Abstract Details

Treatment with DMF, an oral therapy approved for relapsing forms of multiple sclerosis (RMS), leads to pleiotropic immune changes, which are not well-described in older patients.

Describe the impact of delayed-release dimethyl fumarate (DMF) treatment over 2 years on the immune cell compartment in patients < and ≥50 years old.

PROCLAIM (EudraCT 20015-001973-42) is an open-label, 96-week (W96) study of patients aged 18-65 years with RMS (N=218) treated with DMF 240mg twice-daily. Absolute lymphocyte count (ALC) and lymphocyte subset changes were assessed longitudinally by complete blood count and flow cytometry, respectively. The relationship between age and peripheral immune cell compartments changes after DMF treatment was evaluated.

The mean (SD) age was 42 (11) years; 59/218 (27%) patients were ≥50 years old. Baseline CD4⁺ T cell compartment composition was similar for patients <50 and ≥50 (38% vs 36% naïve, 42% vs 44% central memory, 19% vs 19% effector memory) but differed among the CD8⁺ T cells (39% vs 28% naïve, 12% vs 18% central memory, and 20% vs 25% effector memory). Regardless of age, relative proportion of naïve CD4⁺ and CD8⁺ T cells increased and central and effector memory CD4⁺ and CD8⁺ T cells decreased at W96. Similarly, from baseline to W96, relative proportion of naïve B cells increased <50 and ≥50 (baseline: 63% vs 68%, W96 75% vs 80%) and transitional B cells increased (baseline: 5% vs 4%, W96 11% vs 12%). SAE incidence was similar, 13% (<50) vs 10% (≥50).

Immune cell changes with DMF treatment were similar in patients <50 to ≥50 years old apart from the CD8⁺ compartment where age impacted the proportion of naïve and activated cells. Otherwise, for all age groups, memory populations were selectively reduced, while the naïve compartment increased. SAEs did not increase with age.

Support: Biogen