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Lessons from Psoriasis: What Can We Apply to Alopecia Areata?

By identifying key cells and cytokines that play roles in the development of diseases like psoriasis and atopic dermatitis, we have been able to target very specific parts of the immune system and thereby treat these diseases more effectively and more safely. Following the same methodology, we hope to identify key targets that allow us to do the same for alopecia areata.

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Lessons from Psoriasis: What Can We Apply to Alopecia Areata?

  1. 1. Lessons from Psoriasis-What Can We Apply to Alopecia Areata? Mark Lebwohl, MD ProfessorAnd Chairman Kimberly and Eric J. Waldman Department of Dermatology Icahn School of Medicine at Mount Sinai
  2. 2. IL-17A IL-17F IL-17R IL-12 Antimicrobial peptides IL-1β IL-6 TNF-α S100 CXCL8 CXCL9 CXCL10 CXCL11 CCL20 Activation Natural killer T cell Keratinocyt e Myeloid dendritic cell Plasmacytoid dendritic cell Macrophage IL-1β IL-6 TNF-αTNF-α INF-γ INF-γ Th1 cell Th17 cell TNF-α INF-γ Keratinocyt e TNF- α Adaptive immunity Innate immunity Innate immunity IL-20 Adapted from: Nestle F, et al, NEJM 2009; 501. Pathogenesis of Psoriasis Th22 cell IL-22 IL-20 IL-23
  3. 3. Abnormal cell proliferation in psoriasis. Weinstein GD, Frost P. J Invest Dermatol. 1968;50(3):254-9. Autoradiographic analysis of turnover times of normal and psoriatic epidermis. Weinstein GD, Van Scott EJ. J Invest Dermatol. 1965;45:257-62.
  4. 4. normal psoriasis
  5. 5. Immunologic mechanisms in psoriasis. Gottlieb AB. J Am Acad Dermatol.1988;18:1376-80. Lymphocyte trafficking in psoriasis: a new perspective emphasizing the dermal dendrocyte with active dermal recruitment mediated via endothelial cells followed by intra- epidermal T-cell activation. Nickoloff BJ, Griffiths CE. J Invest Dermatol. 1990;95:35S-37S.
  6. 6. Resistant severe psoriasis controlled with systemic cyclosporine therapy. Picascia DD, Garden JM, Freinkel RK, Roenigk HH Jr. Transplant Proc. 1988;20(3Suppl 4):58-62. Cyclosporine A in the treatment of psoriasis: a clinical and mechanistic perspective. Griffiths CE, Voorhees JJ. J Invest Dermatol.1990;95(5 Suppl):53S-55S.
  7. 7. An international, randomized, double- blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis. Lebwohl M, Christophers E, Langley R, Ortonne JP, Roberts J, Griffiths CE; Alefacept Clinical Study Group. Arch Dermatol. 2003;139:719-27.
  8. 8. Efalizumab Study Group. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. Lebwohl M, Tyring SK, Hamilton TK, Toth D, Glazer S, Tawfik NH, Walicke P, Dummer W, Wang X, Garovoy MR, Pariser D; N Engl J Med. 2003 Nov 20;349(21):2004-13.
  9. 9. Efficacy and safety of infliximab monotherapy for plaque-type psoriasis: a randomized trial. Chaudhari U, et al. Lancet 2002 June 9;357(9271):1842-1847.
  10. 10. 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). Papp KA,et al. Lancet. 2008;371(9625):1675-84. Efficacy and safety of ustekinumab, a human interleukin- 12/23 monocl onal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Leonardi CL,et al. Lancet. 2008;371(9625):1665-74
