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BMC Dermatology
Published in: BMC Dermatology 1/2015

Open Access 01-12-2015 | Research article

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

Authors: Fernando Valenzuela, Kim A Papp, David Pariser, Stephen K Tyring, Robert Wolk, Marjorie Buonanno, Jeff Wang, Huaming Tan, Hernan Valdez

Published in: BMC Dermatology | Issue 1/2015

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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.
Literature
1.
Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133:377–85.CrossRefPubMed
2.
Griffiths CE, Iaccarino L, Naldi L, Olivieri I, Pipitone N, Salvarini C, et al. Psoriasis and psoriatic arthritis: immunological aspects and therapeutic guidelines. Clin Exp Rheumatol. 2014;24(1 Suppl 40):S72–8.
3.
Boy MG, Wang C, Wilkinson BE, Chow VF, Clucas AT, Krueger JG, et al. Double-blind, placebo-controlled, dose-escalation study to evaluate the pharmacologic effect of CP-690,550 in patients with psoriasis. J Invest Dermatol. 2009;129:2299–302.CrossRefPubMed
4.
Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R, et al. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol. 2012;167:668–77.CrossRefPubMed
5.
Bissonnette R, Iversen L, Sofen H, Griffiths CE, Foley P, Romiti R, et al. Tofacitinib withdrawal and re-treatment in moderate-to-severe chronic plaque psoriasis: a randomised controlled trial. Br J Dermatol. 2014. Epub ahead of print.
6.
Bachelez H, van de Kerkof PCM, Strohal R, Kubanov A, Valenzuela F, Lee JH, et al. Comparison of tofacitinib versus etanercept or placebo in moderate-to-severe chronic plaque psoriasis: a Phase 3 randomized trial [abstract]. Presented at the American Academy of Dermatology - 72nd Annual Meeting. 2014.
7.
8.
Li DQ, Chen Z, Song XJ, Luo L, Pflugfelder SC. Stimulation of matrix metalloproteinases by hyperosmolarity via a JNK pathway in human corneal epithelial cells. Invest Ophthalmol Vis Sci. 2004;45:4302–11.CrossRefPubMed
9.
10.
11.
Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol. 2011;186:4234–43.CrossRefPubMedPubMedCentral
12.
Miquel FJ, Colomina J, Maríi JI, Ortega C. Cytomegalovirus infection in a patient treated with efalizumab for psoriasis. Arch Dermatol. 2009;145:961–2.CrossRefPubMed
13.
Petersen B, Lorentzen H. Cytomegalovirus complicating biological immunosuppressive therapy in two patients with psoriasis receiving treatment with etanercept or efalizumab. Acta Derm Venereol. 2008;88:523–4.CrossRefPubMed
14.
Kikuchi K, Miyazaki Y, Tanaka A, Shigematu H, Kojima M, Sakashita H, et al. Methotrexate-related Epstein-Barr virus (EBV)-associated lymphoproliferative disorder--so-called “Hodgkin-like lesion”--of the oral cavity in a patient with rheumatoid arthritis. Head Neck Pathol. 2010;4:305–11.CrossRefPubMedPubMedCentral
15.
Mahé E, Descamps V, Grossin M, Fraitag S, Crickx B. CD30+ T-cell lymphoma in a patient with psoriasis treated with ciclosporin and infliximab. Br J Dermatol. 2003;149:170–3.CrossRefPubMed
16.
Oh MJ, Lee HJ. A study of hepatitis B virus reactivation associated with rituximab therapy in real-world clinical practice: a single-center experience. Clin Mol Hepatol. 2013;19:51–9.CrossRefPubMedPubMedCentral
17.
Erard V, Guthrie KA, Varley C, Heugel J, Wald A, Flowers ME, et al. One-year acyclovir prophylaxis for preventing varicella-zoster virus disease after hematopoietic cell transplantation: no evidence of rebound varicella-zoster virus disease after drug discontinuation. Blood. 2007;110:3071–7.CrossRefPubMed
18.
19.
Talamonti M, Spallone G, Di Stefani A, Costanzo A, Chimenti S. Efalizumab. Expert Opin Drug Saf. 2011;10:239–51.CrossRefPubMed
20.
21.
Nathan DM, Angus PW, Gibson PR. Hepatitis B and C virus infections and anti-tumor necrosis factor-alpha therapy: guidelines for clinical approach. J Gastroenterol Hepatol. 2006;21:1366–71.CrossRefPubMed
22.
Tan X, Balkrishnan R, Feldman SR. Infections associated with the use of tumor necrosis factor-α inhibitors in psoriasis. J Drugs Dermatol. 2013;12:e41–5.PubMed
23.
