INTRODUCTION: Real-world studies in the USA report that 41-56% of patients with multiple sclerosis (MS) are ≥ 50 years old, yet data on their response to disease-modifying therapies (DMTs) is limited. Dimethyl fumarate (DMF) is an oral DMT approved for treating relapsing MS. This analysis evaluated the safety, efficacy, and immunophenotype changes of DMF in patients ≥ 50 years compared with patients <
50 years. METHODS: ESTEEM, a 5-year, real-world, observational phase 4 study, assessed the safety and effectiveness of DMF, including treatment-emergent serious adverse events (SAEs) and adverse events (AEs) leading to treatment discontinuation. Absolute lymphocyte counts (ALCs) were recorded from a subset of patients. The PROCLAIM study, a phase 3b interventional study, reported safety outcomes and lymphocyte subset changes in patients with relapsing-remitting MS (RRMS) treated with DMF. The study evaluated safety outcomes by analyzing the incidence of SAEs and detailed changes in CD4 RESULTS: ESTEEM included 4020 patients aged <
50 years and 1069 aged ≥ 50 years. AEs leading to discontinuation were reported by 19.6% patients <
50 years and 29.6% of patients ≥ 50 years, with gastrointestinal disorders being the most common. SAEs were reported by 5.2% of patients <
50 years and 8.9% those ≥ 50 years. In PROCLAIM, SAEs were reported in 13% of patients <
50 years and 10% of those ≥ 50 years. Median ALC decreased by 35% in patients <
50 years and 50% in those ≥ 50 years in ESTEEM, with similar patterns observed in PROCLAIM. CONCLUSIONS: ESTEEM found no unexpected safety signals in older patients and annualized relapse rates (ARRs) were significantly reduced in both age groups. Both studies indicated that DMF is efficacious and has a favorable safety profile in patients with RRMS aged ≥ 50 years. CLINICAL TRIAL REGISTRATION: ESTEEM (NCT02047097), PROCLAIM (NCT02525874).