Table 1: Experimental IL-17 agents Agent
MSB0010841 (ALX-0761) (anti-IL-17A/F Nanobody)
COVA322 (dual TNF-a/ IL-17A inhibitor)
Intravenous Ixekizumab (LY2439821) Subcutaneous
Brodalumab (AMG 827)
Study name/reference NCT02156466
UNCOVER-1/NCT01474512 UNCOVER-2 /NCT01597245 UNCOVER-3 /NCT01646177
AMAGINE-1 /NCT01708590 AMAGINE-2 /NCT01708603 AMAGINE-3 /NCT01708629
~40 adult patients with moderate-to-severe chronic plaque psoriasis
~39 adult patients with moderate-to-severe chronic plaque psoriasis
~3746 adult patients* with moderate-to-severe chronic plaque psoriasis
~4373 adult patients* with moderate-to-severe stable plaque psoriasis
*Calculated number of patients for the three trials together. IL: interleukin; TNF: tumour necrosis factor.
IL-13 signaling attenuates Th17 cytokine production. J Immunol 2009;182:5317–21.
11. Cumberbatch M et al. Impaired Langerhans cell migration in psoriasis. J Exp Med 2006;203(4):953–60.
12. Awasthi A, Kuchroo VK. Th17 cells: from precursors to players in inflammation and infection. Intern Immunol 2009;21:489–98.
13. Conrad C et al. a1b1 Integrin is crucial for accumulation of epidermal T cells and the development of psoriasis. Nature Med 2007;13:836–42.
14. Austin LM 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;113:752–9.
15. Wilson NJ et al. Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 2007;8:950–7.
16. Zheng Y et al. Interleukin-22, a Th17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature 2007;445(7128):648–51.
17. Caruso R et al. Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis. Nat Med 2009;15(9):10135.
18. Monteleone G, Pallone F, Macdonalds TT. Interleukin-21: a critical regulator of the balance between effector and regulatory T cell response. Trends Immunol 2008;29:290–4.
19. Oppmann 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. 2000 Immunity 2000;13(5):715–25.
20. Kryczek I et al. Induction of memory IL-17+ T cell trafficking and expansion by IFN-gamma: Mechanism and pathological relevance. J Immunology 2008;181:4733–41.
21. Chen Z et al. Distinct regulation of interleukin-17 in human T helper lymphocytes. Arthritis Rheum 2007;56:2936–46.
22. Harper EG et al. Th17 cytokines stimulate CCL20 expression in keratinocytes in vitro and in vivo:
implications for psoriasis pathogenesis. J Invest Dermatol 2009;129(9):2175–83.
23. Wolk K et al. The Th17 cytokine IL-22 induces IL-20 production in keratinocytes: a novel immunological cascade with potential relevance in psoriasis. Eur J Immunol 2009;39(12):3570–81.
24. Nestle FO et al. Plasmacitoid predendritic cells initiate psoriasis through interferon-α production. J Exp Med 2005;202:135–43.
25. Eyerich S et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest 2009;119(12):3573–85.
26. Sugiyama H et al. Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. J Immunol 2005;174:164–73.
27. National Clinical Guideline Centre. Psoriasis: Assessment and Management of Psoriasis. Royal College of Physicians;October 2012.
28. Wang J et al. Biological products for the treatment of psoriasis: therapeutic targets, pharmacodynamics and disease-drug-drug interaction implications. AAPS J. 2014;16(5):938–47.
29. Girolomoni G et al. Psoriasis: rationale for targeting interleukin-17. Br J Dermatol 2012;167:717–24.
30. Golden JA et al. IL-17 in psoriasis: implications for therapy and cardiovascular co-morbidities. Cytokine 2013;62(2):195–201.
31. Novartis. Press release 19 January 2015.www. novartis.com/news/media-releases/novartis-
cosentyxtm-first-il-17-inhibitor-receive-eu-approval- first-line?utm_source=drupal&utm_ medium=redirect&utm_
tml (accessed 3 August 2015).
32. Novartis. Press release 21 January 2015. www.novartis.com/news/media-releases/
novartis-announces-fda-approval-first-il-17a- antagonist-cosentyxtm-secukinumab (accessed 3 August 2015).
33. Langley R et al. Secukinumab in plaque psoriasis: results of two phase three trials. N Engl J Med 2014;371(4):326–38.
34. Blauvelt A et al. Secukinumab administration by
pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol 2015;172(2):484–93.
35. Paul C et al. Efficacy, safety and usability of secukinumab administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J Eur Acad Dermatol Venereol 2015;29(6):1082–90.
36. Novartis. Press release 21 March 2015. www. novartis.com/news/media-releases/novartis-
cosentyxtm-two-year-data-shows-sustained-effect- and-favorable-safety (accessed 3 August 2015).
37. Thaçi D 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;S0190-9622(15):01683–7.
38. Griffiths CE 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;S0140–6736(15):60125–8.
39. Lilly. Press release 21 August 2014.ht
(accessed 3 August 2015).
40. Papp KA et al. Brodalumab, an anti-interleukin-17- receptor antibody for psoriasis. N Engl J Med 2012;366(13):1181–9.
41. Amgen and AstraZeneca. Press release 9 May 2014. www.amgen.com/media/media_pr_detail
42. Amgen and AstraZeneca. Press release 11 November 2014.www.amgen.com/media/media_
43. Amgen and AstraZeneca. Press release 25 November 2014. www.amgen.com/media/media_
44. Amgen. Press release 22 May 2015. www.am
gen. com/media/media_pr_detail. jsp?year=2015&releaseID=2052862
45. Vanheusden K et al. Pre-clinical proof-of-concept of ALX-0761, a nanobody neutralizing both IL-17A and F in a Cynomolgus monkey collagen-induced arthritis model. Annual Meeting of the American College of Rheumatology, 26–30 October 2013, San Diego, California. www.ablynx.com/uploads/data/files/
poster-acr-2013-c076.pdf (accessed 3 August 2015).
Randomised, double-blind, Phase I Control: placebo
Multiple ascending doses
Randomised, double-blind, Phase I/II Control: placebo
Single ascending doses
Randomised, double-blind, Phase III Control: placebo (UNCOVER-1) and etanercept (UNCOVER-2, -3)
Randomised, double-blind, Phase III Control: placebo (AMAGINE-1) and ustekinumab (AMAGINE-2, -3)
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