title: Combined MRI lesions and relapses as a surrogate for disability in multiple sclerosis.
abstract: 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.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy. mariapia.sormani@unige.it
authors.forename: M P
authors.initials: MP
authors.lastname: Sormani
authors.forename: D K
authors.initials: DK
authors.lastname: Li
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.forename: B
authors.initials: B
authors.lastname: Stubinski
authors.forename: P
authors.initials: P
authors.lastname: Cornelisse
authors.forename: S
authors.initials: S
authors.lastname: Rocak
authors.forename: N
authors.initials: N
authors.lastname: De Stefano
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D004185:Disability Evaluation; D018450:Disease Progression; D005500:Follow-Up Studies; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control*; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D010919:Placebos; D016899:Interferon-beta; D000068556:Interferon beta-1a