title: Pharmacokinetics of IL-18 binding protein in healthy volunteers and subjects with rheumatoid arthritis or plaque psoriasis.
abstract: IL-18 binding protein (BP) neutralizes the activity of IL-18, a cytokine implicated in psoriasis and rheumatoid arthritis (RA). We investigated the pharmacokinetics, pharmacodynamics and safety of recombinant human IL-18 BP (r-hIL-18 BP) in healthy volunteers and subjects with psoriasis or RA in four phase I studies. A) Healthy volunteers (n = 24) were randomised to receive a single subcutaneous (sc) injection of r-hIL-18 BP (20, 70, 210 or 350 mg) or placebo. B) Healthy volunteers (n = 10) were randomised to receive six sc injections of r-hIL-18 BP (35 or 175 mg, 48 h between injections) or placebo. C) Subjects with moderate-to-severe plaque psoriasis (n = 35) were randomised to receive r-hIL-18 BP (20, 160 or 320 mg, sc tiw) or placebo for 6 weeks. D) Subjects with active, moderate-to-severe RA (n = 36) were randomised to receive r-hIL-18 BP (20, 80, 160 mg, sc tiw) or placebo for 6 weeks. Pharmacokinetics, pharmacodynamics and safety were assessed in all four studies. r-hIL-18 BP showed a dose-dependent pharmacokinetic profile, with a peak serum concentration of 6-48 hours. With repeated sc injections tiw, a steady state was achieved in 1-2 weeks among subjects with psoriasis or RA. The majority of adverse events were mild or moderate in severity. Injection site reactions were the most frequently reported event in subjects with psoriasis or RA. r-hIL-18 BP displays dose-dependent pharmacokinetics, has a favourable safety profile and is well-tolerated in healthy volunteers and in subjects with moderate-to-severe plaque psoriasis or active, moderate-to-severe RA.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Marisa
authors.initials: M
authors.lastname: Bacchi
authors.forename: Mauro
authors.initials: M
authors.lastname: Bertolino
mesh_terms: D000293:Adolescent; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; C118370:interleukin-18 binding protein