Fox, Robert JRobert JFoxChan, Andrew Hao-KuangAndrew Hao-KuangChanGold, RalfRalfGoldPhillips, J TheodoreJ TheodorePhillipsSelmaj, KrzysztofKrzysztofSelmajChang, IhIhChangNovas, MarkMarkNovasRana, JiteshJiteshRanaMarantz, Jing LJing LMarantz2024-10-242024-10-242016-06https://boris-portal.unibe.ch/handle/20.500.12422/149324BACKGROUND Delayed-release dimethyl fumarate (DMF), indicated for the treatment of patients with relapsing-remitting multiple sclerosis (MS), is a disease-modifying therapy with potential immunomodulatory and neuroprotective effects. In clinical trials, DMF was associated with reduced white blood cell and absolute lymphocyte counts. Current US 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 = 2,470) to characterize ALC profiles. RESULTS Mean ALCs decreased by 30% during the first year and then plateaued, remaining above the lower limit of normal (LLN). Among patients treated ≥6 months (N = 2,099), 2.2% experienced ALCs <500 mm(3) 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 mm(3) 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.en600 - Technology::610 - Medicine & healtharticle10.7892/boris.947222734743910.1212/CPJ.0000000000000238