Guselkumab in the treatment of patients with plaque psoriasis of moderate and severe severity: Efficacy and safety of interleukin-23 blockade

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Abstract

Materials and methods. In this paper, we review publications on the significance of interleukin-(IL)-23 in the pathogenesis of plaque psoriasis and analyse the results of the 1st and 2nd phase clinical studies, as well as the 3rd phase comparative studies VOYAGE 1, VOYAGE 2, NAVIGATE and ECLIPSE on the efficacy and safety of Guselkumab — a blocker of the p19 subunit in IL-23. The review was conducted using the scientific literature databases PubMed and RSCI.
Results. The high efficiency and safety of Guselkumab in the treatment of patients with plaque psoriasis is demonstrated. The PASI 90 value during Guselkumab treatment reached 73.3 % and 80.2 % at the 24th and 16th week (VOYAGE 1). The therapeutic effect persisted following treatment for 48 weeks. It is shown that Guselkumab therapy is effective in patients having undergone unsuccessful therapy with other genetically engineered biological preparations. The reviewed comparative studies show a higher  therapeutic efficacy of Guselkumab compared to TNF-α blockers, IL-12/23 p40 subunit, IL-17. The incidence of adverse events during therapy using Guselkumab and other biological drugs used in comparative studies
was low and comparable.
Conclusion. The IL-23 subunit p19 blocker Guselkumab is an effective and safe drug for the treatment of patients with plaque psoriasis of moderate and severe severity.

About the authors

V. V. Chikin

State Research Center of Dermatovenereology and Cosmetology, Ministry of Health of the Russian Federation

