Signaling Рathway Blockers: Action Mechanism, Efficacy, Safety of Therapy for Patients with Psoriasis and Psoriatic Arthritis

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Abstract

In the literature review, contemporary data on immune pathogenesis of psoriasis and the emergence of comorbid states against the background of systemic chronic inflammation among patients is discussed. On the example of the apremilast medical preparation, the information on a new class of therapeutic agents for the treatment of psoriasis and psoriatic arthritis – “small molecules” is given, including their physicochemical properties and action mechanism, as well as on the key differences from immune-suppressive and genetically engineered biological preparations. Data on large-scale international randomised clinical trials of the efficacy and safety of the PDE4 inhibitor of apremilast among patients with moderate to severe psoriasis and psoriatic arthritis is presented. The published international clinical recommendations on the use of apremilast among patients with psoriasis and psoriatic arthritis, the criteria for evaluating the response to therapy, as well as the potential profile of patients for the use of apremilast in real clinical practice are discussed.

About the authors

A. A. Bakulev

Saratov State Medical University named after V. I. Razumovsky of the Ministry of Health of Russian Federation, Saratov

Author for correspondence.
Email: al_ba05@mail.ru
Bolshaya Kazachia str, 112, 410012 Russian Federation

References

  1. Langley R. G. Exploring new concepts in the successful management of psoriasis. J EADV. 2012. Vol.26. March. 2012.
  2. Coimbra S., Catarino C., Santos-Silva A. The triad psoriasisobesity-adipokine profile. J Eur Acad Dermatol Venereol. 2016. Nov;30(11):1876–1885.
  3. Gerdes S., Mrowietz U. Comorbidities and psoriasis. Impact on clinical practice]. Hautarzt. 2012. Mar;63(3):202–213.
  4. Onumah N., Kircik L. H. Psoriasis and its comorbidities. J Drugs Dermatol. 2012. May;11(5 Suppl):5–10.
  5. Lotti T., Hercogova J., Prignano F. The concept of psoriatic disease: can cutaneous psoriasis any longer be separated by the systemic comorbidities? Dermatol Ther. 2010. Mar–Apr;23(2):119–122.
  6. Gisondi P., Ferrazzi A., Girolomoni G. Metabolic comorbidities and psoriasis. Acta Dermatovenerol Croat. 2010;18(4):297–304.
  7. Lynch M., Ahern T., Sweeney C. M., Malara A., Tobin A. M., O'Shea D., Kirby B. Adipokines, psoriasis, systemic inflammation, and endothelial dysfunction. Int J Dermatol. 2017. Aug 1. doi: 10.1111/ijd.13699.
  8. Takeshita J., Grewal S., Langan S. M., Mehta N. N., Ogdie A., Van Voorhees A. S., Gelfand J. M. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol. 2017. Mar; 76(3):393–403.
  9. Lichtman A. H., Binder C. J., Tsimikas S., Witztum J. Adaptive immunity in atherogenesis: new insights and therapeutic approaches. The Journal of Clinical Investigation. 2013;№1:27–36.
  10. Gelfand J. M., Troxel A. B., Lewis J. D., Kurd S. K., Shin D. B., Wang X., Margolis D. J., Strom B. L. The risk of mortality in patients with psoriasis: results from a population-based study. Arch Dermatol. 2007. Dec;143(12):1493–1499.
  11. Kim J., Krueger J. G. The immunopathogenesis of psoriasis. Dermatol Clin. 2015. Jan;33(1):13–23.
  12. Bos J. D., de Rie M. A., Teunissen M. B., Piskin G. Psoriasis: dysregulation of innate immunity. Br J Dermatol. 2005. Jun; 152(6):1098– 1107.
  13. Zhang Z., Fan W., Yang G., Xu Z., Wang J., Cheng Q., Yu M. Risk of tuberculosis in patients treated with TNF-Į antagonists: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2017. Mar22;7(3):e012567.
  14. Бакулев А. Л. Селективное внутриклеточное ингибирование сигнальных путей – новое направление системной терапии больных псориазом. Вестник дерматол. 2017;№ 5:55–62 [ Bakulev A. L. Selektivnoe vnutrikletochnoe ingibirovanie signal'nyh putej – novoe napravlenie sistemnoj terapii bol'nyh psoriazom. Vestnik dermatol. 2017;(5):55–62]
  15. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis.Biochem Pharmacol. 2012. Jun15; 83(12):1583–1590. Epub 2012 Jan 10.
