Clinical improvement in psoriasis with specific targeting of interleukin-23

Tamara Kopp, Elisabeth Riedl, Christine Bangert, Edward P Bowman, Elli Greisenegger, Ann Horowitz, Harald Kittler, Wendy M Blumenschein, Terrill K McClanahan, Thomas Marbury, Claus Zachariae, Danlin Xu, Xiaoli Shirley Hou, Anish Mehta, Anthe S Zandvliet, Diana Montgomery, Frank van Aarle, Sauzanne Khalilieh

186 Citations (Scopus)

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.

Original languageEnglish
JournalNature
Volume521
Issue number7551
Pages (from-to)222-6
Number of pages5
ISSN0028-0836
DOIs
Publication statusPublished - 14 May 2015

Keywords

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal
  • Double-Blind Method
  • Epithelium
  • Gene Expression Regulation
  • Humans
  • Immunotherapy
  • Interleukin-23
  • Middle Aged
  • Molecular Targeted Therapy
  • Protein Subunits
  • Psoriasis
  • Skin
  • Treatment Outcome
  • Young Adult

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