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Avonex Combination Trial in relapsing–remitting MS: rationale, design and baseline data

¹ Mellen Center, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
² Department of Neurology, Johns Hopkins, Baltimore, MD 21287, USA
³ Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
⁴ MS Center of Southern Vermont, Bennington, VT 05201, USA
⁵ Medical Affairs, Biogen Idec, Inc., Cambridge, MA 02142, USA
⁶ Department of Neurology, Virginia Commonwealth University Medical Center, Richmond, VA 23298, USA
⁷ Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
⁸ Department of Neurology, University of Rochester, Rochester, NY 14642, USA
⁹ Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA
¹⁰ Department of Rheumatic and Immunologic Disease, Cleveland Clinic Foundation, Cleveland, OH 44195, USA
¹¹ Drexel College of Medicine, Pittsburgh, PA 15212, USA

^* To whom correspondence should be addressed.

	Abstract

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_-1a) combined with methotrexate (MTX) and/or IV methylprednisolone (IVMP) in relapsing–remitting multiple sclerosis (RRMS) patients with continued disease activity on IM IFN_-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_-1a monotherapy. Subjects continued IFN_-1a 30 mcg IM weekly and were randomized in a 2 _ 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_ 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.

Key Words: clinical trial; interferon beta-1a; methotrexate; methylprednisolone; multiple sclerosis

First published on January 21, 2008, doi:10.1177/1352458507083189

Multiple Sclerosis 2008;14:370.

A more recent version of this article appeared on April 1, 2008


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