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.
Article first published online 4 November 2013
*Biologics Clinical Pharmacology,
‡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.
Reprints: Omoniyi J Adedokun, MS, RPh, Janssen Research & Development, LLC., 1400 McKean Road, Spring House, PA 19477 (e-mail: firstname.lastname@example.org).
O. J. Adedokun, Z. Xu, L. Padgett, M. Blank, J. Johanns, J. Ford, H. Zhou, C. Guzzo, and H. M. Davis are employees of Janssen Research & Development, LLC. or Janssen Biotech, Inc. J. Hyams and A. Griffiths received research funding in conjunction with the conduct of this study and other studies sponsored by, and have served as consultants to, Janssen Research & Development, LLC.
Supported by Janssen Research & Development, LLC. (Spring House, PA).
Received June 05, 2013
Accepted September 06, 2013