title: Effects of tofacitinib on lymphocyte sub-populations, CMV and EBV viral load in patients with plaque psoriasis.
abstract: BACKGROUND
  Plaque psoriasis is a debilitating skin condition that affects approximately 2% of the adult population and for which there is currently no cure. Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis.
  
  
  METHODS
  The design of this study has been reported previously (NCT00678210). Patients with moderate to severe chronic plaque psoriasis received tofacitinib (2 mg, 5 mg, or 15 mg) or placebo, twice daily, for 12 weeks. Lymphocyte sub-populations, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA were measured at baseline and up to Week 12.
  
  
  RESULTS
  Tofacitinib was associated with modest, dose-dependent percentage increases from baseline in median B cell count at Week 4 (24-68%) and Week 12 (18-43%) and percentage reductions from baseline in median natural killer cell count at Week 4 (11-40%). The proportion of patients with detectable CMV and EBV DNA (defined as >0 copies/500 ng total DNA) increased post-baseline in tofacitinib-treated patients. However, multivariate analyses found no relationship between changes in CMV or EBV viral load and changes in lymphocyte sub-populations or tofacitinib treatment.
  
  
  CONCLUSIONS
  Twelve weeks of treatment with tofacitinib had no clinically significant effects on CMV or EBV viral load, suggesting that lymphocyte sub-populations critical to the response to chronic viral infections and viral reactivation were not significantly affected. Replication of these findings during long-term use of tofacitinib will allow confirmation of this observation.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Chile and Probity Medical Research, Santiago, Chile. fvalenzuela.cl@gmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Valenzuela
authors.affiliation: Clinical Research and Probity Medical Research, Waterloo, ON, Canada. kapapp@probitymedical.com.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Papp
authors.affiliation: Department of Dermatology, Eastern Virginia Medical School and Virginia Clinical Research Inc., Norfolk, VA, USA. dpariser@pariserderm.com.
authors.forename: David
authors.initials: D
authors.lastname: Pariser
authors.affiliation: Department of Dermatology, University of Texas Medical School, Houston, TX, USA. styring@ccstexas.com.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
authors.affiliation: Pfizer Inc, Groton, CT, USA. Robert.Wolk@pfizer.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Wolk
authors.affiliation: Pfizer Inc, Groton, CT, USA. marjorie.s.buonanno@pfizer.com.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Buonanno
authors.affiliation: Quintiles, Cambridge, MA, USA. jianyuanwang@yahoo.com.|Present address: Statistical Consulting & Solutions, LLC, Brookline, MA, USA. jianyuanwang@yahoo.com.
authors.forename: Jeff
authors.initials: J
authors.lastname: Wang
authors.affiliation: Pfizer Inc, Groton, CT, USA. Huaming.Tan@pfizer.com.
authors.forename: Huaming
authors.initials: H
authors.lastname: Tan
authors.affiliation: Pfizer Inc, New York, NY, USA. hernan.valdez@pfizer.com.|Specialty Care Medicines Development Group, Pfizer Inc, 219 E 42nd Street, 7th Floor Room 50, NYO 219/07/01, New York, NY, 10017, USA. hernan.valdez@pfizer.com.
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D003587:Cytomegalovirus / Q000502:physiology*; D004279:DNA, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects*
chemical_list: D004279:DNA, Viral; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D002097:C-Reactive Protein