Combination Therapy With Immunomodulators Improves the Pharmacokinetics of Infliximab But Not Vedolizumab or Ustekinumab.
Humans
Infliximab
/ therapeutic use
Azathioprine
/ therapeutic use
Ustekinumab
/ therapeutic use
Mercaptopurine
Methotrexate
/ therapeutic use
Prospective Studies
Immunologic Factors
/ therapeutic use
Antibodies, Monoclonal, Humanized
/ therapeutic use
Inflammatory Bowel Diseases
/ drug therapy
Immunosuppressive Agents
/ therapeutic use
6-Thioguanine Nucleotide
Azathioprine
Infliximab
Mercaptopurine
Methotrexate
Therapeutic Drug Monitoring, Remission
Ustekinumab
Vedolizumab
Journal
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
18
07
2022
revised:
06
10
2022
accepted:
11
10
2022
medline:
23
10
2023
pubmed:
25
10
2022
entrez:
24
10
2022
Statut:
ppublish
Résumé
The aim of this study was to assess how 6-thioguanine nucleotide (6-TGN) levels and use of oral methotrexate relate to the pharmacokinetics of biologics. This was a prospective cohort study including patients with inflammatory bowel diseases on maintenance doses of infliximab, vedolizumab, or ustekinumab on monotherapy or combination with a thiopurine or oral methotrexate. We collected 6-TGN concentrations, biomarker levels, and clinical and endoscopic disease activity. The primary outcomes were infliximab, vedolizumab, and ustekinumab concentrations as well as anti-drug antibodies (ADAs). A total of 369 patients were recruited (113 infliximab, 133 vedolizumab, and 123 ustekinumab). Patients with 6-TGN levels ≥146 pmol per 8 × 10 Achieving higher 6-TGN levels or the use of methotrexate improved the pharmacokinetics of infliximab. Conversely, these data do not support the use of combination therapy to augment pharmacokinetics with vedolizumab or ustekinumab.
Sections du résumé
BACKGROUND AND AIMS
The aim of this study was to assess how 6-thioguanine nucleotide (6-TGN) levels and use of oral methotrexate relate to the pharmacokinetics of biologics.
METHODS
This was a prospective cohort study including patients with inflammatory bowel diseases on maintenance doses of infliximab, vedolizumab, or ustekinumab on monotherapy or combination with a thiopurine or oral methotrexate. We collected 6-TGN concentrations, biomarker levels, and clinical and endoscopic disease activity. The primary outcomes were infliximab, vedolizumab, and ustekinumab concentrations as well as anti-drug antibodies (ADAs).
RESULTS
A total of 369 patients were recruited (113 infliximab, 133 vedolizumab, and 123 ustekinumab). Patients with 6-TGN levels ≥146 pmol per 8 × 10
CONCLUSIONS
Achieving higher 6-TGN levels or the use of methotrexate improved the pharmacokinetics of infliximab. Conversely, these data do not support the use of combination therapy to augment pharmacokinetics with vedolizumab or ustekinumab.
Identifiants
pubmed: 36280102
pii: S1542-3565(22)01005-9
doi: 10.1016/j.cgh.2022.10.016
pii:
doi:
Substances chimiques
Infliximab
B72HH48FLU
Azathioprine
MRK240IY2L
vedolizumab
9RV78Q2002
Ustekinumab
FU77B4U5Z0
Mercaptopurine
E7WED276I5
Methotrexate
YL5FZ2Y5U1
Immunologic Factors
0
Antibodies, Monoclonal, Humanized
0
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2908-2917.e10Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.