The role of IL 23 in the treatment of psoriasis

Expert Review of Clinical Immunology

Volumn 13, Issue 6, 2017, Pages 525-534

  Puig, Lluís ^a  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

Author keywords

brodalumab; guselkumab; IL 17; IL 23; p19; p40; Psoriasis; psoriatic arthritis; risankizumab; tildrakizumab; ustekinumab

Indexed keywords

BRIAKINUMAB; GUSELKUMAB; INTERLEUKIN 12; INTERLEUKIN 12P40; INTERLEUKIN 17; INTERLEUKIN 17F; INTERLEUKIN 22; INTERLEUKIN 23; INTERLEUKIN 23 RECEPTOR; INTERLEUKIN 23P19; MONOCLONAL ANTIBODY; RISANKIZUMAB; TILDRAKIZUMAB; USTEKINUMAB; BLOCKING ANTIBODY; INTERLEUKIN DERIVATIVE; INTERLEUKIN-22;

ARTICLE; CLINICAL TRIAL (TOPIC); CYTOKINE RESPONSE; DRUG TARGETING; HUMAN; IMMUNOREGULATION; IMMUNOTHERAPY; PATHOGENESIS; PROTEIN EXPRESSION; PSORIASIS; PSORIATIC ARTHRITIS; REMISSION; ANTIGEN PRESENTING CELL; CELL DIFFERENTIATION; IMMUNOLOGY; METABOLISM; PROCEDURES; TH17 CELL;

ANTIBODIES, BLOCKING; ANTIGEN-PRESENTING CELLS; ARTHRITIS, PSORIATIC; CELL DIFFERENTIATION; CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOTHERAPY; INTERLEUKIN-17; INTERLEUKIN-23; INTERLEUKINS; PSORIASIS; TH17 CELLS;

EID: 85013156558     PISSN: 1744666X     EISSN: 17448409     Source Type: Journal    
DOI: 10.1080/1744666X.2017.1292137     Document Type: Article

References (95)