  16. Schafer P. H., Parton A., Gandhi A. K., Capone L., Adams M., Wu L., Bartlett J. B., Loveland M. A., Gilhar A., Cheung Y.F. et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol. 2010. Feb;159(4):842– 855. Epub 2009 Dec 24.
  17. Кубанова А. А., Кубанов А. А., Насонов Е. Л., Соколовский Е. В., Знаменская Л. Ф., Рахматулина М. Р., Бакулев А. Л., Хобейш М. М., Чикин В. В., Коротаева Т. В., Логинова Е. Ю., Корсакова Ю. Л. Псориатический артрит. Клинические рекомендации РОДВК и Ассоциации ревматологов России. М., 2015. [Kubanova A. A., Kubanov A. A., Nasonov E. L., Sokolovskij E. V., Znamenskaya L. F., Rahmatulina M. R., Bakulev A. L., Hobejsh M. M., CHikin V. V., Korotaeva T. V., Loginova E. YU., Korsakova YU. L. Psoriaticheskij artrit. Klinicheskie rekomendacii RODVK i Associacii revmatologov Rossii. M., 2015]
  18. Houslay M. D., Schafer P., Zhang K. Y. Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today. 2005;10:1503–1519.
  19. 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.
  20. Shepherd M. C., Baillie G. S., Stirling D. I., Houslay M. D. Remodelling of the PDE4 cAMP phosphodiesterase isoform profile upon monocyte-macrophage differentiation of human U937 cells. Br J Pharmacol. 2004;142:339–351.
  21. Bjorgo E., Tasken K. Role of cAMP phosphodiesterase 4 in regulation of T-cell function. Crit Rev Immunol. 2006;26:443–451.
  22. 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– 835.
  23. Schett G., Sloan V. S., Stevens R. M., Schafer P. Apremilast: a novel PDE4 inhibitor in the treatment of autoimmune and inflammatory diseases. Ther Adv Musculoskelet Dis. 2010;2:271–278.
  24. 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;135:609–618.
  25. Papp K., Reich K., Leonardi C. L. et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (ESTEEM 1). J Am Acad Dermatol. 2015;73:37–49.
  26. Paul С., Cather J., Gooderham M. at al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with moderateto-severe plaque psoriasis over 52 weeks: a phase III, randomized controlled trial (ESTEEM 2). BJD. 2015;173:1387–1399.
  27. Rich P., Gooderham M., Bachelez H., Goncalves J., Day R. M., Chen R., Crowley J. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with difficult-to-treat nail and scalp psoriasis: Results of 2 phase III randomized, controlled trials (ESTEEM 1 and ESTEEM 2). J Am Acad Dermatol.2016;74:134–142.
  28. Kavanaugh A., Mease P.J., Gomez-Reino J.J., Adebajo A.O., Wollenhaupt J., Gladman D.D., Hochfeld M., Teng L.L., Schett G., Lespessailles E., Hall S. Longterm (52-week) results of a phase III randomized, controlled trial of apremilast in patients with psoriatic arthritis. J Rheumatol. 2015. Mar;42(3):479–488.
  29. Gladman D., Kavanaugh A., Adebajo A. O. et al. Apremilast, an Oral Phosphodiesterase 4 Inhibitor, Is Associated with Long-Term (104-Week) Improvements in Enthesitis and Dactylitis in Patients with Psoriatic Arthritis: Pooled Results from Three Phase III, Randomized, Controlled Trials. ACR/ ARHP Annual Meeting, 2015. Abstract 2888.
  30. Reich K., Gooderham M., Green L., Bewley A., Zhang Z., Khanskaya I., Day R. M., Goncalves J., Shah K., Piguet V., Soung J. The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE). J Eur Acad Dermatol Venereol. 2017. Mar;31(3):507–517.
  31. Papp K., Chen R., Day R., Paul C., Shah K., Sobell J. Safety and Tolerability of Apremilast Up to 182 Weeks: Pooled Analyses From Phase 3 Clinical Trials. 74th Annual Meeting AAD. Washington, 2016. Poster 2347.
  32. Инструкция по медицинскому применению препарата Отесла. 2016. [Instrukciya po medicinskomu primeneniyu preparata Otesla. 2016]
  33. Apremilast for treating moderate to severe plaque psoriasis. NICE Guideline, 2016:TA419.
  34. 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.
  35. 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.
  36. Apremilast for treating active psoriatic arthritis. NICE Guideline, 2017:TA433. 37. Псориаз. Проект клинических рекомендаций. М, 2016. http:// cr.rosminzdrav.ru/schema.html?id=866#/text

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