Comparative multicentre, randomised, assessor-blinded study of efficacy and safety of interferon-β-1a (Rebif®) and glatiramer acetate (Copaxone®) in relapsing-remitting multiple sclerosis

Interferon (IFN) b-1a and glatiramer acetate (GA) are commonly prescribed as disease-modifying therapies for relapsing /remitting multiple sclerosis (RRMS). Both have been shown to reduce relapse rates, but differences are apparent on disability scores and magnetic resonance imaging (MRI) findings. Debate continues as to the relative benefits of IFN and GA thus emphasizing the need for randomized direct comparisons of their efficacy. MS drug efficacy is important, as it is now known that permanent axonal damage occurs early, even when patients appear to be doing well clinically. MRI can detect changes in disease state before these are clinically evident, hence it has been suggested that disease activity is underestimated, by a factor of 5- to 10-fold, for clinical vs MRI measures. Such observations support use of the most effective therapy early to help prevent the subclinical progression of demyelination and axon destruction leading to permanent disability. This multinational study will enroll 736 IFN- and GA-naı¨ve subjects with definite RRMS, Expanded Disability Status Scale scores 0 /5.5 and clinically active disease (]/1 relapse in the prior 12 months). Randomized patients will receive IFN b-1a, 44 mcg sc tiw, or GA, 20 mg sc od, for 96 weeks. Efficacy will be assessed by neurological examinations by blinded physicians, and serial MRIs analyzed by blinded radiologists at a central reading facility. Routine clinical follow up, hematology, clinical chemistry, urinalysis, antibody titers to GA and IFN, and adverse event monitoring will also be performed. The primary and main secondary outcomes will be time to first relapse, and mean number of T2 active (new or enlarging) lesions per patient per scan. Additional secondary outcomes include proportion of relapse-free patients, proportion with 3-month confirmed disability progression, brain volume change, number and volume of gadolinium-enhanced lesions, mean number of new T1 hypointense lesions per patient per scan, and change in volume of T2 and T1 hypointense lesion volume. This study will provide important data on the comparative efficacy and safety of IFN b-1a and GA in early treatment of patients with RRMS.