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Selective Interleukin-23 p19 Inhibition: Another Game Changer in Psoriasis? Focus on Risankizumab

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Abstract

The history of psoriasis treatment has been marked by several milestones. Corticosteroids, cyclosporine, tumor necrosis factor alpha (TNF-α) inhibitors and, more recently, interleukin (IL)-17A inhibitors have revolutionized the treatment of psoriasis, each in its own way and time. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis and selective IL-23p19 inhibition may bring several advantages with respect to IL-12/23p40 inhibition, or distal blockade of IL-17A or its receptor. In fact, IL-12 axis inhibition does not appear to be essential in psoriasis and IL-12 inhibition may even have a negative effect in the treatment of psoriasis and have potential risks in tumor immune surveillance and in host defense against intracellular pathogens. On the other hand, contrary to IL-17 inhibition, IL-23p19 blockade does not increase the risk of candida infection, nor is it associated with inflammatory bowel disease worsening. Several IL-23p19 inhibitors are currently being developed for the treatment of psoriasis, such as tildrakizumab, guselkumab, and risankizumab. Although clinical data on risankizumab is still scarce, it has shown characteristics that signify a major advance in the treatment of this disease, offering comparable or higher efficacy than IL-17 inhibitors, without the safety concerns of this therapeutic class, combined with the excellent dosing regimen of ustekinumab. Currently, only phase II trial data is available; thus, the results of the large phase III trials will be essential to establish the efficacy and safety profile of risankizumab and its value in the biological armamentarium for the treatment of psoriatic patients.

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References

  1. Sulzberger MB, Witten VH. The effect of topically applied compound F in selected dermatoses. J Invest Dermatol. 1952;19(2):101–2.

    Article  CAS  PubMed  Google Scholar 

  2. Mueller W, Herrmann B. Cyclosporin A for psoriasis. N Engl J Med. 1979;301(10):555.

    CAS  PubMed  Google Scholar 

  3. Mansouri B, Patel M, Menter A. Biological therapies for psoriasis. Expert Opin Biol Ther. 2013;13(12):1715–30.

    Article  CAS  PubMed  Google Scholar 

  4. Kirkham BW, Kavanaugh A, Reich K. Interleukin-17A: a unique pathway in immune-mediated diseases: psoriasis, psoriatic arthritis and rheumatoid arthritis. Immunology. 2014;141(2):133–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Torres T, Puig L. Treatment goals for psoriasis: Should PASI 90 become the standard of care? Actas Dermosifiliogr. 2015;106(3):155–7.

    Article  CAS  PubMed  Google Scholar 

  6. Canavan TN, Elmets CA, Cantrell WL, Evans JM, Elewski BE. Anti-IL-17 medications used in the treatment of plaque psoriasis and psoriatic arthritis: a comprehensive review. Am J Clin Dermatol. 2016;17(1):33–47.

    Article  PubMed  Google Scholar 

  7. Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, et al. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61(12):1693–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Targan SR, Feagan B, Vermeire S, Panaccione R, Melmed GY, Landers C, et al. A randomized, double-blind, placebo-controlled phase 2 study of brodalumab in patients with moderate-to-severe Crohn’s disease. Am J Gastroenterol. 2016;111(11):1599–607.

    Article  CAS  PubMed  Google Scholar 

  9. Blauvelt A. Safety of secukinumab in the treatment of psoriasis. Expert Opin Drug Saf. 2016;15(10):1413–20.

    Article  CAS  PubMed  Google Scholar 

  10. Saunte DM, Mrowietz U, Puig L, Zachariae C. Candida infections in psoriasis and psoriatic arthritis patients treated with IL-17 inhibitors and their practical management. Br J Dermatol. 2016. doi:10.1111/bjd.15015.

    PubMed  Google Scholar 

  11. Singh S, Kroe-Barrett RR, Canada KA, Zhu X, Sepulveda E, Wu H, et al. Selective targeting of the IL23 pathway: generation and characterization of a novel high-affinity humanized anti-IL23A antibody. MAbs. 2015;7(4):778–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Fragoulis GE, Siebert S, McInnes IB, Gaffen SL, Jain R, Garg AV, et al. Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Annu Rev Med. 2016;67:337–53.

    Article  CAS  PubMed  Google Scholar 

  13. Toussirot E. The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14:585–600.

    Article  Google Scholar 

  14. Toussirot E. The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases. Inflamm Allergy Drug Targets. 2012;11(2):159–68.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. Levin AA, Gottlieb AB. Specific targeting of interleukin-23p19 as effective treatment for psoriasis. J Am Acad Dermatol. 2014;70(3):555–61.

    Article  CAS  PubMed  Google Scholar 

  17. Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, Chamian F, et al. Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med. 2004;199:125–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 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.

    Article  Google Scholar 

  19. 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. Ann Rev Immunol. 1998;16:495–521.

    Article  CAS  Google Scholar 

  20. Deng Y, Chang C, Lu Q. The inflammatory response in psoriasis: a comprehensive review. Clin Rev Allergy Immunol. 2016;50(3):377–89.

