Abstract
Vedolizumab immunogenicity has been assessed using an enzyme-linked immunosorbent assay (ELISA) with a ~ 0.5 μg/mL drug interference, which may underestimate on-drug immunogenicity. We aimed to compare immunogenicity results between ELISA and the new drug-tolerant electrochemiluminescence (ECL) assay (and the two versions of neutralizing assays, drug-sensitive versus drug-tolerant). The ECL assay drug tolerance is ~ 100 times higher than that of the ELISA (≥ 50 μg/mL vs. 0.5 μg/mL with a 500 ng/mL positive control), and assay sensitivity is < 5 ng/mL for both assays. Vedolizumab immunogenicity was assessed in 2000 GEMINI 1 and 2 patients originally tested by ELISA and retested by ECL assay. Anti-drug antibody (ADA) impact on infusion-related reactions and pharmacokinetics (PK) was examined using descriptive statistics and population PK analyses. By ECL assay, 6% (86/1427) of patients treated with vedolizumab as induction and maintenance therapy tested ADA-positive. Of these, 20 patients were persistently positive and 56 had neutralizing antibodies. By ELISA, 4% (56/1434) of these patients were ADA-positive, 9 were persistently positive, and 33 had neutralizing antibodies. Among 61 patients with infusion-related reactions, 6 (10%) were ADA-positive (2 persistently positive) by ECL assay. By ELISA, 3 (5%) patients were both ADA-positive and persistently positive. Most results (96%) were similar with both assays. In the updated population PK model, ADA-positive status was estimated to increase vedolizumab linear clearance by a factor of 1.10 (95% credible interval 1.03–1.17), which is consistent with previous reports. The impact of ADA on safety and PK modeling remained generally consistent using either ELISA or ECL assay. ClinicalTrials.gov: NCT00783718 and NCT00783692
Highlights
Biologic therapies can trigger the formation of anti-drug antibodies (ADAs), an immune reaction identified as a contributor to loss of therapeutic response [1]
Among the 1427 patients who received vedolizumab continuously during induction and maintenance and had an immunogenicity sample available, 86 (6%) were ADA-positive with the ECL assay at any time during or after study treatment; 66 were transiently ADA-positive and 20 persistently ADApositive
With the enzyme-linked immunosorbent assay (ELISA), 56 of 1434 patients (4%) who received vedolizumab continuously as part of GEMINI 1 or GEMINI 2 were ADA-positive
Summary
Biologic therapies can trigger the formation of anti-drug antibodies (ADAs), an immune reaction identified as a contributor to loss of therapeutic response [1]. As such, it is Statement of Prior Presentation This manuscript has not been previously published and is not under consideration in the same or substantially similar form in any other peer-reviewed media. It is Statement of Prior Presentation This manuscript has not been previously published and is not under consideration in the same or substantially similar form in any other peer-reviewed media These data were partially presented at the 2018 Advances in Inflammatory Bowel Diseases (AIBD) Annual Conference (Abstract P010). Pivotal vedolizumab phase 3, randomized, placebo-controlled, double-blind studies included GEMINI 1 (NCT00783718) in UC and GEMINI 2 (NCT00783692) and 3 (NCT01224171) in CD [3,4,10]
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