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Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection
Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced treatment efficacy, and increased risk of infusion‐related reactions. The aim of this study was to identify predictors of baseline inflixim...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821183/ https://www.ncbi.nlm.nih.gov/pubmed/32905628 http://dx.doi.org/10.1002/jcph.1732 |
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author | Eser, Alexander Reinisch, Walter Schreiber, Stefan Ahmad, Tariq Boulos, Suliman Mould, Diane R. |
author_facet | Eser, Alexander Reinisch, Walter Schreiber, Stefan Ahmad, Tariq Boulos, Suliman Mould, Diane R. |
author_sort | Eser, Alexander |
collection | PubMed |
description | Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced treatment efficacy, and increased risk of infusion‐related reactions. The aim of this study was to identify predictors of baseline infliximab clearance and early antidrug antibody formation. Pharmacokinetic and pharmacokinetic/pharmacodynamic models for infliximab were developed using 21 178 observations from 859 patients from the PLANETRA (ClinicalTrials.gov identifier: NCT01217086) and PLANETAS (NCT01220518) studies in rheumatoid arthritis and ankylosing spondylitis, respectively, to address the specified aims. Infliximab pharmacokinetics were well described by a 2‐compartment model with linear mean estimated baseline clearance of 0.26 L/day. Alongside increased body weight, serum C‐reactive protein, and antidrug antibody concentrations and decreased serum albumin, elevated serum glucose levels predicted higher clearance. In patients with rheumatoid arthritis, baseline infliximab clearance and body weight were the only identified predictors of early antidrug antibody detection. The odds ratio for antidrug antibody detection for each 0.1 L/day increase in baseline infliximab clearance was 1.78 (95% confidence interval, 1.50–2.12); for each 10‐kg increase in body weight, this was 1.19 (1.06–1.33). Here we describe increased serum glucose levels as a novel independent predictor of baseline infliximab clearance. Estimates of baseline infliximab clearance should be incorporated to guide dosing modifications and/or antidrug antibody prophylaxis in clinical practice. |
format | Online Article Text |
id | pubmed-7821183 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-78211832021-01-29 Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection Eser, Alexander Reinisch, Walter Schreiber, Stefan Ahmad, Tariq Boulos, Suliman Mould, Diane R. J Clin Pharmacol Therapeutics Treatment of patients with biologics such as infliximab may trigger development of antidrug antibodies, which are associated with faster drug clearance, reduced treatment efficacy, and increased risk of infusion‐related reactions. The aim of this study was to identify predictors of baseline infliximab clearance and early antidrug antibody formation. Pharmacokinetic and pharmacokinetic/pharmacodynamic models for infliximab were developed using 21 178 observations from 859 patients from the PLANETRA (ClinicalTrials.gov identifier: NCT01217086) and PLANETAS (NCT01220518) studies in rheumatoid arthritis and ankylosing spondylitis, respectively, to address the specified aims. Infliximab pharmacokinetics were well described by a 2‐compartment model with linear mean estimated baseline clearance of 0.26 L/day. Alongside increased body weight, serum C‐reactive protein, and antidrug antibody concentrations and decreased serum albumin, elevated serum glucose levels predicted higher clearance. In patients with rheumatoid arthritis, baseline infliximab clearance and body weight were the only identified predictors of early antidrug antibody detection. The odds ratio for antidrug antibody detection for each 0.1 L/day increase in baseline infliximab clearance was 1.78 (95% confidence interval, 1.50–2.12); for each 10‐kg increase in body weight, this was 1.19 (1.06–1.33). Here we describe increased serum glucose levels as a novel independent predictor of baseline infliximab clearance. Estimates of baseline infliximab clearance should be incorporated to guide dosing modifications and/or antidrug antibody prophylaxis in clinical practice. John Wiley and Sons Inc. 2020-09-09 2021-02 /pmc/articles/PMC7821183/ /pubmed/32905628 http://dx.doi.org/10.1002/jcph.1732 Text en © 2020 The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Therapeutics Eser, Alexander Reinisch, Walter Schreiber, Stefan Ahmad, Tariq Boulos, Suliman Mould, Diane R. Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection |
title | Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection |
title_full | Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection |
title_fullStr | Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection |
title_full_unstemmed | Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection |
title_short | Increased Induction Infliximab Clearance Predicts Early Antidrug Antibody Detection |
title_sort | increased induction infliximab clearance predicts early antidrug antibody detection |
topic | Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821183/ https://www.ncbi.nlm.nih.gov/pubmed/32905628 http://dx.doi.org/10.1002/jcph.1732 |
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