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From the Mellen Center for Multiple Sclerosis Treatment and Research (Drs. Rudick, Fischer, Kinkel, and Weistock-Guttman), Department of Neurology, The Cleveland Clinic Foundation, Cleveland, OH; University of California at San Francisco (Dr. Goodkin), San Francisco, CA; University of Buffalo(Drs. Jacobs, Cookfair, Granger, Brownscheidle, Munschauer, Priore, and Pullicino), Buffalo, NY; Good Samaritan Hospital and Medical Center(Drs. Herndon and Mass), Portland, OR; Georgetown University Medical Center (Drs. Richert and Cohan), Washington, DC; Walter Reed Army Medical Center (Drs. Salazar, Bartoszak, Braiman, and Coats), Washington, DC; University of Colorado Health Sciences Center (Dr. Simon), Denver, CO; Biogen, Inc. (Drs. Alam, Simonian, and Campion), Cambridge, MA; Oregon Health Sciences University (Drs. Bourdette and Whitham), Portland, OR; and Kaiser Permanente Medical Center (Dr Scherokman), Springfield, VA.
Address correspondence and reprint requests to Dr. Richard A. Rudick, Mellen Center (U-10), The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195-5244.
Background and Objective: A phase III double-blind, placebo-controlled clinical trial demonstrated that interferon beta-la (IFNß-1a) (Avonex, Biogen) significantly delayed progression of disability in relapsing MS patients. The primary clinical outcome was time from study entry until disability progression, defined as
1.0 point worsening from baseline Kurtzke Expanded Disability Status Scale (EDSS) score persisting for at least two consecutive scheduled visits separated by 6 months. The objective of this study was to examine the magnitude of benefit on EDSS and its clinical significance.
Methods: Post hoc analyses related to disability outcomes using data collected during the double-blind, placebo-controlled phase III clinical trial.
Results: (1) Clinical efficacy related to disability did not depend on the definition of disability progression. A significant benefit in favor of IFNß-1a was observed when 2.0 point worsening from baseline EDSS was required or when worsening was required to persist for 1.0 year. (2) Placebo recipients who reached the primary clinical outcome worsened by a larger amount from baseline EDSS than did IFNß-1a recipients who reached the primary study outcome. (3) Significantly fewer IFNß-1a recipients progressed to EDSS milestones of 4.0 (relatively severe impairment) or 6.0(unilateral assistance needed to walk). (4) Cox proportional hazards models demonstrated that the only baseline characteristic strongly correlated with longer time to disability progression was IFNß-1a treatment.
Conclusions: The primary clinical outcome for the IFNß-1a clinical trial underestimated clinical benefits of treatment. Results in this report demonstrate that IFNß-1a treatment is associated with robust, clinically important beneficial effects on disability progression in relapsing MS patients.
Supported by the National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS) grant RO1-26321, and Blogen, Inc., Cambridge, Mass.
Received January 23, 1997. Accepted in final form April 10, 1997.
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