Article Text

Research paper
Factors influencing long-term outcomes in relapsing–remitting multiple sclerosis: PRISMS-15
  1. Ludwig Kappos1,
  2. Jens Kuhle1,
  3. Juha Multanen2,
  4. Marcelo Kremenchutzky3,
  5. Elisabetta Verdun di Cantogno4,
  6. Peter Cornelisse5,
  7. Lorenz Lehr4,
  8. Florence Casset-Semanaz6,
  9. Delphine Issard7,
  10. Bernard M J Uitdehaag8
    1. 1Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Basel, Switzerland
    2. 2Helsinki MS Center/The Finnish MS Society, Helsinki, Finland
    3. 3MS Clinic, University Hospital, London Health Sciences Centre, London, Ontario, Canada
    4. 4Global Clinical Development Unit, Merck Serono SA, Geneva, Switzerland
    5. 5Global Biostatistics, Merck Serono SA, Geneva, Switzerland
    6. 6Global Biostatistics, EMD Serono, Inc, Rockland, Massachusetts, USA
    7. 7Cytel Inc, Geneva, Switzerland
    8. 8VU University Medical Center, Amsterdam, The Netherlands
    9. EVdC, PC and LL affiliations were those at the time of the study. These authors are no longer employees of Merck Serono.
    1. Correspondence to Professor Ludwig Kappos, Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital, Petersgraben 4, 4031 Basel, Switzerland lkappos{at}


    Aim An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing–remitting multiple sclerosis (RRMS).

    Methods Patients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN β-1a dose groups, and according to total time receiving sc IFN β-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed.

    Results Of 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS ≥4 or ≥6, ≤5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years.

    Conclusions These findings suggest that higher cumulative exposure to sc IFN β-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS.

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