Clinical improvement in psoriasis with specific targeting of interleukin-23

Nature. 2015 May 14;521(7551):222-6. doi: 10.1038/nature14175. Epub 2015 Mar 9.

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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Double-Blind Method
  • Epithelium / drug effects
  • Epithelium / pathology
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunotherapy*
  • Interleukin-23 / antagonists & inhibitors*
  • Interleukin-23 / chemistry
  • Interleukin-23 / immunology
  • Middle Aged
  • Molecular Targeted Therapy*
  • Protein Subunits / antagonists & inhibitors
  • Protein Subunits / chemistry
  • Protein Subunits / immunology
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Psoriasis / metabolism
  • Psoriasis / pathology
  • Skin / drug effects
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-23
  • Protein Subunits
  • tildrakizumab