Selective intracellular inhibition of signalling pathways - new direction in systematic treatment of psoriasis patients

Cover Page


Cite item

Full Text

Abstract

This article presents current data from publications on new direction in systematic treatment of patients with psoriasis with help of "small molecules" that act intracellularly, selectively inhibiting signaling pathways responsible for production of key pro- and anti-inflammatory mediators that play an important role in the pathophysiology of psoriasis. We discuss key issues that refer to immunopathogenesis of psoriasis, targeted influence of "small molecules" on key components of innate and adaptive immune system of patients psoriasis. This article presents results of the studies performed according to the evidence-based medicine approaches, on the efficiency and safety of apremilast - the first and only current selective inhibitor of intracellular phosphodiesterase 4 - for treating medium-severe and severe psoriasis, including patients with problematic localizations of dermatosis (psoriasis of scalp pilar part, palms, soles, nail plates), as well as in the long run. It is shown that continuous apremilast therapy for the term of 52-156 weeks was accompanied by a significant decrease in prevalence and severity of psoriasis. Adverse events were recorded rarely, they were mild, and frequency of serious adverse reactions was comparable to placebo.

About the authors

A. L. Bakulev

Saratov State Medical University named after V.I. Razumovsky

Author for correspondence.
Email: al_ba05@mail.ru
Russian Federation

References

  1. Kurd S.K., Gelfand J.M. The prevalence of previously diagnosed and undiagnosed psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol 2009; 60: 218-24.
  2. Augustin M., Reich K., Glaeske G. et al. M. Co-morbidity and agerelated prevalence of psoriasis: analysis of health insurance data in Germany. Acta Derm Venereol 2010; 90: 147-51.
  3. Gottlieb A., Korman N.J., Gordon K.B. et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section. Psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol 2008; 58: 851-64.
  4. Gladman D.D., Antoni C., Mease P. et al. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 2005; 64(Suppl. 2): ii14-7.
  5. Feldman SR. Disease burden and treatment adherence in psoriasis patients. Cutis 2013; 92: 258-63.
  6. Augustin M., Kruger K., Radtke M.A. et al. Disease severity, quality of life and health care in plaquetype psoriasis: a multicenter cross-sectional study in Germany. Dermatology 2008; 216: 366-372.
  7. Kimball A.B., Jacobson C., Weiss S. et al. The psychosocial burden of psoriasis. Am J Clin Dermatol 2005; 6: 383-392.
  8. Sampogna F., Tabolli S., Soderfeldt B. et al. Measuring quality of life of patients with different clinical types of psoriasis using the SF-36. Br J Dermatol 2006; 154: 844-849.
  9. Radtke M.A., Augustin M. Economic considerations in psoriasis management. Clinics in Dermatology 2008: 26; 424-431.
  10. Lowes M.A., Bowcock A.M., Krueger J.G. Pathogenesis and therapy of psoriasis. Nature 2007; 445: 866-73.
  11. Fuentes-Duculan J., Suarez-Farinas M., Zaba L.C. et al. A subpopulation of CD163-positive macrophages is classically activated in psoriasis. J Invest Dermatol 2010; 130: 2412-22.
  12. Menter A., Gottlieb A., Feldman S.R. et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol 2008; 58: 826-50.
  13. Menter A., Korman N.J., Elmets C.A. et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol 2009; 61: 451-85.
  14. Burden A.D., Hilton Boon M., Leman J. et al. Diagnosis and management of psoriasis and psoriatic arthritis in adults: summary of SIGN guidance. BMJ 2010; 341: 5623.
  15. Lowes M.A., Chamian F., Abello M.V. et al. Increase in TNF-a' and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a). Proc Natl Acad Sci USA 2005; 102: 19057-62.
  16. Austin L.M., Ozawa M., Kikuchi T. The majority of epidermal T cells in Psoriasis vulgaris lesions can produce type 1 cytokines, interferon-gamma, interleukin-2, and tumor necrosis factor-alpha, defining TC1 (cytotoxic T lymphocyte) and TH1 effector populations: a type 1 differentiation bias is also measured in circulating blood T cells in psoriatic patients. J Invest Dermatol 1999; 113: 752-9.
  17. Nestle F., Kaplan D.H., Barker J.H. Psoriasis. N Engl J Med 2009; 361: 496-509.
  18. Henno A., Blacher S., Lambert C.A. et al. Histological and transcriptional study of angiogenesis and lymphangiogenesis in uninvolved skin, acute pinpoint lesions and established psoriasis plaques: an approach of vascular development chronology in psoriasis. J Dermatol Sci 2010; 57: 162-9.
  19. Houslay M.D., Schafer P., Zhang K.Y. Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today 2005; 10: 1503-19.
