Abstract
Population pharmacokinetics (PK) and exposure-response (E-R) analyses were conducted to compare the PK and E-R relationships of golimumab between children and adults with ulcerative colitis. PK data following subcutaneous golimumab administration to children with ulcerative colitis (6-17 years) in the PURSUIT-PEDS-PK study, adults with ulcerative colitis in the PURSUIT study, and children with pediatric polyarticular juvenile idiopathic arthritis (2-17 years) in the GO-KIDS study, were included in the population PK analysis. E-R analysis was conducted using logistic regression to link serum golimumab concentration and Mayo score–based efficacy outcomes in pediatric and adult ulcerative colitis. Golimumab PK was adequately described by a 1-compartment model with first-order absorption and elimination. Golimumab apparent clearance and volume of distribution increased with body weight. Golimumab apparent clearance was higher in patients with lower serum albumin, no methotrexate use, and positive antibodies to golimumab; age was not an influential factor after accounting for body weight. Model-estimated terminal half-life (9.2 days in children; 9.5 days in adults) and other PK parameters suggest that golimumab PK properties are generally comparable between children and adults with ulcerative colitis. Simulations suggest that a higher induction dose than that tested in PURSUIT-PEDS-PK may be needed for children ≤45 kg to achieve exposures comparable to adults. Comparable E-R relationships between children and adults with ulcerative colitis were observed, although children appeared to be more responsive for the more stringent remission end point. The overall comparable PK and E-R relationships between children and adults support the extrapolation of golimumab efficacy from the adult to the pediatric ulcerative colitis population.
| Original language | American English |
|---|---|
| Pages (from-to) | 590-604 |
| Number of pages | 15 |
| Journal | Journal of Clinical Pharmacology |
| Volume | 59 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2019 |
Bibliographical note
Funding Information:This work was supported by Janssen Research & Development, LLC, Pharmaceutical Companies of Johnson & Johnson. The authors thank the patients who participated in the clinical trials and the investigators and their staff at the clinical study sites for their valuable contributions. Editorial support was provided by James P. Barrett, BS, of Janssen Scientific Affairs, LLC. Data presented in this manuscript cannot be shared. For any questions, please contact Janssen Research & Development, LLC. Y.X., O.J.A., D.C., Z.X., C.H., R.S.S., and H.Z. were employees of Janssen Research & Development, LLC, at the time of the study, and may own stock and/or stock options in the company. During the past 3 years, D.T. has received consultation fees, research grants, royalties, or honoraria from Janssen, Pfizer, the Hospital for Sick Children, Ferring, AstraZeneca, Abbvie, Takeda, Boehringer Ingelheim, Biogen, Atlantic Health, Shire, Celgene, and Lilly. J.S.H. was an advisory board member for Janssen Research and Development, LLC, at the time of the study, and has received consultation fees, research grants, royalties, or honoraria from Abbvie, Pfizer, Lilly, Allergan, Boehringer-Ingelheim, Receptos, and Roche. This work was supported by Janssen Research & Development, LLC, Pharmaceutical Companies of Johnson & Johnson.
Funding Information:
The authors thank the patients who participated in the clinical trials and the investigators and their staff at the clinical study sites for their valuable contributions. Editorial support was provided by James P. Barrett, BS, of Janssen Scientific Affairs, LLC.
Publisher Copyright:
© 2018, The American College of Clinical Pharmacology
Keywords
- exposure-response
- extrapolation
- golimumab
- pediatrics
- population pharmacokinetics
- ulcerative colitis