, Volume 32, Issue 2, pp 119–128 | Cite as

Guselkumab for the Treatment of Psoriasis

  • Álvaro Machado
  • Tiago Torres
Review Article


Psoriasis is a common, chronic, immune-mediated, inflammatory skin disease with systemic involvement and significant impact on patients’ quality of life. Several biologic treatments have been developed in recent decades, such as tumor necrosis factor (TNF)-α inhibitors, a non-selective interleukin (IL)-23 inhibitor (ustekinumab, which also inhibits IL-12), and—most recently—IL-17 inhibitors. Guselkumab is a novel biological therapy that selectively targets IL-23 and is the first-in-class selective IL-23 inhibitor approved to treat moderate-to-severe plaque psoriasis. These inhibitors are expected to have some advantages over the highly effective IL-17 inhibitors, as they do not worsen inflammatory bowel disease and are not involved in the development of candida infections. Additionally, selective inhibition of IL-23 may have additional benefits over ustekinumab as the IL-12-dependent cascades remain functional. These benefits include a decrease in IL-17A-producing T cells in the skin and the promotion of an anti-inflammatory effect through production of interferon-γ and IL-10. In terms of efficacy, guselkumab showed promising results in the treatment of psoriasis and psoriatic arthritis, although it did not show significant clinical improvement in rheumatoid arthritis. Studies in other inflammatory diseases and Crohn’s disease are expected to begin soon. Overall, guselkumab was well tolerated; the most common adverse event was nasopharyngitis. Head-to-head studies comparing IL-23 inhibitors with agents in different classes, namely IL-17 inhibitors, will be crucial to establish the true role of these agents in psoriasis treatment.



No sources of funding were used to conduct this study or prepare this manuscript.

Compliance with ethical standards

Conflicts of interest

Álvaro Machado has no conflicts of interest. Tiago Torres has participated in clinical trials sponsored by AbbVie, Amgen, and Novartis and has received honoraria for acting as a consultant and/or as a speaker at events sponsored by AbbVie, Boehringer Ingelheim, Celgene, Janssen, Leo-Pharma, Lilly-Eli, MSD, Novartis, and Pfizer.


