Microsampling Assays for Immunosuppressive Drugs in Children - PROJECT SUMMARY Immunosuppressive therapy is the foundation of successful long-term outcomes after solid organ and bone marrow/stem cell transplants and as a treatment for various auto-inflammatory conditions, including rheumatoid arthritis, eczema, psoriasis, Crohn's disease, and nephrotic syndrome in adults and children. The optimal blood concentrations of these drugs are critical to minimize toxicity and to prevent rejection in transplant recipients. These drugs require frequent and often life-long therapeutic drug monitoring (TDM) to ensure that dosing maintains the optimal therapeutic concentrations. Current TDM (clinical standard) used for the dosing guidance of cyclosporine A (CYA), tacrolimus (TAC), and sirolimus (SIR) are derived from whole blood immunoassays or liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays. This requires immunosuppressed individuals to go to outpatient laboratories for phlebotomy, potentially increasing their risk of acquiring infections. The development of an easy-to-use, small volume, blood sampling approach can facilitate home sampling and reduce the burden on pediatric patients and their families. Current TDM requires 0.5 to 1.0 mL of whole blood, typically via phlebotomy. Volumetric absorptive microsampling (VAMS) with Mitra devices or Tasso-M20 devices allows for the collection of a fixed small volume of blood (e.g., 20 µL) from a capillary needle without the need for phlebotomy. Clinical validation studies for CYA, TAC, and SIR with Mitra devices in adults were recently reported. While one study showed a good correlation for TAC analysis, the other study showed inconsistency with sample collection using Mitra devices. Therefore, the potential utility of Mitra devices for routine TDM is uncertain. FDA-approved Tasso-M20 devices allow for an accurate, precise, painless, and consistent collection of a fixed small volume of blood. However, the implementation of Tasso-M20 devices into the clinical setting for TDM requires both analytical and clinical validation. The objectives of the proposed Microsampling Assays for Immunosuppressive Drugs in childrEN (MAIDEN) study is to: 1) validate Tasso-M20 VAMS LC-MS/MS assays for CYA, TAC, and SIR, 2) evaluate in vitro stability of CYA, TAC, and SIR in Tasso-M20 devices under the conditions of shipping and storage, 3) clinically validate Tasso-M20 VAMS LC-MS/MS assays for CYA, TAC, and SIR against current venous whole blood TDM immunoassays in pediatric patients, and 4) confirm the stability of CYA, TAC, and SIR in Tasso-M20 VAMS clinical samples under the conditions of shipping and storage. If successful, this research will enable the use of the microsampling method for TDM in the clinical setting (obviating the need for invasive phlebotomy), and at home (reducing the burden on families to bring the immunosuppressed children out of the home for routine TDM), and revolutionize remote sampling for TDM of immunosuppressant drugs in children and adults.
