title: The long-term safety and tolerability of high-dose interferon beta-1a in relapsing-remitting multiple sclerosis: 4-year data from the PRISMS study.
abstract: 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.
authors.affiliation: Institut fuer MS-Forschung, Bereich Humanmedizin der Universitaet Goettingen und Gemeinnuetzige Hertie-Stiftung, Waldweg, Goettingen, Germany. r.gold@med.uni-goettingen.de
authors.forename: R
authors.initials: R
authors.lastname: Gold
authors.forename: P
authors.initials: P
authors.lastname: Rieckmann
authors.forename: P
authors.initials: P
authors.lastname: Chang
authors.forename: J
authors.initials: J
authors.lastname: Abdalla
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D003863:Depression / Q000209:etiology; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance / Q000502:physiology*; D004827:Epilepsy / Q000209:etiology; D005260:Female; D006261:Headache / Q000209:etiology; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000009:adverse effects / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010919:Placebos; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D010919:Placebos; D016899:Interferon-beta; D000068556:Interferon beta-1a