Conference Coverage
In patients presenting with a first clinical demyelinating event, early treatment with subcutaneous interferon beta-1a three times per week over five years prolonged the time to clinically definite multiple sclerosis (MS), compared with delayed treatment, according to research published online ahead of print December 30, 2016 in the Journal of Neurology, Neurosurgery and Psychiatry. Compared with delayed treatment, early treatment also prolonged the time to McDonald MS conversion.
Giancarlo Comi, MD
Giancarlo Comi, MD, Professor of Neurology at the Scientific Institute H.S. Raffaele in Milan, and colleagues conducted REFLEXION, a preplanned extension of the REFLEX study, to compare the effect of more frequent and early dosing with that of delayed treatment. Eligible patients were between ages 18 and 50, had an Expanded Disability Status Scale (EDSS) score of 5.0 or lower, and a single clinical event suggestive of MS within 60 days of enrollment. In REFLEX, patients had been randomized to interferon beta-1a (44 μg) thrice weekly or once weekly, or placebo. Treatment lasted for 24 months or until a patient developed clinically definite MS.
In REFLEXION, patients first randomized to interferon beta-1a who had not converted to clinically definite MS continued their original dosing regimen. Patients originally receiving placebo who had not converted to clinically definite MS were switched to interferon beta-1a (44 μg thrice weekly). These patients became the delayed-treatment group. Patients who converted to clinically definite MS during REFLEX or REFLEXION received open-label interferon beta-1a 44 μg thrice weekly from then on.
EDSS scores and clinically definite MS assessments were recorded at extension baseline (ie, month 24) and every six months thereafter. The primary end point was time to conversion to clinically definite MS from first randomization to month 36. Time to clinically definite MS to month 60 was a secondary end point.
The extension study included 127 participants originally randomized to interferon beta-1a thrice weekly, 142 participants originally randomized to interferon beta-1a once weekly, and 133 patients originally randomized to placebo. At month 36, the proportion of patients who had converted to clinically definite MS was lower among patients receiving interferon thrice weekly or weekly, compared with the delayed-treatment group (25.1%, 25.7%, and 38.6%, respectively). The risk of conversion to clinically definite MS was significantly reduced for patients receiving early treatment, compared with delayed treatment. The researchers found no significant difference between the early-treatment groups.
The analysis for month 60 also found that both early-treatment groups had longer times to clinically definite MS, compared with delayed treatment. The proportion of patients who converted to clinically definite MS increased at month 60, but was still lower among participants receiving thrice-weekly or weekly interferon than among patients on delayed treatment (32.2%, 36.0%, and 40.4%, respectively). Cumulative probability of conversion was lower with thrice-weekly and weekly early treatment than with delayed treatment (39.2%, 40.7%, and 44.6%, respectively).
—Erik Greb
Suggested Reading
Comi G, De Stefano N, Freedman MS, et al. Subcutaneous interferon β-1a in the treatment of clinically isolated syndromes: 3-year and 5-year results of the phase III dosing frequency-blind multicentre REFLEXION study. J Neurol Neurosurg Psychiatry. 2016 Dec 30 [Epub ahead of print].