  20. Wright L.C., Seybold J., Robichaud A. et al. Phosphodiesterase expression in human epithelial cells. Am J Physiol Lung Cell Mol Physiol 1998; 275(4 Pt 1): L694-700.
  21. Shepherd M.C., Baillie G.S., Stirling D.I., Houslay M.D. Remodelling of the ФДЭ4 cAMP phosphodiesterase isoform profile upon monocyte-macrophage differentiation of human U937 cells. Br J Pharmacol 2004; 142: 339-51.
  22. Bjorgo E., Tasken K. Role of cAMP phosphodiesterase 4 in regulation of T-cell function. Crit Rev Immunol 2006; 26: 443-51.
  23. Heystek H.C., Thierry A.-C., Soulard P., Moulon C. Phosphodiesterase 4 inhibitors reduce human dendritic cell inflammatory cytokine production and Th1 -polarizing capacity. Int Immunol 2003; 15: 827-35.
  24. Schett G., Sloan V.S., Stevens R.M., Schafer P. Apremilast: a novel ФДЭ4 inhibitor in the treatment of autoimmune and inflammatory diseases. Ther Adv Musculoskelet Dis 2010; 2: 271-8.
  25. Tenor H., Hedbom E., Hauselmann H.J. et al. Phosphodiesterase isoenzyme families in human osteoarthritis chondrocytes-functional importance of phosphodiesterase 4. Br J Pharmacol 2002; 135: 609-18.
  26. Zambon A.C., Zhang L., Minovitsky S. et al. Gene expression patterns define key transcriptional events in cell-cycle regulation by cAMP and protein kinase A. Proc Natl Acad Sci USA 2005; 102: 8561-6.
  27. Houslay M.D. Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. Trends Biochem Sci 2010; 35: 91-100.
  28. Claveau D., Chen S.L., O’Keefe S. et al. Preferential inhibition of T helper 1, but not T helper 2, cytokines in vitro by L-826,141 [4- [2-(3,4 Bisdifluromethoxyphenyl)-2-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-phenyl]-ethyl]3-methylpyridine-1-oxide], a potent and selective phosphodiesterase 4 inhibitor. J Pharmacol Exp Ther 2004; 310: 752-60.
  29. Eigler A., Siegmund B., Emmerich U. Antiinflammatory activities of cAMP-elevating agents: enhancement of IL-10 synthesis and concurrent suppression of TNF production. J Leukoc Biol 1998; 63: 101-7.
  30. Schafer P.H., Parton A., Gandhi A.K. et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. BJD 2010; 159: 842-55.
  31. Paul С., Cather J, Gooderham M at al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate-to-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). BJD 2015; 173: 1387-99.
  32. Kavanaugh A., Adebajo A.O., Gladman D.D. et al. Long-Term (156-Week) Efficacy and Safety Profile of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients with Psoriatic Arthritis: Results from a Phase III, Randomized, Controlled Trial and Open-Label Extension (PALACE 1). ACR/ARHP Annual Meeting. Abstract 2843.
  33. Yosipovitch G., Goon A., Wee J. et al. The prevalence and clinical characteristics of pruritus among patients with extensive psoriasis. Br J Dermatol 2000; 143: 969-973.
  34. Lebwohl M.G., Bachelez H., Barker J. et al. Patient perspectives in the management of psoriasis: results from the populationbased Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol 2014; 70: 871-881.
  35. Szepietowski J.C., Reich A. Pruritus in psoriasis: An update. EJP 2015; 20: 40-46.
  36. Zachariae R., Zachariae C.O., Lei U., Pedersen A.F. Affective and sensory dimensions of pruritus severity: associations with psychological symptoms and quality of life in psoriasis patients. Acta Derm Venereol 2008; 88: 121-127.
  37. Bissonnette R., Pariser D.M., Wasel N.A. Apremilast, an oral phosphodiesterase-4 inhibitor, in the treatment of palmoplantar psoriasis: Results of a pooled analysis from phase II PSOR-005 and phase III Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis (ESTEEM) clinical trials in patients with moderate to severe psoriasis. J Am Acad Dermatol 2016; July: 99-105.
  38. Instuktsiya po primeneniyu lekarstvennogo preparata Otesla. Minzdrav Rossii. 2016. [Инстукция по применению лекарственного препарата Отесла. Минздрав России, 2016.]
  39. Zoratti М., Cividino А., Bensen W. et al. The Efficacy and Safety of Biological Disease Modifying Anti-Rheumatic Drugs and Apremilast in the Treatment of Psoriatic Arthritis: A Systematic Review and Meta-Analysis. ACR/ARHP Annual Meeting 2014: Abstract 1566.
  40. Contes L., Kavanaugh A., Mease P.J. et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic Arthritis. Arthritis & Rheumatology 2016; Marth: 1-12.
  41. Gossec J., Smolen J.S., Ramiro S at al. Eurupean League Against Rheumatism (EULAR) recommendations for the management of psoriatic artritis with pharmacological therapies: 2015 update. Ann Rheum Dis 2015: 0; 1-12.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2016 Bakulev A.L.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 60448 от 30.12.2014.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies