Document Detail


Combined MRI lesions and relapses as a surrogate for disability in multiple sclerosis.
MedLine Citation:
PMID:  21975200     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE:In multiple sclerosis (MS), the aim of therapies is to prevent the accumulation of irreversible disability. This is difficult to assess given the short time course of clinical trials. MRI markers and relapses are often used as surrogate of disability in MS studies, but their validity remains controversial. We sought to validate, at the individual patient level, MRI lesions and relapses as surrogates for disability progression over the course of MS trials. METHODS:Individual patient data from a large, placebo-controlled trial of interferon β-1a in relapsing-remitting MS (RRMS) were analyzed. The Prentice criteria were applied to evaluate surrogacy of 1-year MRI active lesions and relapses for disability worsening (Expanded Disability Status Scale [EDSS]) over the 2-year follow-up. RESULTS:All Prentice criteria were satisfied. Treatment reduced by 31% the odds of having EDSS worsening over 2 years, reducing the mean number of MRI lesions by 61% and the mean number of relapses by 36% over 1 year. Both 1-year MRI lesion activity and relapses, when considered independently, accounted for more than 60% of the treatment effect on 2-year EDSS worsening. A combination of 1-year MRI lesion activity and relapses explained 100% of the treatment effect on EDSS worsening over 2 years. CONCLUSIONS:A combined measure of 1-year changes in MRI lesions and relapses after interferon therapy fully estimated the corresponding effect on 2-year EDSS worsening. This short-term combined measure appears to be a surrogate for disability progression over a longer term when evaluating the effect of interferon in RRMS.
Authors:
M P Sormani; D K Li; P Bruzzi; B Stubinski; P Cornelisse; S Rocak; N De Stefano
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-5
Journal Detail:
Title:  Neurology     Volume:  -     ISSN:  1526-632X     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401060     Medline TA:  Neurology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
From the Biostatistics Unit (M.P.S.), Department of Health Sciences, University of Genoa, Genoa, Italy; University of British Columbia (D.K.L.), Vancouver, Canada; Department of Epidemiology and Prevention (P.B.), National Cancer Research Institute, Genoa, Italy; Merck Serono S.A.-Geneva (B.S., P.C., S.R.), Geneva, Switzerland; and Department of Neurological & Behavioral Sciences (N.D.), University of Siena, Siena, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The long march to surrogates of meaningful clinical outcomes in MS trials: Are we there yet?
Next Document:  Age-related changes in the default mode network are more advanced in Alzheimer disease.