Effects of tofacitinib on lymphocyte sub-populations, CMV and EBV viral load in patients with plaque psoriasis

BMC Dermatol. 2015 May 8:15:8. doi: 10.1186/s12895-015-0025-y.

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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • C-Reactive Protein / metabolism
  • Cytomegalovirus / physiology*
  • DNA, Viral / blood
  • Dose-Response Relationship, Drug
  • Female
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Lymphocyte Count
  • Lymphocyte Subsets / drug effects*
  • Male
  • Middle Aged
  • Piperidines / administration & dosage
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / therapeutic use*
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Psoriasis / virology
  • Pyrimidines / administration & dosage
  • Pyrimidines / therapeutic use*
  • Pyrroles / administration & dosage
  • Pyrroles / therapeutic use*
  • Viral Load / drug effects*

Substances

  • DNA, Viral
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • tofacitinib
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT00678210