P649 Comparison of the KU Leuven ustekinumab concentration assay and the antibodies-to-ustekinumab assay with assays developed at Janssen R&D and used in clinical studies of IBD patients

Abstract

Monitoring ustekinumab (UST) concentrations and antibodies-to ustekinumab (ATU) during IBD treatment may allow more informed decisions in assessing exposure/response and appropriate dosing. To aid in interpreting results in the context of Janssen's published UST results, the reliability of different assays measuring UST and ATU was compared with those from Janssen. This abstract reports the comparison of the UST and ATU assays from KU Leuven (KUL, Leuven, Belgium) and Janssen (JRD, Spring House, PA, USA). Results from the other companies will be reported at a later time. Blinded test samples, prepared by JRD, were sent to the KUL and JRD labs for UST and ATU assessments. Results were reported to JRD for integrated analyses. All assays were tested for specificity, selectivity, accuracy and precision. ATU assays were evaluated for sensitivity, drug interference, and potential interference of IL-12. UST and ATU were tested at KUL using Enzyme-Linked Immunosorbent Assays (ELISA), and at JRD using Meso Scale Discovery electrochemiluminescent immunoassays (ECLIA). The lower limit of quantification was 0.25 μg/ml for the KUL UST concentration assay and 0.1688 μg/ml for the JRD UST concentration assay. Strong agreement was observed between the JRD and KUL UST assays. Specificity was demonstrated when both UST assays accurately detected 1.0 or 10.0 μg/ml of UST, but did not detect other human monoclonal antibodies (mAb). The presence of ATU titres up to 200 or IL-12 concentrations up to 100 pg/ml did not interfere with the UST assessment in either assay. Accuracy was confirmed by three independent measurements of UST-spiked (0.06–32 μg/ml) human psoriasis (PSO) sera and with UST measured in sera from UST-treated PSO patients. Both UST assays were precise, as determined by inter-occasion reproducibility. Strong agreement was observed between the JRD and KUL ATU assays. Both ATU assays specifically detected anti-UST antibodies; results were not affected by high titre antibodies against other human mAb. The KUL ATU assay was not drug tolerant, while the JRD ATU assay demonstrated drug tolerance to 8.0 μg/ml of UST. Concentrations of free or bound IL-12 (≤100 pg/ml) did not interfere with ATU detection in either assay. Both ATU assays were reproducible. Our study results indicate that the KUL UST concentration and ATU assays strongly correlate with those from JRD. The substantial agreement between the KUL and JRD assays may provide support to clinicians in their use of these assays, and for understanding their patients' UST and ATU result relative to published data from clinical studies of UST.