Clinical Reviews in Allergy & Immunology

, Volume 54, Issue 1, pp 102–113 | Cite as

Psoriasis: from Pathogenesis to Targeted Therapies

  • Curdin ConradEmail author
  • Michel GillietEmail author


Over the last decade, the management of psoriasis has witnessed a paradigm shift. Thanks to the increasing knowledge about the pathogenesis of psoriasis, targeted treatments with monoclonal antibodies have been developed. These antibodies, which target the pathogenic TNF/IL-23/IL-17-pathway, were shown to be safe and efficacious in the management of most patients with moderate to severe chronic plaque psoriasis. Recently, molecular and genetic studies in pustular and erythrodermic psoriasis have identified additional inflammatory pathways, providing evidence that psoriasis is a heterogeneous disease and highlighting the requirement for personalized disease characterization for treatment optimization. In this article, we will review these advances and provide an update on the currently available treatment arsenal. We discuss the efficacy and safety profile of these individual therapeutic agents and describe their use in special indications. We will also describe the current understanding of psoriasis as a systemic disease associated with multiple comorbidities and illustrate its impact in the management of psoriatic patients. Finally, we discuss ongoing therapeutic developments as well as unmet needs and future perspectives in the field of psoriasis.


Psoriasis Pathogenesis Inflammatory pathways Psoriasis comorbidities Treatments Biologicals TNFα inhibitors 



Tumor necrosis factor




Cluster of differentiation


T helper cell


T cytotoxic


A disintegrin and metalloproteinase with thrombospondin motifs like 5


Tumor necrosis factor alpha-induced protein 3


Nuclear factor kappa B


Human histocompatibility antigen Cw6


Endoplasmic reticulum aminopeptidase 1


E26 Transformation-specific transcription factor 1


Suppressor of cytokine signaling 1


Tumor necrosis factor receptor superfamily member 9


Single nucleotide polymorphism


Palmoplantar pustular psoriasis


Generalized pustular psoriasis


Acrodermatitis continua of Hallopeau


Interleukin-36 receptor antagonist

type I IFN

Type 1 interferon


Plasmaytoid dendritic cells


Psoriasis area and severity index


Interferon alpha receptor


Toll-like receptors




Nail Psoriasis Severity Index


Janus kinase


Psoriasis Longitudinal Assessment and Registry


Non-melanoma skin cancer


Major adverse cardiac events


Body mass index


Cardiovascular disease


Rheumatoid arthritis


Human immunodeficiency virus


Ultraviolet B rays


Late cornified envelope 3B


Small interfering ribonucleic acids


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval and Informed Consent

Not applicable.


