Defining interferon beta response status in multiple sclerosis patients

Ann Neurol. 2004 Oct;56(4):548-55. doi: 10.1002/ana.20224.


IFN-beta 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-beta responsiveness have not been validated. Our objective was to evaluate methods to classify IFN-beta 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-beta1a 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-beta1a and placebo arms. In contrast, subgroups with high numbers of new MRI lesions had significantly more disease progression only in the IFN-beta1a arm. Baseline characteristics failed to account for differential outcome. New MRI lesion activity during IFN-beta1a treatment correlates with poor response to IFN-beta1a. MRI classification may facilitate rational therapeutic decisions, better clinical trial designs, and studies correlating biomarkers with therapeutic response.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Brain Infarction / drug therapy
  • Brain Infarction / etiology
  • Brain Infarction / pathology
  • Disability Evaluation
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Gadolinium
  • Humans
  • Image Enhancement / methods
  • Interferon beta-1a
  • Interferon-beta / therapeutic use*
  • Magnetic Resonance Imaging / methods
  • Male
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis, Relapsing-Remitting / prevention & control*
  • Reproducibility of Results
  • Secondary Prevention
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome


  • Interferon-beta
  • Gadolinium
  • Interferon beta-1a