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生物制剂和小分子药物在治疗化脓性汗腺炎中的临床应用。

Clinical Implementation of Biologics and Small Molecules in the Treatment of Hidradenitis Suppurativa.

机构信息

Department of Dermatology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.

Laboratory for Experimental Immunodermatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

出版信息

Drugs. 2021 Aug;81(12):1397-1410. doi: 10.1007/s40265-021-01566-2. Epub 2021 Jul 20.

Abstract

Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory skin disease originating from the hair follicles. The typical inflammatory nodules, abscesses, and draining sinus tracts (tunnels) are characterized by a massive influx of neutrophils, macrophages, B-cells, plasma cells, T helper (Th)1, Th17 cells and upregulation of pro-inflammatory cytokines such as IL-1, IL-17, IL-12/23, and TNF-α. Over the last decades, several clinical trials evaluated the clinical efficacy of different biologics targeting these pro-inflammatory cytokines, in particular TNF-α and IL-1. However, adalimumab is still the only registered drug for HS. This review discusses biologics and small molecules with high level of evidence for their clinical application, provides guidance on when and how to use these biologics and small molecules in clinical practice, and elaborates on the combination with medical and surgical treatment options beyond the current guidelines. Furthermore this review provides an overview of potential biologics and small molecules currently under investigation for novel targets in HS such as IL-36, C5a, Janus kinase family members, CD-40, LTA4 and CXCR1/2.

摘要

化脓性汗腺炎(HS)是一种源于毛囊的慢性、复发性、自身炎症性皮肤病。典型的炎症性结节、脓肿和引流窦道(隧道)的特征是大量中性粒细胞、巨噬细胞、B 细胞、浆细胞、辅助性 T 细胞(Th)1、Th17 细胞浸润,以及促炎细胞因子如白细胞介素-1(IL-1)、白细胞介素-17(IL-17)、白细胞介素-12/23(IL-12/23)和肿瘤坏死因子-α(TNF-α)的上调。在过去的几十年中,多项临床试验评估了靶向这些促炎细胞因子(特别是 TNF-α 和 IL-1)的不同生物制剂的临床疗效。然而,阿达木单抗仍然是唯一被批准用于 HS 的药物。本文综述了生物制剂和小分子药物在 HS 中的临床应用,提供了在临床实践中何时以及如何使用这些生物制剂和小分子药物的指导,并阐述了它们与现有指南之外的医疗和手术治疗选择的联合应用。此外,本文还概述了目前正在研究的针对 HS 中新型靶点(如 IL-36、C5a、Janus 激酶家族成员、CD-40、LTA4 和 CXCR1/2)的潜在生物制剂和小分子药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e06e/8352818/8fe0ec078f64/40265_2021_1566_Fig1_HTML.jpg

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