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关于药物耐受性检测在炎症性肠病监测中的应用价值的系统评价

A Systematic Review on the Interest of Drug-tolerant Assay in the Monitoring of Inflammatory Bowel Disease.

作者信息

Barrau Mathilde, Duprat Manon, Veyrard Pauline, Tournier Quentin, Williet Nicolas, Marc Phelip Jean, Waeckel Louis, Cheifetz Adam S, Papamichael Konstantinos, Roblin Xavier, Paul Stephane

机构信息

Department of Gastroenterology, University Hospital of Saint Etienne, Saint Etienne, France.

Department of Immunology, Centre International de Recherche en Infectiologie, Université Claude Bernard Lyon 1, Saint-Etienne, France.

出版信息

J Crohns Colitis. 2023 Apr 19;17(4):633-643. doi: 10.1093/ecco-jcc/jjac164.

Abstract

Many patients with inflammatory bowel disease [IBD] are treated with anti-tumour necrosis factor [TNF] therapies, of which infliximab [IFX] is most commonly used. Loss of response [LOR] to anti-TNF therapy due to immunogenic failure accounts for 20% of subsequent medical intervention and is defined, using a drug-sensitive assay, as low or undetectable concentration of drug with high titres of anti-drug antibodies [ADAb]. We performed a systematic review to investigate the use of a drug-tolerant assay during both induction and maintenance, to monitor patients treated with anti-TNFs. After the search on PubMed, 90 publications were reviewed. Most ADAb detection methods are drug-sensitive, cannot detect ADAb in the presence of drug, and therefore cannot be used close to drug administration when the drug concentration is too high. To overcome this major limitation, several drug-tolerant techniques have been developed and will be discussed in this review. Using drug-tolerant assays, ADAb against IFX or adalimumab [ADM] can be detected during induction and predict primary non-response or LOR. Drug-sensitive assays do not allow detection of ADAb during the induction phase when IFX or ADM concentration is typically high.

摘要

许多炎症性肠病(IBD)患者接受抗肿瘤坏死因子(TNF)治疗,其中英夫利昔单抗(IFX)最为常用。由于免疫原性失败导致的抗TNF治疗反应丧失(LOR)占后续医疗干预的20%,使用药物敏感试验将其定义为药物浓度低或无法检测到且抗药物抗体(ADAb)滴度高。我们进行了一项系统评价,以研究在诱导期和维持期使用药物耐受试验来监测接受抗TNF治疗的患者。在PubMed上检索后,对90篇出版物进行了综述。大多数ADAb检测方法是药物敏感的,在有药物存在时无法检测到ADAb,因此当药物浓度过高时,在给药附近不能使用。为克服这一主要局限性,已开发出几种药物耐受技术,并将在本综述中进行讨论。使用药物耐受试验,在诱导期可检测到针对IFX或阿达木单抗(ADM)的ADAb,并预测原发性无反应或LOR。当IFX或ADM浓度通常较高时,药物敏感试验在诱导期不允许检测ADAb。

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