  1. 1.
    Lowes MA, Suarez-Farinas M, Krueger JG (2014) Immunology of psoriasis. Annu Rev Immunol 32(1):227–255. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Tonel G, Conrad C (2009) Interplay between keratinocytes and immune cells—recent insights into psoriasis pathogenesis. Int J Biochem Cell Biol 41(5):963–968. CrossRefPubMedGoogle Scholar
  3. 3.
    Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278(3):1910–1914. CrossRefPubMedGoogle Scholar
  4. 4.
    Hijnen D, Knol EF, Gent YY, Giovannone B, Beijn SJ, Kupper TS, Bruijnzeel-Koomen CA, Clark RA (2013) CD8(+) T cells in the lesional skin of atopic dermatitis and psoriasis patients are an important source of IFN-gamma, IL-13, IL-17, and IL-22. J Invest Dermatol 133(4):973–979. CrossRefPubMedGoogle Scholar
  5. 5.
    Di Meglio P, Villanova F, Navarini AA, Mylonas A, Tosi I, Nestle FO, Conrad C (2016) Targeting CD8(+) T cells prevents psoriasis development. J Allergy Clin Immunol 138(1):274–276 e276. CrossRefPubMedGoogle Scholar
  6. 6.
    Boyman O, Hefti HP, Conrad C, Nickoloff BJ, Suter M, Nestle FO (2004) Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor-alpha. J Exp Med 199(5):731–736. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Conrad C, Boyman O, Tonel G, Tun-Kyi A, Laggner U, de Fougerolles A, Kotelianski V, Gardner H, Nestle FO (2007) Alpha1beta1 integrin is crucial for accumulation of epidermal T cells and the development of psoriasis. Nat Med 13(7):836–842. CrossRefPubMedGoogle Scholar
  8. 8.
    Cheuk S, Wiken M, Blomqvist L, Nylen S, Talme T, Stahle M, Eidsmo L (2014) Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis. J Immunol 192(7):3111–3120. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Lande R, Botti E, Jandus C, Dojcinovic D, Fanelli G, Conrad C, Chamilos G, Feldmeyer L, Marinari B, Chon S, Vence L, Riccieri V, Guillaume P, Navarini AA, Romero P, Costanzo A, Piccolella E, Gilliet M, Frasca L (2014) The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun 5:5621. CrossRefPubMedGoogle Scholar
  10. 10.
    Arakawa A, Siewert K, Stohr J, Besgen P, Kim SM, Ruhl G, Nickel J, Vollmer S, Thomas P, Krebs S, Pinkert S, Spannagl M, Held K, Kammerbauer C, Besch R, Dornmair K, Prinz JC (2015) Melanocyte antigen triggers autoimmunity in human psoriasis. J Exp Med 212(13):2203–2212. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Conrad C, Meller S, Gilliet M (2009) Plasmacytoid dendritic cells in the skin: to sense or not to sense nucleic acids. Semin Immunol 21(3):101–109. CrossRefPubMedGoogle Scholar
  12. 12.
    Tsoi LC, Spain SL, Knight J, Ellinghaus E, Stuart PE, Capon F, Ding J, Li Y, Tejasvi T, Gudjonsson JE, Kang HM, Allen MH, McManus R, Novelli G, Samuelsson L, Schalkwijk J, Stahle M, Burden AD, Smith CH, Cork MJ, Estivill X, Bowcock AM, Krueger GG, Weger W, Worthington J, Tazi-Ahnini R, Nestle FO, Hayday A, Hoffmann P, Winkelmann J, Wijmenga C, Langford C, Edkins S, Andrews R, Blackburn H, Strange A, Band G, Pearson RD, Vukcevic D, Spencer CC, Deloukas P, Mrowietz U, Schreiber S, Weidinger S, Koks S, Kingo K, Esko T, Metspalu A, Lim HW, Voorhees JJ, Weichenthal M, Wichmann HE, Chandran V, Rosen CF, Rahman P, Gladman DD, Griffiths CE, Reis A, Kere J, Collaborative Association Study of P, Genetic Analysis of Psoriasis C, Psoriasis Association Genetics E, Wellcome Trust Case Control C, Nair RP, Franke A, Barker JN, Abecasis GR, Elder JT, Trembath RC (2012) Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat Genet 44(12):1341–1348. