title: Effect of tofacitinib, a Janus kinase inhibitor, on haematological parameters during 12 weeks of psoriasis treatment.
abstract: BACKGROUND
  The Janus kinase (JAK) inhibitor, tofacitinib, has shown efficacy for the treatment of psoriasis in a phase IIb trial (A3921047; NCT00678210).
  
  
  OBJECTIVE
  To report haematology data from the phase IIb trial, given the importance of JAK-dependent signalling in haematopoiesis.
  
  
  METHODS
  Patients with moderate-to-severe chronic plaque psoriasis were randomized to receive tofacitinib 2, 5 or 15 mg, or placebo, twice daily over 12 weeks. Blood samples were collected at screening, baseline, weeks 2, 4, 8 and 12 during treatment, and weeks 14 and 16 during off-treatment follow-up.
  
  
  RESULTS
  Baseline haematology was similar across patients receiving tofacitinib 2 mg (n = 49), 5 mg (n = 49) or 15 mg (n = 49), or placebo (n = 50). Tofacitinib conferred dose-dependent decreases in haemoglobin, haematocrit and red blood cell counts, while reticulocyte counts initially declined, before recovering by week 8, and exceeding baseline levels after treatment cessation. With regard to white blood cells, tofacitinib had no clear dose-dependent effects on basophils or monocytes, but appeared to be associated with transient or reversible dose-dependent decreases in neutrophil and eosinophil counts and transient increases in lymphocyte counts, which were primarily attributable to increases in B-cell counts. Natural killer cell counts declined with tofacitinib.
  
  
  CONCLUSIONS
  Tofacitinib conferred tolerable, dose-dependent changes in haematological parameters during short-term administration in patients with psoriasis. The effects did not appear to be progressive, and were often transient or reversible.
authors.affiliation: Department of Dermatology, University of Connecticut School of Medicine, Farmington, CT, 06032, U.S.A; Probity Medical Research, Waterloo, ON, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Strober
authors.forename: M
authors.initials: M
authors.lastname: Buonanno
authors.forename: J D
authors.initials: JD
authors.lastname: Clark
authors.forename: T
authors.initials: T
authors.lastname: Kawabata
authors.forename: H
authors.initials: H
authors.lastname: Tan
authors.forename: R
authors.initials: R
authors.lastname: Wolk
authors.forename: H
authors.initials: H
authors.lastname: Valdez
authors.forename: R G
authors.initials: RG
authors.lastname: Langley
authors.forename: J
authors.initials: J
authors.lastname: Harness
authors.forename: A
authors.initials: A
authors.lastname: Menter
authors.forename: K
authors.initials: K
authors.lastname: Papp
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001491:Basophils / Q000187:drug effects; D001772:Blood Cell Count; D002908:Chronic Disease; D003879:Dermatologic Agents / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000187:drug effects; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage*; D011758:Pyrroles / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D006454:Hemoglobins; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib