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

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 IFNβ-1a) combined with methotrexate (MTX) and/or IV methylprednisolone (IVMP) in relapsing—remitting multiple sclerosis (RRMS) patients with continued disease activity on IM IFNβ-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 IFNβ-1a monotherapy. Subjects continued IFNβ-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 A...