Avonex Combination Trial in relapsing-remitting MS: rationale, design and baseline data
Avonex Combination Trial in relapsing-remitting MS: rationale, design and baseline data
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DOI：
10.1177/1352458507083189
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发表时间：
2008-04-01
期刊：
影响因子：
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通讯作者：
Zhang, H.
中科院分区：
文献类型：
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作者：
Cohen, J. A.;Calabresi, P. A.;Zhang, H.
目的回顾Avonex联合试验（ACT）的基本原理、设计和基线数据，这是一项研究人员开展的肌肉注射干扰素β -1a （IM IFN β -1a）联合甲氨喋呤（MTX）和/或IV甲基强的松龙（IVMP）治疗复发缓解型多发性硬化症（RRMS）持续疾病活动的IM IFN β -1a单药治疗患者的研究。方法入选标准包括RRMS评分、扩展残疾状态量表评分0-5.5分、>= 1在前一年接受IM IFN β -1a单药治疗时复发或钆增强MRI病变。受试者继续每周服用IFN β -1a 30mcg IM，并在2 × 2因子设计中随机分为辅助每周安慰剂或MTX 20mg PO，每隔一个月服用或不服用IVMP 1000 mg/天，每隔一个月服用三天。ACT由行业支持，由独立咨询委员会和数据安全监测委员会的研究者指导委员会共同设计和管理。研究操作、MRI分析和汇总数据由克利夫兰诊所MS学术协调中心管理。结果共纳入313例具有典型RRMS临床和MRI特征的受试者。大多数受试者（86.9%）在前一年有或没有增强MRI病变，符合临床复发的标准。在基线时，21.4%的患者有强化病变，5.1%的患者有抗ifn β中和抗体。ACT的管理和业务结构运作良好。结论：本研究为学术界和产业界的MS合作研究提供了一个创新的模式，并将加强对RRMS患者在已建立的一线治疗基础上持续疾病活动的联合治疗的效用的理解。
Objective To review the rationale, design and baseline data of the Avonex Combination Trial (ACT), an investigator-run study of intramuscular interferon beta-1a (IM IFN beta-1a) combined with methotrexate (MTX) and/or IV methylprednisolone (IVMP) in relapsing-remitting multiple sclerosis (RRMS) patients with continued disease activity on IM IFN beta-1a monotherapy.Methods Eligibility criteria included RRMS, Expanded Disability Status Scale score 0-5.5, and >= 1 relapse or gadolinium-enhancing MRI lesion in the prior year while on IM IFN beta-1a monotherapy. Subjects continued IFN beta-1a 30 mcg IM weekly and were randomized in a 2 x 2 factorial design to adjunctive weekly placebo or MTX 20 mg PO, with or without IVMP 1000 mg/day for three days every other month. ACT was industry-supported, and collaboratively designed and governed by an Investigator Steering Committee with independent Advisory and Data Safety Monitoring Committees. Study operations, MRI analysis and aggregated data were managed by the Cleveland Clinic MS Academic Coordinating Center.Results In total 313 subjects were enrolled with clinical and MRI characteristics typical of RRMS. Most subjects (86.9%) qualified with a clinical relapse, with or without an enhancing MRI lesion, in the preceding year. At baseline, 21.4% had enhancing lesions, and 5.1% had anti-IFN beta neutralizing antibodies. ACT's management and operational structures functioned well.Conclusion This study provides an innovative model for academic-industry collaborative MS research and will enhance understanding of the utility of combination therapy for RRMS patients with continued disease activity on an established first-line treatment.