Abstract

• In the absence of a better alternative, subcutaneous interferon beta is the standard first-line treatment for relapsing-remitting multiple sclerosis.
   
• Fingolimod, an oral immunosuppressant that reduces the circulating lymphocyte count, is in the process of receiving marketing authorisation for this use in the European Union.
   
• Initial clinical evaluation is based on 2 trials. In a 12-month, comparative, double-blind, randomised trial including 1292 patients, daily treatment with oral fingolimod (0.5 mg or 1.25 mg) modestly prolonged the interval between exacerbations compared to weekly intramuscular injections of interferon beta-1a: about one exacerbation prevented every 6 years. No tangible impact on progression of disability was observed.
   
• A double-blind placebo-controlled trial that lasted 2 years also showed a statistically significant reduction in the annual frequency of exacerbations. There was no firm evidence that fingolimod had a tangible effect on progression of disability.
   
• An indirect comparison suggests that the impact of fingolimod on exacerbations is roughly similar to that of cladribine, another oral immunosuppressant that received a negative opinion in this indication from the European Medicines Agency.
   
• Several short-term adverse effects consistent with the pharmacological action of fingolimod and the results of animal pharmacology studies were observed in clinical trials, including infections (especially herpetic), pulmonary disorders, cardiac conduction disorders and macular oedema. A risk of lymphoma and heart failure is possible in the longer term.
   
• Given the modest gain in efficacy compared with interferon beta (based on weak supporting evidence) and the major adverse effects of fingolimod, it is better to continue to use interferon beta for initial treatment of relapsing-remitting multiple sclerosis, and to reserve fingolimod for use in clinical trials in which patients are closely monitored.

©Prescrire 1 July 2011

"Fingolimod. Just another immunosuppressant for multiple sclerosis" Prescrire Int 2011; 20 (118): 173-177. (Pdf, subscribers only)