1. Parisi R, Symmons DP, Griffiths CE, et al.; 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;133:377–385.
2. Lowes MA, Bowcock AM, Krueger JG., Pathogenesis and therapy of psoriasis. Nature. 2007;445:866–873.
3. Lowes MA, Suárez-Fariñas M, Krueger JG., Immunology of psoriasis. Annu Rev Immunol. 2014;32:227–255.
4. Ganguly D, Chamilos G, Lande R, et al. Self-RNA–antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med. 2009;206:1983–1994.
5. Meller S, Di Domizio J, Voo KS, et al. T(H)17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26. Nat Immunol. 2015;16:970–979.
6. Kim J, Krueger JG. The immunopathogenesis of psoriasis. Dermatol Clin. 2015;33:13–23.
7. Nograles KE, Zaba LC, Guttman-Yassky E, et al. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol. 2008;159:1092–1102.• Demonstrates the presence of skin-resident Th17 cells in normal skin and the effect of IL-17 and IL-22 on distinct downstream pathways that contribute to the psoriatic phenotype:IL-17 is more pro-inflammatory, while IL-22 retards keratinocyte differentiation.
8. Chiricozzi A, Guttman-Yassky E, Suárez-Fariñas M, et al. Integrative responses to IL-17 and TNF-α in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol. 2011;131:677–687.
9. Aggarwal S, Ghilardi N, Xie MH, 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.
10. Khan D, Ansar Ahmed S. Regulation of IL-17 in autoimmune diseases by transcriptional factors and microRNAs. Front Genet. 2015 Jul;14(6):236.
11. McGeachy MJ, Cua DJ. Th17 cell differentiation:the long and winding road. Immunity. 2008;28:445–453.•• Excellent review.
12. Harper EG, Guo C, Rizzo H, et al. Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo:implications for psoriasis pathogenesis. J Invest Dermatol. 2009;129:2175–2183.
13. Kryczek I, Zhao E, Liu Y, et al. Human TH17 cells are long-lived effector memory cells. Sci Transl Med. 2011;3:104ra100.
14. Cheuk S, Wikén M, Blomqvist L, et al. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis. J Immunol. 2014;192:3111–3120.
15. Ramírez-Valle F, Gray EE, Cyster JG. Inflammation induces dermal Vγ4+ γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17-driven responses. Proc Natl Acadsci U S A. 2015;112:8046–8051.
16. Lin AM, Rubin CJ, Khandpur R, et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187:490–500.
17. Reich K, Papp KA, Matheson RT, et al. Evidence that a neutrophil-keratinocyte crosstalk is an early target of IL-17A inhibition in psoriasis. Exp Dermatol. 2015;24:529–535.
18. Noordenbos T, Blijdorp I, Chen S, et al. Human mast cells capture, store, and release bioactive, exogenous IL-17A. J Leukoc Biol. 2016;100:453–462.
19. Lowes MA, Russell CB, Martin DA, et al. The IL-23/T17 pathogenic axis in psoriasis is amplified by keratinocyte responses. Trends Immunol. 2013;34:174–181.• Excellent review.
20. Zaba LC, 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.
21. Summers Deluca L, Gommerman JL. Fine-tuning of dendritic cell biology by the TNF superfamily. Nat Rev Immunol. 2012;12:339–351.
22. Johnston A, Guzman AM, Swindell WR, et al. Early tissue responses in psoriasis to the antitumour necrosis factor-α biologic etanercept suggest reduced interleukin-17 receptor expression and signalling. Br J Dermatol. 2014;171:97–107.
23. Bergboer JG, Zeeuwen PL, Schalkwijk J. Genetics of psoriasis:evidence for epistatic interaction between skin barrier abnormalities and immune deviation. J Invest Dermatol. 2012;132:2320–2321.
24. Martin DA, Towne JE, Kricorian G, et al. The emerging role of IL-17 in the pathogenesis of psoriasis:preclinical and clinical findings. J Invest Dermatol. 2013;133:17–26.
25. Di Domizio J, Conrad C, Gilliet M. Xenotransplantation model of Psoriasis. Methods Mol Biol. 2017;1559:83–90.
26. van der Fits L, Mourits S, Voerman JS, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. J Immunol. 2009;182:5836–5845.
27. Rizzo HL, Kagami S, Phillips KG, et al. IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17A. J Immunol. 2011;186:1495–1502.• Demonstration that injection of recombinant IL-23 in wild-type mice induces psoriasis-like lesions with elevated transcription of IL-23/T17 pathway-related genes.
28. Lowes MA, 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.
29. Guttman-Yassky E, Lowes MA, Fuentes-Duculan J, et al. Low expression of the IL-23/ Th17 pathway in atopic dermatitis compared to psoriasis. J Immunol. 2008;181:7420–7427.
30. Johansen C, Usher PA, Kjellerup RB, et al. Characterization of the interleukin-17 isoforms and receptors in lesional psoriatic skin. Br J Dermatol. 2009;160:319–324.
31. Lee E, Trepicchio WL, Oestreicher JL, 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.
32. Piskin G, Sylva-Steenland RM, Bos JD, et al. 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.
33. Arican O, Aral M, Sasmaz S, et al. Serum levels of TNFalpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm. 2005;2005:273–279.
34. Kagami S, Rizzo HL, Lee JJ, et al. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130:1373–1383.
35. Chiricozzi A, Suárez-Fariñas M, Fuentes-Duculan J, et al. Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris. Br J Dermatol. 2016;174:136–145.•• Increased expression of IL-23/IL-17 pathway genes in nonlesional skin of patients with moderate-to-severe psoriasis vulgaris.
