036: Clinical Validation of Two Volumetric Absorptive Microsampling Devices to Support Home-based Therapeutic Drug Monitoring of Immunosuppression in Kidney Transplantation

Statement of Purpose: Precision dosing of immunosuppressive drugs is critical to minimize toxicity and prevent rejection after solid organ transplantation. Currently, dosing empirically balances efficacy and toxicity with tacrolimus trough concentrations. Enhanced therapeutic drug monitoring (TDM) using the area under the curve (AUC), offers a greater understanding of total drug exposure and is associated with improved outcomes. However, AUC is not routinely used because it is impractical, requiring repeated phlebotomy samples over several hours. Home-based sampling employing volumetric absorptive microsamples (VAMS) could facilitate the estimation of AUC to guide precision dosing and reduce patient burden. We aimed to simultaneously quantify tacrolimus and mycophenolic acid from two VAMS devices, the Tasso-M20 and Mitra. Further, we explored the patient-reported experience of the VAMS devices in kidney transplant recipients.

Description of Methods & Materials: Multiple sampling, extraction, and LC-MS/MS methods were trialed to identify the most accurate methods by comparing the analyte peak areas and coefficient of variation to the US FDA Bioanalytical Method Validation acceptance criteria. Capillary whole blood samples were then obtained via the Tasso-M20 and Mitra devices and compared to paired venous whole blood specimens from kidney transplant recipients receiving tacrolimus and mycophenolate. The comparison was made using Passing-Bablok regression. Bland-Altman plots were used to assess agreement and estimate bias. To examine perceptions and preferences, participants completed a questionnaire that included items such as a pain assessment, the system useability scale, and measures of acceptability and feasibility.

Data & Results: For tacrolimus, the results showed no significant differences between methods (Figure 1, panel A, bottom). For mycophenolic acid, a strong linear relationship was found between methods (Figure 1, panel A, top left), but the slope was significantly less than 1. When applying the Bland-Altman plot to study method agreement (Figure 1, panel A, top right), the concentrations were systematically lower in VAMS samples compared to serum. The results were similar for both the Tasso-M20 and Mitra devices. Additional samples are being collected to validate a correction factor to account for the expected dilution observed in whole blood compared to serum.
Most patients reported little or no pain for all sampling techniques but reported lower pain with the Tasso-M20 device. Participants were more willing to collect additional samples for AUC estimated with the VAMS devices than venipuncture (Figure 1, panel B). The usability score was higher for the Tasso-M20 compared to the Mitra device. When directly asked for a preference between Tasso-M20, Mitra, and venipuncture, all participants selected the Tasso-M20.

Interpretation, Conclusion or Significance: Method agreement between venous and capillary blood was demonstrated for tacrolimus. However, mycophenolic acid demonstrated proportional bias supporting the need for a correction factor to obtain agreement with serum or plasma. Participants viewed sample collection using VAMS as useable, acceptable, and feasible, with a preference for the Tasso-M20 device. The Tasso-M20 device is currently undergoing further study to evaluate the home collection of abbreviated AUCs

Disclosures: No disclosures or conflicts of interest.