Author for correspondence.
Email: chikin@cnikvi.ru

Dr. Sci. (Med.), Leading Researcher, Department of Dermatology

Korolenko str., 3, bldg 6, Moscow, 107076, Russian Federation



Russian Federation

References

  1. Helmick C. G., Lee-Han H., Hirsch S. C. et al. Prevalence of psoriasis among adults in the U.S.: 2003–2006 and 2009–2010 National Health and Nutrition Examination Surveys. Am J Prev Med. 2014;47(1):37–45.
  2. Бакулев А. Л., Фитилева Т. В., Новодережкина Е. А. и др. Псориаз: клинико-эпидемиологические особенности и вопросы терапии. Результаты опроса пациентов и врачей, проведенного в медицинских организациях в России. Вестник дерматологии и венерологии. 2018;94(3):67–76.
  3. Кубанов А. А., Богданова Е. В. Организация и результаты оказания медицинской помощи по профилю «дерматовенерология» в Российской Федерации. Итоги 2018 года. Вестник дерматологии и венерологии. 2019;95(4):8–23.
  4. Khawaja A. R., Bokhari S. M., Tariq R. et al. Disease severity, quality of life, and psychiatric morbidity in patients with psoriasis with reference to sociodemographic, lifestyle, and clinical variables: a prospective, cross-sectional study from Lahore, Pakistan. Prim. Care Companion CNS Disord. 2015;17(3). doi: 10.4088/PCC.14m01629
  5. Mattei P. L., Corey K. C., Kimball A. B. Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI): the correlation between disease severity and psychological burden in patients treated with biological therapies. J Eur Acad Dermatol Venereol. 2014;28(3):333–337.
  6. Barankin B., DeKoven J. Psychosocial effect of common skin diseases. Can Fam Physician. 2002;48:712–716.
  7. Kimball A. B., Jacobson C., Weiss S. et al. The psychosocial burden of psoriasis. Am J Clin Dermatol. 2005;6(6):383–392.
  8. Basavaraj K. H., Navya M. A., Rashmi R. Relevance of psychiatry in dermatology: present concepts. Indian J Psychiatry. 2010;52(3):270–275.
  9. Vardy D., Besser A., Amir M. et al. Experiences of stigmatization play a role in mediating the impact of disease severity on quality of life in psoriasis patients. Br J Dermatol. 2002;147(4):736–742.
  10. Schmid-Ott G. Future trends in psychodermatological psoriasis research: somatopsychic or psychosomatic focus? Dermatol Psychosom. 2003;4(3):129–130.
  11. Schmid-Ott G., Künsebeck H. W., Jäger B. et al. Significance of the stigmatization experience of psoriasis patients: a 1-year follow-up of the illness and its psychosocial consequences in men and women. Acta DermVenereol. 2005;85(1):27–32.
  12. Schmid-Ott G., Schallmayer S., Calliess I. T. Quality of life in patients with psoriasis and psoriasis arthritis with a special focus on stigmatization experience. Clin Dermatol. 2007;25(6):547–554.
  13. Kurd S. K., Troxel A. B., Crits-Christoph P. et al. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 2010;146(8):891–895.
  14. Weiss S. C., Kimball A. B., Liewehr D. J. et al. Quantifying the harmful effect of psoriasis on health-related quality of life. J Am Acad Dermatol. 2002;47(4):512–518.
  15. Mattoo S. K., Handa S., Kaur I. et al. Psychiatric morbidity in psoriasis: prevalence and correlates in India. Ger J Psychiatry. 2005;8:17–22.
  16. Russo P. A., Ilchef R., Cooper A. J. Psychiatric morbidity in psoriasis: a review. Australas J Dermatol. 2004;45(3):155–159. Quiz 160–161.
  17. Sharma S., Bassi R., Singh A. A comparative study of depression and anxiety in psoriasis and other chronic skin diseases. J Pakistan Assoc Dermatologists. 2011;21(4):235–240.
  18. Kimball A.B., Gladman D., Gelfand J. M. et al. National Psoriasis Foundation clinical consensus on psoriasis comorbidities and recommendations for screening. J Am Acad Dermatol. 2008;58(6):1031–1042.
  19. Oliveira M. F., Rocha B. O., Duarte G. V. Psoriasis: classical and emerging comorbidities. An Bras Dermatol. 2015;90(1):9–20.
  20. Langan S. M., Seminara N. M., Shin D. B. et al. Prevalence of metabolic syndrome in patients with psoriasis: a population-based study in the United Kingdom. J Invest Dermatol. 2012;132(3 Pt 1):556–562.
  21. Takeshita J., Grewal S., Langan S. M. et al. Psoriasis and comorbid diseases: implications for management. J Am Acad Dermatol. 2017;76:393–403.
  22. Takeshita J., Grewal S., Langan S. M. et al. Psoriasis and comorbid diseases: epidemiology. J Am Acad Dermatol. 2017;76:377–390.
  23. Gelfand J. M., Troxel A. B., Lewis J. D. et al. The risk of mortality in patients with psoriasis: results from a population-based study. Arch Dermatol. 2007;143:1493–1499.
  24. Armstrong E. J., Harskamp C. T., Armstrong A. W. Psoriasis and major adverse cardiovascular events: a systematic review and meta-analysis of observational studies. J Am Heart Assoc. 2013;2(2):e000062.
  25. Samarasekera E. J., Neilson J. M., Warren R. B. et al. Incidence of cardiovascular disease in individuals with psoriasis: a systematic review and meta-analysis. J Invest Dermatol. 2013;133(10):2340–2346.
