Characterizing absolute lymphocyte count profiles in dimethyl fumarate'treated patients with MS Patient management considerations

Abstract

Background: Delayed-release dimethyl fumarate (DMF), indicated for the treatment of patients with relapsingremitting multiple sclerosis (MS), is a disease-modifying therapy with potential immunomodulatory and neuroprotective effects. In clinical trials,DMFwas associatedwith reduced white blood cell and absolute lymphocyte counts. CurrentUS prescribing information recommends obtaining a complete blood count, including absolute lymphocyte count (ALC), before initiating and during DMF treatment. Methods: We conducted an integrated analysis of phase 2b/3/long-term extension studies of DMF in MS (N 5 2,470) to characterize ALC profiles. Results: Mean ALCs decreased by30%during the first year and then plateaued, remaining above the lower limit of normal (LLN). Among patients treated $6 months (N 5 2,099), 2.2% experienced ALCs ,500 mm3 persisting $6 months. ALCs remained $LLN in 84% and 76% of patients during the first 6 and 12 months, respectively; of these, 0.1% and 0%, respectively, developed ALCs ,500 mm3 persisting $6 months at any time. Evidence of ALC improvement following DMF discontinuation was observed. DMF efficacy was not substantially different in patients with and without lymphopenia. Conclusion: Lymphocyte monitoring provides effective means for early identification of patients at risk for developing severe, prolonged lymphopenia.