Ortigosa LC, Silva LC, Duarte AJ, Takahashi MD, Benard G. Infliximab does not lead to reduction in the interferon-gamma and lymphoproliferative responses of patients with moderate to severe psoriasis. Acta Derm Venereol. 2014;94:26–31.CrossRefPubMed
24.
Burmester GR, Mease P, Dijkmans BA, Gordon K, Lovell D, Panaccione R, et al. Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Ann Rheum Dis. 2009;68:1863–9.CrossRefPubMedPubMedCentral
25.
26.
Mocroft A, Furrer HJ, Miro JM, Reiss P, Mussini C, Kirk O, et al. The incidence of AIDS-defining illnesses at a current CD4 count ≥ 200 cells/muL in the post-combination antiretroviral therapy era. Clin Infect Dis. 2013;57:1038–47.CrossRefPubMed
27.
Izadi M, Jonaidi-Jafari N, Saburi A, Eyni H, Rezaiemanesh MR, Ranjbar R. Prevalence, molecular characteristics and risk factors for cryptosporidiosis among Iranian immunocompromised patients. Microbiol Immunol. 2012;56:836–42.CrossRefPubMed
28.
Fedele R, Martino M, Garreffa C, Messina G, Console G, Princi D, et al. The impact of early CD4+ lymphocyte recovery on the outcome of patients who undergo allogeneic bone marrow or peripheral blood stem cell transplantation. Blood Transfus. 2012;10:174–80.PubMedPubMedCentral
29.
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon III RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation. 2003;107:499–511.CrossRefPubMed
30.
Weitz M, Kiessling C, Friedrich M, Prösch S, Höflich C, Kern F, et al. Persistent CMV infection correlates with disease activity and dominates the phenotype of peripheral CD8+ T cells in psoriasis. Exp Dermatol. 2011;20:561–7.CrossRefPubMed
31.
Marcenaro E, Carlomagno S, Pesce S, Della Chiesa M, Parolini S, Moretta A, et al. NK cells and their receptors during viral infections. Immunotherapy. 2011;3:1075–86.CrossRefPubMed
32.
Moseman EA, Iannacone M, Bosurgi L, Tonti E, Chevrier N, Tumanov A, et al. B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity. Immunity. 2012;36:415–26.CrossRefPubMedPubMedCentral
33.
Zinkernagel RM, Hengartner H. Protective ‘immunity’ by pre-existent neutralizing antibody titers and preactivated T cells but not by so-called ‘immunological memory’. Immunol Rev. 2006;211:310–9.CrossRefPubMed
34.
Erice A, Tierney C, Hirsch M, Caliendo AM, Weinberg A, Kendall MA, et al. Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) burden, CMV end-organ disease, and survival in subjects with advanced HIV infection (AIDS Clinical Trials Group Protocol 360). Clin Infect Dis. 2003;37:567–78.CrossRefPubMed
35.
Lautenschlager I, Loginov R, Mäkisalo H, Hockerstedt K. Prospective study on CMV-reactivations under preemptive strategy in CMV-seropositive adult liver transplant recipients. J Clin Virol. 2013;57:50–3.CrossRefPubMed
36.
Levitsky J, Freifeld AG, Puumala S, Bargenquast K, Hardiman P, Gebhart C, et al. Cytomegalovirus viremia in solid organ transplantation: does the initial viral load correlate with risk factors and outcomes? Clin Transplant. 2008;22:222–8.CrossRefPubMed
37.
Comar M, Delbue S, Lepore L, Martelossi S, Radillo O, Ronfani L, et al. Latent viral infections in young patients with inflammatory diseases treated with biological agents: prevalence of JC virus genotype 2. J Med Virol. 2013;85:716–22.CrossRefPubMed
38.
McKeown E, Pope JE, Leaf S. Epstein-Barr virus (EBV) prevalence and the risk of reactivation in patients with inflammatory arthritis using anti-TNF agents and in those who are biologic naive. Open Rheumatol J. 2009;3:30–4.CrossRefPubMedPubMedCentral
39.
Neimann AL, Hodinka RL, Joshi YB, Elkan M, Van Voorhees AS, Gelfand JM. Epstein-Barr virus and human herpesvirus type 6 infection in patients with psoriasis. Eur J Dermatol. 2006;16:548–52.PubMed
40.
Metadata
Title
Effects of tofacitinib on lymphocyte sub-populations, CMV and EBV viral load in patients with plaque psoriasis
Authors
Fernando Valenzuela
Kim A Papp
David Pariser
Stephen K Tyring
Robert Wolk
Marjorie Buonanno
Jeff Wang
Huaming Tan
Hernan Valdez
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Dermatology / Issue 1/2015
Electronic ISSN: 1471-5945
DOI
https://doi.org/10.1186/s12895-015-0025-y

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