36. 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 Feb;81(2):85–92.
37. Bovenschen HJ, van de Kerkhof PC, van Erp PE, 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;131:1853–1860.• Altered function and phenotype of Tregs in psoriasis, characterized by IL-17A and IL-22 production.
38. Murphy CA, Langrish CL, Chen Y, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med. 2003;198:1951–1957.
39. Nakae S, Nambu A, Sudo K, et al. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003;171:6173–6177.
40. Bush KA, Farmer KM, Walker JS, et al. Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum. 2002;46:802–805.
41. Astry B, Venkatesha SH, Moudgil KD. Involvement of the IL-23/IL-17 axis and the Th17/Treg balance in the pathogenesis and control of autoimmune arthritis. Cytokine. 2015;74:54–61.
42. Millar NL, Akbar M, Campbell AL, et al. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy. Sci Rep. 2016;6:27149.
43. Sherlock JP, Joyce-Shaikh B, Turner SP, et al. IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012;18:1069–1076.• Showed that IL-23 is essential in a murine model of enthesitis and acts on previously unidentified IL-23 receptor+ ROR-γt+ CD3+ CD4− CD8− stem cell antigen 1 (Sca1)+ entheseal resident T cells.
44. Menon B, Gullick NJ, Walter GJ, et al. Interleukin-17+CD8+ T cells are enriched in the joints of patients with psoriatic arthritis and correlate with disease activity and joint damage progression. Arthritis Rheumatol. 2014;66:1272–1281.
45. Noordenbos T, Yeremenko N, Gofita I, et al. Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis. Arthritis Rheumatol. 2012;64:99–109.
46. van Baarsen LG, Lebre MC, van der Coelen D, et al. Heterogeneous expression pattern of interleukin 17A(IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis,psoriatic arthritis and osteoarthritis:possible explanation for nonresponse to anti-IL-17 therapy? Arthritis Res Ther. 2014;16:426.
47. Miossec P. IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect. 2009;11:625–630.• Excellent review.
48. Harrington LE, Hatton RD, Mangan PR, et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol. 2005;6:1123–1132.
49. Bystrom J, Taher TE, Muhyaddin MS, et al. Harnessing the Therapeutic Potential of Th17 cells. Mediators Inflamm. 2015;2015:205156.
50. Gaffen SL, Jain R, Garg AV, et al. The IL-23-IL-17 immune axis:from mechanisms totherapeutic testing. Nat Rev Immunol. 2004;14:585–600.•• Excellent review.
51. Massot B, Michel ML, Diem S, et al. TLR-induced cytokines promote effective proinflammatory natural Th17 cell responses. J Immunol. 2014 Jun 15;192(12):5635–5642.
52. Zhu S, Qian Y. IL-17/IL-17 receptor system in autoimmune disease:mechanisms and therapeutic potential. Clin Sci (Lond). 2012;122:487–511.
53. Fragoulis GE, Siebert S, McInnes IB. Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated diseases. Annu Rev Med. 2016;67:337–353.
54. Griffin GK, Newton G, Tarrio ML, et al. IL-17 and TNF-α sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation. J Immunol. 2012;188:6287–6299.
55. Suzuki E, Mellins ED, Gershwin ME, et al. The IL-23/IL-17 axis in psoriatic arthritis. Autoimmun Rev. 2014;13:496–502.
56. 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.
57. Awasthi A, Riol-Blanco L, Jager A, et al. Cutting edge:IL-23 receptor gfp reporter mice reveal distinct populations of IL-17-producing cells. J Immunol. 2009;182:5904–5908.
58. Ruan Q, Kameswaran V, Zhang Y, et al. The Th17 immune response is controlled by the Rel-RORgamma-RORgamma T transcriptional axis. J Exp Med. 2011;208:2321–2333.
59. Ivanov II, McKenzie BS, Zhou L, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006;126:1121–1133.
60. Yang XO, Pappu BP, Nurieva R, et al. T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity. 2008;28:29–39.
61. Cheung PF, Wong CK, Lam CW. Molecular mechanisms of cytokine and chemokine release from eosinophils activated by IL-17A, IL-17F, and IL-23:implication for Th17 lymphocytes-mediated allergic inflammation. J Immunol. 2008;180:5625–5635.
62. European Public Assessments Reports. [cited 2015 Sept8]. Available from: http://www. ema.europa.eu/ema/index.jsp?curl=pages%2Fmedi cines%2Flanding%2Fepar_search.jsp&mid=WC0b01 ac058001d124&searchTab=&alreadyLoaded=true& isNewQuery=true&status=Authorised&keyword=En ter?keywords&searchType=name&taxonomyPath= Diseases.Skin?and?Connective?Tissue?Diseases. Skin?Diseases.Skin?Diseases%2C?Papulosquamous &treeNumber=¤tCategory=Psoriasis&search GenericType=generics
63. Leonardi CL, Kimball AB, Papp KA, et al.; PHOENIX 1 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis:76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet. 2008 May 17;371(9625):1665–1674.
64. Papp KA, Langley RG, M L, et al.; PHOENIX 2 study investigators. 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 May 17;371(9625):1675–1684.
65. Griffiths CE, Strober BE, van de Kerkhof P, et al. Comparison of ustekinumab and etanercept for moderate-to-severe psoriasis. N Engl J Med. 2010;362:118–128.
66. Papp KA, Griffiths CE, Gordon K, et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis:final results from 5 years of follow-up. Br J Dermatol. 2013;168:844–854.
67. Paul C, Puig L, Kragballe K, et al. Transition to ustekinumab in patients with moderate-to-severe psoriasis and inadequate response to methotrexate:a randomized clinical trial (TRANSIT). Br J Dermatol. 2014;170:425–434.
