Therapeutic Drug Monitoring of Infliximab and Adalimumab through Concentration and Anti-Drug Antibodies Assessment; Comparison of Sanquin Diagnostics and Theradiag Assays.

IF 3 Q3 IMMUNOLOGY

Antibodies Pub Date : 2024-09-05 DOI:10.3390/antib13030073

Wim H M Vroemen, Shakira S Agata, Joyce J B C van Beers, Jan G M C Damoiseaux

{"title":"Therapeutic Drug Monitoring of Infliximab and Adalimumab through Concentration and Anti-Drug Antibodies Assessment; Comparison of Sanquin Diagnostics and Theradiag Assays.","authors":"Wim H M Vroemen, Shakira S Agata, Joyce J B C van Beers, Jan G M C Damoiseaux","doi":"10.3390/antib13030073","DOIUrl":null,"url":null,"abstract":"Background: Therapeutic drug monitoring of biological Tumor Necrosis Factor (TNF)-alpha inhibitors is of critical importance. In this study, the performance of practically advantageous chemiluminescent immunoassays of Theradiag, assessing Infliximab and Adalimumab serum concentrations and anti-drug antibodies (ADA) against these biologics, were compared to the Enzyme-Linked Immuno-Sorbent Assays (ELISAs) from Sanquin Diagnostics.Methods: Leftover serum samples (n = 80 for each parameter) from patients treated with Infliximab or Adalimumab were collected. Correlation and agreement analyses for serum concentration and ADAs, respectively, were performed. Both Theradiag ADA assays, an assay targeting both free and bound ADAs and an assay targeting solely free ADAs, were investigated and compared to the Sanquin Diagnostics ADA assay, targeting both free and bound ADAs.Results: Strong positive correlations were observed between the biologic concentration assessment of Infliximab (Spearman's Rho = 0.91) and Adalimumab (Spearman's Rho = 0.94). However, there appeared to be significant bias in the Theradiag assay when compared to Sanquin (Infliximab median (Confidence Interval (CI)) = 2.1 (1.7-2.6) µg/mL; Adalimumab median (CI) = 0.8 (0.5-0.9) µg/mL). Agreement analyses showed moderate to good agreement for the Theradiag and Sanquin Diagnostics ADA assays, when detecting both free and bound ADAs, for Infliximab (Cohen's k = 0.717) and Adalimumab (Cohen's k = 0.802). In contrast, the Theradiag ADA assay detecting solely free ADAs had zero to poor agreement for Infliximab (Cohen's k = 0.458) and Adalimumab (Cohen's k = 0.119), respectively.Conclusions: This study demonstrated strong correlations and good agreement between the Theradiag and Sanquin Diagnostics assays measuring Infliximab and Adalimumab serum concentrations and ADAs, both free and bound, against these biologics. Discordance analyses showed significantly decreased drug concentrations in the solely free assays, indicating that the combined detection of free and bound ADAs better aligns with drug levels.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":"13 3","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417797/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Antibodies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/antib13030073","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Therapeutic drug monitoring of biological Tumor Necrosis Factor (TNF)-alpha inhibitors is of critical importance. In this study, the performance of practically advantageous chemiluminescent immunoassays of Theradiag, assessing Infliximab and Adalimumab serum concentrations and anti-drug antibodies (ADA) against these biologics, were compared to the Enzyme-Linked Immuno-Sorbent Assays (ELISAs) from Sanquin Diagnostics.

Methods: Leftover serum samples (n = 80 for each parameter) from patients treated with Infliximab or Adalimumab were collected. Correlation and agreement analyses for serum concentration and ADAs, respectively, were performed. Both Theradiag ADA assays, an assay targeting both free and bound ADAs and an assay targeting solely free ADAs, were investigated and compared to the Sanquin Diagnostics ADA assay, targeting both free and bound ADAs.

