P010 Results from a new anti-vedolizumab antibody assay

Abstract

BACKGROUND: Immunogenicity was assessed in GEMINI I (NCT00783718) and II (NCT00783692) using an enzyme-linked immunosorbent assay (ELISA). 1,2 It was later determined that the presence of ∼0.5 μg/mL of vedolizumab interferes with the ELISA, which potentially might have underestimated on-drug immunogenicity. Therefore, a new acid dissociation electrochemiluminescence (ECL) anti-vedolizumab antibody (AVA) assay was developed with a drug tolerance of ≥50 μg/mL. In addition, a more drug-tolerant ECL assay was developed to quantify the ability of AVAs to neutralize vedolizumab (neutralizing assay). The current study reassessed vedolizumab immunogenicity using banked serum samples from GEMINI I and II with the ECL assays. METHODS: Positive or negative AVA status was determined according to the previous ELISA assay definitions, and overall AVA positivity was summarized using descriptive statistics. The effect of AVA on vedolizumab pharmacokinetics (PK) was assessed using a previously reported population PK model 1 that was updated with data from the ECL assay. Serum samples from 1,427 of 1,434 patients who received continuous treatment with vedolizumab for 52 weeks were available for reanalyses. Samples confirmed as AVA positive were further characterized using the neutralizing assay. RESULTS: With the ECL assay, 6% (86/1,427) of patients were AVA positive at any time during the study. Of these, 20 patients were considered persistently positive (confirmed AVA positive in ≥2 consecutive AVA samples) and 56 had neutralizing antibodies. With the ELISA, 4% (56/1,434) of patients were AVA positive at any time. Of these, 9 patients were considered persistently positive and 33 had neutralizing antibodies. 2 Parameter estimates, precision of PK structural parameters, interindividual and residual variabilities, and covariate effects (including AVA effects) were comparable between the previous and updated final population PK models. Therefore, inferences regarding the clinical relevance of covariates were also similar between the 2 PK models. In the updated PK model, AVA presence was estimated to increase vedolizumab linear clearance (CLL) by a factor of 1.10 (95% credible interval [CDI]: 1.03, 1.17), consistent with the previous final model where AVA was estimated to increase CLL by a factor of 1.12 (95% CDI: 1.05, 1.2). With the ECL assay, of the 61 patients who had an adverse event assessed by the investigator as an infusion-related reaction, 6 (10%) were AVA positive, 2 of whom were persistently positive. With the prior ELISA, 3 of 61 (5%) patients were AVA positive, all 3 of whom were persistently positive. 2 CONCLUSION(S): Vedolizumab immunogenicity rates and PK were similar between the ECL and ELISA assays. Compared to the ELISA assay, the ECL assay detected slightly more AVA-positive patients among patients with infusion reactions.