Anti-infliximab antibodies: How to compare old and new data?


Journal

Journal of pharmaceutical and biomedical analysis
ISSN: 1873-264X
Titre abrégé: J Pharm Biomed Anal
Pays: England
ID NLM: 8309336

Informations de publication

Date de publication:
05 Jan 2020
Historique:
received: 10 07 2019
revised: 23 08 2019
accepted: 26 08 2019
pubmed: 19 9 2019
medline: 24 3 2020
entrez: 19 9 2019
Statut: ppublish

Résumé

Anti-drug-antibodies (ADA) against infliximab are frequently measured in patients receiving infliximab treatment with loss of response and undetectable infliximab concentrations. Different ADA bridging assays (1st generation, 2nd generation and ready-to-use kit) have been developed successively and were applied over the last 10 years, making comparison between ADA concentrations very challenging. A cutoff of 8 μg/ml was established to discriminate low from high ADA concentrations using the 1st generation ADA bridging assay. The objective of this study was to enable comparison of ADA concentrations determined with the different assays that were developed over the years. 166 serum samples were collected from patients with inflammatory bowel disease treated with infliximab. 98 samples were measured simultaneously with the 1st and 2nd generation ADA assay, 67 serum samples were measured with the 2nd generation assay and the ready-to-use kit. From our ADA concentration comparison experiments, we deduced that the previously established cutoff of 8 μg/ml with the 1st generation ELISA has a similar impact as the cutoff of 374 ng/ml with the 2nd generation ELISA and a cutoff of 119 ng/ml in the ready-to-use ELISA kit. ADA concentrations measured with the different assays were compared and a cutoff concentration was determined for each of them to distinguish between low and high ADA concentrations. These cutoff concentrations may serve as a tool for clinicians to make treatment decisions for patients with a loss of response to infliximab and undetectable infliximab serum concentrations.

Sections du résumé

BACKGROUND BACKGROUND
Anti-drug-antibodies (ADA) against infliximab are frequently measured in patients receiving infliximab treatment with loss of response and undetectable infliximab concentrations. Different ADA bridging assays (1st generation, 2nd generation and ready-to-use kit) have been developed successively and were applied over the last 10 years, making comparison between ADA concentrations very challenging. A cutoff of 8 μg/ml was established to discriminate low from high ADA concentrations using the 1st generation ADA bridging assay. The objective of this study was to enable comparison of ADA concentrations determined with the different assays that were developed over the years.
METHODS METHODS
166 serum samples were collected from patients with inflammatory bowel disease treated with infliximab. 98 samples were measured simultaneously with the 1st and 2nd generation ADA assay, 67 serum samples were measured with the 2nd generation assay and the ready-to-use kit.
RESULTS RESULTS
From our ADA concentration comparison experiments, we deduced that the previously established cutoff of 8 μg/ml with the 1st generation ELISA has a similar impact as the cutoff of 374 ng/ml with the 2nd generation ELISA and a cutoff of 119 ng/ml in the ready-to-use ELISA kit.
CONCLUSION CONCLUSIONS
ADA concentrations measured with the different assays were compared and a cutoff concentration was determined for each of them to distinguish between low and high ADA concentrations. These cutoff concentrations may serve as a tool for clinicians to make treatment decisions for patients with a loss of response to infliximab and undetectable infliximab serum concentrations.

Identifiants

pubmed: 31526960
pii: S0731-7085(19)31709-1
doi: 10.1016/j.jpba.2019.112842
pii:
doi:

Substances chimiques

Antibodies 0
Gastrointestinal Agents 0
Infliximab B72HH48FLU

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

112842

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Auteurs

Maya Imbrechts (M)

KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium. Electronic address: maya.imbrechts@kuleuven.be.

Thomas Van Stappen (T)

KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.

Griet Compernolle (G)

KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.

Sophie Tops (S)

KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.

Ann Gils (A)

KU Leuven, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium.

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Classifications MeSH