Effect of Two Dosing Frequencies of Subcutaneous Interferon (scIFN) β-1a on MRI Lesion and Brain Volume Changes in Patients with a First Clinical Demyelinating Event (FCDE): 5-year Results of Phase III REFLEX Study Extension (REFLEXION) (P7.250)

OBJECTIVE: Determine the effects of scIFN β-1a, initiated early after an FCDE, on changes in MRI lesion volume and brain volume over 5 years compared with delayed treatment (DT). BACKGROUND: Early treatment with scIFN β-1a 44 µg three times weekly (tiw) or once weekly (qw) significantly delayed McDonald MS diagnosis (2005 criteria) and CDMS versus placebo over 24 months in the REFLEX study. In the REFLEX extension (REFLEXION), early initiation of scIFN β-1a significantly benefited MRI lesion and brain volume changes at 36 months. DESIGN/METHODS: In REFLEX, patients were randomized to double-blind scIFN β-1a 44 µg tiw or qw, or placebo for 24 months; upon CDMS diagnosis, patients switched to open-label scIFN β-1a 44 µg tiw. In REFLEXION, placebo patients not reaching CDMS were switched to tiw (DT); qw and tiw patients not reaching CDMS continued their regimen for up to 60 months after randomization. MRI and brain volume assessments were performed annually.Statistical analyses were exploratory; all p-values were nominal. RESULTS: 402/517 (77.8[percnt]) REFLEX patients entered REFLEXION (DT, n=133; tiw, n=127; qw, n=142). At Month 60, mean numbers of new T2, gadolinium-enhancing and T1 hypointense lesions/subject/scan were lower with scIFN β-1a 44 µg qw (all p 3 versus -33.6 (2513.13) mm 3 (p 3 versus 329.8 (939.33) mm 3 (p=0.007). Mean (SD) percentage change from baseline in brain volume at LOV was DT -1.49 (1.46)[percnt], qw -1.33 (1.35)[percnt] and tiw -1.70 (1.58)[percnt] (p=0.032 qw versus tiw). CONCLUSIONS: Over 5 years, scIFN β-1a, initiated early after an FCDE, improved changes in MRI lesion number and volume, and brain volume compared with DT. Study Supported by: Merck Serono. Disclosure: Dr. Barkhof has received personal compensation for activities with Bayer Schering Pharma, Sanofi, Genzyme, Biogen Idec, Teva, Merck Serono, Novartis, Roche, Synthon BV, and Janssen Research as a consultant. Dr. Comi has received personal compensation for activities with Teva, Novartis, Genzyme, Merck Serono, Biogen Idec, Bayer, Actelion Pharmaceuticals, Almirall, and Serono. Dr. Freedman has received personal compensation for activities with Bayer Healthcare, Biogen Idec, Chugai, EMD Canada, Genzyme, Novartis, Sanofi-Aventis, and Teva Canada Innovation. Dr. Uitdehaag has received personal compensation for activities with Biogen Idec, Novartis, EMD Serono, Teva Neuroscience, Genzyme Corporation, and Roche Diagnostics Corporation. Dr. Fischer has received personal compensation for activities with EMD Serono as an employee. Dr. Chen has received personal compensation for activities with EMD Serono as an employee. Dr. Kappos has received personal compensation for activities with Actelion Pharmaceuticals. Dr. De Stefano has received personal compensation for activities with Teva Neuroscience, Bayer, Sanofi-Aventis, Biogen Idec, Novartis, and Merck Serono.