| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From the University of Vermont, Burlington.
Address correspondence and reprint requests to Dr. Hillel Panitch, University of Vermont College of Medicine, FAHC-UHC Campus, 1 S. Prospect St., Burlington, VT 05401; e-mail: hillel.panitch{at}vtmednet.org
Objective: To evaluate the efficacy and safety of interferon beta-1b (IFNß-1b) in subjects with secondary progressive multiple sclerosis (SPMS).
Methods: This 3-year, multicenter, double-blind, placebo-controlled, randomized trial of IFNß-1b included 939 subjects from the United States and Canada with SPMS and Expanded Disability Status Scale (EDSS) scores ranging from 3.0 to 6.5. Subjects were randomly assigned to receive either placebo or IFNß-1b (250 µg or 160 µg/m2 body surface area), administered subcutaneously every other day. The primary outcome was time to progression by 
1.0 EDSS point (0.5 point if EDSS score was 6.0 to 6.5 at entry) confirmed at 6 months. Secondary outcomes included mean change in EDSS score from baseline, relapse-related measures, MRI activity, and a standardized neuropsychological function test.
Results: There was no significant difference in time to confirmed progression of EDSS scores between placebo-treated patients and either of the IFNß-1b treatment groups. However, IFNß-1b treatment resulted in improvement on secondary outcome measures involving clinical relapses, newly active MRI lesions, and accumulated burden of disease on T2-weighted MRI. Effects were similar for both IFNß-1b treatment groups. Neutralizing antibodies to IFNß-1b were detected in 23% of 250-µg and 32% of 160-µg/m2 recipients, but their presence did not consistently affect clinical or MRI outcomes. IFNß-1b was also well tolerated at both doses.
Conclusions: Although no treatment benefit was seen on the time to confirmed progression of disability, relapse- and MRI-related outcomes showed significant benefit with both dosing regimens tested, a result consistent with the outcomes of earlier clinical trials.
Received December 11, 2003. Accepted in final form September 27, 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 link for this article.
*Members of the North American Study Group on Interferon beta-1b in Secondary Progressive MS are listed in the Appendix on page 1794.
Members of the writing committee and advisory board have received honoraria to lecture at conferences or participate at advisory meetings, but none of them holds any financial interest in the pharmaceutical company.
This article has been cited by other articles:
|
|
 |
|
  D. R. Altmann, B. Jasperse, F. Barkhof, K. Beckmann, M. Filippi, L. D. Kappos, P. Molyneux, C. H. Polman, C. Pozzilli, A. J. Thompson, et al. Sample sizes for brain atrophy outcomes in trials for secondary progressive multiple sclerosis Neurology, February 17, 2009; 72(7): 595 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. S. Giacomini, D. L. Arnold, A. Bar-Or, and J. P. Antel Defining Multiple Sclerosis Treatment Response With Magnetic Resonance Imaging: How Much Activity Is Too Much? Arch Neurol, January 1, 2009; 66(1): 19 - 20. [Full Text] [PDF]
|
|
|
|
|
|
D. S. Goodin Disease-modifying therapy in multiple sclerosis: Update and clinical implications Neurology, December 9, 2008; 71(24_suppl_3): S8 - S13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Soelberg Sorensen Review: Neutralizing antibodies against interferon-beta Therapeutic Advances in Neurological Disorders, September 1, 2008; 1(2): 125 - 141. [Abstract] [PDF]
|
|
|
|
 |
|
 D Bar-Zohar, F Agosta, D Goldstaub, and M Filippi Magnetic resonance imaging metrics and their correlation with clinical outcomes in multiple sclerosis: a review of the literature and future perspectives Multiple Sclerosis, July 1, 2008; 14(6): 719 - 727. [Abstract] [PDF]
|
|
|
|
|
|
P. Sorensen, N Koch-Henriksen, E. Flachs, and K Bendtzen Is the treatment effect of IFN-{beta} restored after the disappearance of neutralizing antibodies? Multiple Sclerosis, July 1, 2008; 14(6): 837 - 842. [Abstract] [PDF]
|
|
|
|
 |
|
 T. R Fleming, K. Sharples, J. McCall, A. Moore, A. Rodgers, and R. Stewart Maintaining confidentiality of interim data to enhance trial integrity and credibility Clinical Trials, April 1, 2008; 5(2): 157 - 167. [Abstract] [PDF]
|
|
|
|
 |
|
