The long-term safety and tolerability of high-dose interferon beta-1a in relapsing-remitting multiple sclerosis: 4-year data from the PRISMS study

Eur J Neurol. 2005 Aug;12(8):649-56. doi: 10.1111/j.1468-1331.2005.01083.x.


In the prevention of relapses and disability by interferon subcutaneously in multiple sclerosis (PRISMS) study, 560 patients with relapsing-remitting multiple sclerosis were randomized to receive subcutaneous interferon (IFN) beta-1a, 22 or 44 mug three times weekly, or placebo, for 2 years. Patients receiving placebo were then re-randomized to one of the two doses of IFN beta-1a for a further 2 years, whilst patients receiving active treatment continued their original treatment. Safety assessments were performed throughout the study. The most common adverse events for patients originally randomized to active treatment were injection-site inflammation (72% of patients had at least one event), headache (71%) and influenza-like symptoms (69%). These were generally mild in nature and most frequent during the first month of treatment. The 4-year adverse event profiles for the two IFN beta-1a doses were comparable with those observed during the initial phase of the study and, for the most part, with each other. There was no association between IFN beta-1a and depression or suicide/attempted suicide. The most common laboratory abnormalities were asymptomatic lymphopenia and elevated serum liver transaminase levels. These were generally mild and resolved spontaneously. Therapy with subcutaneous IFN beta-1a three times weekly for up to 4 years was well tolerated without dose-limiting safety concerns.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Adolescent
  • Adult
  • Depression / etiology
  • Disability Evaluation
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Tolerance / physiology*
  • Epilepsy / etiology
  • Female
  • Headache / etiology
  • Humans
  • Interferon beta-1a
  • Interferon-beta / adverse effects
  • Interferon-beta / therapeutic use*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Placebos
  • Time Factors
  • Treatment Outcome


  • Adjuvants, Immunologic
  • Placebos
  • Interferon-beta
  • Interferon beta-1a