Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain; Clinical Laboratory, Hospital Universitario de La Princesa, Madrid, Spain; Instituto de Investigación Sanitaria de La Princesa, Madrid, Spain.
Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
J Pharm Biomed Anal. 2021 May 10;198:114003. doi: 10.1016/j.jpba.2021.114003. Epub 2021 Mar 6.
Adalimumab (ADL), infliximab (IFX) and their biosimilars are widely used biological drugs. Some patients, however, generate neutralizing antibodies that hamper the effectiveness of these drugs. Evidence shows therapeutic drug monitoring of serum levels ADL/IFX and anti-drug antibodies (ADA) is useful to improve treatment effectiveness. We evaluated a new rapid quantitative method, Quantum Blue (QB), for determining serum anti-ADL and anti-IFX antibodies (Research Use Only labelling) by comparing it with two established ELISA kits, Promonitor (PM) and Lisa-Tracker (LT).
Eighty samples (40 for each drug type) were analysed. Percentage of agreement and kappa statistic were used to compare positive/negative ADA results. Clinical implications for drug treatment in the patients with discordant results were evaluated. The Chi-square test was used to analyze differences for ADA detection in patients with disease flare and without concomitant immunosuppressant treatment.
Agreement exceeded 80 % among anti-ADL methods. Although LT ELISA showed a lower capacity in detecting anti-ADL antibodies, discrepancies were found for levels close to the cut-off concentration, thus having minimal impact on clinical decisions. Conversely, QB anti-IFX displayed low agreement with PM and LT ELISA kits (67.5 % and 50 %, respectively), and was unable to detect high levels of antibodies, therefore having major clinical implications. Agreement between PM and LT ELISA anti-IFX kits was 82.5 % with all discordant results being undetected for PM and slightly positive for LT.
QB anti-ADL shows similar performance to ELISA kits while QB anti-IFX needs further improvements to achieve reliable antibody detection.
阿达木单抗（ADL）、英夫利昔单抗（IFX）及其生物类似药被广泛应用于临床。但部分患者会产生中和抗体，从而降低药物疗效。研究表明，检测血清 ADL/IFX 水平和抗药物抗体（ADA）有助于提高治疗效果。本研究旨在评估一种新的快速定量检测方法——Quantum Blue（QB），并与两种已建立的 ELISA 试剂盒（Promonitor [PM] 和 Lisa-Tracker [LT]）进行比较，以评估其检测血清抗 ADL 和抗 IFX 抗体的能力（仅供研究使用）。
对 80 例样本（每种药物各 40 例）进行分析。采用一致性百分比和 Kappa 统计比较 ADA 阳性/阴性结果。对结果不一致的患者进行药物治疗的临床意义评估。采用卡方检验分析疾病活动期和未同时使用免疫抑制剂治疗患者的 ADA 检测差异。
抗 ADL 方法的一致性均超过 80%。虽然 LT ELISA 检测抗 ADL 抗体的能力较低，但在接近临界值时，差异较小，对临床决策影响不大。相比之下，QB 抗 IFX 与 PM 和 LT ELISA 试剂盒的一致性分别为 67.5%和 50%，且无法检测高水平抗体，对临床有重要影响。PM 和 LT ELISA 抗 IFX 试剂盒之间的一致性为 82.5%，所有不一致的结果均为 PM 检测阴性、LT 检测弱阳性。
QB 抗 ADL 的性能与 ELISA 试剂盒相似，而 QB 抗 IFX 需要进一步改进以实现可靠的抗体检测。
