Early versus delayed treatment with glatiramer acetate: Analysis of up to 27 years of continuous follow-up in a US open-label extension study.

BACKGROUND: Glatiramer acetate (GA) is US-approved for relapsing multiple sclerosis. OBJECTIVES: To describe GA long-term clinical profile. To compare effectiveness of early start (ES) versus delayed start (DS; up to 3 years) with GA. METHODS: Phase 3 trial participants entered a randomized placebo-controlled period then an open-label extension (OLE) with GA. RESULTS: Overall, 208 out of 251 (82.9%) randomized participants entered the OLE; 24 out of 101 (23.8%, ES) and 28 out of 107 (26.2%, DS) participants completed the OLE. Median GA treatment was 9.8 (0.1-26.3) years. Annualized change in Expanded Disability Status Scale (EDSS) score was lower with ES versus DS (p = 0.0858: full study; p = 0.002; Year 5). Participants with improved/stable EDSS was consistently higher with ES versus DS: 40.3% versus 31.6% (p = 0.1590; full study); 70.8% versus 55.6% (p = 0.015; Year 5). ES prolonged time-to-6-month confirmed disease worsening (CDW) versus DS (9.8 vs 6.7 years), time-to-12-month CDW (18.9 vs 11.6 years), and significantly reduced time-to-second-6-month CDW (p = 0.0441). No new safety concerns arose. CONCLUSION: GA long-term treatment maintained clinical benefit with a similar safety profile to phase 3 results; a key limitation was that only 25% of participants completed the OLE. Early initiation of GA had sustained benefits versus delayed treatment.

Long-term efficacy and safety of three times weekly dosing regimen of glatiramer acetate in relapsing multiple sclerosis patients: Seven-year results of the Glatiramer Acetate Low-frequency Administration (GALA) open-label extension study.

OBJECTIVE: Describe the long-term outcomes of early-start (ES) and delayed-start (DS) glatiramer acetate 40 mg/mL treatment three times weekly (GA40) for up to seven years in the Glatiramer Acetate Low-frequency Administration (GALA) study in patients with relapsing multiple sclerosis (RMS). METHODS: Patients were evaluated every three to six months. The primary efficacy endpoint was annualized relapse rate (ARR); additional endpoints were exploratory or post hoc. For efficacy, data from the entire exposure period were used for the ES and DS cohorts. For safety, exposure only under GA40 was considered. RESULTS: Of the patients who continued into the open-label extension (OLE), 580/834 (70%) ES and 261/419 (62%) DS completed the OLE. For the entire placebo-controlled and OLE study period, ARR was 0.26 for ES and 0.31 for DS patients (risk ratio = 0.83; 95% confidence interval [CI]: 0.70-0.99). ES prolonged median time to first relapse versus DS (4.9 versus 4.3 years; hazard ratio = 0.82; 95% CI: 0.6-0.96). OLE-only results showed DS patients experienced similar efficacy for relapse and disability outcomes as ES patients. Adverse events were consistent with the well-established GA safety profile. CONCLUSIONS: GA40 treatment conferred clinical benefit up to seven years, resulting in sustained efficacy and was generally well tolerated in RMS patients.