(C-244) Long-Term Safety of Glatiramer Acetate: Evidence from Randomized Trials and Observational Studies in Patients with Multiple Sclerosis

Background: Copaxone (glatiramer acetate, [GA]) is a widely used disease-modifying therapy (DMT) for managing relapse-remitting multiple sclerosis (MS). GA is a non-biological complex drug with an established efficacy and safety profile. While the short-term safety of GA use has been well documented, a comprehensive review of long-term safety, integrating evidence from randomized controlled trials (RCTs) and real-world data (RWD), remains limited.

Objectives: This scoping review aims to evaluate the available evidence on the long-term safety outcomes of GA in MS patients.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) framework was used to perform this scoping review. Databases including PubMed, EMBASE, and Cochrane were utilized to search for studies that focused on the long-term safety of GA among adult patients with relapsing-remitting MS. Studies included in this review ranged from the inception of time to December 2024. Full-text studies that reported safety outcomes of GA use for more than 2 years were included. Excluded studies were those with integrated analyses, interim results, and those focusing on treatment switching as an intervention or efficacy outcomes. Data extraction included patient characteristics, duration of follow-up, and type and rate of adverse events.

Results: Out of 992 studies, five studies that involved long-term safety evaluation of GA were included. The final selection comprised three multi-centered observational studies using registry-based data and two RCTs with follow-up durations ranging from 3 to 15 years. Patient populations were predominantly female (67-75.8%), with mean ages of 37-40 years, disease durations of 3.8-22 years, and Expanded Disability Status Scale scores between 2.5 and 2.8. The rate of adverse event rate ranged from 68.5% to 81%, with injection-site reactions (39.8–68.5%) and systemic post-injection reactions (4.1–19.7%) being the most reported adverse events. Serious adverse events and tolerability-related discontinuations were also reported across all studies (4.6–11%).

Conclusions: Findings from both RCTs and observational studies support the long-term safety of GA, demonstrating consistent tolerability. Although injection-site and systemic reactions are commonly reported among GA users, serious adverse events were limited. Future observational studies are warranted to examine its long-term safety in vulnerable populations, including older adults, to provide a more comprehensive evaluation of GA.