Verdon Christine, Vande Casteele Niels, Heron Valérie, Germain Pascale, Afif Waqqas
McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
Department of Medicine, University of California San Diego, La Jolla, California, USA.
J Can Assoc Gastroenterol. 2020 Mar 31;4(2):73-77. doi: 10.1093/jcag/gwaa003. eCollection 2021 Apr.
Data on the association of ustekinumab (UST) drug concentrations and clinical outcomes are conflicting. We assessed serum UST drug and anti-UST antibody concentrations using three commercially available assays.
Sixty-one blood samples were analyzed for serum UST drug and anti-UST antibody concentrations using three assays: one homogeneous mobility shift assay (HMSA, Prometheus, Assay A), and two enzyme-linked immunosorbent assays (ELISA; Progenika, Dynacare, Assay B and Theradiag, Assay C).
The median (IQR) serum UST concentrations for the three assays were: Assay A 7.50 (5.35 to 12.88) µg/mL, Assay B 4.02 (2.46 to 6.95) µg/mL and Assay C 4.35 (2.62 to 7.50) µg/mL. A Kruskal-Wallis test confirmed a statistically significant difference between the different assays, X(2) = 30.606, < 0.001. Linear regression showed near twofold increased difference in the absolute drug concentrations between the HMSA and either ELISA. Linear quantitative correlation was observed for all three assays ( = 0.836 for A versus B, = 0.792 for A versus C, = 0.936 for B versus C; < 0.01). The intraclass correlation coefficient (ICC) between assay A and B was 0.649 (95% confidence interval [CI] -0.208 to 0.874); assay A and C was 0.671 (95% CI -0.165 to 0.878); and assay B and C was 0.958 (95% CI 0.928 to 0.975); < 0.001. No anti-UST antibodies were detected.
A good correlation was observed for serum UST drug concentrations and a good agreement was observed between the ELISA tests. However, agreement was poor between the HMSA and each ELISA tests. Clinical recommendations regarding drug concentrations should be based on assay type used.
关于优特克单抗（UST）药物浓度与临床结局之间关联的数据存在矛盾。我们使用三种市售检测方法评估了血清UST药物和抗UST抗体浓度。
使用三种检测方法对61份血样进行血清UST药物和抗UST抗体浓度分析：一种均相迁移率变动分析（HMSA，Prometheus公司，检测方法A），以及两种酶联免疫吸附测定（ELISA；Progenika公司、Dynacare公司，检测方法B和Theradiag公司，检测方法C）。
三种检测方法的血清UST浓度中位数（四分位间距）分别为：检测方法A 7.50（5.35至12.88）μg/mL，检测方法B 4.02（2.46至6.95）μg/mL，检测方法C 4.35（2.62至7.50）μg/mL。Kruskal-Wallis检验证实不同检测方法之间存在统计学显著差异，X(2)=30.606，P<0.001。线性回归显示，HMSA与任一ELISA之间的绝对药物浓度差异增加近两倍。所有三种检测方法均观察到线性定量相关性（检测方法A与B之间r=0.836，检测方法A与C之间r=0.792，检测方法B与C之间r=0.936；P<0.01）。检测方法A与B之间的组内相关系数（ICC）为0.649（95%置信区间[CI] -0.208至0.874）；检测方法A与C之间为0.671（95%CI -0.165至0.878）；检测方法B与C之间为0.958（95%CI 0.928至0.975）；P<0.001。未检测到抗UST抗体。
观察到血清UST药物浓度之间具有良好相关性，且ELISA检测之间具有良好一致性。然而，HMSA与各ELISA检测之间的一致性较差。关于药物浓度的临床建议应基于所使用的检测方法类型。
