title: Initial lymphocyte count and low BMI may affect fingolimod-induced lymphopenia.
abstract: OBJECTIVE
  To assess whether pretreatment-lymphocyte counts, treatment before fingolimod, age, sex, or body mass index (BMI) affects the risk of fingolimod-induced lymphopenia in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  Data were obtained from a German multicenter, single-arm, open-label study of patients with RRMS treated with fingolimod, and findings were validated in an independent Swedish national pharmacovigilance study.
  
  
  RESULTS
  Four hundred eighteen patients with RRMS from Germany and 438 patients from Sweden were included. A nadir ≤0.2 × 10(9) lymphocytes/L was reached in 15% (95% confidence interval [CI] 12%-17%) of all 856 patients. Patients with lower starting lymphocyte counts (below 1.6 × 10(9)/L) and patients with BMI lower than 18.5 kg/m(2) (women only) were at higher risk of developing lymphopenia with values ≤0.2 × 10(9)/L in the combined analysis, increasing the risk in these subgroups to 26% (95% CI 20%-31%) or 46% (95% CI 23%-71%), respectively. In the German cohort, infection rates were similar in patients who developed severe lymphopenia and those who did not.
  
  
  CONCLUSIONS
  Our findings suggest that patients with low baseline lymphocyte counts and underweight women in which fingolimod treatment will be initiated should possibly be monitored more closely.
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden.
authors.forename: Clemens
authors.initials: C
authors.lastname: Warnke
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dehmel
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden.
authors.forename: Ryan
authors.initials: R
authors.lastname: Ramanujam
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden.
authors.forename: Carolina
authors.initials: C
authors.lastname: Holmen
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden.
authors.forename: Nina
authors.initials: N
authors.lastname: Nordin
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wolfram
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden.
authors.forename: Verena I
authors.initials: VI
authors.lastname: Leussink
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.affiliation: From the Department of Neurology (C.W., T.D., K.W., V.I.L., H.-P.H., B.C.K.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; and Department of Clinical Neuroscience (R.R., C.H., N.N., T.O.), Karolinska Institute, Stockholm, Sweden. bernd.kieseier@uni-duesseldorf.de.
authors.forename: Bernd C
authors.initials: BC
authors.lastname: Kieseier
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000139:chemically induced*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy*; D011409:Propylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D013110:Sphingosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine