Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis

R. A. Rudick, D. E. Goodkin, L. D. Jacobs, D. L. Cookfair, R. M. Herndon, J. R. Richert, A. M. Salazar, J. S. Fischer, C. V. Granger, J. H. Simon, J. J. Alam, N. A. Simonian, M. K. Campion, D. M. Bartoszak, Dennis Bourdette, J. Braiman, C. M. Brownscheidle, M. E. Coats, S. L. Cohan, D. S. Dougherty & 8 others R. P. Kinkel, Michele Mass, F. E. Munschauer, R. L. Priore, P. M. Pullicino, B. J. Scherokman, B. Weistock-Guttman, Ruth Whitham

Research output: Contribution to journalArticle

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Abstract

Background and Objective: A phase III double-blind, placebo-controlled clinical trial demonstrated that interferon beta-1a (IFNβ-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 IFNβ-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 IFNβ-1a recipients who reached the primary study outcome. (3) Significantly fewer IFNβ-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 IFNβ-1a treatment. Conclusions: The primary clinical outcome for the IFNβ-1a clinical trial underestimated clinical benefits of treatment. Results in this report demonstrate that IFNβ-1a treatment is associated with robust, clinically important beneficial effects on disability progression in relapsing MS patients.

Original languageEnglish (US)
Pages (from-to)358-363
Number of pages6
JournalNeurology
Volume49
Issue number2
StatePublished - Aug 1997

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Nervous System
Multiple Sclerosis
Placebos
Controlled Clinical Trials
Phase III Clinical Trials
Time and Motion Studies
Interferon beta-1a
Proportional Hazards Models
Therapeutics
Outcome Assessment (Health Care)
Clinical Trials

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Rudick, R. A., Goodkin, D. E., Jacobs, L. D., Cookfair, D. L., Herndon, R. M., Richert, J. R., ... Whitham, R. (1997). Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. Neurology, 49(2), 358-363.

Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. / Rudick, R. A.; Goodkin, D. E.; Jacobs, L. D.; Cookfair, D. L.; Herndon, R. M.; Richert, J. R.; Salazar, A. M.; Fischer, J. S.; Granger, C. V.; Simon, J. H.; Alam, J. J.; Simonian, N. A.; Campion, M. K.; Bartoszak, D. M.; Bourdette, Dennis; Braiman, J.; Brownscheidle, C. M.; Coats, M. E.; Cohan, S. L.; Dougherty, D. S.; Kinkel, R. P.; Mass, Michele; Munschauer, F. E.; Priore, R. L.; Pullicino, P. M.; Scherokman, B. J.; Weistock-Guttman, B.; Whitham, Ruth.

In: Neurology, Vol. 49, No. 2, 08.1997, p. 358-363.

Research output: Contribution to journalArticle

Rudick, RA, Goodkin, DE, Jacobs, LD, Cookfair, DL, Herndon, RM, Richert, JR, Salazar, AM, Fischer, JS, Granger, CV, Simon, JH, Alam, JJ, Simonian, NA, Campion, MK, Bartoszak, DM, Bourdette, D, Braiman, J, Brownscheidle, CM, Coats, ME, Cohan, SL, Dougherty, DS, Kinkel, RP, Mass, M, Munschauer, FE, Priore, RL, Pullicino, PM, Scherokman, BJ, Weistock-Guttman, B & Whitham, R 1997, 'Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis', Neurology, vol. 49, no. 2, pp. 358-363.
Rudick RA, Goodkin DE, Jacobs LD, Cookfair DL, Herndon RM, Richert JR et al. Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. Neurology. 1997 Aug;49(2):358-363.
Rudick, R. A. ; Goodkin, D. E. ; Jacobs, L. D. ; Cookfair, D. L. ; Herndon, R. M. ; Richert, J. R. ; Salazar, A. M. ; Fischer, J. S. ; Granger, C. V. ; Simon, J. H. ; Alam, J. J. ; Simonian, N. A. ; Campion, M. K. ; Bartoszak, D. M. ; Bourdette, Dennis ; Braiman, J. ; Brownscheidle, C. M. ; Coats, M. E. ; Cohan, S. L. ; Dougherty, D. S. ; Kinkel, R. P. ; Mass, Michele ; Munschauer, F. E. ; Priore, R. L. ; Pullicino, P. M. ; Scherokman, B. J. ; Weistock-Guttman, B. ; Whitham, Ruth. / Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis. In: Neurology. 1997 ; Vol. 49, No. 2. pp. 358-363.
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abstract = "Background and Objective: A phase III double-blind, placebo-controlled clinical trial demonstrated that interferon beta-1a (IFNβ-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 IFNβ-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 IFNβ-1a recipients who reached the primary study outcome. (3) Significantly fewer IFNβ-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 IFNβ-1a treatment. Conclusions: The primary clinical outcome for the IFNβ-1a clinical trial underestimated clinical benefits of treatment. Results in this report demonstrate that IFNβ-1a treatment is associated with robust, clinically important beneficial effects on disability progression in relapsing MS patients.",
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T1 - Impact of interferon beta-1a on neurologic disability in relapsing multiple sclerosis

AU - Rudick, R. A.

AU - Goodkin, D. E.

AU - Jacobs, L. D.

AU - Cookfair, D. L.

AU - Herndon, R. M.

AU - Richert, J. R.

AU - Salazar, A. M.

AU - Fischer, J. S.

AU - Granger, C. V.

AU - Simon, J. H.

AU - Alam, J. J.

AU - Simonian, N. A.

AU - Campion, M. K.

AU - Bartoszak, D. M.

AU - Bourdette, Dennis

AU - Braiman, J.

AU - Brownscheidle, C. M.

AU - Coats, M. E.

AU - Cohan, S. L.

AU - Dougherty, D. S.

AU - Kinkel, R. P.

AU - Mass, Michele

AU - Munschauer, F. E.

AU - Priore, R. L.

AU - Pullicino, P. M.

AU - Scherokman, B. J.

AU - Weistock-Guttman, B.

AU - Whitham, Ruth

PY - 1997/8

Y1 - 1997/8

N2 - Background and Objective: A phase III double-blind, placebo-controlled clinical trial demonstrated that interferon beta-1a (IFNβ-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 IFNβ-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 IFNβ-1a recipients who reached the primary study outcome. (3) Significantly fewer IFNβ-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 IFNβ-1a treatment. Conclusions: The primary clinical outcome for the IFNβ-1a clinical trial underestimated clinical benefits of treatment. Results in this report demonstrate that IFNβ-1a treatment is associated with robust, clinically important beneficial effects on disability progression in relapsing MS patients.

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