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Tsoi LC, Spain SL, Ellinghaus E, Stuart PE, Capon F, Knight J, Tejasvi T, Kang HM, Allen MH, Lambert S, Stoll SW, Weidinger S, Gudjonsson JE, Koks S, Kingo K, Esko T, Das S, Metspalu A, Weichenthal M, Enerback C, Krueger GG, Voorhees JJ, Chandran V, Rosen CF, Rahman P, Gladman DD, Reis A, Nair RP, Franke A, Barker JN, Abecasis GR, Trembath RC, Elder JT (2015) Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. Nat Commun 6:7001. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Marrakchi S, Guigue P, Renshaw BR, Puel A, Pei XY, Fraitag S, Zribi J, Bal E, Cluzeau C, Chrabieh M, Towne JE, Douangpanya J, Pons C, Mansour S, Serre V, Makni H, Mahfoudh N, Fakhfakh F, Bodemer C, Feingold J, Hadj-Rabia S, Favre M, Genin E, Sahbatou M, Munnich A, Casanova JL, Sims JE, Turki H, Bachelez H, Smahi A (2011) Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med 365(7):620–628. CrossRefPubMedGoogle Scholar
  15. 15.
    Onoufriadis A, Simpson MA, Pink AE, Di Meglio P, Smith CH, Pullabhatla V, Knight J, Spain SL, Nestle FO, Burden AD, Capon F, Trembath RC, Barker JN (2011) Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease known as generalized pustular psoriasis. Am J Hum Genet 89(3):432–437. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Setta-Kaffetzi N, Navarini AA, Patel VM, Pullabhatla V, Pink AE, Choon SE, Allen MA, Burden AD, Griffiths CE, Seyger MM, Kirby B, Trembath RC, Simpson MA, Smith CH, Capon F, Barker JN (2013) Rare pathogenic variants in IL36RN underlie a spectrum of psoriasis-associated pustular phenotypes. J Invest Dermatol 133(5):1366–1369. CrossRefPubMedGoogle Scholar
  17. 17.
    Viguier M, Guigue P, Pages C, Smahi A, Bachelez H (2010) Successful treatment of generalized pustular psoriasis with the interleukin-1-receptor antagonist anakinra: lack of correlation with IL1RN mutations. Ann Intern Med 153(1):66–67. CrossRefPubMedGoogle Scholar
  18. 18.
    Huffmeier U, Watzold M, Mohr J, Schon MP, Mossner R (2014) Successful therapy with anakinra in a patient with generalized pustular psoriasis carrying IL36RN mutations. Br J Dermatol 170(1):202–204. CrossRefPubMedGoogle Scholar
  19. 19.
    Tauber M, Viguier M, Alimova E, Petit A, Liote F, Smahi A, Bachelez H (2014) Partial clinical response to anakinra in severe palmoplantar pustular psoriasis. Br J Dermatol 171(3):646–649. CrossRefPubMedGoogle Scholar
  20. 20.
    Lutz V, Lipsker D (2012) Acitretin- and tumor necrosis factor inhibitor-resistant acrodermatitis continua of hallopeau responsive to the interleukin 1 receptor antagonist anakinra. Arch Dermatol 148(3):297–299. CrossRefPubMedGoogle Scholar
  21. 21.
    Mrowietz U, Bachelez H, Burden D, M. R, Sieder C, Orsenigo R, Chaouche-Teyara K Efficacy and safety of secukinumab regimens in moderate to severe pustular palmoplantar psoriasis; results from the largest multicenter, randomized, double-blind, placebo-controlled study (2PRECISE). Presented at: European Academy of Dermatology and Venereology 2016 Annual Meeting Vienna, Austria, September 28 - October 2, 2016Google Scholar
  22. 22.
    Johnston A, Xing X, Wolterink L, Barnes DH, Yin Z, Reingold L, Kahlenberg JM, Harms PW, Gudjonsson JE (2017) IL-1 and IL-36 are dominant cytokines in generalized pustular psoriasis. J Allergy Clin Immunol 140(1):109–120. CrossRefPubMedGoogle Scholar
  23. 23.
