title: 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 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 mm3persisting ≥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 mm3persisting ≥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.
  
  
  CONCLUSIONS
  Lymphocyte monitoring provides effective means for early identification of patients at risk for developing severe, prolonged lymphopenia.
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, Cleveland, OH; St. Josef Hospital (AC, RG), Ruhr University, Bochum, Germany; Multiple Sclerosis Program (JTP), Baylor Institute for Immunology Research, Dallas, TX; Medical University of Lodz (KS), Lodz, Poland; and Biogen (IC, MN, JR, JLM), Cambridge, MA. Dr. Novas is currently with Alexion Pharmaceuticals, Chesire, CT; and Dr. Rana is currently with Sanofi-Genzyme, Cambridge, MA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, Cleveland, OH; St. Josef Hospital (AC, RG), Ruhr University, Bochum, Germany; Multiple Sclerosis Program (JTP), Baylor Institute for Immunology Research, Dallas, TX; Medical University of Lodz (KS), Lodz, Poland; and Biogen (IC, MN, JR, JLM), Cambridge, MA. Dr. Novas is currently with Alexion Pharmaceuticals, Chesire, CT; and Dr. Rana is currently with Sanofi-Genzyme, Cambridge, MA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chan
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, Cleveland, OH; St. Josef Hospital (AC, RG), Ruhr University, Bochum, Germany; Multiple Sclerosis Program (JTP), Baylor Institute for Immunology Research, Dallas, TX; Medical University of Lodz (KS), Lodz, Poland; and Biogen (IC, MN, JR, JLM), Cambridge, MA. Dr. Novas is currently with Alexion Pharmaceuticals, Chesire, CT; and Dr. Rana is currently with Sanofi-Genzyme, Cambridge, MA.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, Cleveland, OH; St. Josef Hospital (AC, RG), Ruhr University, Bochum, Germany; Multiple Sclerosis Program (JTP), Baylor Institute for Immunology Research, Dallas, TX; Medical University of Lodz (KS), Lodz, Poland; and Biogen (IC, MN, JR, JLM), Cambridge, MA. Dr. Novas is currently with Alexion Pharmaceuticals, Chesire, CT; and Dr. Rana is currently with Sanofi-Genzyme, Cambridge, MA.
authors.forename: J Theodore
authors.initials: JT
authors.lastname: Phillips
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, Cleveland, OH; St. Josef Hospital (AC, RG), Ruhr University, Bochum, Germany; Multiple Sclerosis Program (JTP), Baylor Institute for Immunology Research, Dallas, TX; Medical University of Lodz (KS), Lodz, Poland; and Biogen (IC, MN, JR, JLM), Cambridge, MA. Dr. Novas is currently with Alexion Pharmaceuticals, Chesire, CT; and Dr. Rana is currently with Sanofi-Genzyme, Cambridge, MA.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Selmaj
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, Cleveland, OH; St. Josef Hospital (AC, RG), Ruhr University, Bochum, Germany; Multiple Sclerosis Program (JTP), Baylor Institute for Immunology Research, Dallas, TX; Medical University of Lodz (KS), Lodz, Poland; and Biogen (IC, MN, JR, JLM), Cambridge, MA. Dr. Novas is currently with Alexion Pharmaceuticals, Chesire, CT; and Dr. Rana is currently with Sanofi-Genzyme, Cambridge, MA.
authors.forename: Ih
authors.initials: I
authors.lastname: Chang
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, Cleveland, OH; St. Josef Hospital (AC, RG), Ruhr University, Bochum, Germany; Multiple Sclerosis Program (JTP), Baylor Institute for Immunology Research, Dallas, TX; Medical University of Lodz (KS), Lodz, Poland; and Biogen (IC, MN, JR, JLM), Cambridge, MA. Dr. Novas is currently with Alexion Pharmaceuticals, Chesire, CT; and Dr. Rana is currently with Sanofi-Genzyme, Cambridge, MA.
authors.forename: Mark
authors.initials: M
authors.lastname: Novas
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, Cleveland, OH; St. Josef Hospital (AC, RG), Ruhr University, Bochum, Germany; Multiple Sclerosis Program (JTP), Baylor Institute for Immunology Research, Dallas, TX; Medical University of Lodz (KS), Lodz, Poland; and Biogen (IC, MN, JR, JLM), Cambridge, MA. Dr. Novas is currently with Alexion Pharmaceuticals, Chesire, CT; and Dr. Rana is currently with Sanofi-Genzyme, Cambridge, MA.
authors.forename: Jitesh
authors.initials: J
authors.lastname: Rana
authors.affiliation: Mellen Center for Multiple Sclerosis Treatment and Research (RJF), Cleveland Clinic, Cleveland, OH; St. Josef Hospital (AC, RG), Ruhr University, Bochum, Germany; Multiple Sclerosis Program (JTP), Baylor Institute for Immunology Research, Dallas, TX; Medical University of Lodz (KS), Lodz, Poland; and Biogen (IC, MN, JR, JLM), Cambridge, MA. Dr. Novas is currently with Alexion Pharmaceuticals, Chesire, CT; and Dr. Rana is currently with Sanofi-Genzyme, Cambridge, MA.
authors.forename: Jing L
authors.initials: JL
authors.lastname: Marantz