IL-23 Inhibitors for Psoriasis

  • Kristen M. Beck
  • Eric J. Yang
  • Sahil Sekhon
  • Tina Bhutani
Psoriasis (J Wu, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Psoriasis

Abstract

Purpose of Review

The purpose of this article is to review current understanding of the role of IL-23 in psoriasis and the available results to date on clinical trials establishing the efficacy and safety of IL-23 inhibitors for use in adults with moderate-to-severe plaque psoriasis.

Recent Findings

Interleukin-23, a cytokine involved in activation and maintenance of the T-helper 17 pathway, plays a key role in the immunopathogenesis of psoriasis. While antibodies to IL-12 and IL-23 have been approved in psoriasis treatment for several years, robust evidence on the key role of IL-23 has led to the newest class of biologics for the treatment of psoriasis specifically targeting only IL-23. Guselkumab, tildrakizumab, risankizumab, and mirikizumab are fully human (guselkumab) or humanized (tildrakizumab, risankizumab, and mirikizumab) monoclonal antibodies that bind to the unique p19 subunit of IL-23. Guselkumab was recently approved for use in psoriasis, while the three others remain under investigation in clinical trials.

Summary

Early data from clinical trials shows high efficacy and low short-term safety risks of IL-23 inhibition.

Keywords

Psoriasis IL-23 IL-23p19 Biologics Guselkumab Tildrakizumab Risankizumab Mirikizumab 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70(3):512–6.CrossRefPubMedGoogle Scholar
  2. 2.
    Takeshita J, Grewal S, Langan SM, Mehta NN, Ogdie A, Van Voorhees AS, et al. Psoriasis and comorbid diseases: epidemiology. J Am Acad Dermatol. 2017;76(3):377–90.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Rapp SR, Feldman SR, Exum ML, Fleischer AB, Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol. 1999;41(3):401–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Pearce DJ, Singh S, Balkrishnan R, Kulkarni A, Fleischer Jr AB, Feldman SR. The negative impact of psoriasis on the workplace. J Dermatol Treat. 2006;17(1):24–8.CrossRefGoogle Scholar
  5. 5.
    Di Cesare A, Di Meglio P, Nestle FO. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Investig Dermatol. 2009;129(6):1339–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. Novel p 19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13(5):715–25.Google Scholar
  7. 7.
    Gerosa F, Baldani-Guerra B, Lyakh LA, Batoni G, Esin S, Winkler-Pickett RT, et al. Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells. J Exp Med. 2008;205(6):1447–61.Google Scholar
  8. 8.
    Piskin G, Tursen U, Sylva-Steenland R, Bos J, Teunissen M. Clinical improvement in chronic plaque-type psoriasis lesions after narrow-band UVB therapy is accompanied by a decrease in the expression of IFN-γ inducers–IL-12, IL-18 and IL-23. Exp Dermatol. 2004;13(12):764–72.CrossRefPubMedGoogle Scholar
  9. 9.
    Chan JR, Blumenschein W, Murphy E, Diveu C, Wiekowski M, Abbondanzo S, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med. 2006;203(12):2577–87.Google Scholar
  10. 10.
    Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, Chamian F, et al. Increased expression of interleukin 23 p 19 and p 40 in lesional skin of patients with psoriasis vulgaris. J Exp Med. 2004;199(1):125–30.Google Scholar
  11. 11.
    Rizzo HL, Kagami S, Phillips KG, Kurtz SE, Jacques SL, Blauvelt A. IL-23–mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A. J Immunol. 2011;186(3):1495–502.CrossRefPubMedGoogle Scholar
  12. 12.
    Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, et al. Interleukin-22, a T H 17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007;445(7128):648–51.Google Scholar
  13. 13.
    Tonel G, Conrad C, Laggner U, Di Meglio P, Grys K, McClanahan TK, et al. Cutting edge: a critical functional role for IL-23 in psoriasis. J Immunol. 2010;185(10):5688–91.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, et al. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet. 2008;4(4):e1000041.Google Scholar
  15. 15.
    Duvallet E, Semerano L, Assier E, Falgarone G, Boissier M-C. Interleukin-23: a key cytokine in inflammatory diseases. Ann Med. 2011;43(7):503–11.CrossRefPubMedGoogle Scholar
  16. 16.
    Sherlock JP, Joyce-Shaikh B, Turner SP, Chao C-C, Sathe M, Grein J, et al. IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+ CD4− CD8− entheseal resident T cells. Nat Med. 2012;18(7):1069–76.Google Scholar
  17. 17.
    Krueger GG, Langley RG, Leonardi C, Yeilding N, Guzzo C, Wang Y, et al. A human interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N Engl J Med. 2007;356(6):580–92.Google Scholar
  18. 18.
    Levin AA, Gottlieb AB. Specific targeting of interleukin-23p19 as effective treatment for psoriasis. J Am Acad Dermatol. 2014;70(3):555–61.CrossRefPubMedGoogle Scholar
  19. 19.
    Kulig P, Musiol S, Freiberger SN, Schreiner B, Gyülveszi G, Russo G, et al. IL-12 protects from psoriasiform skin inflammation. Nat Commun. 2016;7:13466.Google Scholar
