Expanding the clinical utility of reporter gene assay to infliximab biosimilars

IF 3.2 3区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Clinica Chimica Acta Pub Date : 2025-05-02 DOI:10.1016/j.cca.2025.120337

Dharmendra Jain , Igor Y. Pavlov , Saša Čučnik , Julio C. Delgado , Eszter Lázár-Molnár

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引用次数: 0

Abstract

Objective

Infliximab and its biosimilars are approved for the treatment of inflammatory diseases. Monitoring of serum drug and anti-drug antibody levels is essential for managing patients with treatment failure. A reporter gene assay (RGA), previously developed for infliximab, was validated for the measurement of biosimilars infliximab-dyyb and infliximab-abda, and detection of anti-drug antibodies (ADA).

Method

65 de-identified residual serum samples from patients receiving infliximab or its biosimilars, were tested. ELISA and cell-based reporter gene assay were performed to measure drug while a bridging ELISA and a modified RGA assay were performed to detect ADA.

Results

Analysis of assay analytical parameters showed acceptable linearity (systematic error < 15 %), recovery (82–119 %), precision and reproducibility (coefficient of variation < 15 %) of the RGA assay for measuring biosimilars. Detection of ADA developed against infliximab or biosimilars showed a complete agreement (Cohen’s k = 1; 95 % CI = 1.0 to 1.0) between the RGA assays using infliximab, versus infliximab-dyyb, or infliximab-abda as assay reagents.

Conclusions

A functional cell-based reporter gene assay was validated for measuring serum concentrations of infliximab biosimilars and neutralizing antibodies. This study supports the bio- equivalency and cross-immunogenicity of parent drug and biosimilars and offers guidance for management of patients switching therapies between parent drug and biosimilars.

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扩大报告基因检测在英夫利昔单抗生物类似药中的临床应用。

目的：英夫利昔单抗及其生物仿制药获批用于炎症性疾病的治疗。监测血清药物和抗药物抗体水平对治疗失败患者的管理至关重要。先前为英夫利昔单抗开发的报告基因测定（RGA）被验证用于测量英夫利昔单抗-dyyb和英夫利昔单抗-abda的生物类似药，以及检测抗药物抗体（ADA）。方法：对使用英夫利昔单抗或其生物类似药的患者的65份去鉴定残留样本进行检测。采用酶联免疫吸附试验（ELISA）和基于细胞的报告基因测定法（RGA）检测药物，采用桥接酶联免疫吸附试验（ELISA）和改良的RGA法检测ADA。结果：分析分析参数呈可接受的线性（系统误差 ）结论：基于功能细胞的报告基因检测方法可用于测量英夫利昔单抗生物类似药和中和抗体的血清浓度。本研究支持母药和生物仿制药的生物等效性和交叉免疫原性，并为患者在母药和生物仿制药之间切换治疗提供指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinica Chimica Acta 医学-医学实验技术

CiteScore

10.10

自引率

2.00%

发文量

1268

审稿时长

23 days

期刊介绍： The Official Journal of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Clinica Chimica Acta is a high-quality journal which publishes original Research Communications in the field of clinical chemistry and laboratory medicine, defined as the diagnostic application of chemistry, biochemistry, immunochemistry, biochemical aspects of hematology, toxicology, and molecular biology to the study of human disease in body fluids and cells. The objective of the journal is to publish novel information leading to a better understanding of biological mechanisms of human diseases, their prevention, diagnosis, and patient management. Reports of an applied clinical character are also welcome. Papers concerned with normal metabolic processes or with constituents of normal cells or body fluids, such as reports of experimental or clinical studies in animals, are only considered when they are clearly and directly relevant to human disease. Evaluation of commercial products have a low priority for publication, unless they are novel or represent a technological breakthrough. Studies dealing with effects of drugs and natural products and studies dealing with the redox status in various diseases are not within the journal''s scope. Development and evaluation of novel analytical methodologies where applicable to diagnostic clinical chemistry and laboratory medicine, including point-of-care testing, and topics on laboratory management and informatics will also be considered. Studies focused on emerging diagnostic technologies and (big) data analysis procedures including digitalization, mobile Health, and artificial Intelligence applied to Laboratory Medicine are also of interest.