68. Thaçi D, Blauvelt A, Reich 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;73:400–409.
69. Blauvelt A, Reich K, Tsai TF, 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):60-69.e9.
70. Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;373:1318–1328.
71. Puig L, Ruiz-Salas V. Long-term efficacy, safety and drug survival of ustekinumab in a Spanish cohort of patients with moderate to severe plaque psoriasis. Dermatology. 2015;230:46–54.
72. Wilder EG, Patel M, Hebeler K, et al. Ustekinumab treatment for psoriasis in 119 patients maintained on therapy for a minimum of one year:a review. J Drugs Dermatol. 2014;13:905–910.
73. Papp K, Gottlieb AB, Naldi L, et al. Safety surveillance for ustekinumab and other psoriasis treatments from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol. 2015;14:706–714.
74. Gniadecki R, Bang B, Bryld LE, et al. Comparison of long-term drug survival and safety of biologic agents in patients with psoriasis vulgaris. Br J Dermatol. 2015;172:244–252.
75. Warren RB, Smith CH, Yiu ZZ, 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;135:2632–2640.
76. Menter A, Papp KA, Gooderham M, et al. Drug survival of biologic therapy in a large, disease-based registry of patients with psoriasis:results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Eur Acad Dermatol Venereol. 2016;30:1148–1158.
77. Vilarrasa E, Notario J, Bordas X, et al. ORBIT (Outcome and Retention Rate of Biologic Treatments for Psoriasis):a retrospective observational study on biologic drug survival in daily practice. J Am Acad Dermatol. 2016;74:1066–1072.
78. McInnes IB, Kavanaugh A, Gottlieb AB, et al.; PSUMMIT 1 Study Group. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis:1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 2013;382(9894):780–789.
79. Ritchlin C, Rahman P, Kavanaugh A, et al.; PSUMMIT 2 Study Group. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy:6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73:990–999.
80. Kavanaugh A, Ritchlin C, Rahman P, et al. Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis:results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. Ann Rheum Dis. 2014;73:1000–1006.
81. Kavanaugh A, Puig L, Gottlieb AB, et al. Maintenance of clinical efficacy and radiographic benefit through 2 years of ustekinumab therapy in patients with active psoriatic arthritis:results from the PSUMMIT 1 trial. Arthritis Care Res (Hoboken). 2015;67:1739–1749.
82. Gordon KB, Langley RG, Gottlieb AB, et al. A phase III, randomized, controlled trial of the fully human IL-12/23 mAb briakinumab in moderate-to-severe psoriasis. J Invest Dermatol. 2012;132:304–314.
83. Strober BE, Crowley JJ, Yamauchi PS, et al. Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol. 2011;165:661–668.
84. Gottlieb AB, Leonardi C, Kerdel F, et al. Efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Br J Dermatol. 2011;165:652–660.
85. Reich K, Langley RG, Papp KA, et al. A 52-week trial comparing briakinumab with methotrexate in patients with psoriasis. N Engl J Med. 2011;365:1586–1596.
86. Gordon KB, Duffin KC, Bissonnette R, et al. A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N Engl J Med. 2015;373:136–144.• Phase II trial of guselkumab.
87. Blauvelt A, Papp KA, Griffiths CE, 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. 2016 Dec 29. pii:S0190-9622(16)31157–4. doi:10.1016/j.jaad.2016.11.041. [Epub ahead of print]• Phase III trial of guselkumab.
88. Reich K, Armstrong AW, 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. 2016 Dec 29. pii:S0190-9622(16)31158–6. doi:10.1016/j.jaad.2016.11.042. [Epub ahead of print]• Phase III trial of guselkumab.
89. Papp K, Thaci D, Reich K, 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(4):930–939.• Phase II trial of tildrakizumab.
90. Papp K, Blauvelt A, Tyring S, et al. Tildrakizumab, a selective IL-23p19 antibody, in the treatment of chronic plaque psoriasis:results from two randomized, controlled, phase 3 trials (reSURFACE 1 and reSURFACE 2). Annual European Academy of Dermatology and Venereology (EADV 2016); 28 Sept–02 Oct, 2016; Vienna, Austria; D3T01.1I.
91. Singh S, Kroe-Barrett RR, Canada KA, et al. Selective targeting of the IL23 pathway:generation and characterization of a novel high-affinity humanized anti-IL23A antibody. MAbs. 2015;7(4):778–791.
92. Krueger JG, Ferris LK, Menter A, 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.
93. Papp KA, Menter A, Sofen H, et al. Efficacy and safety of different dose regimens of a novel selective IL-23p19 inhibitor (BI 655066) compared with ustekinumab in patients with moderate-to-severe psoriasis. J Am Acad Dermatol. 2016;74(Suppl 1):AB274.
94. Papp KA, Gooderham M, Blauvelt A, et al. Clinical response following retreatment with a selective IL-23p19 inhibitor risankizumab (BI 655066) or switching from ustekinumab to risankizumab in patients with moderate-to-severe chronic plaque psoriasis. Annual European Academy of Dermatology and Venereology (EADV 2016); 28 Sept–02 Oct, 2016; Vienna, Austria; Free Communication VIE16ABS-0359.
95. Kulig P, Musiol S, Freiberger SN, et al. IL-12 protects from psoriasiform skin inflammation. Nat Commun. 2016 Nov 28;7:13466.