P0532 - Clinical Utility of Homogenous Mobility Shift Assay Method for Vedolizumab Bioactivity and Precision Dosing in Inflammatory Bowel Diseases

Judson McFarland, BS, Hong Law, BS, Owen McLachlan, BS, Anjali Jain, PhD, Patricia Hughes, BS, Thierry Dervieux, PhD, PharmD
Prometheus Laboratories, Inc., San Diego, CA

Introduction: Therapeutic drug monitoring (TDM) of Vedolizumab (VDZ) can improve outcomes in inflammatory bowel disease (IBD). Our objective was to evaluate the performance characteristics of the Homogenous Mobility Shift Assay (HMSA) method as a precision dosing tool for VDZ in IBD.

Methods: Testing was conducted in a clinical laboratory accredited by the American College of Pathologists using liquid chromatography size exclusion HMSA. The evaluated performance characteristics consisted of linearity, accuracy, precision, specificity, and lower limit and upper limit of quantification using spiked human serum. Following validation and implementation in the clinical laboratory, estimates of VDZ exposure associated with higher likelihood (Odds Ratio = 4.0) of endoscopic remission ( >10.7 μg/mL) was assessed using de-identified samples, as established during clinical validation (J Crohns Colitis 2019 13:963-969).

Results: The reportable range was 1.6 μg/mL LLOQ (precision = 10.6% CV; accuracy = 89.0% recovery) to 40 µg/mL ULOQ: (precision = 5.3% CV; accuracy = 99.1% recovery). Intra-day, inter-day precision (CV) and accuracy (% recovery) across the reportable range were 3.4%, 6.9% and 100.7%, respectively. The HMSA method was specific with interfering substances yielding < 8% error. The method was linear (slope=0.978; intercept=-0.016; R²=0.999). In practice, over a one-year period (01/2020 to 12/2020), VDZ levels from 1695 specimens from IBD patients receiving 300 mg VDZ every 8 weeks yielded a mean VDZ of 14.8 µg/mL (SD=12.9 µg/mL) with 57% of patients presenting exposure above the threshold ( >10.7 μg/mL). As presented in Figure 1, inter-dose interval shortening from every 8 weeks (n=1695) to every 6 weeks (n=299) and 4 weeks (n=525) resulted in higher likelihood of VDZ levels above the threshold.

Discussion: Our data indicate the VDZ-HMSA method is validated to report VDZ concentrations with acceptable consistency to be used for optimal TDM dosing relative to the endoscopic remission threshold.


Figure: VDZ Exposure in Relation to Interval Dosing and ICD-10 Diagnosis


Disclosures:
Judson McFarland indicated no relevant financial relationships.
Hong Law indicated no relevant financial relationships.
Owen McLachlan indicated no relevant financial relationships.
Anjali Jain indicated no relevant financial relationships.
Patricia Hughes indicated no relevant financial relationships.
Thierry Dervieux indicated no relevant financial relationships.


Judson McFarland, BS, Hong Law, BS, Owen McLachlan, BS, Anjali Jain, PhD, Patricia Hughes, BS, Thierry Dervieux, PhD, PharmD. P0532 - Clinical Utility of Homogenous Mobility Shift Assay Method for Vedolizumab Bioactivity and Precision Dosing in Inflammatory Bowel Diseases, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.