Efficacy of subcutaneous interferon β-1a on MRI outcomes in a randomised controlled trial of patients with clinically isolated syndromes.

AIM: The REbif FLEXible dosing in early MS (REFLEX) study compared several brain MRI outcomes in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis and treated with two dose-frequencies of subcutaneous interferon (IFN) beta-1a or placebo. METHODS: Patients were randomised (1:1:1) to IFN beta-1a, 44 g subcutaneously three times a week or once a week, or placebo three times a week for up to 24 months. MRI scans were performed every 3 months, or every 6 months if the patient developed clinically definite multiple sclerosis. End points analysed included: number of combined unique active lesions per patient per scan; numbers and volumes of new T2, T1 hypointense and gadolinium-enhancing (Gd+) lesions per patient per scan; and brain volume. RESULTS: 517 patients were randomised (intent-to-treat population: subcutaneous IFN beta-1a three times a week, n=171; subcutaneous IFN beta-1a once a week, n=175; placebo, n=171). Combined unique active lesions were lower in patients treated with subcutaneous IFN beta-1a versus placebo (mean (SD) lesions per patient per scan: three times a week 0.6 (1.15); once a week 1.23 (4.26); placebo 2.70 (5.23); reduction versus placebo: three times a week 81%; once a week 63%; p<0.001) and with three times a week versus once a week (48% reduction; p=0.002). The mean numbers of new T2, T1 hypointense and Gd+ lesions were all significantly lower in the two active treatment arms compared with placebo (p≤0.004 for three times a week or once a week) and in the three times a week group compared with once a week (p≤0.012). CONCLUSIONS: Both subcutaneous IFN beta-1a 44 g regimens improved MRI outcomes versus placebo, with the three times a week regimen having a more pronounced effect than once a week dosing. TRIAL REGISTRATION: clinicaltrial.gov identifier, NCT00404352.