Gomes Luis Eduardo Miani, Genaro Livia Moreira, de Castro Marina Moreira, Ricci Renato Lazarin, Pascoal Livia Bitencourt, Silva Filipe Botto Crispim, Bonfitto Pedro Henrique Leite, Camargo Michel Gardere, Corona Ligiana Pires, Ayrizono Maria de Lourdes Setsuko, de Azevedo Anibal Tavares, Leal Raquel Franco
Inflammatory Bowel Disease Research Laboratory (LabDII), Gastrocenter, Colorectal Surgery Unit, Surgery Department, School of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil.
Nutritional Epidemiology Laboratory, School of Applied Sciences, University of Campinas, Limeira, São Paulo, Brazil.
Therap Adv Gastroenterol. 2024 May 10;17:17562848241251949. doi: 10.1177/17562848241251949. eCollection 2024.
The treatment for Crohn's disease (CD) has increasingly required the use of biological agents. Safe and affordable tests have led to the active implementation of therapeutic drug monitoring (TDM) in clinical practice, which, although not yet widely available across all health services, has been proven effective.
To analyze serum infliximab (IFX) and antidrug antibody (ADA) levels in CD patients, compare two tests, as well as construct a prediction of neural network using a combination of clinical, epidemiological, and laboratory variables.
Cross-sectional observational study.
A cross-sectional observational study was conducted on 75 CD patients in the maintenance phase of IFX treatment. The participants were allocated into two groups: CD in activity (CDA) and in remission (CDR). Disease activity was defined by endoscopic or radiological criteria. Serum IFX levels were measured by enzyme-linked immunosorbent assay (ELISA) and rapid lateral flow assay; ADA levels were measured by ELISA. A nonparametric test was used for statistical analysis; value of ⩽0.05 was considered significant. Differences between ELISA and rapid lateral flow results within the measurement range were assessed by the Wilcoxon test, Passing-Bablok regression, and Bland-Altman method. Prediction models were created using four neural network sets. Neural networks and performance receiver operating characteristic curves were created using the Keras package in Python software.
Most participants exhibited supratherapeutic IFX levels (>7 mg/mL). Both tests showed no difference in IFX levels between the CDA and CDR groups ( > 0.05). The use of immunosuppressive therapy did not affect IFX levels ( > 0.05). Only 14.66% of patients had ADA levels >5 AU/mL, and all ADA-positive participants exhibited subtherapeutic IFX levels in both tests. The median results of both tests showed significant differences and moderate agreement ( = -0.6758, < 0.001). Of the four neural networks developed, two showed excellent performance, with area under the curve (AUCs) of 82-92% and 100%.
Most participants exhibited supratherapeutic IFX levels, with no significant serum level difference between the groups. There was moderate agreement between tests. Two neural network sets showed disease activity and the presence of ADA, noninvasively determined in patients using IFX by presenting an AUC of >80%.
克罗恩病（CD）的治疗越来越需要使用生物制剂。安全且经济实惠的检测方法已促使治疗药物监测（TDM）在临床实践中积极开展，尽管尚未在所有医疗服务中广泛应用，但已被证明是有效的。
分析CD患者血清英夫利昔单抗（IFX）和抗药物抗体（ADA）水平，比较两种检测方法，并结合临床、流行病学和实验室变量构建神经网络预测模型。
横断面观察性研究。
对75例处于IFX治疗维持期的CD患者进行横断面观察性研究。参与者被分为两组：活动期CD（CDA）和缓解期CD（CDR）。疾病活动度通过内镜或放射学标准定义。血清IFX水平采用酶联免疫吸附测定（ELISA）和快速侧向流测定法测量；ADA水平采用ELISA测量。采用非参数检验进行统计分析；P值≤0.05被认为具有统计学意义。通过Wilcoxon检验、Passing-Bablok回归和Bland-Altman方法评估测量范围内ELISA和快速侧向流结果之间的差异。使用四个神经网络集创建预测模型。使用Python软件中的Keras包创建神经网络和性能受试者工作特征曲线。
大多数参与者的IFX水平高于治疗剂量（>7 mg/mL）。两种检测方法均显示CDA组和CDR组之间的IFX水平无差异（P>0.05）。使用免疫抑制疗法对IFX水平无影响（P>0.05）。仅14.66%的患者ADA水平>5 AU/mL，且所有ADA阳性参与者在两种检测中IFX水平均低于治疗剂量。两种检测方法的中位数结果显示出显著差异和中度一致性（r=-0.6758，P<0.001）。在开发的四个神经网络中，有两个表现出优异的性能，曲线下面积（AUC）分别为82%-92%和100%。
大多数参与者的IFX水平高于治疗剂量，各组之间血清水平无显著差异。检测方法之间存在中度一致性。两个神经网络集通过呈现>80%的AUC，非侵入性地确定了使用IFX患者的疾病活动度和ADA的存在情况。
