Lymphopenia is Not the Primary Therapeutic Mechanism of Diroximel Fumarate in Relapsing–Remitting Multiple Sclerosis: Subgroup Analyses of the EVOLVE-MS-1 Study

Dimethyl fumarate Quartile Relapsing remitting
DOI: 10.1007/s40120-024-00637-2 Publication Date: 2024-06-27T11:02:25Z
ABSTRACT
In EVOLVE-MS-1 (NCT02634307), mean absolute lymphocyte count (ALC) on diroximel fumarate (DRF) declined from baseline by approximately 28% in year 1, then stabilized, similar to ALC decline observed with dimethyl (DMF). Prior studies reported that clinical efficacy of DMF was not substantially different patients and without lymphopenia. EVOLVE-MS-1—an open-label, 96-week, phase 3 study—assessed DRF safety exploratory relapsing–remitting multiple sclerosis. This study analyzes efficacy-related outcomes comparing (1) lymphopenia (≥ 1 below lower limit normal [LLN]) (all ALCs ≥ LLN); (2) across quartiles stratified week 96 baseline: Q1 47% decline); Q2 (30% < Q3 (12% 30% Q4 (< 12% decline). Baseline characteristics were between (n = 593) 452). At 96, adjusted annualized relapse rate (ARR; 95% confidence interval) 0.14 (0.11–0.17) 0.12 (0.09–0.15) Estimated proportions 12-week confirmed disability progression (CDP12) at 10.2% 9.3% When (Q1–Q4), ARR 0.11 (Q1), 0.09 (Q2), 0.13 (Q3), 0.17 (Q4). CDP12 9.6% 5.7% 10.9% no evidence disease activity achieved 47.2% 47.8% 45.4% 37.3% (Q4) patients. DRF-treated EVOLVE-MS-1, radiological measurements indicated reduced regardless or magnitude baseline; however, who had greater declines appeared have numerically higher free relapses gadolinium-enhancing lesions compared those smallest decline. supports prior that, while may contribute outcomes, it is the primary mechanism action. ClinicalTrials.gov identifier NCT02634307.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (21)
CITATIONS (2)