title: PRISMS: the story of a pivotal clinical trial series in multiple sclerosis.
abstract: 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 relapsing-remitting 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 1-8 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.
  
  
  RESULTS
  In the 2-year, double-blind, randomized, placebo-controlled study, IFN beta-1a (22 or 44 mcg three times weekly [tiw]) was associated with significantly lower relapse rates, disability progression, and MRI burden of disease compared with placebo (p <or= 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 1-4.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. bac106@northwestern.edu
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Cohen
authors.forename: Victor M
authors.initials: VM
authors.lastname: Rivera
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D016899:Interferon-beta; D000068556:Interferon beta-1a