    Nestle FO, Conrad C, Tun-Kyi A, Homey B, Gombert M, Boyman O, Burg G, Liu YJ, Gilliet M (2005) Plasmacytoid predendritic cells initiate psoriasis through interferon-alpha production. J Exp Med 202(1):135–143. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Conrad C, Di Domizio J, Mylonas A, Belkhodja C, Demaria O, Navarini A, Lapointe A, French L, Vernez M, Gilliet M TNF blockade induces a dysregulated type I IFN response without autoimmunity in paradoxical psoriasis. Nat Commun.
  25. 25.
    Reich K, Burden AD, Eaton JN, Hawkins NS (2012) Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials. Br J Dermatol 166(1):179–188. CrossRefPubMedGoogle Scholar
  26. 26.
    Reich K, Ortonne JP, Gottlieb AB, Terpstra IJ, Coteur G, Tasset C, Mease P (2012) Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension. Br J Dermatol 167(1):180–190. CrossRefPubMedGoogle Scholar
  27. 27.
    Cohen AD, Wu JJ, Puig L, Chimenti S, Vender R, Rajagopalan M, Romiti R, de la Cruz C, Skov L, Zachariae C, Young HS, Foley P, van der Walt JM, Naldi L, Blauvelt A (2017) Biosimilars for psoriasis: worldwide overview of regulatory guidelines, uptake and implications for dermatology clinical practice. Br J Dermatol.
  28. 28.
    Jorgensen KK, Olsen IC, Goll GL, Lorentzen M, Bolstad N, Haavardsholm EA, KEA L, Mork C, Jahnsen J, Kvien TK, group N-Ss (2017) Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet 389(10086):2304–2316. CrossRefPubMedGoogle Scholar
  29. 29.
    Papp K, Bachelez H, Costanzo A, Foley P, Gooderham M, Kaur P, Narbutt J, Philipp S, Spelman L, Weglowska J, Zhang N, Strober B (2017) Clinical similarity of biosimilar ABP 501 to adalimumab in the treatment of patients with moderate to severe plaque psoriasis: a randomized, double-blind, multicenter, phase III study. J Am Acad Dermatol 76(6):1093–1102. CrossRefPubMedGoogle Scholar
  30. 30.
    Griffiths CEM, Thaci D, Gerdes S, Arenberger P, Pulka G, Kingo K, Weglowska J, group Es, Hattebuhr N, Poetzl J, Woehling H, Wuerth G, Afonso M (2017) The EGALITY study: a confirmatory, randomized, double-blind study comparing the efficacy, safety and immunogenicity of GP2015, a proposed etanercept biosimilar, vs. the originator product in patients with moderate-to-severe chronic plaque-type psoriasis. Br J Dermatol 176(4):928–938. CrossRefPubMedGoogle Scholar
  31. 31.
    Gerdes S, Thaci D, Griffiths CEM, Arenberger P, Poetzl J, Wuerth G, Afonso M, Woehling H (2017) Multiple switches between GP2015, an etanercept biosimilar, with originator product do not impact efficacy, safety and immunogenicity in patients with chronic plaque-type psoriasis: 30-week results from the phase 3, confirmatory EGALITY study. J Eur Acad Dermatol Venereol.
  32. 32.
    Langley RG, Lebwohl M, Krueger GG, Szapary PO, Wasfi Y, Chan D, Hsu MC, You Y, Poulin Y, Korman N, Prinz JC, Reich K, Investigators P (2015) Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up. Br J Dermatol 172(5):1371–1383. CrossRefPubMedGoogle Scholar
  33. 33.
    Papp K, Gottlieb AB, Naldi L, Pariser D, Ho V, Goyal K, Fakharzadeh S, Chevrier M, Calabro S, Langholff W, Krueger G (2015) Safety surveillance for Ustekinumab and other psoriasis treatments from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol 14(7):706–714PubMedGoogle Scholar
  34. 34.
    Fiorentino D, Ho V, Lebwohl MG, Leite L, Hopkins L, Galindo C, Goyal K, Langholff W, Fakharzadeh S, Srivastava B, Langley RG (2017) Risk of malignancy with systemic psoriasis treatment in the Psoriasis Longitudinal Assessment Registry. J Am Acad Dermatol 77(5):845–854 e845. CrossRefPubMedGoogle Scholar