  11. 11. Adapted from Nestle FO, et al. N Engl J Med. 2009;361:496-509. Ixekizumab, Secukinumab, Bimekizumab IL-17A IIL-17F IL-23 IL-12 Antimicrobial peptides IL-1β IL-6 TNF-α S100 CXCL8 CXCL9 CXCL10 CXCL11 CCL20 Activation Natural killer T cell Keratinocyte Myeloid dendritic cell Plasmacytoid dendritic cell Macrophage IL-1β IL-6 TNF-αTNF-α INF-γ INF-α Th1 cell Th17 cell TNF-α INF-γ Keratinocyte TNF-α Adaptive immunity Innate immunityInnate immunity IL-20 Th22 cell IL-22 IL-20 Secukinumab Ixekizumab Key Cells and Mediators in Psoriasis
  12. 12. IL-17A IL-17F IL-17R IL-12 Antimicrobial peptides IL-1β IL-6 TNF-α S100 CXCL8 CXCL9 CXCL10 CXCL11 CCL20 Activation Natural killer T cell Keratinocyte Myeloid dendritic cell Plasmacytoid dendritic cell Macrophage IL-1β IL-6 TNF-αTNF-α INF-γ INF-γ Th1 cell Th17 cell TNF-α INF-γ Keratinocyte TNF-α Adaptive immunity Innate immunityInnate immunity IL-20 Adapted from: Nestle F, et al, NEJM 2009; 501. Mechanism of Brodalumab Th22 cell IL-22 IL-20 IL-23
  13. 13. IL-17A IL-17F IL-17R IL-12 Antimicrobial peptides IL-1β IL-6 TNF-α S100 CXCL8 CXCL9 CXCL10 CXCL11 CCL20 Activation Natural killer T cell Keratinocyte Myeloid dendritic cell Plasmacytoid dendritic cell Macrophage IL-1β IL-6 TNF-αTNF-α INF-γ INF-γ Th1 cell Th17 cell TNF-α INF-γ Keratinocyte TNF-α Adaptive immunity Innate immunityInnate immunity IL-20 Adapted from: Nestle F, et al, NEJM 2009; 501. Mechanism of Guselkumab, Risankizumab, Mirikizumab Th22 cell IL-22 IL-20 IL-23
  14. 14. Secukinumab in plaque psoriasis--results of two phase 3 trials. Langley RG, Elewski BE, Lebwohl M, Reich K, Griffiths CE, Papp K, Puig L, Nakagawa H, Spelman L, Sigurgeirsson B, Rivas E, Tsai TF, Wasel N, Tyring S, Salko T, Hampele I, Notter M, Karpov A, Helou S, Papavassilis C; ERASURE Study Group; FIXTURE Study Group. N Engl J Med. 2014 Jul 24;371(4):326-38.
  15. 15. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A, Cameron GS, Erickson J, Zhang L, Secrest RJ, Ball S, Braun DK, Osuntokun OO, Heffernan MP, Nickoloff BJ, Papp K; UNCOVER-2 and UNCOVER-3 investigators. Lancet. 2015;386(9993):541-51.
  16. 16. Phase 3 Studies Evaluating Brodalumab Compared to Ustekinumab In Psoriasis MLebwohl, BStrober, AMenter, KGordon, JWeglowska, LPuig, KPapp, LSpelman, DToth, FKerdel, AArmstrong, G Stingl, AKimball, HBachelez, JWu, JCrowley, RLangley, TBlicharski,CPaul, JLacour,STyring,LKircik,SChimenti, KCallis Duffin, JBagel, JKoo, GAras, JLi, W Song, C Milmont, YShi, N Erondu, PKlekotka, BKotzin, A Nirula NEJM in press
  17. 17. Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis. Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG, Lacour JP, Menter A, Philipp S, Sofen H, Tyring S, Berner BR, Visvanathan S, Pamulapati C, Bennett N, Flack M, Scholl P, Padula SJ. N Engl J Med. 2017;376:1551-1560.
  18. 18. Confidential TSLP Gittler JK…and Guttman-Yassky E. J Allergy Clin Immunol Sep 2012
  19. 19. • Gottlieb, A • Krueger, G • Menter, A • Papp, K • Gelfand, J • Gisondi, P • Krueger, J • Reich, K • Kimball, A • Smith, CH • Feldman, S • Gordon, K • Griffiths, CEM • Kirby, B • Saurat, JH • Neimann, A • Sterry, W • Pathirana, D • Sampogna, F • Van de Kerkhof, PCM • Leonardi, C • Raychaudhuri, SP • Kragballe, K. • Prodanovich, S

By identifying key cells and cytokines that play roles in the development of diseases like psoriasis and atopic dermatitis, we have been able to target very specific parts of the immune system and thereby treat these diseases more effectively and more safely. Following the same methodology, we hope to identify key targets that allow us to do the same for alopecia areata.

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