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

Background: The ongoing US glatiramer acetate (GA) Trial, begun in 1991, is the longest prospective evaluation of continuous immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS). Objective: To assess benefits of continuous long-term GA treatment, as sole disease-modifying therapy. Methods: The modified intention-to-treat (mITT, n=232) cohort included all study patients receiving greater than or equal to 1 GA dose. Ongoing patients (n=100; 43%) have continued on-study to February, 2008. Patients were evaluated every 6 months (Expanded Disability Status Scale - EDSS). Confirmed disability progression was defined as greater than or equal to 1.0 EDSS point increase sustained for 6 months. Patients were classified as 'stable/improved' if EDSS score changes were less than or equal to 0.5 points. Proportions of patients who reached confirmed thresholds of EDSS 4, 6, or 8 while on GA, and Kaplan-Meier (KM) estimates of median times to these thresholds were obtained. Results: Mean GA exposure was 8.6 plus or minus 5.2 and 13.6 plus or minus 1.3 years for mITT and ongoing cohorts. While on GA, mITT cohort relapse rates declined from 1.18 plus or minus 0.82 to 0.43 plus or minus 0.58/year; 32% experienced disease progression; 54% had stable/improved EDSS scores; and 39%, 23%, and 5% reached EDSS 4, 6, and 8, respectively. All ongoing patients completed the 15 year clinical visit. For ongoing patients, relapse rate declined from 1.12+/-0.82 to 0.25 plus or minus 0.34/year, 38% experienced disease progression; 57% were stable/improved; and 38%, 18%, and 3% reached EDSS 4, 6, and 8, respectively. Estimated time for one quartile of patients to reach EDSS 4 was 3.98 years in the mITT cohort and 6.8 years in the ongoing cohort. Less than 25% of either cohort reached EDSS 6 and 8. An excellent safety profile was maintained. Conclusions: This prospective, ongoing, open-label study of continuous use of GA demonstrates the benefits of long-term GA use. With a mean disease duration of similar to 22 years, approximately one-third of patients experienced disease progression and >80% of patients remained ambulatory without aids. Patients will continue to be followed for 20 years.