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接受白细胞介素-17抑制剂治疗的银屑病患者的不良事件和免疫反应

Adverse Events and Immune Response in Psoriasis Patients Receiving Interleukin-17 Inhibitors.

作者信息

Schwarz Christopher Willy, Näslund-Koch Charlotte, Zachariae Claus, Seidelin Jakob Benedict, Nielsen Susanne Dam, Ostrowski Sisse Rye, Astvad Karen Marie Thyssen, Brock Inger, Iversen Lars, Rasmussen Mads Kirchheiner, Loft Nikolai, Skov Lone

机构信息

Department of Dermatology and Allergy, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

1Department of Dermatology and Allergy, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.

出版信息

Acta Derm Venereol. 2025 Aug 18;105:adv43685. doi: 10.2340/actadv.v105.43685.

Abstract

Interleukin-17 inhibitors are effective in psoriasis; however, they are associated with an increased risk of infections, particularly oral candidiasis, and new-onset/flares of inflammatory bowel disease. This study aimed to identify predictive markers for these adverse events and to describe the functional immune response in patients treated with interleukin-17 inhibitors using a whole-blood stimulation system (TruCulture®). Patients with psoriasis initiating an interleukin-17 inhibitor (n = 36) or adalimumab (n = 24) were enrolled. Patients attended visits at baseline, week 12, and week 52, during which skin and mucosal swabs, and faecal and blood samples were collected. Baseline oral Candida albicans colonization with no clinical symptoms was associated with an increased risk of oral candidiasis during the first year of interleukin-17 inhibitor therapy, with no cases of oral candidiasis observed in the adalimumab group. Gut inflammation, measured by faecal calprotectin, remained stable in both the adalimumab and interleukin-17 inhibitor group. Colonization with Staphylococcus aureus did not change during treatment. It was found that interleukin-17 inhibitors induced an anti-inflammatory state and potentially more active toll-like receptor 3-mediated antiviral responses compared with adalimumab. In conclusion, screening for oral Candida albicans colonization prior to initiation of interleukin-17 inhibitor therapy may be a useful strategy for risk stratification and early intervention.

摘要

白细胞介素-17抑制剂对银屑病有效;然而,它们与感染风险增加有关,尤其是口腔念珠菌病,以及炎症性肠病的新发/发作。本研究旨在确定这些不良事件的预测标志物,并使用全血刺激系统(TruCulture®)描述接受白细胞介素-17抑制剂治疗的患者的功能性免疫反应。招募了开始使用白细胞介素-17抑制剂(n = 36)或阿达木单抗(n = 24)的银屑病患者。患者在基线、第12周和第52周就诊,在此期间收集皮肤和粘膜拭子、粪便和血液样本。基线时无症状的口腔白色念珠菌定植与白细胞介素-17抑制剂治疗第一年口腔念珠菌病风险增加相关,阿达木单抗组未观察到口腔念珠菌病病例。通过粪便钙卫蛋白测量的肠道炎症在阿达木单抗组和白细胞介素-17抑制剂组中均保持稳定。治疗期间金黄色葡萄球菌定植情况未发生变化。发现与阿达木单抗相比,白细胞介素-17抑制剂诱导了一种抗炎状态,并可能诱导更活跃的Toll样受体3介导的抗病毒反应。总之,在开始白细胞介素-17抑制剂治疗前筛查口腔白色念珠菌定植可能是一种有用的风险分层和早期干预策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32de/12376385/c0554298c8d3/ActaDV-105-43685-g001.jpg

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