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From the Outpatient Clinic Neurology-Neurosurgery (Dr. Kappos), University Hospital Basel, Switzerland; Department of Neurology (Dr. Weinshenker), Mayo Clinic and Foundation, Rochester, MN; Department of Neurology (Dr. Pozzilli), University of Rome "La Sapienza," Italy; Department of Neurology (Dr. Thompson), National Hospital, London, UK; Schering AG (Dr. Dahlke and K. Beckmann), Berlin, Germany; Department of Neurology (Dr. Polman), VU Medical Center, Amsterdam, the Netherlands; and Neuroimmunology Branch (Dr. McFarland), National Institutes of Health, Bethesda, MD.
Address correspondence and reprint requests to Dr. Ludwig Kappos, Outpatient Clinic Neurology-Neurosurgery, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland; e-mail: lkappos{at}uhbs.ch
Background: A European (EU) and a North American (NA) placebo-controlled study with interferon beta-1b (IFNB-1b) in secondary progressive multiple sclerosis (SPMS) showed divergent results with regard to their primary outcome of sustained Expanded Disability Status Scale (EDSS) progression, while effects were similar on relapse and MRI-related endpoints. Reasons for this discrepancy were explored in the combined dataset.
Methods: Baseline characteristics and variability in EDSS assessments were compared. Retrospective combined analyses for time to confirmed progression were performed to assess treatment effects overall and in subgroups defined by pre-study disease activity criteria and other key baseline variables.
Results: The variance of EDSS measurements was 6.5% higher in the NA-SPMS study. The EU study included patients in an earlier phase of SPMS and with more active disease both pre-study (relapses, MRI) as well as on study (EDSS, relapses, and MRI variables as assessed in the placebo groups). The pooled analysis showed an overall risk reduction by about 20% in patients treated with 8 MIU (250 mcg) IFNB-1b for EDSS progression confirmed at 6 months (p = 0.008). Risk reduction by 30% to 40% was found for patients with at least one relapse or change in EDSS by >1 in the 2 years prior to study entry. No other consistent across-studies relation of clinical and MRI variables at baseline to potential treatment response was found.
Conclusions: Although post hoc, this combined analysis of the two large studies with IFNB-1b in secondary progressive multiple sclerosis suggests that both pronounced disability progression and continuing relapse activity might help in identifying those patients in the secondary progressive phase of the disease who are more likely to benefit from treatment.
Received December 9, 2003. Accepted in final form September 9, 2004.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the November 23 issue to find the title link for this article.
*Members of the EU-SPMS Steering Committee and the EU-SPMS Advisory Board are listed in the Appendix on page 1787.
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