Effect of Two Dosing Frequencies of Subcutaneous Interferon (scIFN) β-1a on Conversion to Multiple Sclerosis (MS) in Patients with a First Clinical Demyelinating Event (FCDE): 5-year Results of Phase III, Double-blind, Multicenter Trials (REFLEX/REFLEXION) (P7.206)

OBJECTIVE: Determine the benefits of early versus delayed treatment (DT) with scIFN β-1a in patients with an FCDE, up to 60 months after randomization. BACKGROUND: Early treatment with scIFN β-1a 44 µg three times weekly (tiw) or once weekly (qw) after an FCDE significantly delays time to McDonald MS (2005 criteria) and clinically definite MS (CDMS). 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 patients switched to open-label scIFN β-1a 44 µg tiw). In REFLEXION, placebo patients not reaching CDMS were switched to tiw (DT); scIFN β-1a patients not reaching CDMS continued their initial regimen (qw or tiw) for up to 60 months after randomization. RESULTS: 402/517 (77.8[percnt]) REFLEX patients entered REFLEXION (DT, n=133; tiw, n=127; qw, n=142). At Month 60, cumulative probability of CDMS (defined as a second attack or a sustained increase [蠅1.5 points] in EDSS score) was: DT 44.6[percnt] [95[percnt] CI 36.6-52.6[percnt]]; qw 40.7[percnt] [32.8-48.6[percnt]] (nominal p=0.084 vs DT); tiw 39.2[percnt] [30.8-47.6[percnt]] (nominal p=0.032 vs DT; nominal p=0.852 vs qw). Results were very similar using a definition of CDMS conversion as either a second attack or a sustained 3-month increase in EDSS (蠅2.5 points). Minimal differences were seen for numbers of confirmed EDSS progression between groups. Proportion of subjects who converted to McDonald MS was higher with DT (84.2[percnt] at Month 60) than qw (82.9[percnt]) and tiw (72.5[percnt]). The cumulative probability of McDonald MS conversion at Month 60 was: DT 86.5[percnt] (81.2-91.8[percnt]); qw 89.5[percnt] (84.1-94.9[percnt]); tiw 79.2[percnt] (72.3-86.1[percnt]). Risk reduction for tiw vs DT was 45.4[percnt] (nominal p<0.001). CONCLUSIONS: Over 5 years, early scIFN β-1a tiw treatment prolonged time to CDMS and McDonald MS versus DT in patients initially presenting with an FCDE. Study Supported by: Merck Serono Disclosure: 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. Comi has received personal compensation for activities with Teva, Novartis, Genzyme, Merck Serono, Biogen Idec, Bayer, Actelion Pharmaceuticals, Almirall, and Serono. Dr. De Stefano has received personal compensation for activities with Teva Neuroscience, Bayer, Sanofi-Aventis, Biogen Idec, Novartis, and Merck Serono. 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. Uitdehaag has received personal compensation for activities with Biogen Idec, Novartis, EMD Serono, Teva Neuroscience, Genzyme Corporation, and Roche Diagnostics Corporation. Dr. Kappos has received personal compensation for activities with Actelion Pharmaceuticals. 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.