  35. 35.
    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, Group ES, Group FS (2014) Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med 371(4):326–338. CrossRefPubMedGoogle Scholar
  36. 36.
    Thaci D, Blauvelt A, Reich K, Tsai TF, Vanaclocha F, Kingo K, Ziv M, Pinter A, Hugot S, You R, Milutinovic M (2015) 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 73(3):400–409. CrossRefPubMedGoogle Scholar
  37. 37.
    Blauvelt A, Reich K, Tsai TF, Tyring S, Vanaclocha F, Kingo K, Ziv M, Pinter A, Vender R, Hugot S, You R, Milutinovic M, Thaci D (2017) 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 76(1):60–69 e69. CrossRefPubMedGoogle Scholar
  38. 38.
    Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M, Reich K, Amato D, Ball SG, Braun DK, Cameron GS, Erickson J, Konrad RJ, Muram TM, Nickoloff BJ, Osuntokun OO, Secrest RJ, Zhao F, Mallbris L, Leonardi CL, Group U-S, Group U-S, Group U-S (2016) Phase 3 trials of Ixekizumab in moderate-to-severe plaque psoriasis. N Engl J Med 375(4):345–356. CrossRefPubMedGoogle Scholar
  39. 39.
    Bagel J, Duffin KC, Moore A, Ferris LK, Siu K, Steadman J, Kianifard F, Nyirady J, Lebwohl M (2017) The effect of secukinumab on moderate-to-severe scalp psoriasis: results of a 24-week, randomized, double-blind, placebo-controlled phase 3b study. J Am Acad Dermatol 77(4):667–674. CrossRefPubMedGoogle Scholar
  40. 40.
    Reich K, Arenberger P, Mrowietz U, Jazayeri S, Augustin M, Parneix A, Tao A, Milutinovic M (2017) Secukinumab shows high and sustained efficacy in nail psoriasis: Week 80 results from the TRANSFIGURE study. Presented at: American Academy of Dermatology 2017 Annual Meeting Orlando, FL, March 3-7, 2017Google Scholar
  41. 41.
    Langley RG, Rich P, Menter A, Krueger G, Goldblum O, Dutronc Y, Zhu B, Wei H, Cameron GS, Heffernan MP (2015) Improvement of scalp and nail lesions with ixekizumab in a phase 2 trial in patients with chronic plaque psoriasis. J Eur Acad Dermatol Venereol 29(9):1763–1770. CrossRefPubMedGoogle Scholar
  42. 42.
    Papp KA, Reich K, Paul C, Blauvelt A, Baran W, Bolduc C, Toth D, Langley RG, Cather J, Gottlieb AB, Thaci D, Krueger JG, Russell CB, Milmont CE, Li J, Klekotka PA, Kricorian G, Nirula A (2016) A prospective phase III, randomized, double-blind, placebo-controlled study of brodalumab in patients with moderate-to-severe plaque psoriasis. Br J Dermatol 175(2):273–286. CrossRefPubMedGoogle Scholar
  43. 43.
    Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J, Puig L, Papp K, Spelman L, Toth D, Kerdel F, Armstrong AW, Stingl G, Kimball AB, Bachelez H, Wu JJ, Crowley J, Langley RG, Blicharski T, Paul C, Lacour JP, Tyring S, Kircik L, Chimenti S, Callis Duffin K, Bagel J, Koo J, Aras G, Li J, Song W, Milmont CE, Shi Y, Erondu N, Klekotka P, Kotzin B, Nirula A (2015) Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med 373(14):1318–1328. CrossRefPubMedGoogle Scholar
  44. 44.
    Lebwohl M, Iversen L, Eidsmo L, Messina I, You R, Milutinovic M (2017) Long-term psoriasis control following secukinumab discontinuation indicated disease modification of moderate to severe psoriasis. Presented at: 13th Annual Maui Derm for Dermatologists 20-24th March, 2017Google Scholar
  45. 45.
