即时检测用于抗TNF药物监测及反应丧失的临床效用与准确性

Clinical Utility and Accuracy of Point-of-Care Testing for Anti-TNF Drug Monitoring and Loss of Response.

作者信息

Teichert Christoph, Anjie Suzanne I, Stevens Toer W, Bahur Bayda, Bray Kurtis R, Gecse Krisztina B, D'Haens Geert R

机构信息

Department of Gastroenterology and Hepatology, Amsterdam University Medical Centre, Amsterdam, The Netherlands.

ProciseDx Inc., 9449 Carroll Park Drive, San Diego, CA, USA.

出版信息

Inflamm Bowel Dis. 2025 May 7. doi: 10.1093/ibd/izaf101.

DOI:10.1093/ibd/izaf101

PMID:40334112

Abstract

BACKGROUND AND AIMS

Point-of-care tests (POCT) enable immediate measurement of anti-TNF blood concentrations. This study examined the association between loss of response (LOR) to infliximab (IFX) or adalimumab (ADL) and serum concentrations measured with POCT and enzyme-linked immunosorbent assay (ELISA) in inflammatory bowel disease (IBD) patients.

METHODS

Patients with IBD with stored IFX or ADL serum samples were recruited. POCT was conducted, agreement with ELISA was evaluated using Bland-Altman plots. The primary endpoint was LOR defined as change in therapy, IBD-related surgery, new actively draining fistula, and/or endoscopic deterioration. ROC curves and quartile analysis assessed the association between concentrations and LOR.

RESULTS

A total of 176 patients were included (92 IFX/84 ADL, 154 Crohn's disease, and 22 ulcerative colitis). Median follow-up time was 20 months (interquartile range 9-38). LOR occurred in 37/84 (44%) ADL users and 55/92 (60%) IFX users. Median serum concentrations were significantly lower in LOR patients compared with sustained response, measured by both techniques for ADL (POCT: 6.45 vs 13.48 µg/mL, P <.001; ELISA: 4.80 vs 8.80 µg/mL, P <.001) and IFX (POCT: 2.39 vs 6.50 µg/mL, P <.001; ELISA: 1.70 vs 4.40 µg/mL, P <.001). Quartile analysis revealed that higher serum concentrations were associated with maintained response. ROC curve analysis demonstrated good or excellent discrimination for POCT and ELISA in association with LOR (AUC IFX: POCT = 0.82, ELISA = 0.76; AUC ADL: POCT = 0.82, ELISA = 0.81; all P <.0001). An overestimation of serum concentrations with POCT was observed.

CONCLUSIONS

Serum ADL and IFX POCT concentrations are comparable to ELISA and associated with LOR, indicating its clinical utility.

摘要

背景与目的

即时检验（POCT）能够即时测定抗TNF血液浓度。本研究调查了炎症性肠病（IBD）患者中对英夫利昔单抗（IFX）或阿达木单抗（ADL）治疗反应丧失（LOR）与通过POCT和酶联免疫吸附测定（ELISA）所测血清浓度之间的关联。

方法

招募保存有IFX或ADL血清样本的IBD患者。进行POCT检测，使用Bland-Altman图评估与ELISA的一致性。主要终点为LOR，定义为治疗改变、IBD相关手术、新出现的有活动性引流的瘘管和/或内镜下病情恶化。ROC曲线和四分位数分析评估浓度与LOR之间的关联。

结果

共纳入176例患者（92例使用IFX/84例使用ADL，154例克罗恩病，22例溃疡性结肠炎）。中位随访时间为20个月（四分位间距9 - 38个月）。37/84（44%）例ADL使用者和55/92（60%）例IFX使用者出现LOR。与持续缓解患者相比，LOR患者的血清中位浓度显著更低，ADL通过两种技术测量均如此（POCT：6.45对13.48 μg/mL，P <.001；ELISA：4.80对8.80 μg/mL，P <.001），IFX也是如此（POCT：2.39对6.50 μg/mL，P <.001；ELISA：1.70对4.40 μg/mL，P <.001）。四分位数分析显示更高的血清浓度与持续缓解相关。ROC曲线分析表明POCT和ELISA与LOR的辨别能力良好或优异（AUC IFX：POCT = 0.82，ELISA = 0.76；AUC ADL：POCT = 0.82，ELISA = 0.81；所有P <.0001）。观察到POCT对血清浓度有高估现象。