title: Magnetic resonance active lesions as individual-level surrogate for relapses in multiple sclerosis.
abstract: BACKGROUND
  Use of quantitative magnetic resonance imaging (MRI) metrics as surrogates for clinical outcomes in multiple sclerosis (MS) trials is controversial.
  
  
  OBJECTIVE
  We sought to validate, at the individual-patient level, the number of MRI active lesions, as a surrogate marker for relapses in MS.
  
  
  METHODS
  Individual-patient data from two large, placebo-controlled clinical trials of subcutaneous interferon β-1a in patients with relapsing-remitting or secondary progressive (SP) MS were analysed separately and as pooled data. The four Prentice criteria were applied to assess surrogacy for the number of new T2 MRI lesions. The predictive value of short-term treatment effects on this MRI marker for longer-term clinical relapses was also assessed.
  
  
  RESULTS
  All Prentice criteria were satisfied. The number of new T2 MRI lesions correlated with the number of relapses over the follow-up period. The proportion of treatment effect on relapses accounted for by the effect of treatment on new T2 MRI lesions over 2 years was 53% in patients with relapsing-remitting MS, 67% in patients with secondary progressive MS, and 62% in pooled data. In the pooled data, treatment effects on new lesions over 1 year mediated a good proportion (70%) of effects on relapses over the subsequent year.
  
  
  CONCLUSIONS
  This study provides evidence that new T2 MRI lesion count is a surrogate for relapses in patients with MS treated with interferon or drugs with a similar mechanism of action. Short-term treatment effects on this MRI measure can predict longer-term effects on relapses.
authors.affiliation: Biostatistics Unit, Department of Health Sciences, University of Genoa, Genoa, Italy. mariapia.sormani@unige.it
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.forename: Bettina
authors.initials: B
authors.lastname: Stubinski
authors.forename: Peter
authors.initials: P
authors.lastname: Cornelisse
authors.forename: Sanda
authors.initials: S
authors.lastname: Rocak
authors.forename: David
authors.initials: D
authors.lastname: Li
authors.forename: Nicola
authors.initials: N
authors.lastname: De Stefano
mesh_terms: D001921:Brain / Q000187:drug effects / Q000473:pathology*; D016009:Chi-Square Distribution; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D011237:Predictive Value of Tests; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D016899:Interferon-beta; D000068556:Interferon beta-1a