    Tonel G, Conrad C, Laggner U, Di Meglio P, Grys K, McClanahan TK, Blumenschein WM, Qin JZ, Xin H, Oldham E, Kastelein R, Nickoloff BJ, Nestle FO (2010) Cutting edge: a critical functional role for IL-23 in psoriasis. J Immunol 185(10):5688–5691. CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kopp T, Riedl E, Bangert C, Bowman EP, Greisenegger E, Horowitz A, Kittler H, Blumenschein WM, McClanahan TK, Marbury T, Zachariae C, Xu D, Hou XS, Mehta A, Zandvliet AS, Montgomery D, van Aarle F, Khalilieh S (2015) Clinical improvement in psoriasis with specific targeting of interleukin-23. Nature 521(7551):222–226. CrossRefPubMedGoogle Scholar
  47. 47.
    Blauvelt A, Papp KA, Griffiths CE, Randazzo B, Wasfi Y, Shen YK, Li S, Kimball AB (2017) 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 76(3):405–417. CrossRefPubMedGoogle Scholar
  48. 48.
    Gordon KB, Duffin KC, Bissonnette R, Prinz JC, Wasfi Y, Li S, Shen YK, Szapary P, Randazzo B, Reich K (2015) A phase 2 trial of guselkumab versus adalimumab for plaque psoriasis. N Engl J Med 373(2):136–144. CrossRefPubMedGoogle Scholar
  49. 49.
    Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, Gottlieb AB, Nakagawa H, Bowman EP, Mehta A, Li Q, Zhou Y, Shames R (2015) Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol 173(4):930–939. CrossRefPubMedGoogle Scholar
  50. 50.
    Reich K, Papp KA, Blauvelt A, Tyring SK, Sinclair R, Thaci D, Nograles K, Mehta A, Cichanowitz N, Li Q, Liu K, La Rosa C, Green S, Kimball AB (2017) Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet 390(10091):276–288. CrossRefPubMedGoogle Scholar
  51. 51.
    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 (2017) Risankizumab versus ustekinumab for moderate-to-severe plaque psoriasis. N Engl J Med 376(16):1551–1560. CrossRefPubMedGoogle Scholar
  52. 52.
    Bissonnette R, Papp K, Maari C, Yao Y, Robbie G, White WI, Le C, White B (2010) A randomized, double-blind, placebo-controlled, phase I study of MEDI-545, an anti-interferon-alfa monoclonal antibody, in subjects with chronic psoriasis. J Am Acad Dermatol 62(3):427–436. CrossRefPubMedGoogle Scholar
  53. 53.
    Papp K, Reich K, Leonardi CL, Kircik L, Chimenti S, Langley RG, Hu C, Stevens RM, Day RM, Gordon KB, Korman NJ, Griffiths CE (2015) Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1). J Am Acad Dermatol 73(1):37–49. CrossRefPubMedGoogle Scholar
  54. 54.
    Bissonnette R, Haydey R, Rosoph L, Lynde CW, Bukhalo M, Fowler J, Delorme I, Gagne-Henley A, Gooderham M, Poulin Y, Barber K, Jenkin P, Landells I, Pariser D (2017) Apremilast for the treatment of moderate to severe palmoplantar psoriasis: results from a double-blind, placebo-controlled, randomized study. J Eur Acad Dermatol Venereol.
  55. 55.
    Rich P, Gooderham M, Bachelez H, Goncalves J, Day RM, Chen R, Crowley J (2016) Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with difficult-to-treat nail and scalp psoriasis: results of 2 phase III randomized, controlled trials (ESTEEM 1 and ESTEEM 2). J Am Acad Dermatol 74(1):134–142. CrossRefPubMedGoogle Scholar
  56. 56.
    Papp KA, Menter MA, Abe M, Elewski B, Feldman SR, Gottlieb AB, Langley R, Luger T, Thaci D, Buonanno M, Gupta P, Proulx J, Lan S, Wolk R, Pivotal OPT, investigators OPTP (2015) Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: results from two randomized, placebo-controlled, phase III trials. Br J Dermatol 173(4):949–961. CrossRefPubMedGoogle Scholar
  57. 57.
