Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate

Abstract

The ongoing US Glatiramer Acetate (GA) Trial is the longest evaluation of continuous immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to evaluate up to 15 years of GA as a sole disease-modifying therapy. Two hundred and thirty-two patients received at least one GA dose since study initiation in 1991 (mITT cohort), and 100 (43%, Ongoing cohort) continued as of February 2008. Patients were evaluated every 6 months using the Expanded Disability Status Scale (EDSS). Mean GA exposures were 8.6 +/- 5.2, 4.81 +/- 3.69, and 13.6 +/- 1.3 years and mean disease durations were 17, 13, and 22 years for mITT, Withdrawn and Ongoing cohorts, respectively. For Ongoing patients, annual relapse rates (ARRs) maintained a decline from 1.12 +/- 0.82 at baseline to 0.25 +/- 0.34 per year; 57% had stable/improved EDSS scores (change < or = 0.5 points); 65% had not transitioned to secondary progressive multiple sclerosis (SPMS); 38%, 18%, and 3% reached EDSS 4, 6, and 8. For all patients on GA therapy (the mITT cohort), ARRs declined from 1.18 +/- 0.82 to 0.43 +/- 0.58 per year; 54% had stable/improved EDSS scores; 75% had not transitioned to SPMS; 39%, 23%, and 5% reached EDSS 4, 6, and 8. In conclusion, multiple sclerosis patients with mean disease duration of 22 years administering GA for up to 15 years had reduced relapse rates, and decreased disability progression and transition to SPMS. There were no long-term safety issues.

Figure 1.

Study design for the long-term glatiramer acetate (GA) study of patients who participated in the placebo-controlled study and were entered into the open-label study of GA. Patients on placebo in the placebo-controlled phase were switched to active treatment with GA in the open-label phase and those on GA in the placebo-controlled phase continued on it. The mean number of years of GA treatment for the Ongoing cohort was 13.6 years, for the mITT cohort was 8.6 years and for the Withdrawn cohort was 4.8 years.

Figure 2.

Yearly mean Expanded Disability Status Scale (EDSS) scores for Ongoing patients (n ¼ 100) in the glatiramer acetate (GA) study at the 15-year analysis. The asterisk (∗) indicates that the yearly mean EDSS scores for years 14 and 15 are derived from the scores of patients who were originally randomized to GA in the placebo-controlled phase of the study (n ¼ 50).

Figure 3.

Time to reach confirmed Expanded Disability Status Scale 4, 6, and 8 for the mITT and Ongoing cohorts while they were on glatiramer acetate therapy. The mean disease duration at glatiramer acetate start for the mITT cohort was 8.3 years and for the Ongoing cohort was 8.4 years.

Figure 4.

Proportion of Low and High strata mITT patients reaching Expanded Disability Status Scale (EDSS) 4, 6, and 8. The proportion of patients in the Low and High strata mITT cohorts reaching the EDSS thresholds of EDSS 4, 6, and 8 was significantly different (∗p < 0.02). Patients in the Low strata had EDSS scores of 0-2.0 at glatiramer acetate (GA) start (n= 103) and those in the High strata had EDSS scores >2.5 at GA start (n= 129).