Monitoraggio terapeutico dei farmaci immunosoppressori: confronto tra metodiche

BACKGROUND: Therapeutic drug monitoring (TDM) of Immunosuppressive drugs (ISD) is crucial to the success of organ transplantation. Considering this background, the analytical performance of the assays for the ISD dosing performed on Dimension EXL 200 platform and on the currently in use analyzers for ISD were compared. We evaluated the possible performance improvement due to pre-treatment standardization, consolidation of TDM on a single platform and TAT reduction. METHODS: We evaluated our conventional assays i.e., Abbott CMIA™ cyclosporine, tacrolimus and sirolimus (on EDTA-anticoagulated whole blood) performed on Architect i1000SR platform, ThermoFisher Scientific QMS™ everolimus (K2EDTA-whole blood) on CDX90 analyzer and ThermoFisher Scientific CEDIA™ mycophenolic acid (on plasma/serum) on ILab Taurus, in comparison with the equivalent Siemens ACMIA™ (cyclosporine, tacrolimus, sirolimus, everolimus) and Petinia™ (mycophenolic acid) Dimension EXL 200 assays. For the comparison, a total of 450 consecutive samples were processed and results were statistically compared. Within-run and within-laboratory precision on Dimension were evaluated using quality control materials. RESULTS: Within-run and within-laboratory CVs% are ≤10% for all the Siemens assays, according to the IATDMCT guidelines for ISD monitoring. The regression analysis of tacrolimus, cyclosporine, sirolimus and mycophenolic acid data show good linear correlation (r≥0.96). Bland-Altman plots reveal a positive percent bias for cyclosporine (+19.9%), sirolimus (+22.8%) and mycophenolic acid (+9.65%) while tacrolimus assay shows a slight negative absolute bias (-0.23 ng/mL). Everolimus assay shows the weakest correlation between methods (r=0.95) and Bland-Altman plots show an increasing absolute bias (+3.1 ng/mL) in association with a positive 48.8% bias which tends to decrease with increasing everolimus concentrations. CONCLUSIONS: Our findings suggest that the automated assays lead to workflow improvement giving an edge to Dimension analyzer as compared to other platforms. Tacrolimus, cyclosporine, sirolimus and mycophenolic acid assays demonstrated good precision and good correlation between methods and we also quite clearly managed to identify the bias type for these assays. Everolimus assay shows the weakest correlation between methods and the simultaneous presence of two different types of bias.