To study 15-year outcomes of treatment with interferon beta-1b at or within <=2 years after clinically isolated syndrome (CIS)

Early treatment with interferon beta-1b after CIS has proven beneficial in the short term, but long-term data, especially up to advanced disease stages, are limited.

Patients with CIS and >=2 MRI lesions were randomly assigned to receive interferon beta-1b (early treatment) or placebo. After 2 years or conversion to clinically definite MS (CDMS), patients on placebo were offered treatment with interferon beta-1b (delayed treatment). Fifteen years after initial randomization, all patients from participating study centers were approached for reassessment.

261/468 initially randomized patients were enrolled (early: 161, delayed: 100; 7 patients deceased, information available for 268 [57.3% of the original cohort, 67.8% from 73 participating or contributing sites]). Mean observation time was 15.2 years. Mean delay in treatment start in the delayed group was 1.53 years. Kaplan-Meier estimate of risk of conversion to CDMS was 30.5% lower for the early vs delayed group (P=.0029). Similarly, PASAT scores throughout the study were higher for the early vs the delayed treatment group (P=.0036 over the 15 years). The annualized relapse rate was 0.2083 overall over 15 years. Kaplan-Meier estimate of risk of SPMS at 15 years was 10.2% overall. Mean (SD) EDSS score at 15 years was (2.5 [1.76]). No consistent differences were seen between treatment groups in MRI outcomes.

BENEFIT 15 provides important evidence supporting a sustained benefit of early intervention in reducing the risk of conversion to CDMS. The high PASAT scores, low EDSS, and low SPMS conversion rate further support the value of starting interferon beta-1b treatment at or shortly after CIS.