Predictors of long-term outcome in multiple sclerosis patients treated with interferon β.

Objective: To identify early predictors of long-term outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) treated with intramuscular (IM) interferon beta-1a (IFN beta-1a). Methods: A multicenter, observational, 15-year follow-up study of patients who completed >= 2 years in the pivotal trial of IM IFN beta-1a for RRMS was conducted. One hundred thirty-six patients participated in the 15-year follow-up (69 originally randomized to IM IFN beta-1a and 67 to placebo). After the 2-year clinical trial, treatment was not regulated by study protocol. Disease activity during the 2-year trial was defined as: >= 2 gadolinium-enhancing lesions (cumulative) on year 1 and/or year 2 magnetic resonance imaging (MRI); >= 3 new T2 lesions on year 2 MRI compared to baseline; and >= 2 relapses over 2 years. Odds ratios were calculated for early disease activity predicting severe Expanded Disability Status Scale (EDSS) worsening (worst quartile of change, >= 4.5 EDSS points) during the 15-year interval. Results: The proportion of patients experiencing early disease activity was lower in patients on IM IFN beta-1a than placebo for all disease activity markers (range, 23.5-29.0% vs 41.0-45.5%). In the IM IFN beta-1a group, persistent disease activity predicted severe EDSS worsening: gadolinium-enhancing lesions (odds ratio [OR], 8.96; p < 0.001); relapses (OR, 4.44; p = 0.010); and new T2 lesions (OR, 2.90; p = 0.080). In placebo patients, early disease activity was not as strongly associated with long-term outcomes (OR range, 1.53-2.62; p = 0.069-0.408). Interpretation: Disease activity despite treatment with IFN beta is associated with unfavorable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFN beta therapy, as their presence strongly correlates with severe disability 15 years later. The results provide rationale for monitoring IFN beta-treated patients with MRI, and for changing therapy in patients with active disease. ANN NEUROL 2013;73:95-103