Defining interferon beta response status in multiple sclerosis patients.
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.
Rudick
Richard A
RA
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Foundation, OH 44195, USA. rudick@cdf.org
Lee
Jar-Chi
JC
Simon
Jack
J
Ransohoff
Richard M
RM
Fisher
Elizabeth
E
D000328:Adult; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005682:Gadolinium; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000517:prevention & control*; D015203:Reproducibility of Results; D055502:Secondary Prevention; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D016899:Interferon-beta; D005682:Gadolinium; D000068556:Interferon beta-1a