    Kalb RE, Fiorentino DF, Lebwohl MG, Toole J, Poulin Y, Cohen AD, Goyal K, Fakharzadeh S, Calabro S, Chevrier M, Langholff W, You Y, Leonardi CL (2015) Risk of serious infection with biologic and systemic treatment of psoriasis: results from the Psoriasis Longitudinal Assessment and Registry (PSOLAR). JAMA Dermatol 151(9):961–969. CrossRefPubMedGoogle Scholar
  58. 58.
    Cantini F, Nannini C, Niccoli L, Petrone L, Ippolito G, Goletti D (2017) Risk of tuberculosis reactivation in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis receiving non-anti-TNF-targeted biologics. Mediat Inflamm 2017:8909834. CrossRefGoogle Scholar
  59. 59.
    Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, Davis J, Hsu A, Asher AI, O'Shea J, Holland SM, Paul WE, Douek DC (2008) Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452(7188):773–776. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Puel A, Cypowyj S, Bustamante J, Wright JF, Liu L, Lim HK, Migaud M, Israel L, Chrabieh M, Audry M, Gumbleton M, Toulon A, Bodemer C, El-Baghdadi J, Whitters M, Paradis T, Brooks J, Collins M, Wolfman NM, Al-Muhsen S, Galicchio M, Abel L, Picard C, Casanova JL (2011) Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science 332(6025):65–68. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Conrad C, Reich K, Blauvelt A, Armstrong A, Krueger J, Gong Y, Milutinovic M, Langley R (2016) Secukinumab-treated subjects experience low rates of Candida and recurrent Candida infections: a pooled analysis from 10 phase 2 and 3 clinical studies in psoriasis. Presented at American Academy of Dermatology 2016 Annual Meeting, Washington, DC, 4-8th MarchGoogle Scholar
  62. 62.
    Burmester GR, Panaccione R, Gordon KB, McIlraith MJ, Lacerda AP (2013) Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis 72(4):517–524. CrossRefPubMedGoogle Scholar
  63. 63.
    Ryan C, Leonardi CL, Krueger JG, Kimball AB, Strober BE, Gordon KB, Langley RG, de Lemos JA, Daoud Y, Blankenship D, Kazi S, Kaplan DH, Friedewald VE, Menter A (2011) Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials. JAMA 306(8):864–871. CrossRefPubMedGoogle Scholar
  64. 64.
    Bissonnette R, Kerdel F, Naldi L, Papp K, Galindo C, Langholff W, Tang KL, Szapary P, Fakharzadeh S, Srivastava B, Goyal K, Gottlieb AB (2017) Evaluation of risk of major adverse cardiovascular events with biologic therapy in patients with psoriasis. J Drugs Dermatol 16(10):1002–1013PubMedGoogle Scholar
  65. 65.
    TNF neutralization in MS: results of a randomized, placebo-controlled multicenter study. The Lenercept Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group (1999). Neurology 53 (3):457–465Google Scholar
  66. 66.
    Hueber W, Sands BE, Lewitzky S, Vandemeulebroecke M, Reinisch W, Higgins PD, Wehkamp J, Feagan BG, Yao MD, Karczewski M, Karczewski J, Pezous N, Bek S, Bruin G, Mellgard B, Berger C, Londei M, Bertolino AP, Tougas G, Travis SP, Secukinumab in Crohn's Disease Study G (2012) 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 61(12):1693–1700. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Blauvelt A (2016) Safety of secukinumab in the treatment of psoriasis. Expert Opin Drug Saf 15(10):1413–1420. CrossRefPubMedGoogle Scholar
  68. 68.
    Reich K, Leonardi C, Langley RG, Warren RB, Bachelez H, Romiti R, Ohtsuki M, Xu W, Acharya N, Solotkin K, Colombel JF, Hardin DS (2017) Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: a presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials. J Am Acad Dermatol 76(3):441–448 e442. CrossRefPubMedGoogle Scholar
  69. 69.
