PT  - JOURNAL ARTICLE
AU  - Fox, Robert J.
AU  - Chan, Andrew
AU  - Gold, Ralf
AU  - Phillips, J. Theodore
AU  - Selmaj, Krzysztof
AU  - Chang, Ih
AU  - Novas, Mark
AU  - Rana, Jitesh
AU  - Marantz, Jing L.
TI  - Characterizing absolute lymphocyte count profiles in dimethyl fumarate–treated patients with MS
AID  - 10.1212/CPJ.0000000000000238
DP  - 2016 Jun 01
TA  - Neurology: Clinical Practice
PG  - 220--229
VI  - 6
IP  - 3
4099  - http://cp.neurology.org/content/6/3/220.short
4100  - http://cp.neurology.org/content/6/3/220.full
AB  - Background: 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 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.