  26. Abuabara K., Azfar R. S., Shin D. B. et al. Cause-specific mortality in patients with severe psoriasis: a population-based cohort study in the U.K. Br J Dermatol. 2010;163(3):586–592.
  27. Svedbom A., Dalen J., Mamolo C. et al. Increased cause-specific mortality in patients with mild and severe psoriasis: a population-based Swedish register study. Acta DermVenereol. 2015;95(7):809–815.
  28. Lew W., Bowcock A. M., Krueger J. G. Psoriasis vulgaris: cutaneous lymphoid tissue supports T-cell activation and “Type 1” inflammatory gene expression. Trends Immunol. 2004;25:295–305.
  29. Austin L. M., Ozawa M., Kikuchi T. et al. 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;113:752–759.
  30. Yawalkar N., Karlen S., Hunger R. et al. Expression of interleukin-12 is increased in psoriatic skin. J Invest Dermatol. 1998;111:1053–1057.
  31. Brembilla N. C., Senra L., Boehncke W.-H., The IL-17 family of cytokines in psoriasis: IL-17A and beyond. Front Immunol. 2018 Aug 2;9:1682.
  32. Lin A. M., Rubin C. J., Khandpur R. et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187:490–500.
  33. Schön M. P., Erpenbeck L. The Interleukin-23/Interleukin-17 axis links adaptive and innate immunity in psoriasis. Front Immunol. 2018 Jun 15;9:1323.
  34. Lowes M. A., Kikuchi T., Fuentes-Duculan J. et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008;128:1207–1211.
  35. Haider A. S., Lowes M. A., Suarez-Farinas M. et al. Identification of cellular pathways of “type 1,” Th17 T cells, and TNF- and inducible nitric oxide synthase-producing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis. J Immunol. 2008;180:1913–1920.
  36. Lowes M. A., Russell C. B., Martin D. A. et al. The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol. 2013;34:174–181.
  37. Zaba L. C., Cardinale I., Gilleaudeau P. et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med. 2007;204:3183–3194.
  38. Kryczek I., Bruce A.T., Gudjonsson J. E. et al. Induction of IL-171 T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol. 2008;181:4733–4741.
  39. Kagami S., Rizzo H. L., Lee J. J. et al. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130:1373–1383.
  40. Zhang L., Yang X. Q., Cheng J. et al. Increased Th17 cells are accompanied by FoxP3(1) Treg cell accumulation and correlated with psoriasis disease severity. Clin Immunol. 2010;135:108–117.
  41. Hawkes J. E., Chan T. C., Krueger J. G. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017;140(3):645–653.
  42. Hawkes J. E., Yan B. Y., Chan T. C., Krueger J. G. Discovery of the IL-23/IL-17 Signaling Pathway and the Treatment of Psoriasis. J Immunol. 2018;201(6):1605–1613.
  43. Bettelli E., Oukka M., Kuchroo V. K. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol. 2007;8(4):345–350.
  44. Raychaudhuri S. P. Role of IL-17 in psoriasis and psoriatic arthritis. Clin Rev Allergy Immunol. 2013;44(2):183–193.
  45. Wang X., Wei Y., Xiao H. et al. A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice. Eur J Immunol. 2016;46(6):1343–1350.
  46. Vignali D. A., Kuchroo V. K. IL-12 family cytokines: immunological playmakers. Nat Immunol. 2012;13(8):722–728.
  47. Oppmann B., Lesley R., Blom B. et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715–725.
  48. Krueger J. G., Bowcock A. Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis. 2005;64(Suppl 2):ii30–36.
  49. Nograles K. E., Davidovici B., Krueger J. G. New insights in the immunologic basis of psoriasis. Semin Cutan Med Surg. 2010;29:3–9.
  50. Yawalkar N., Tscharner G. G., Hunger R. E., Hassan A.S. Increased expression of IL-12p70 and IL-23 by multiple dendritic cell and macrophage subsets in plaque psoriasis. J Dermatol Sci. 2009;54:99–105.
  51. Gordon K. B., Duffin K. C., Bissonnette R. et al. A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N Engl J Med. 2015;373(2):136–144.
  52. di Cesare A., di Meglio P., Nestle F. O. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009;129(6):1339–1350.
  53. Shuai K., Liu B. Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol. 2003;3:900–911.
  54. Zúñiga L. A., Jain R., Haines C., Cua D. J. Th17 cell development: from the cradle to the grave. Immunol Rev. 2013;252(1):78–88.
  55. Gaffen S. L., Jain R., Garg A. V., Cua D. J. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14(9):585–600.
  56. Aggarwal S., Ghilardi N., Xie M. H. et al. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278:1910–1914.
  57. Ferber I. A., Brocke S., Taylor-Edwards C. et al. Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol. 1996;156:5–7.
  58. Langrish C. L., Chen Y., Blumenschein W. M. et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 2005;201:233–240.
  59. Chan T. C., Hawkes J. E., Krueger J. G. Interleukin 23 in the skin: role in psoriasis pathogenesis and selective interleukin 23 blockade as treatment. Ther Adv Chronic Dis. 2018;9(5):111–119.
