title: Pharmacokinetics of infliximab in children with moderate-to-severe ulcerative colitis: results from a randomized, multicenter, open-label, phase 3 study.
abstract: BACKGROUND
  To assess infliximab pharmacokinetics in pediatric ulcerative colitis (UC).
  
  
  METHODS
  This phase 3, randomized, open-label multicenter study enrolled 60 children (6-17 yr) with moderate-to-severely active UC (Mayo score, 6-12; endoscopic subscore, ≥2), despite conventional therapy. Patients received infliximab 5-mg/kg induction infusions at weeks 0, 2, and 6. Week 8 clinical responders (n = 45) were randomized to infliximab 5 mg/kg given every 8 weeks (q8w) through week 46 or every 12 weeks (q12w) through week 42. Patients losing response during maintenance infliximab were eligible to increase the dose (5→10 mg/kg) and/or shorten the dosing interval (q12w→q8w). Blood samples were collected for infliximab concentration and pharmacokinetic determinations.
  
  
  RESULTS
  Infliximab pharmacokinetics were not influenced by age (6-11 yr versus 12-17 yr), baseline immunomodulator use, or the extent of UC. At week 8, higher serum infliximab concentrations (≥41.1 μg/mL) were associated with greater proportions of patients achieving efficacy endpoints (clinical response, 92.9%; mucosal healing, 92.9%; and clinical remission, 64.3%) versus those with lower serum concentrations (<18.1 μg/mL; 53.9%, 53.9%, and 30.8%, respectively). At week 30, higher median trough serum infliximab concentrations were observed with infliximab 5 mg/kg q8w (1.9 μg/mL) versus q12w (0.8 μg/mL) and with infliximab 10 mg/kg (2.9 μg/mL) versus 5 mg/kg (1.1 μg/mL) among patients who are regimen adjusted.
  
  
  CONCLUSIONS
  Infliximab pharmacokinetics/exposure-response relationship in patients with UC aged 6 to 17 years were generally comparable with those observed in reference adult UC populations, supporting using infliximab 5 mg/kg at weeks 0, 2, and 6 followed by maintenance dosing with 5 mg/kg q8w in these patients. A positive relationship was noted between serum infliximab level and clinical effect following induction therapy similar to adults.
authors.affiliation: *Biologics Clinical Pharmacology, †Biostatistics, ‡Medical Affairs (formerly Janssen R&D), and §Clinical Biostatistics, Spring House, Pennsylvania; ¶Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Toronto, ON, Canada; ‖Biologics Clinical Pharmacology, Radnor, Pennsylvania; and **Gastroenterology, Digestive Diseases, Hepatology & Nutrition, Connecticut Children's Medical Center, Hartford, Connecticut.
authors.forename: Omoniyi J
authors.initials: OJ
authors.lastname: Adedokun
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xu
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Padgett
authors.forename: Marion
authors.initials: M
authors.lastname: Blank
authors.forename: Jewel
authors.initials: J
authors.lastname: Johanns
authors.forename: Anne
authors.initials: A
authors.lastname: Griffiths
authors.forename: Joyce
authors.initials: J
authors.lastname: Ford
authors.forename: Honghui
authors.initials: H
authors.lastname: Zhou
authors.forename: Cynthia
authors.initials: C
authors.lastname: Guzzo
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Davis
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hyams
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D003093:Colitis, Ulcerative / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D000069285:Infliximab; D008297:Male; D014018:Tissue Distribution; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D000069285:Infliximab