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

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.