  60. Yang L., Li B., Dang E. et al. Impaired function of regulatory T cells in patients with psoriasis is mediated by phosphorylation of STAT3. J Dermatol Sci. 2016;81(2):85–92.
  61. Bovenschen H. J., van de Kerkhof P. C., van Erp P. E. et al. Foxp3+ regulatory T cells of psoriasis patients easily differentiate into IL-17A-producing cells and are found in lesional skin. J Invest Dermatol. 2011;131(9):1853–1860.
  62. Lee E., Trepicchio W. L., Oestreicher J. L. et al. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med. 2004;199:125–130.
  63. Michalak-Stoma A., Bartosińska J., Kowal M. et al. Serum levels of selected Th17 and Th22 cytokines in psoriatic patients. Dis Markers. 2013;35(6):625–631.
  64. Lupardus P. J., Garcia K. C. The structure of interleukin-23 reveals the molecular basis of p40 subunit sharing with interleukin-12. J Mol Biol. 2008;382(4):931–941.
  65. Chan J. R., Blumenschein W., Murphy E. et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med. 2006;203:2577–2587.
  66. Piskin G., Sylva-Steenland R. M., Bos J. D., Teunissen M. B. In vitro and in situ expression of IL-23 by keratinocytes in healthy skin and psoriasis lesions: enhanced expression in psoriatic skin. J Immunol. 2006;176:1908–1915.
  67. Kulig P., Musiol S., Freiberger S. N. et al. IL-12 protects from psoriasiform skin inflammation. Nat Commun. 2016 Nov 28;7:13466.
  68. Sofen H., Smith S., Matheson R. T. et al. Guselkumab (an IL-23-specific mAb) demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol. 2014;133(4):1032–1040.
  69. Mylle S., Grine L., Speeckaert R. et al. Targeting the IL-23/IL-17 Pathway in Psoriasis: the Search for the Good, the Bad and the Ugly. Am J Clin Dermatol. 2018;19(5):625–637.
  70. Gooderham M. J., Papp K. A., Lynde C. W. Shifting the focus — the primary role of IL-23 in psoriasis and other inflammatory disorders. J Eur Acad Dermatol Venereol. 2018;32(7):1111–1119.
  71. Blauvelt A., Papp K. A., Griffiths C. E. et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the continuous treatment of patients with moderate to severe psoriasis: results from the phase III, double-blinded, placebo- and active comparator-controlled VOYAGE 1 trial. J Am Acad Dermatol. 2017;76:405–417.
  72. Reich K., Armstrong A. W., Foley P. et al. Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial. J Am Acad Dermatol. 2017;76:418–431.
  73. Langley R. G., Tsai T.-F., Flavin S. et al. Efficacy and safety of guselkumab in patients with psoriasis who have an inadequate response to ustekinumab: results of the randomized, double-blind, phase III NAVIGATE trial. Br J Dermatol. 2018;178:114–123.
  74. Ohtsuki M., Kubo H., Morishima H. et al. Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. J Dermatol. 2018;45:1053–1062.
  75. Puig L. Guselkumab for the treatment of adults with moderate to severe plaque psoriasis. Expert Rev Clin Immunol. 2019;15(6):589–597.
  76. Reich K., Armstrong A. W., Langley R. W. et al. Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE): results from a phase 3, randomised controlled trial. Lancet. 2019;394(10201):831–839.
  77. Foley P., Gordon K., Griffiths C. E. et al. Efficacy of guselkumab compared with adalimumab and placebo for psoriasis in specific body regions: a secondary analysis of 2 randomized clinical trials. JAMA Dermatol. 2018;154:676–683.
  78. Hu C., Yao Z., Chen Y. et al. A comprehensive evaluation of exposure-response relationships in clinical trials: application to support guselkumab dose selection for patients with psoriasis. J Pharmacokinet Pharmacodyn. 2018;45:523–535.
  79. Griffiths C. E., Radtke M. A., Youn S. W. Clinical Response after Guselkumab Treatment among Adalimumab PASI 90 Non-responders: Results from the VOYAGE 1 and 2 Trials. Poster P6858 presented at EADV Congress 2019, Madrid.
  80. Griffiths C. E., Papp K. A., Song M. et al. Maintenance of response with guselkumab for up to 3 years’ treatment in the phase 3 VOYAGE 1 trial of patients with plaque psoriasis. SKIN The Journal of Cutaneous Medicine. 2018;2:S90. https://jofskin.org/index.php/skin/article/view/487 (accessed 16.12.2019).
  81. Gordon K. B., Armstrong A. W., Foley P. Guselkumab efficacy after withdrawal is associated with suppression of serum IL-23-regulated IL-17 and IL-22 in psoriasis: VOYAGE 2 Study. J Invest Dermatol. 2019;139(12):2437–2446.
  82. Reich K., Papp K. A., Armstrong A. W. et al. Safety of guselkumab in patients with moderate-to-severe psoriasis treated through 100 weeks: a pooled analysis from the randomized VOYAGE 1 and VOYAGE 2 studies. Br J Dermatol. 2019;180(5):1039–1049.
  83. Wechter T., Cline A., Feldman S. R. Targeting p19 as a treatment option for psoriasis: an evidence-based review of guselkumab. Ther Clin Risk Manag. 2018;14:1489–1497.
  84. Al-Salama Z. T., Scott L. J. Guselkumab: a review in moderate to severe plaque psoriasis. Am J Clin Dermatol. 2018;19:907–918.

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