The effect of aging on infliximab exposure and response in patients with inflammatory bowel diseases.
elderly
inflammation
monoclonal antibodies
pharmacokinetic-pharmacodynamic
population analysis
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
revised:
11
02
2021
received:
30
10
2020
accepted:
13
02
2021
pubmed:
20
2
2021
medline:
28
10
2021
entrez:
19
2
2021
Statut:
ppublish
Résumé
Controversies regarding infliximab treatment in elderly patients with inflammatory bowel diseases remain. We evaluated the effect of patient's age on infliximab exposure, efficacy and safety. Retrospective case-control data of patients receiving infliximab induction treatment were analysed. A population pharmacokinetic model was developed to estimate individual pharmacokinetic parameters. A logistic regression model was used to investigate the effect of exposure on endoscopic remission. Repeated time-to-event models were developed to describe the hazard of safety events over time. A total of 104 patients (46 elderly, ≥65 years) were included. A two-compartment population pharmacokinetic model with linear elimination adequately described the data. Infliximab clearance decreased with older age, higher serum albumin, lower fat-free mass, lower C-reactive protein and absence of immunogenicity. Yet, infliximab exposure was not significantly different between elderly and nonelderly. Regardless of age, an infliximab trough concentration at week (w)14 of 15.6 mg/L was associated with a 50% probability of attaining endoscopic remission between w6 and w22. Infliximab exposure during induction treatment was not a risk factor of (severe) adverse events. The hazard of severe adverse events and malignancy increased by 2% and 7%, respectively, with increasing year of age. Concomitant immunomodulator use increased the hazard of infection by 958%, regardless of age. Elderly patients attained infliximab exposure and endoscopic remission similarly to nonelderly patients. Therefore, the same infliximab trough concentration target can be used in therapeutic drug monitoring. The hazards of severe adverse events and malignancy increased with age, but not with infliximab exposure.
Substances chimiques
Gastrointestinal Agents
0
Infliximab
B72HH48FLU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3776-3789Informations de copyright
© 2021 British Pharmacological Society.
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