title: Tildrakizumab, a novel anti-IL-23 monoclonal antibody, is unaffected by ethnic variability in Caucasian, Chinese, and Japanese subjects.
abstract: OBJECTIVE
  To evaluate the effect of ethnicity on the pharmacokinetics (PK) of tildrakizumab, a novel anti-IL-23 monoclonal antibody for the treatment of psoriasis.
  
  
  METHODS
  This was an open-label, 2-part study in healthy adult subjects. In part 1, Japanese subjects and matched Caucasian and Chinese subjects (to Japanese) were assigned to 1 of 3 cohorts and administered tildrakizumab 50, 200, or 400 mg subcutaneously (SC). In part 2, Japanese subjects received tildrakizumab 10 mg/kg IV. Pre- and post-treatment antidrug antibodies were assessed. Safety and tolerability were assessed throughout the study.
  
  
  RESULTS
  59 subjects were enrolled; 53 in part 1 and 6 in part 2. Overall geometric mean AUC∞ was 6.15, 6.05, and 6.32 day×μg/mL/mg in Japanese, Caucasian, and Chinese subjects, respectively, after administration of a single SC dose. Bioavailability was ~92%. Six out of 58 evaluable subjects were positive for post-treatment ADA; 2 of these positive subjects had reduced tildrakizumab exposure. Most AEs were mild in intensity and the most frequent treatment-related AEs were injection site hematoma (15%), injection site pain (10%), and injection site erythema (8%).
  
  
  CONCLUSIONS
  The pharmacokinetics of tildrakizumab were similar in Japanese, Caucasian, and Chinese subjects. Tildrakizumab exposure increased proportionally with dose in the range of 50-400 mg. A single SC dose of 50, 200, and 400 mg or a single IV dose of 10 mg/kg was generally well tolerated.
authors.forename: Anthe
authors.initials: A
authors.lastname: Zandvliet
authors.forename: Shirley
authors.initials: S
authors.lastname: Glasgow
authors.forename: Ann
authors.initials: A
authors.lastname: Horowitz
authors.forename: Diana
authors.initials: D
authors.lastname: Montgomery
authors.forename: Joanne
authors.initials: J
authors.lastname: Marjason
authors.forename: Anish
authors.initials: A
authors.lastname: Mehta
authors.forename: Christine
authors.initials: C
authors.lastname: Xu
authors.forename: Marianne
authors.initials: M
authors.lastname: van Vugt
authors.forename: Sauzanne
authors.initials: S
authors.lastname: Khalilieh
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053759:Interleukin-23 / Q000276:immunology*; D008297:Male; D044465:White People; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053759:Interleukin-23; C000598434:tildrakizumab