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This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 69, Number 15, October 9, 2007 All Versions of this Article: 01.wnl.0000271884.11129.f3v1 69/15/1498    most recent Correspondence: Submit a response Correspondence: View responses Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brown, M. G. Articles by Sketris, I. S. Search for Related Content PubMed PubMed Citation Articles by Brown, M. G. Articles by Sketris, I. S. Related Collections All Health Services Research Outcome research Quality of life Autoimmune diseases Clinical trials Observational study (Cohort, Case control) Multiple sclerosis Natural history studies (prognosis) Risk factors in epidemiology

How effective are disease-modifying drugs in delaying progression in relapsing-onset MS?

From the Health Outcomes Research Unit (M.G.B.) and Department of Medicine, Neurology (S.K., T.J.M., V.B.) and Department of Medicine (C.S.), Department of Psychiatry (J.D.F.), and Department of Community Health and Epidemiology (M.G.B., T.J.M., I.S.S.), Capital Health District, Nova Scotia; College of Pharmacy (I.S.S.), Dalhousie University, Halifax, Nova Scotia, Canada.

Address correspondence and reprint requests to Dr. Murray G. Brown, Centre for Clinical Research, 5890 University Avenue, Halifax, NS, Canada B3H 1V7 murray.brown{at}dal.ca

Objective: Our objective was to estimate the effectiveness of disease-modifying drugs (DMDs) in delaying multiple sclerosis (MS) disability progression in relapsing-onset (R-onset) definite MS patients under "real-world" conditions.

Methods: Treatment effect size, for DMDs as a class, was estimated in absolute terms and relative to MS natural history. A basic model estimated annual Expanded Disability Status Scale (EDSS) change before and after treatment. An expanded model estimated annual EDSS change in pretreatment years, treatment years on first drug, treatment years after drugs were switched, and in years after treatment stopped. Models were populated with 1980 through 2004 clinical data, including 1988 through 2004 data for all Nova Scotians treated with DMDs. Estimates were made for relapsing–remitting MS (RRMS), secondary progressive MS (SPMS), and R-onset groups.

Results: Estimated pretreatment annual EDSS increases were approximately 0.10 of one EDSS point for the RRMS group, 0.31 for the SPMS group, and 0.16 for the R-onset group. Estimates of EDSS increase avoided per treatment year on the first drug were significant for the RRMS group (–0.103, 0.000), the SPMS group (–0.065, 0.011), and the R-onset group (–0.162, 0.000); relative effect size estimates were 112%, 21%, and 105%. Estimated EDSS progression was faster in years after drug switches and treatment stops.

Conclusions: Our estimates of disease-modifying drug (DMD) relative treatment effect size, in the context of "real-world" clinical practice, are similar to DMD treatment efficacy estimates in pivotal trials, though our findings attained statistical significance. DMDs, as a class, are effective in delaying Expanded Disability Status Scale progression in patients with relapsing-onset definite multiple sclerosis (MS) (90%), although effectiveness is much better for relapsing–remitting MS than for secondary progressive MS groups.

Editorial, see page 1478

e-Pub ahead of print on August 15, 2007, at www.neurology.org.

Supported by Health Research and Policy Program, Health Canada; Multiple Sclerosis Society of Canada; Nova Scotia Health Research Foundation; Capital Health, Nova Scotia Health. Ingrid Sketris holds a CIHR/CHSRF Chair in Health Services Research, which is cosponsored by the Nova Scotia Health Research Foundation.

Disclosure: M.G. Brown has done consulting research and/or workshops from Serono, AstraZeneca, Aventis Pharma, and Biogen-Idec. J.D. Fisk has received honoraria for lecturing and workshop participation, and providing outcomes research consultation services for AstraZeneca, Bayer, Biogen-Idec, Bristol-Myers Squibb, Novartis, Sanofi-Aventis, and TEVA Neuroscience. T.J. Murray has received honoraria for advisory councils and travel expenses for attending meetings from Biogen-Idec, Serono, Teva, and Berlex. V. Bhan has received honoraria for advisory councils and travel expenses for attending meetings from Biogen-Idec, Serono, Teva, and Berlex. No other authors reported competing interests.

Received January 21, 2007. Accepted in final form April 30, 2007.

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