the Research Ethics committee of St. Vincent's University Hospital. The results will be published in a peer-reviewed journal and shared with the worldwide medical community.
TRIAL REGISTRATION NUMBERS
EudraCT number: 2015-004724-62; Clinicaltrials.gov Identifier: NCT0268772; Pre-results.
引言
溃疡性结肠炎（UC）是一种慢性炎症性肠病（IBD），常导致患者生活质量受损。目前的治疗方式包括抗肿瘤坏死因子（抗TNF）单克隆抗体（mABs），如英夫利昔单抗、阿达木单抗和戈利木单抗（GLM）。最近的几项回顾性和前瞻性研究表明，抗TNF药物的固定给药方案往往无法持续达到足够的循环治疗药物水平（DL），从而导致免疫原性治疗失败的风险，以及UC患者住院和结肠切除术的潜在风险。戈利木单抗剂量优化至足够水平以实现结肠炎反应的设计旨在解决诱导后立即以及随后维持阶段因DL未达最佳或粪便钙卫蛋白（FCP）升高所代表的持续炎症负担而进行的GLM剂量递增的影响。
目的
本研究的主要目的是确定监测FCP和GLM的DL以指导剂量优化（维持期间）是否能提高UC患者持续临床反应率并降低疾病活动度。
方法与分析
一项随机、多中心双臂试验，研究基于FCP和DL的GLM剂量优化与按照药品说明书治疗的效果对比。符合条件的患者将按1:1比例随机分为2个治疗组中的1组，并接受为期46周的治疗。
伦理与传播
研究方案已获圣文森特大学医院研究伦理委员会批准。研究结果将发表在同行评审期刊上，并与全球医学界共享。
试验注册号
欧洲临床试验数据库（EudraCT）编号：2015 - 004724 - 62；美国国立医学图书馆临床试验注册中心标识符：NCT0268772；预结果。
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