新西门子亲和铬介导免疫分析法依维莫司检测的分析性能及其与热定量微球系统在实体器官移植后患者常规治疗药物监测中的互换性。

Analytical Performance of the New Siemens Affinity Chrome-Mediated Immunoassay Everolimus Assay and Its Interchangeability With the Thermo Quantitative Microsphere System for Routine Therapeutic Drug Monitoring of Patients After Solid Organ Transplantation.

机构信息

Department of Experimental Medicine, Policlinico Umberto I, "Sapienza" University, Rome, Italy.

出版信息

Ther Drug Monit. 2023 Apr 1;45(2):217-222. doi: 10.1097/FTD.0000000000001009.

DOI:10.1097/FTD.0000000000001009

PMID:36920504

Abstract

BACKGROUND

A new homogeneous affinity chrome-mediated immunoassay (ACMIA) "EVRO" from Siemens Healthcare was evaluated for therapeutic drug monitoring of everolimus (EVL) with automated sample pretreatment and compared with quantitative microsphere system (QMS) "EVER" from Thermo Fisher Scientific.

METHODS

Imprecision, inaccuracy, and limit of quantitation (LoQ) of ACMIA/EVRO were verified using both hemolysate quality control (QC) samples and pooled whole blood specimens. The interchangeability of methods and the agreement of results were analyzed using 72 specimens (from 38, 30, and 4 kidney, liver, and lung transplant recipients, respectively).

RESULTS

Within-run imprecision ranged within %CV = 2.81-2.53 with pooled whole blood specimens and within %CV = 2.88-2.53 with QCs; total imprecision with QCs was within %CV = 2.14-1.51. Inaccuracy with value assigned QC was %△ = 5.36 at the 5.6 ng/mL level and %△ = 5.56 at the 11.7 ng/mL level. LoQ was 0.93 ng/mL (%CV = 10). Passing-Bablok regression showed a constant bias of 0.679 ng/mL (95% CI: 0.216-1.026) and a proportional bias of 1.326 (95% CI: 1.240-1.425). Bland-Altman analysis showed 5/72 (6.9%) paired differences exceeding the limits of agreement and 1/72 (1.4%) paired differences exceeding 1.96 SD to a combined bias of 39.9% after detrending.

CONCLUSIONS

ACMIA/EVRO shows satisfactory analytical performances that comply with recommendations, but it does not fulfill requirements for interchangeability with QMS/EVER. Particularly, this new assay using sirolimus-specific antibody shows a sizable proportional bias versus the more specific comparator, which may be because of EVL metabolites. This is supported by the lack of agreement for individual differences in most samples collected at the peak concentration (C2). Therefore, further evidence is needed to support the transition of EVL level monitoring from QMS/EVER to ACMIA/EVRO without making extensive changes to both reference interval and patient's baseline.

摘要

背景

西门子医疗的新型均相亲和铬介导免疫分析（ACMIA）“EVRO”用于依维莫司（EVL）的治疗药物监测，具有自动化样本预处理功能，并与赛默飞世尔科技的定量微球系统（QMS）“EVER”进行了比较。

方法

使用溶血质控（QC）样本和混合全血标本验证 ACMIA/EVRO 的精密度、不准确度和定量下限（LoQ）。使用 72 份标本（分别来自 38 例、30 例和 4 例肾、肝和肺移植受者）分析方法的互换性和结果的一致性。

结果

混合全血标本的批内精密度在 %CV 为 2.81-2.53 范围内，QC 的批内精密度在 %CV 为 2.88-2.53 范围内；QC 的总不精密度在 %CV 为 2.14-1.51 范围内。QC 值分配的不准确度为 5.6ng/mL 水平的 %△=5.36 和 11.7ng/mL 水平的 %△=5.56。LoQ 为 0.93ng/mL（%CV=10）。Passing-Bablok 回归显示，固定偏倚为 0.679ng/mL（95%CI：0.216-1.026），比例偏倚为 1.326（95%CI：1.240-1.425）。Bland-Altman 分析显示，5/72（6.9%）对配对差异超过了可接受范围，1/72（1.4%）对配对差异超过了 1.96SD，导致总偏倚为 39.9%，去趋势后。

结论

ACMIA/EVRO 显示出符合建议的满意分析性能，但不符合与 QMS/EVER 互换性的要求。特别是，这种使用西罗莫司特异性抗体的新测定法与更具特异性的比较剂相比，显示出相当大的比例偏差，这可能是由于依维莫司代谢物所致。这一点得到了大多数在峰值浓度（C2）时采集的样本中个体差异缺乏一致性的支持。因此，需要进一步的证据来支持在不广泛改变参考区间和患者基线的情况下，将 EVL 水平监测从 QMS/EVER 过渡到 ACMIA/EVRO。