Results: Strong positive correlations were observed between the biologic concentration assessment of Infliximab (Spearman's Rho = 0.91) and Adalimumab (Spearman's Rho = 0.94). However, there appeared to be significant bias in the Theradiag assay when compared to Sanquin (Infliximab median (Confidence Interval (CI)) = 2.1 (1.7-2.6) µg/mL; Adalimumab median (CI) = 0.8 (0.5-0.9) µg/mL). Agreement analyses showed moderate to good agreement for the Theradiag and Sanquin Diagnostics ADA assays, when detecting both free and bound ADAs, for Infliximab (Cohen's k = 0.717) and Adalimumab (Cohen's k = 0.802). In contrast, the Theradiag ADA assay detecting solely free ADAs had zero to poor agreement for Infliximab (Cohen's k = 0.458) and Adalimumab (Cohen's k = 0.119), respectively.

Conclusions: This study demonstrated strong correlations and good agreement between the Theradiag and Sanquin Diagnostics assays measuring Infliximab and Adalimumab serum concentrations and ADAs, both free and bound, against these biologics. Discordance analyses showed significantly decreased drug concentrations in the solely free assays, indicating that the combined detection of free and bound ADAs better aligns with drug levels.

查看原文本刊更多论文

通过浓度和抗药抗体评估监测英夫利昔单抗和阿达木单抗的治疗用药；Sanquin Diagnostics 和 Theradiag 检测法的比较。

背景：肿瘤坏死因子（TNF）-α 生物抑制剂的治疗药物监测至关重要。本研究比较了 Theradiag 公司的化学发光免疫测定与 Sanquin Diagnostics 公司的酶联免疫吸附测定 (ELISAs) 的性能，前者具有实际优势，可评估英夫利昔单抗和阿达木单抗血清浓度以及针对这些生物制剂的抗药性抗体 (ADA)：方法：收集接受英夫利西单抗或阿达木单抗治疗的患者的剩余血清样本（每种参数的样本数均为 80）。分别对血清浓度和 ADA 进行相关性和一致性分析。研究了Theradiag ADA测定（一种针对游离和结合ADA的测定）和Sanquin Diagnostics ADA测定（一种只针对游离ADA的测定），并与Sanquin Diagnostics ADA测定（针对游离和结合ADA）进行了比较：在英夫利西单抗（Spearman's Rho = 0.91）和阿达木单抗（Spearman's Rho = 0.94）的生物浓度评估之间观察到了很强的正相关性。然而，与Sanquin相比，Theradiag测定似乎存在明显偏差（英夫利昔单抗中位数（置信区间（CI））= 2.1 (1.7-2.6) µg/mL；阿达木单抗中位数（CI）= 0.8 (0.5-0.9) µg/mL）。一致性分析表明，Theradiag 和 Sanquin Diagnostics ADA 检测试剂盒在检测游离和结合 ADA 时，对于英夫利西单抗（Cohen's k = 0.717）和阿达木单抗（Cohen's k = 0.802）的一致性为中等至良好。相比之下，仅检测游离 ADAs 的 Theradiag ADA 检测法与英夫利西单抗（Cohen's k = 0.458）和阿达木单抗（Cohen's k = 0.119）的一致性为零或较差：这项研究表明，Theradiag 和 Sanquin Diagnostics 检测仪在测量英夫利西单抗和阿达木单抗血清浓度以及游离和结合的 ADAs 时，与这些生物制剂之间存在很强的相关性和良好的一致性。不一致性分析表明，单用游离检测法检测的药物浓度明显降低，这表明联合检测游离和结合的ADA能更好地与药物水平保持一致。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Antibodies IMMUNOLOGY-

CiteScore

7.10

自引率

6.40%

发文量

审稿时长

11 weeks

期刊介绍： Antibodies (ISSN 2073-4468), an international, peer-reviewed open access journal which provides an advanced forum for studies related to antibodies and antigens. It publishes reviews, research articles, communications and short notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided. Electronic files or software regarding the full details of the calculation and experimental procedure - if unable to be published in a normal way - can be deposited as supplementary material. This journal covers all topics related to antibodies and antigens, topics of interest include (but are not limited to): antibody-producing cells (including B cells), antibody structure and function, antibody-antigen interactions, Fc receptors, antibody manufacturing antibody engineering, antibody therapy, immunoassays, antibody diagnosis, tissue antigens, exogenous antigens, endogenous antigens, autoantigens, monoclonal antibodies, natural antibodies, humoral immune responses, immunoregulatory molecules.