Immunogenicity is not the driving force of treatment failure in vedolizumab-treated inflammatory bowel disease patients.
immunogenicity
inflammatory bowel disease
treatment discontinuation
vedolizumab
Journal
Journal of gastroenterology and hepatology
ISSN: 1440-1746
Titre abrégé: J Gastroenterol Hepatol
Pays: Australia
ID NLM: 8607909
Informations de publication
Date de publication:
Jul 2019
Jul 2019
Historique:
received:
04
10
2018
revised:
17
12
2018
accepted:
18
12
2018
pubmed:
28
12
2018
medline:
30
1
2020
entrez:
28
12
2018
Statut:
ppublish
Résumé
The pivotal GEMINI trials reported low immunogenicity of vedolizumab. However, anti-vedolizumab antibodies (AVA) are frequently underestimated because most assays are not drug-tolerant and unable to detect antidrug antibodies while there is drug in the circulation. This study aimed to explore which antidrug antibody assay is best suited to detect AVA and investigated immunogenicity of vedolizumab in inflammatory bowel disease (IBD) patients discontinuing vedolizumab therapy. A drug-tolerant affinity capture elution (ACE) assay was developed for the measurement of AVA in the presence of vedolizumab and compared with the previously established drug-resistant and drug-sensitive assays. Vedolizumab and AVA were measured at week 6, at the last infusion, and 12-20 weeks after treatment discontinuation in a cohort of 40 vedolizumab-treated IBD patients who stopped treatment due to primary non-response, loss of response, or adverse events. The drug-tolerant ACE assay could detect AVA in samples that the drug-resistant and drug-sensitive assays were unable to. Using the drug-tolerant ACE assay, 3 (8%) out of 40 vedolizumab-treated IBD patients who discontinued therapy were AVA positive at week 6, whereas no AVA were detected at the last infusion nor after treatment discontinuation. Primary non-responders had numerically lower median vedolizumab concentrations at week 6 compared with patients with loss of response (20.3 vs 30.7 μg/mL, respectively, P = 0.0570). Immunogenicity of vedolizumab is not the driving force of treatment failure, and AVA do not increase upon treatment discontinuation in vedolizumab-treated IBD patients. Underexposure during induction might partially be responsible for primary non-response.
Sections du résumé
BACKGROUND AND AIM
OBJECTIVE
The pivotal GEMINI trials reported low immunogenicity of vedolizumab. However, anti-vedolizumab antibodies (AVA) are frequently underestimated because most assays are not drug-tolerant and unable to detect antidrug antibodies while there is drug in the circulation. This study aimed to explore which antidrug antibody assay is best suited to detect AVA and investigated immunogenicity of vedolizumab in inflammatory bowel disease (IBD) patients discontinuing vedolizumab therapy.
METHODS
METHODS
A drug-tolerant affinity capture elution (ACE) assay was developed for the measurement of AVA in the presence of vedolizumab and compared with the previously established drug-resistant and drug-sensitive assays. Vedolizumab and AVA were measured at week 6, at the last infusion, and 12-20 weeks after treatment discontinuation in a cohort of 40 vedolizumab-treated IBD patients who stopped treatment due to primary non-response, loss of response, or adverse events.
RESULTS
RESULTS
The drug-tolerant ACE assay could detect AVA in samples that the drug-resistant and drug-sensitive assays were unable to. Using the drug-tolerant ACE assay, 3 (8%) out of 40 vedolizumab-treated IBD patients who discontinued therapy were AVA positive at week 6, whereas no AVA were detected at the last infusion nor after treatment discontinuation. Primary non-responders had numerically lower median vedolizumab concentrations at week 6 compared with patients with loss of response (20.3 vs 30.7 μg/mL, respectively, P = 0.0570).
CONCLUSIONS
CONCLUSIONS
Immunogenicity of vedolizumab is not the driving force of treatment failure, and AVA do not increase upon treatment discontinuation in vedolizumab-treated IBD patients. Underexposure during induction might partially be responsible for primary non-response.
Substances chimiques
Antibodies
0
Antibodies, Monoclonal, Humanized
0
Biomarkers
0
Gastrointestinal Agents
0
vedolizumab
9RV78Q2002
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1175-1181Subventions
Organisme : Fonds Wetenschappelijk Onderzoek
ID : Personal grant NV/ FWO-SB 1S12318N
Organisme : Fonds Wetenschappelijk Onderzoek
ID : TBM Grant T003716N
Organisme : Research Foundation-Flanders (FWO)
ID : T003716N
Informations de copyright
© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.