    van de Kerkhof PC, Griffiths CE, Reich K, Leonardi CL, Blauvelt A, Tsai TF, Gong Y, Huang J, Papavassilis C, Fox T (2016) Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol 75(1):83–98 e84. CrossRefPubMedGoogle Scholar
  70. 70.
    Verstockt B, Deleenheer B, Van Assche G, Vermeire S, Ferrante M (2017) A safety assessment of biological therapies targeting the IL-23/IL-17 axis in inflammatory bowel diseases. Expert Opin Drug Saf 16(7):809–821. PubMedGoogle Scholar
  71. 71.
    Gelfand JM, Neimann AL, Shin DB, Wang X, Margolis DJ, Troxel AB (2006) Risk of myocardial infarction in patients with psoriasis. JAMA 296(14):1735–1741. CrossRefPubMedGoogle Scholar
  72. 72.
    Yeung H, Takeshita J, Mehta NN, Kimmel SE, Ogdie A, Margolis DJ, Shin DB, Attor R, Troxel AB, Gelfand JM (2013) Psoriasis severity and the prevalence of major medical comorbidity: a population-based study. JAMA Dermatol 149(10):1173–1179. CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Boehncke WH, Boehncke S, Tobin AM, Kirby B (2011) The ‘psoriatic march’: a concept of how severe psoriasis may drive cardiovascular comorbidity. Exp Dermatol 20(4):303–307. CrossRefPubMedGoogle Scholar
  74. 74.
    Ahlehoff O, Skov L, Gislason G, Gniadecki R, Iversen L, Bryld LE, Lasthein S, Lindhardsen J, Kristensen SL, Torp-Pedersen C, Hansen PR (2015) Cardiovascular outcomes and systemic anti-inflammatory drugs in patients with severe psoriasis: 5-year follow-up of a Danish nationwide cohort. J Eur Acad Dermatol Venereol 29(6):1128–1134. CrossRefPubMedGoogle Scholar
  75. 75.
    Wu JJ, Guerin A, Sundaram M, Dea K, Cloutier M, Mulani P (2017) Cardiovascular event risk assessment in psoriasis patients treated with tumor necrosis factor-alpha inhibitors versus methotrexate. J Am Acad Dermatol 76(1):81–90. CrossRefPubMedGoogle Scholar
  76. 76.
    Talamonti M, Botti E, Galluzzo M, Teoli M, Spallone G, Bavetta M, Chimenti S, Costanzo A (2013) Pharmacogenetics of psoriasis: HLA-Cw6 but not LCE3B/3C deletion nor TNFAIP3 polymorphism predisposes to clinical response to interleukin 12/23 blocker ustekinumab. Br J Dermatol 169(2):458–463. CrossRefPubMedGoogle Scholar
  77. 77.
    Langan EA, Griffiths CEM, Solbach W, Knobloch JK, Zillikens D, Thaci D (2017) The role of the microbiome in psoriasis: moving from disease description to treatment prediction? Br J Dermatol.
  78. 78.
    Dimasi N, Fleming R, Hay C, Woods R, Xu L, Wu H, Gao C (2015) Development of a trispecific antibody designed to simultaneously and efficiently target three different antigens on tumor cells. Mol Pharm 12(9):3490–3501. CrossRefPubMedGoogle Scholar
  79. 79.
    Kisiel B, Kisiel K, Szymanski K, Mackiewicz W, Bialo-Wojcicka E, Uczniak S, Fogtman A, Iwanicka-Nowicka R, Koblowska M, Kossowska H, Placha G, Sykulski M, Bachta A, Tlustochowicz W, Ploski R, Kaszuba A (2017) The association between 38 previously reported polymorphisms and psoriasis in a Polish population: high predicative accuracy of a genetic risk score combining 16 loci. PLoS One 12(6):e0179348. CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Yin X, Cheng H, Lin Y, Wineinger NE, Zhou F, Sheng Y, Yang C, Li P, Li F, Shen C, Yang S, Schork NJ, Zhang X (2015) A weighted polygenic risk score using 14 known susceptibility variants to estimate risk and age onset of psoriasis in Han Chinese. PLoS One 10(5):e0125369. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyLausanne University Hospital CHUVLausanneSwitzerland

Personalised recommendations