    Article  CAS  PubMed  Google Scholar 

  21. 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.e7–124.e7.

    Article  Google Scholar 

  22. Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG, Lacour JP, et al. Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med. 2017;376(16):1551–60.

    Article  CAS  PubMed  Google Scholar 

  23. Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Lacour JP, Menter A, et al. Selective blockade of IL-23p19 with BI 655066 is associated with significant improvement in QoL outcomes compared with ustekinumab in patients with moderate-to-severe plaque psoriasis. J Am Acad Dermatol. 2017;74(5):AB275.

    Google Scholar 

  24. Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Lacour JP, Menter A, et al. Comparison of a selective IL-23p19 inhibitor (BI 655066) with ustekinumab in patients with moderate-to-severe plaque psoriasis: analysis of scalp, palmoplantar, and nail psoriasis subgroups. J Am Acad Dermatol. 2017;74(5):240.

    Google Scholar 

  25. Papp K, Menter A, Sofen H, Tyring S, Lacour JP, Berner B, et al. Efficacy and safety of different dose regimens of a selective IL-23p19 inhibitor (BI 655066) compared with ustekinumab in patients with moderate-to-severe plaque psoriasis with and without psoriatic arthritis. Arthritis Rheumatol. 2015;67(suppl 10):1–4046.

    Google Scholar 

  26. 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;S0140–6736(17):30570–6.

    Google Scholar 

  27. Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016;375(20):1946–60.

    Article  CAS  PubMed  Google Scholar 

  28. Chan AC, Carter PJ. Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol. 2010;10(5):301–16.

    Article  CAS  PubMed  Google Scholar 

  29. Harding FA, Stickler MM, Razo J, DuBridge RB. The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. MAbs. 2010;2(3):256–65.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 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;373:136–44.

    Article  CAS  PubMed  Google Scholar 

  31. 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;76:418–31.

    Article  CAS  PubMed  Google Scholar 

  32. Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, 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;76:405–17.

    Article  CAS  PubMed  Google Scholar 

  33. Gottlieb A, Deodhar A, Boehncke WH, Dong B, Wang Y, Barchuk Y, et al. Efficacy and safety of guselkumab, an anti-IL23 monoclonal antibody, in patients with active psoriatic arthritis: a phase 2a, randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2017; 76:6(suppl 1): AB111.

  34. Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, et al. Tildrakizumab (MK-3222), an anti-IL-23p19 monoclonal antibody, improves psoriasis in a phase 2b randomized placebo-controlled trial. Br J Dermatol. 2015;173:930–9.

    Article  CAS  PubMed  Google Scholar 

  35. 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.

  36. Signorovitch JE, Betts KA, Yan YS, LeReun C, Sundaram M, Wu EQ, et al. Comparative efficacy of biological treatments for moderate-to-severe psoriasis: a network meta-analysis adjusting for cross-trial differences in reference arm response. Br J Dermatol. 2015;172:504–12.

    Article  CAS  PubMed  Google Scholar 

  37. Blauvelt A, Reich K, Tsai TF, Tyring S, Vanaclocha F, Kingo K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: results from the CLEAR study. J Am Acad Dermatol. 2017;76(1):60–699.

    Article  CAS  PubMed  Google Scholar 

  38. 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 3 study. Br J Dermatol. 2017.

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. Papp KA, Griffiths CE, Gordon K, Lebwohl M, Szapary PO, Wasfi Y, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of followup. Br J Dermatol. 2013;168(4):844–54.

    Article  CAS  PubMed  Google Scholar 

  41. Papp K, Gottlieb AB, Naldi L, Pariser D, Ho V, Goyal K, et al. Safety surveillance for ustekinumab and other psoriasis treatments from the psoriasis longitudinal assessment and registry (PSOLAR). J Drugs Dermatol. 2015;14(7):706–14.

    CAS  PubMed  Google Scholar 

  42. Paine A, Ritchlin C. Bone remodeling in psoriasis and psoriatic arthritis: an update. Curr Opin Rheumatol. 2016;28(1):66–75.

    Article  CAS  PubMed  Google Scholar 

  43. Warren RB, Smith CH, Yiu ZZ, Ashcroft DM, Barker JN, Burden AD, et al. Differential drug survival of biologic therapies for the treatment of psoriasis: a prospective observational cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR). J Invest Dermatol. 2015;135(11):2632–40.

    Article  CAS  PubMed  Google Scholar 

  44. Zhang M, Brenneman SK, Carter CT, Essoi BL, Farahi K, Johnson MP, et al. Patient-reported treatment satisfaction and choice of dosing frequency with biologic treatment for moderate to severe plaque psoriasis. Patient Prefer Adherence. 2015;16(9):777–84.

    Article  Google Scholar 

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Correspondence to Tiago Torres.

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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.

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Torres, T. Selective Interleukin-23 p19 Inhibition: Another Game Changer in Psoriasis? Focus on Risankizumab. Drugs 77, 1493–1503 (2017). https://doi.org/10.1007/s40265-017-0794-1

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