Defining interferon β response status in multiple sclerosis patients

IFN‐β is effective in reducing relapses and magnetic resonance imaging (MRI) lesions in multiple sclerosis (MS). It is assumed that individual therapeutic responses vary, but methods to identify IFN‐β responsiveness have not been validated. Our objective was to evaluate methods to classify IFN‐β responder status using relapses and MRI lesions. Data was analyzed from 172 patients who were followed up in a placebo‐controlled clinical trial of IFN‐β1a for 2 years. Patients were classified as responders or nonresponders using (1) the number of relapses during the 2‐year trial; (2) the number of new T2 lesions after 2 years; and (3) the number of gadolinium‐enhancing lesions at year 1 and year 2 on study. Outcomes included 2‐year change in the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, and brain parenchymal fraction. We found that subgroups with high on‐study relapse numbers had more disease progression, differences between responder subgroups were similar in the IFN‐β1a and placebo arms. In contrast, subgroups with high numbers of new MRI lesions had significantly more disease progression only in the IFN‐β1a arm. Baseline characteristics failed to account for differential outcome. New MRI lesion activity during IFN‐β1a treatment correlates with poor response to IFN‐β1a. MRI classification may facilitate rational therapeutic decisions, better clinical trial designs, and studies correlating biomarkers with therapeutic response. Ann Neurol 2004