title: Clinical improvement in psoriasis with specific targeting of interleukin-23.
abstract: Psoriasis is a chronic inflammatory skin disorder that affects approximately 2-3% of the population worldwide and has severe effects on patients' physical and psychological well-being. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index (PASI) score (PASI75) was achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg(-1) groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg(-1) group and 13 out of 14 subjects in the 10 mg kg(-1) group achieved a PASI75 by day 112. Tildrakizumab demonstrated important clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples.
authors.affiliation: 1] Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, 1090 Vienna, Austria [2] Juvenis Medical Center, 1010 Vienna, Austria.
authors.forename: Tamara
authors.initials: T
authors.lastname: Kopp
authors.affiliation: Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, 1090 Vienna, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Riedl
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, 1090 Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Bangert
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Bowman
authors.affiliation: Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, University of Vienna Medical School, 1090 Vienna, Austria.
authors.forename: Elli
authors.initials: E
authors.lastname: Greisenegger
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Ann
authors.initials: A
authors.lastname: Horowitz
authors.affiliation: Department of Dermatology, Division of General Dermatology, University of Vienna Medical School, 1090 Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Kittler
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Blumenschein
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Terrill K
authors.initials: TK
authors.lastname: McClanahan
authors.affiliation: Orlando Clinical Research Center, Orlando, Florida 32809, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Marbury
authors.affiliation: Department of Dermato-allergology, Gentofte Hospital, University of Copenhagen, Kildegaardsvej 28, DK-2900 Hellerup, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Zachariae
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Danlin
authors.initials: D
authors.lastname: Xu
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Xiaoli Shirley
authors.initials: XS
authors.lastname: Hou
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Anish
authors.initials: A
authors.lastname: Mehta
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Anthe S
authors.initials: AS
authors.lastname: Zandvliet
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Montgomery
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: van Aarle
authors.affiliation: Merck &Co., Inc., Whitehouse Station, New Jersey 08889, USA.
authors.forename: Sauzanne
authors.initials: S
authors.lastname: Khalilieh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy; D053759:Interleukin-23 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000276:immunology; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053759:Interleukin-23; D021122:Protein Subunits; C000598434:tildrakizumab