Immunogenicity is not the driving force of treatment failure in vedolizumab-treated inflammatory bowel disease patients.
J Gastroenterol Hepatol. 2018 Dec 27;:
Authors: Van den Berghe N, Verstockt B, Tops S, Ferrante M, Vermeire S, Gils A
BACKGROUND AND AIM: The pivotal GEMINI trials reported low immunogenicity of vedolizumab. However, anti-vedolizumab antibodies (AVA) are frequently underestimated since most assays are not drug-tolerant and unable to detect anti-drug antibodies while there is drug in the circulation. This study aimed to explore which anti-drug antibody assay is best suited to detect AVA and investigated immunogenicity of vedolizumab in inflammatory bowel disease (IBD) patients discontinuing vedolizumab therapy.
METHODS: A drug-tolerant affinity capture elution (ACE) assay was developed for the measurement of AVA in the presence of vedolizumab and compared to the previously established drug-resistant and drug-sensitive assay. 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: The drug-tolerant ACE assay could detect AVA in samples that the drug-resistant and drug-sensitive assay were unable to. Using the drug-tolerant ACE assay, three (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 to patients with loss of response (20.3 vs 30.7 μg/ml, respectively, p = 0.0570).
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.
PMID: 30589948 [PubMed – as supplied by publisher]