Safety profile of copolymer 1: Analysis of cumulative experience in the United States and Israel

This paper summarizes the worldwide cumulative experience with copolymer 1 (Copaxone) in 857 patients who were enrolled in open-label (n = 586), double-blind (n = 201), and compassionate-use studies (n = 70). The results of a phase III study, including previously unpublished information, are employed to delineate adverse events that occur more frequently among patients treated with copolymer 1 than in placebo-treated controls, and to provide qualitative information. In the cumulative database, patients usually had relapsing-remitting multiple sclerosis and typically received a dose of 20 mg by daily subcutaneous injection for at least 1 year, and occasionally for more than 10 years. Withdrawal rates were 8% for copolymer 1 and 2% for placebo. The most common adverse event was mild injection-site reaction, manifested by erythema, inflammation, and induration. The most remarkable adverse event was a systemic post-injection reaction that occurred in 10% of patients. It was manifested by flushing, chest tightness, palpitations, dyspnea, and anxiety, and was acute and transient. The incidence of adverse events associated with interferon beta, such as flulike syndrome, depression, hematologic abnormalities, cardiotoxicity, and elevated hepatic enzymes, was not increased among patients treated with copolymer 1. Evaluation of the extensive experience with copolymer 1 confirms that it is well tolerated and suitable for self-administration by patients with multiple sclerosis.