Therapeutic Drug Monitoring of Everolimus: Comparability of Concentrations Determined by 2 Immunoassays and a Liquid Chromatography Tandem Mass Spectrometry Method.

Background: Therapeutic drug monitoring is recommended to guide therapy with the immunosuppressant everolimus (EVL) in solid organ transplantation to prevent rejections and to limit toxicity. For therapeutic drug monitoring, predose EVL concentrations are measured in whole blood mainly by liquid chromatography tandem mass spectrometry (LC-MS/MS). In addition, 2 immunoassays [Quantitative Microsphere System (QMS) EVL and Elecsys EVL] are commercially available. The aim of this study was to evaluate the comparability of EVL results determined with the 2 immunoassays and a validated LC-MS/MS test using samples from kidney, liver, and heart transplant (KT, LT, and HT, respectively) recipients.

Methods: Analysis of predose samples from KT (n = 56), LT (n = 60), and HT (n = 59) recipients, obtained at variable time points after transplantation, was performed by LC-MS/MS and with the 2 immunoassays. The QMS EVL assay was applied on Dimension Xpand Plus and the Elecsys EVL assay on cobas e 411 analyzer. Results were compared by the Spearman's rank correlation coefficient, unbiased Passing and Bablok linear regression test, and Bland-Altman plot.

Results: Results generated with both immunoassays correlated well with those of LC-MS/MS. An overestimation of EVL concentrations by the Elecsys EVL compared with LC-MS/MS was observed (mean bias: 34.2%). Using the QMS EVL, a small but significant negative deviation (mean bias: -8.0%) was found. Looking at KT, HT, and LT samples separately, the bias to LC-MS/MS seen with the Elecsys EVL was similar. With the QMS EVL, the best agreement was observed with the KT samples followed by LT and HT.

Conclusions: Results generated by the 3 methods are not consistent regarding their diagnostic value. Both laboratories and manufacturers should take care to inform their costumers about the between-method differences to avoid misinterpretation of the results in clinical practice.