  20. 20.
    Gaspari AA, Tyring S. New and emerging biologic therapies for moderate-to-severe plaque psoriasis: mechanistic rationales and recent clinical data for IL-17 and IL-23 inhibitors. Dermatol Ther. 2015;28(4):179–93.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Tugues S, Burkhard S, Ohs I, Vrohlings M, Nussbaum K, Vom Berg J, et al. New insights into IL-12-mediated tumor suppression. Cell Death Differ. 2015;22(2):237–46.CrossRefPubMedGoogle Scholar
  22. 22.
    Köck K, Pan W, Gow J, Horner M, Gibbs J, Colbert A, et al. Preclinical development of AMG 139, a human antibody specifically targeting IL-23. Br J Pharmacol. 2015;172(1):159–72.Google Scholar
  23. 23.
    Tremfya (guselkumab) [prescribing information]. Horsham PJB, Inc; October 2017.Google Scholar
  24. 24.
    •• Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen Y-K, 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(3):405–17. Phase III clinical trial of guselkumab. CrossRefPubMedGoogle Scholar
  25. 25.
    •• Reich K, Armstrong AW, Foley P, Song M, Wasfi Y, Randazzo B, 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(3):418–31. Phase III clinical trial of guselkumab. CrossRefPubMedGoogle Scholar
  26. 26.
    Reich K, Papp KA, Blauvelt A, Tyring SK, Sinclair R, Thaçi D, et al. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017;390(10091):276–88.Google Scholar
  27. 27.
    Gordon KB, et al. Efficacy and safety of risankizumab: results from two double-blind, placebo- and ustekinumab-controlled, phase 3 trials in moderate-to-severe plaque psoriasis. Presented at: 2018 American Academy of Dermatology Annual Meeting. February 16–20, 2017; San Diego, CA. Abstract 6495.Google Scholar
  28. 28.
    AbbVie. Risankizumab meets all co-primary and ranked secondary endpoints, achieving significantly greater efficacy versus standard biologic therapies in three pivotal phase 3 psoriasis studies. [Online Press Release]. https://news.abbvie.com/news/risankizumab-meets-all-co-primary-and-ranked-secondary-endpoints-achieving-significantly-greater-efficacy-versus-standard-biologic-therapies-in-three-pivotal-phase-3-psoriasis-studies.htm. Accessed 1 February 2018.
  29. 29.
    Blauvelt A, Papp KA, Gooderham M, Langley R, Leonardi C, Lacour J-P et al. Efficacy and safety of risankizumab, an interleukin-23 inhibitor in patients with moderate-to-severe chronic plaque psoriasis: 16-week results from the phase III IMMhance trial [Abstract] FC29. Psoriasis: From Gene to Clinic International Congress, London, 2nd December 2017, 1115. 2017:69.Google Scholar
  30. 30.
    Gordon K MA, Ferris L, Martorell A, Kim B, Song M, Wasfi Y, You Y, Shen YK, Langley R. Consistency of response (PASI 90 or 100 and IGA 0 or 0/1) in patients with moderate to severe psoriasis treated with guselkumab: results from the VOYAGE 1 and 2 trials. AAD Anual Meeting. [Poster presentation]. 2018.Google Scholar
  31. 31.
    Gordon K, Blauvelt A, Foley P, Song M, Wasfi Y, Randazzo B, et al. Efficacy of guselkumab in subpopulations of patients with moderate-to-severe plaque psoriasis: a pooled analysis of the phase III VOYAGE 1 and VOYAGE 2 studies. Br J Dermatol. 2018;178(1):132–9.CrossRefPubMedGoogle Scholar
  32. 32.
    •• Langley RG, Tsai TF, Flavin S, Song M, Randazzo B, Wasfi Y, 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. The British journal of dermatology. 2018;178(1):114–23.  https://doi.org/10.1111/bjd.15750. Phase III clinical trial of guselkumab in patients without complete response to ustekinumab.
  33. 33.
    •• Terui T, Kobayashi S, Okubo Y, Murakami M, Hirose K, Kubo H. Efficacy and Safety of Guselkumab, an Anti-interleukin 23 Monoclonal Antibody, for Palmoplantar Pustulosis: A Randomized Clinical Trial. JAMA Dermatol. 2018;154(3):309–16.  https://doi.org/10.1001/jamadermatol.2017.5937. Phase III clinical trials of tildrakizumab.
  34. 34.
    •• Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG, Lacour J-P, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376(16):1551–60. Phase II clinical trial of risankizumab. CrossRefPubMedGoogle Scholar
  35. 35.
    Krueger JG, Ferris LK, Menter A, Wagner F, White A, Visvanathan S, et al. Anti–IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2015;136(1):116–24. e7.CrossRefPubMedGoogle Scholar
  36. 36.
    Rich P, Maari C, Leonardi C, Klekotka P, Patel D, Li J et al. Efficacy, safety, and quality of life in patients with moderate-to-severe plaque psoriasis treated with mirikizumab (LY3074828) in a phase 2 study [Meeting Abstract]. AAD Annual Meeting, San Diego, CA; February 16–20, 2018.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Kristen M. Beck
    • 1
  • Eric J. Yang
    • 1
  • Sahil Sekhon
    • 1
  • Tina Bhutani
    • 1
  1. 1.Department of DermatologyUniversity of California, San FranciscoSan FranciscoUSA

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