  1. 1.
    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
  2. 2.
    Parisi R, Symmons DPM, Griffiths CEM, Ashcroft DM. Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133(2):377–85.CrossRefPubMedGoogle Scholar
  3. 3.
    Sulzberger MB, Witten VH. The effect of topically applied compound F in selected dermatoses. J Invest Dermatol. 1952;19(2):101–2.CrossRefPubMedGoogle Scholar
  4. 4.
    Mueller W, Herrmann B. Cyclosporin A for psoriasis. N Engl J Med. 1979;301(10):555.PubMedGoogle Scholar
  5. 5.
    Torres T. Selective interleukin-23 p19 Inhibition: another game changer in psoriasis? Focus on Risankizumab. Drugs. 2017;77(14):1493–503.CrossRefPubMedGoogle Scholar
  6. 6.
    Piskin G, Sylva-Steenland RMR, Bos JD, Teunissen MBM. 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(3):1908–15.CrossRefPubMedGoogle Scholar
  7. 7.
    Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008;371(9625):1675–84.CrossRefPubMedGoogle Scholar
  8. 8.
    Strober BE, Bissonnette R, Fiorentino D, Kimball AB, Naldi L, Shear NH, et al. Comparative effectiveness of biologic agents for the treatment of psoriasis in a real-world setting: results from a large, prospective, observational study (Psoriasis Longitudinal Assessment and Registry [PSOLAR]). J Am Acad Dermatol. 2016;74(5):851–61.e4.CrossRefPubMedGoogle Scholar
  9. 9.
    Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, et al. Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med. 2016;375(4):345–56. e4.CrossRefPubMedGoogle Scholar
  10. 10.
    Thaçi D, Blauvelt A, Reich K, Tsai T-F, Vanaclocha F, Kingo K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dermatol. 2015;73(3):400–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Puig L. Brodalumab: the first anti-IL-17 receptor agent for psoriasis. Drugs Today. 2017;53(5):283.CrossRefPubMedGoogle Scholar
  12. 12.
    Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CEM, Papp K, et al. Secukinumab in plaque psoriasis—results of two phase 3 trials. N Engl J Med. 2014;371(4):326–38.CrossRefPubMedGoogle Scholar
  13. 13.
    Griffiths CEM, Reich K, Lebwohl M, Van De Kerkhof P, Paul C, Menter A, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541–51.CrossRefPubMedGoogle Scholar
  14. 14.
    Reich K, Pinter A, Lacour JP, Ferrandiz C, Micali G, French LE, et al. Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study. Br J Dermatol. 2017;177(4):1014–23.CrossRefPubMedGoogle Scholar
  15. 15.
    Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373(14):1318–28.CrossRefPubMedGoogle Scholar
  16. 16.
    Blauvelt A, Papp KA, Griffiths CEM, 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.CrossRefPubMedGoogle Scholar
  17. 17.
    Fragoulis GE, Siebert S, Mcinnes IB. Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Annu Rev Med. 2016;67:337–53.CrossRefPubMedGoogle Scholar
  18. 18.
    Gordon KB, Duffin KC, Bissonnette R, Prinz JC, Wasfi Y, Li S, et al. A Phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N Engl J Med. 2015;373(2):136–44.CrossRefPubMedGoogle Scholar
  19. 19.
    Langley RG, Tsai T-F, 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 3 NAVIGATE trial. Br J Dermatol. 2017;38(1):42–9.Google Scholar
  20. 20.
    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.CrossRefPubMedGoogle Scholar
  21. 21.
    Markham A. Guselkumab: first global approval. Drugs. 2017;74(13):1555–8.CrossRefGoogle Scholar
  22. 22.
    Ault A. Guselkumab (Tremfya) Gets CHMP Backing for Plaque Psoriasis. 2017. Accessed Jan 24 2018.
  23. 23.
    Tonini A, Gualtieri B, Panduri S, Romanelli M, Chiricozzi A. A new class of biologic agents facing the therapeutic paradigm in psoriasis: anti-IL-23 agents. Expert Opin Biol Ther. 2017;6:1–14.Google Scholar
  24. 24.
    Chiricozzi A, Saraceno R, Chimenti MS, Guttman-Yassky E, Krueger JG. Role of IL-23 in the pathogenesis of psoriasis: a novel potential therapeutic target? Expert Opin Ther Targets. 2014;18(5):513–25.CrossRefPubMedGoogle Scholar
  25. 25.
    Girolomoni G, Strohal R, Puig L, Bachelez H, Barker J, Boehncke WH, et al. The role of IL-23 and the IL-23/T H 17 immune axis in the pathogenesis and treatment of psoriasis. J Eur Acad Dermatol Venereol. 2017;31(10):1616–26.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Chiricozzi A, Romanelli P, Volpe E, Borsellino G, Romanelli M. Scanning the Immunopathogenesis of Psoriasis. Int J Mol Sci. 2018;19(1):179.CrossRefPubMedCentralGoogle Scholar
  27. 27.
    Kulig P, Musiol S, Freiberger SN, Schreiner B, Gyülveszi G, Russo G, et al. IL-12 protects from psoriasiform skin inflammation. Nat Commun. 2016;28(7):13466.CrossRefGoogle Scholar
