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对TNFα抑制剂和IL-17A抑制剂有反应者与无反应者体内炎性细胞因子的变化:一项针对银屑病关节炎患者的研究

Changes in Inflammatory Cytokines in Responders and Non-Responders to TNFα Inhibitor and IL-17A Inhibitor: A Study Examining Psoriatic Arthritis Patients.

作者信息

Skougaard Marie, Søndergaard Magnus Friis, Ditlev Sisse Bolm, Kristensen Lars Erik

机构信息

The Parker Institute, Copenhagen University Hospital Bispebjerg and Frederiksberg, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark.

Copenhagen Center for Translational Research, Copenhagen University Hospital Bispebjerg and Frederiksberg, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.

出版信息

Int J Mol Sci. 2024 Mar 5;25(5):3002. doi: 10.3390/ijms25053002.

Abstract

This study aimed to examine the changes in biomarker levels in responders and non-responders to tumor necrosis factor alpha inhibitor (TNFi) and interleukin-17A inhibitor (IL-17Ai) in psoriatic arthritis (PsA) patients over a 4-month period after treatment initiation. A total of 68 PsA patients initiating either TNFi, IL-17Ai, or methotrexate treatment were included. Blood plasma and clinical outcome measures were collected adjacent to treatment initiation and after four months. A commercially available multiplex immunoassay was included to evaluate 54 biomarkers. Mean changes were used to evaluate change over time. A statistically significant decrease in pro-inflammatory cytokines IL-6 (log-transformed mean change -0.97, 95%CI -4.30; 2.37, [ = 0.032]) and an increase in anti-inflammatory IL-10 (0.38, 95%CI 1.74; 2.50 [ = 0.010]) were seen in TNFi responders. Meanwhile, a statistically significant increase in the target cytokine IL-17A was seen in both IL-17Ai responders (2.49, 95%CI -1.84; 6.85 [ = 0.031]) and non-responders (2.48, 95%CI -1.46; 6.41 [ = 0.001]). This study demonstrated differing changes in cytokine levels when comparing treatment responders and non-responders, highlighting the need to improve the understanding of the different immune response mechanisms explaining different responses to medical treatment in PsA patients.

摘要

本研究旨在检测银屑病关节炎(PsA)患者在开始使用肿瘤坏死因子α抑制剂(TNFi)和白细胞介素-17A抑制剂(IL-17Ai)治疗后4个月内,应答者和非应答者生物标志物水平的变化。总共纳入了68例开始使用TNFi、IL-17Ai或甲氨蝶呤治疗的PsA患者。在开始治疗时和4个月后采集血浆和临床结局指标。采用一种商用多重免疫测定法评估54种生物标志物。用平均变化来评估随时间的变化。在TNFi应答者中,促炎细胞因子IL-6有统计学意义的下降(对数转换后的平均变化为-0.97,95%置信区间为-4.30;2.37,P = 0.032),抗炎性IL-10有增加(0.38,95%置信区间为1.74;2.50,P = 0.010)。同时,在IL-17Ai应答者(2.49,95%置信区间为-1.84;6.85,P = 0.031)和非应答者(2.48,95%置信区间为-1.46;6.41,P = 0.001)中,目标细胞因子IL-17A均有统计学意义的增加。本研究表明,在比较治疗应答者和非应答者时,细胞因子水平存在不同变化,这凸显了有必要加深对不同免疫反应机制的理解,以解释PsA患者对药物治疗的不同反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ded/10932211/f5df1acaee11/ijms-25-03002-g001.jpg

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