P717 Comparison of two different techniques to assess vedolizumab trough levels in adult patients with IBD

Abstract

Vedolizumab (VLZ), an α4β7 integrin antagonist, is a therapeutic monoclonal antibody recently approved for use in moderate-to-severe Crohn's disease (CD) and ulcerative colitis (UC). Since loss of response to VLZ in patients with inflammatory bowel disease is likely due to low drug serum levels, modifying dosage on the basis of VLZ drug concentrations may improve patient outcomes. However, there are limited data on the diagnostic accuracy and utility of currently available assays for measuring VLZ levels. In this study, our aim was to compare serum VLZ concentrations using two different techniques. Up to November 2017, we assessed serum VLZ concentrations in 63 IBD patients (30 CD/33 UC). Serum VLZ trough levels were assessed using a sandwich principle-based enzyme-linked immunosorbent assay (ELISA; Berger et al., JCC 2017;11:S320) and an ultra-performance liquid chromatography (UPLC)-MS/MS system (Thermo Scientific, Waltham, MA, USA) with an H-ESI II ionisation source. Tryptic peptides for quantification were identified for VLZ using a selective reaction monitoring (SRM) mass spectrometry method (Christ et al. JCC 2016; 10: S380). VLZ trough levels were significantly lower in patients who experienced relapse compared with patients in remission, using both ELISA: 19.7 μg/ml vs. 33.9 μg/ml in CD (p = 0.002) and 15.6 μg/ml vs. 34.2 μg/ml in UC (p = 0.005) and LC-MS/MS: 12.3 μg/ml vs. 35.1 μg/ml in CD (p = 0.003) and 16.9 μg/ml vs. 36.2 μg/ml in UC (p = 0.004). There was a significant correlation between ELISA and LC-MS/MS VLZ trough levels at both week 48 (r = 0.691, p = 0.0003) and week 96 (r = 0.822, p = 0.0001). ELISA and LC-MS/MS are accurate methods to assess VLZ trough levels in both CD and UC patients and those who experience loss of response, offering effective and reliable tools for the monitoring and modification of individual treatment schedules. The preferential use of one of the two techniques should be based on local availability and the physician’s experience.