Glatiramer acetate: a review of its use in relapsing-remitting multiple sclerosis and in delaying the onset of clinically definite multiple sclerosis.

Glatiramer acetate is a synthetic analogue of the multiple sclerosis (MS)-associated antigen, myelin basic protein. It is indicated in the EU, US and many other countries to reduce the frequency of relapses in patients with relapsing-remitting MS (RRMS), and for the treatment of patients who have experienced a well defined first clinical episode and are at high risk of developing clinically definite MS or have features of MS on MRI. The efficacy of glatiramer acetate in patients with RRMS has been shown in two randomized, double-blind, multicentre phase III trials. In one trial, glatiramer acetate was associated with a significantly lower mean relapse rate than placebo after 24 months' treatment (primary endpoint). In an ongoing open-label extension to this trial, glatiramer acetate was associated with a sustained reduction in the relapse rate at the 6-, 8- and 15-year follow-ups. In the other trial, the mean cumulative number of gadolinium-enhancing lesions on T1-weighted MRI images was significantly lower in glatiramer acetate versus placebo recipients after 9 months' treatment (primary endpoint). Glatiramer acetate also had generally similar efficacy to subcutaneous interferon (IFN)-beta-1a or IFNbeta-1b in two large randomized, open-label, multicentre phase III trials conducted over 96 weeks or >or=2 years. These data were supported by those from a smaller randomized, open-label phase IV trial that utilized a unique imaging protocol to evaluate the efficacy of glatiramer acetate versus that of IFNbeta-1b over >or=2 years. In these trials, there was no significant difference between glatiramer acetate and IFNbeta recipients in any of the clinical endpoints at study end (e.g. time to first relapse [primary endpoint of the REGARD trial] or risk of relapse [primary endpoint of the BEYOND trial]). Moreover, there was no significant difference between glatiramer acetate and IFNbeta-1b recipients in the median number of combined active lesions per patient per monthly MRI scan during the first 12 months of treatment (primary endpoint of the BECOME trial). In general, there was no significant between-group difference in the majority of other MRI-assessed endpoints in any of the trials. The efficacy of glatiramer acetate in patients with clinically isolated syndrome (CIS) was established in a randomized, double-blind, double-dummy, multicentre phase III trial (the PreCISe trial). In this study, glatiramer acetate was associated with a significantly longer time to conversion to clinically definite MS than placebo (primary endpoint). Glatiramer acetate was generally well tolerated in clinical trials, with most adverse events being mild to moderate in severity. Injection site-related reactions and immediate post-injection systemic reactions were the most frequently observed adverse events associated with glatiramer acetate in clinical studies. In conclusion, glatiramer acetate is a valuable first-line option in the treatment of RRMS, as well as being an option in the treatment of CIS.