  28. 28.
    van der Fits L, Mourits S, Voerman JSA, Kant M, Boon L, Laman JD, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009;182(9):5836–45.CrossRefPubMedGoogle Scholar
  29. 29.
    Chang HD, Radbruch A. The pro- and anti-inflammatory potential of interleukin-12. Ann N Y Acad Sci. 2007;1109(30):40–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Kim J, Krueger JG. The Immunopathogenesis of Psoriasis. Dermatol Clin. 2015;33(1):13–23.CrossRefPubMedGoogle Scholar
  31. 31.
    Hamza T, Barnett JB, Li B. Interleukin 12 a key immunoregulatory cytokine in infection applications. Int J Mol Sci. 2010;11(3):789–806.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Gately MK, Renzetti LM, Magram J, Stern AS, Adorini L, Gubler U, et al. The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu Rev Immunol. 1998;16(1):495–521.CrossRefPubMedGoogle Scholar
  33. 33.
    Lu X. Impact of IL-12 in cancer. Curr Cancer Drug Targets. 2017;17(8):682–97.CrossRefPubMedGoogle Scholar
  34. 34.
    Zhuang Y, Calderon C, Marciniak SJ, Bouman-Thio E, Szapary P, Yang TY, et al. First-in-human study to assess guselkumab (anti-IL-23 mAb) pharmacokinetics/safety in healthy subjects and patients with moderate-to-severe psoriasis. Eur J Clin Pharmacol. 2016;72(11):1303–10.CrossRefPubMedGoogle Scholar
  35. 35.
    Smolen JS, Agarwal SK, Ilivanova E, Xu XL, Miao Y, Zhuang Y, et al. A randomised phase II study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate. Ann Rheum Dis. 2017;13:1–9.Google Scholar
  36. 36.
    Sofen H, Smith S, Matheson RT, Leonardi CL, Calderon C, Brodmerkel C, 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):1032–40.CrossRefPubMedGoogle Scholar
  37. 37.
    Gordon KB, 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 3 VOYAGE 1 and VOYAGE 2 studies. Br J Dermatol. 2017;140(6):874–88.Google Scholar
  38. 38.
    Raposo I, Torres T. Nail psoriasis as a predictor of the development of psoriatic arthritis. Actas Dermosifiliogr. 2015;106(6):452–7.CrossRefPubMedGoogle Scholar
  39. 39.
    Deodhar AA, Gottlieb AB, Boehncke WH, Dong B, Wang Y, Barchuk W, Xu X, Hsia EC. Efficacy and safety results of guselkumab, an anti-IL23 monoclonal antibody, in patients with active psoriatic arthritis over 24 weeks: a phase 2a, randomized, double-blind, placebo-controlled study [abstract]. Arthritis Rheumatol. 2016;68(suppl 10). Accessed Jan 24 2018.
  40. 40.
    Deepak P, Sandborn WJ. Ustekinumab and anti-interleukin-23 agents in Crohn’s disease. Gastroenterol Clin N Am. 2017;46(3):603–26.CrossRefGoogle Scholar
  41. 41.
    Papp K, Thaçi D, Reich K, Riedl E, Langley RG, Krueger JG, et al. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015;173(4):930–9.CrossRefPubMedGoogle Scholar
  42. 42.
    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 (London, England). 2017;6736(17):1–13.Google Scholar
  43. 43.
    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.CrossRefPubMedGoogle Scholar
  44. 44.
    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. 2017. Accessed Jan 24 2018.
  45. 45.
    Feagan BG, Sandborn WJ, D’Haens G, Panés J, Kaser A, Ferrante M, et al. Induction therapy with the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn’s disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2017;389(10080):1699–709.CrossRefPubMedGoogle Scholar
  46. 46.
    Verstockt B, Deleenheer B, Van Assche G, Vermeire S, Ferrante M. A safety assessment of biological therapies targeting the IL-23/IL-17 axis in inflammatory bowel diseases. Expert Opin Drug Saf. 2017;16(7):809–21.PubMedGoogle Scholar
  47. 47.
    Maxwell JR, Zhang Y, Brown WA, Smith CL, Byrne FR, Fiorino M, et al. Differential roles for interleukin-23 and interleukin-17 in intestinal immunoregulation. Immunity. 2015;43(4):739–50.CrossRefPubMedGoogle Scholar
  48. 48.
    Saunte DM, Mrowietz U, Puig L, Zachariae C. Candida infections in patients with psoriasis and psoriatic arthritis treated with interleukin-17 inhibitors and their practical management. Br J Dermatol. 2017;177(1):47–62.CrossRefPubMedGoogle Scholar
  49. 49.
    Sbidian E, Chaimani A, Garcia-Doval I, Do G, Hua C, Mazaud C, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane database Syst Rev. 2017;12(12):CD011535.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyCentro Hospitalar do PortoPortoPortugal
  2. 2.Instituto de Ciências Biomédicas Abel SalazarUniversity of PortoPortoPortugal
  3. 3.Dermatology Research UnitCentro Hospitalar do PortoPortoPortugal

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