 N. L. Sicotte, K. C. Kern, B. S. Giesser, A. Arshanapalli, A. Schultz, M. Montag, H. Wang, and S. Y. Bookheimer Regional hippocampal atrophy in multiple sclerosis Brain, April 1, 2008; 131(4): 1134 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Sorensen, A. Bertolotto, and D. S. Goodin Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: An evidence report: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology, October 9, 2007; 69(15): 1552 - 1553. [Full Text] [PDF]
|
|
|
|
|
|
M. G. Brown, S. Kirby, C. Skedgel, J. D. Fisk, T. J. Murray, V. Bhan, and I. S. Sketris How effective are disease-modifying drugs in delaying progression in relapsing-onset MS? Neurology, October 9, 2007; 69(15): 1498 - 1507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Leray, S. Morrissey, J. Yaouanq, M. Coustans, E. Le Page, J. Chaperon, and G. Edan Long-term survival of patients with multiple sclerosis in West France Multiple Sclerosis, August 1, 2007; 13(7): 865 - 874. [Abstract] [PDF]
|
|
|
|
|
|
P. K. Coyle Evidence-based medicine and clinical trials Neurology, June 12, 2007; 68(24_suppl_4): S3 - S7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hamamcioglu and A. Reder Interferon-{beta} regulates cytokines and BDNF: greater effect in relapsing than in progressive multiple sclerosis Multiple Sclerosis, May 1, 2007; 13(4): 459 - 470. [Abstract] [PDF]
|
|
|
|
|
|
M. Cantillon and I. Antonijevic Clinical relevance of anti-drug antibodies with interferon beta-1b therapy in multiple sclerosis Multiple Sclerosis, May 1, 2007; 13(1_suppl): 21 - 27. [Abstract] [PDF]
|
|
|
|
|
|
D. S. Goodin, E. M. Frohman, B. Hurwitz, P. W. O'Connor, J. J. Oger, A. T. Reder, and J. C. Stevens Neutralizing antibodies to interferon beta: Assessment of their clinical and radiographic impact: An evidence report: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology, March 27, 2007; 68(13): 977 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tremlett and V. Devonshire Is late-onset multiple sclerosis associated with a worse outcome? Neurology, September 26, 2006; 67(6): 954 - 959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Petersen, K. Bendtzen, N. Koch-Henriksen, M. Ravnborg, C. Ross, P. S. Sorensen, and The Danish Multiple Sclerosis Group Persistence of neutralizing antibodies after discontinuation of IFN{beta} therapy in patients with relapsing-remitting multiple sclerosis Multiple Sclerosis, June 1, 2006; 12(3): 247 - 252. [Abstract] [PDF]
|
|
|
|
|
|
S. J. Pittock, B. G. Weinshenker, J. H. Noseworthy, C. F. Lucchinetti, M. Keegan, D. M. Wingerchuk, J. Carter, E. Shuster, and M. Rodriguez Not every patient with multiple sclerosis should be treated at time of diagnosis. Arch Neurol, April 1, 2006; 63(4): 611 - 614. [Full Text] [PDF]
|
|
|
|
|
|
E. M. Frohman, E. Havrdova, F. Lublin, F. Barkhof, A. Achiron, M. K. Sharief, O. Stuve, M. K. Racke, L. Steinman, H. Weiner, et al. Most patients with multiple sclerosis or a clinically isolated demyelinating syndrome should be treated at the time of diagnosis. Arch Neurol, April 1, 2006; 63(4): 614 - 619. [Full Text] [PDF]
|
|
|
|
|
|
E. M. Frohman, O. Stuve, E. Havrdova, J. Corboy, A. Achiron, R. Zivadinov, P. S. Sorensen, J. T. Phillips, B. Weinshenker, K. Hawker, et al. Therapeutic Considerations for Disease Progression in Multiple Sclerosis: Evidence, Experience, and Future Expectations Arch Neurol, October 1, 2005; 62(10): 1519 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Boskovic, R. Wide, J. Wolpin, D. J. Bauer, and G. Koren The reproductive effects of beta interferon therapy in pregnancy: A longitudinal cohort Neurology, September 27, 2005; 65(6): 807 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Francis, G. P.A. Rice, J. C. Alsop, and for the PRISMS (Prevention of Relapses and Disabil Interferon {beta}-1a in MS: Results following development of neutralizing antibodies in PRISMS Neurology, July 12, 2005; 65(1): 48 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Interferon-{beta} Therapy for Secondary Progressive Multiple Sclerosis Journal Watch Neurology, February 11, 2005; 2005(211): 4 - 4. [Full Text]
|
|
|
|
|
|
J. A. Cohen and J. P. Antel Does interferon beta help in secondary progressive MS? Neurology, November 23, 2004; 63(10): 1768 - 1769. [Full Text] [PDF]
|
|
|
|
|
|
L. Kappos, B. Weinshenker, C. Pozzilli, A. J. Thompson, F. Dahlke, K. Beckmann, C. Polman, H. McFarland, and for the European and North American Interferon b Interferon beta-1b in secondary progressive MS: A combined analysis of the two trials Neurology, November 23, 2004; 63(10): 1779 - 1787. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
