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: Fernando Valenzuela, Kim A Papp, David Pariser, Stephen K Tyring, Robert Wolk, Marjorie Buonanno, Jeff Wang, Huaming Tan, Hernan Valdez
• Journal: BMC dermatology (BMC Dermatol) Vol. 15 Pg. 8 (May 08 2015) ISSN: 1471-5945 [Electronic] England
• PMID: 25951857 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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, therapeutic use)
• Protein Kinase Inhibitors (administration & dosage, therapeutic use)
• Psoriasis (drug therapy, immunology, virology)
• Pyrimidines (administration & dosage, therapeutic use)
• Pyrroles (administration & dosage, therapeutic use)
• Viral Load (drug effects)