Introduction: Multiple sclerosis is a chronic progressive neurological disorder. For this reason, the clinician needs to have access to treatments that are effective and well-tolerated over decades. However, in the absence of long-term controlled clinical trials, it is difficult to assess the long-term benefit provided by currently available immunomodulatory treatments. The objective of this report is to review the strengths and limitations of available long-term data obtained in different phases of the randomized phase III clinical trial with glatiramer acetate collected over a 10-year period in particular.
Methods: Data were obtained from six published analyses of data from the phase III randomized clinical trial of glatiramer acetate performed at different times over a 10-year period. Initially patients were randomized to receive glatiramer acetate (n=125) or placebo (n=126) for 24 months under a double blind scheme, which was subsequently extended to up to 35 months. All patients were then proposed to continue glatiramer acetate treatment in an open-label prospective extension. Analyses of this extension study were performed at six and eight years after initial randomization. Finally, a pooled analysis was performed after a mean treatment duration of 10 years of all patients who had ever received glatiramer acetate during the study. Data were available for 68% of the original cohort at 10 years. At this stage, 108 patients (46.6%) had been continually treated with glatiramer acetate for a mean duration of 10 years.
Results: After one year of treatment, the annualized relapse rate decreased by around 50% from 1.18 relapses/year before inclusion to 0.60 relapses/year. Thereafter, relapse rates continued to decline progressively, reaching less than 0.2 relapses/year from the ninth year of treatment onward. For 65% of patients, EDSS disability scores remained stable or improved over the entire treatment period, and 8% had reached a score of 6 on the EDSS scale (inability to walk unaided) after a mean continuous treatment duration of 10 years. With respect to safety, 23 patients (< 10%) needed to stop treatment due to an adverse event over the 10-year follow-up period. The most frequently encountered adverse events were local injection site reactions and systemic immediate postinjection reactions. No specific safety issue associated with long-term treatment was identified.
Conclusions: The information collected from prospective long-term follow-up of patients treated with glatiramer acetate extending out to 10 years provide clear evidence for the long-term efficacy and adequate safety of this immunomodulatory treatment in the treatment of relapsing-remitting multiple sclerosis over a period of at least 10 years.