PRISMS: The story of a pivotal clinical trial series in multiple sclerosis

Bruce A. Cohen, Victor M. Rivera

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations


Background: The PRISMS (Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) study was initiated in 1994, at which time there were few disease-modifying drugs for multiple sclerosis (MS). The PRISMS series of studies has since provided up to 8 years of clinical, magnetic resonance imaging (MRI), safety, and immunogenicity data on the use of subcutaneous (sc) interferon (IFN) beta-1a in patients with relapsingremitting MS. This review is the first collation of all these data in one article, with a look ahead to the next generation of studies involving the new formulation of sc IFN beta-1a. Methods: Published efficacy, safety, and immunogenicity data, in terms of prospectively defined endpoints and later post hoc analyses, from years 18 of the PRISMS series are summarized and collated for the first time. Some of the studies of sc IFN beta-1a that evolved from the PRISMS studies are also discussed. Findings: In the 2-year, double-blind, randomized, placebo-controlled study, IFN beta-1a (22 or 44mcg three times weekly [tiw]) was associated with significantly lower relapse rates, disability progression, and MRI burden of disease compared with placebo (p≤0.05). Subsequently, in the 2-year extension, patients previously receiving placebo were re-randomized to active treatment, and a further 2 years of open-label treatment confirmed good long-term safety and therapeutic efficacy. Follow-up visits at years 7 or 8 (68.2 of initial population) demonstrated a continued benefit for patients originally randomized to the 44-mcg dose compared with those receiving the 22-mcg dose or whose treatment had been delayed by 2 years. Neutralizing antibodies were more common in patients receiving the 22-mcg dose and attenuated treatment efficacy during years 14. Conclusion: Class I and long-term data from PRISMS support the use of sc IFN beta-1a tiw as a first-line treatment for MS, as evidenced by sustained efficacy rates, acceptable safety profiles, and high patient retention rates.

Original languageEnglish (US)
Pages (from-to)827-838
Number of pages12
JournalCurrent Medical Research and Opinion
Issue number4
StatePublished - Apr 2010


  • Disability
  • Interferon beta-1a
  • Magnetic resonance imaging
  • Neutralizing antibody
  • Relapse
  • Relapsing
  • Remitting multiple sclerosis
  • Safety

ASJC Scopus subject areas

  • Medicine(all)


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