Up to 85% of patients who eventually receive a diagnosis of multiple sclerosis (MS) will initially present with a first clinical demyelinating event (FCDE) [Freedman M. Ther Adv Neurol Disord. 2014]. If left untreated, up to 45% of patients will convert to clinically definite MS (CDMS) within 2 years [Kappos L et al. Neurology. 2006]. Results from the REFLEX trial [Comi G et al. Lancet Neurol. 2012] suggest that 2 different dosing frequencies of interferon beta-1a (IFN-β-1a) were able to significantly delay clinical relapses following an FCDE (IFN-β-1a once a week [P = .0023]; IFN-β-1a 3 times a week [P = .0004]) compared with placebo.

Mark Freedman, MD, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada, presented data from the REFLEXION trial [NCT00813709], an open-label extension of the REFLEX trial. The objective of the trial was to determine the benefits of early vs delayed treatment over 60 months in patients who experienced an FDCE.

In the REFLEX trial, patients were blindly randomized to 3 treatment groups for 24 months: (1) subcutaneous IFN-β-1a 44 µg once weekly, (2) the same dose of IFN-β-1a 3 times a week, or (3) placebo. If patients converted to CDMS, they were switched to IFN-β-1a 44 µg 3 times per week. In REFLEXION, patients previously on placebo who did not convert to CDMS were switched to IFN-β-1a 44 µg 3 times per week (delayed treatment). Those patients randomized to IFN-β-1a who did not reach CDMS continued their initial regimen for up to 60 months after randomization.

Almost 78% of the 517 REFLEX patients (n = 402) entered REFLEXION and were stratified into 3 groups: delayed treatment (placebo), IFN-β-1a 44 µg 3 times weekly, or IFN-β-1a 44 µg once weekly. Conversion to CDMS was defined as a second attack or a sustained increase in ≥ 1.5 points on the Expanded Disability Status Scale. Of note is that all 517 patients were included in the 60-month intention-to-treat analysis.

Patients in the 2 INF-β-1a groups had a longer time to conversion than those in the delayed treatment group. Further, 32.2% and 36% of patients in the IFN-β-1a 44 µg 3 times weekly and IFN-β-1a 44 µg once weekly groups converted to CDMS over 60 months, compared with 40.4% of patients in the delayed treatment group.

The cumulative probability of CDMS conversion was 38.6% (95% CI, 30.8% to 47.6%) with IFN-β-1a 44 µg 3 times weekly, 40.7% (95% CI, 32.8% to 48.6%) with IFN-β-1a 44 µg once weekly, and 44.6% (95% CI, 36.6% to 52.6%) with delayed treatment. Results were similar when the definition of CDMS was changed to a sustained 3-month increase (≥ 2.5 points) on the Expanded Disability Status Scale, with a cumulative probability of CDMS conversion of 38.6% vs 39.6% vs 43.8%, respectively, in the 3 groups.

At month 60, the annualized relapse rate was higher for patients in the delayed-treatment group and fewer patients in the delayed-treatment group were free of relapse compared with those who received IFN-β-1a.

To conclude, early treatment with IFN-β-1a appears to prolong time to CDMS over 60 months and is associated with fewer relapses. According to Prof Freedman, these data reinforce the benefits of initiating early treatment with IFN-β-1a following an FDCE.