Assessment of Lesion Activity Analysis in the Avonex- Steroid Azathioprine (ASA) Study
Condition: Multiple Sclerosis, Relapsing-remitting
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Observational

Summary: 
      -  To examine short- and long-term value of appearance of new active lesions in predicting
           extent of cortical and subcortical deep gray matter (SDGM) atrophy over 5 years in ASA
           (Avonex- Steroid-Azathioprine)study.

        -  To explore how accumulation of cortical and SDGM atrophy over 5 years differs with
           respect to the number of new active lesions or amount of disease activity, in early
           relapsing-remitting multiple sclerosis (RRMS) patients who did or did not develop
           sustained disability progression.

        -  To examine the relationship between development of cortical and SDGM atrophy and
           regional likelihood of development of new active lesions over 5 years.
    

Detailed description: 
      Historically, MS has been classified as a disease predominantly affecting the white matter
      (WM) of the central nervous system. However, pathological changes in gray matter (GM) are
      increasingly recognized as an important component of the MS disease process. Advances in MRI
      have enabled detection of changes in GM morphology.

      The ASA study was a placebo-controlled trial that evaluated efficacy of Avonex® alone and in
      combination with azathioprine (AZA) or AZA and corticosteroids as initial MS therapy in 181
      patients with early RRMS over 5 years. The study was conducted in the Czech Republic, and all
      clinical and MRI examinations were concluded at 5 years.

      No study has evaluated the evolution of cortical and SDGM atrophy in relation to global or
      regional accumulation of active lesions and/or occurrence of relapses both from predictive
      short- and long-term perspective. The ASA study provides a unique opportunity to
      prospectively study the impact of cortical and SDGM atrophy accumulation on long-term
      disability progression in a defined cohort of early RRMS patients who presented with various
      amount of disease activity, as measured by the appearance of new active lesions and
      occurrence of relapses.

      By assessing lesion activity in the 0-6 and 6-12 months in the ASA study we will be able to
      evaluate predictive value for development of cortical and SDGM atrophy in early RRMS patients
      over 5 years with respect to the number of new active lesions or amount of disease activity
      in the first year. We will also evaluate lesion development from 12-60 months in relation to
      development of cortical and SDGM atrophy. We will also analyze accumulation of cortical and
      SDGM atrophy in early RRMS patients who will or will not develop sustained disability
      progression, based on the number of new active lesions or amount of clinical and MRI disease
      activity in short- and long-term. Regional classification of new active lesions over 5 years
      in cortical, subcortical and fossa posterior will allow prospective examination of cortical
      and SDGM atrophy and appearance of the new lesions.
    

Intervention name(s): MRI
Intervention type(s): Device
Intervention description(s): Annual MRIs as part of participation in the ASA study.
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        -  Multiple Sclerosis, relapsing-remitting

          -  Enrolled into the 2-year, double-blind, placebo-controlled ASA study
      
Keywords: Multiple Sclerosis; ASA; MRI; Lesion activity