Advances in biological therapies for hidradenitis suppurativa
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摘要: 化脓性汗腺炎是一种发生在腋窝、腹股沟、臀部、肛周等皮肤褶皱部位的慢性复发性炎症性皮肤病。该病好发于年轻女性，主要的临床表现为疼痛性炎性结节、脓肿、破溃以及窦道和瘢痕形成。该病病程长且反复发作，严重影响患者的生活质量。化脓性汗腺炎还可与其他代谢性疾病或心血管疾病并发，缩短患者的寿命。化脓性汗腺炎的确切发病机制目前仍不清楚，学术界认为包括遗传因素在内的多种因素起综合的致病作用。目前化脓性汗腺炎的治疗手段限于抗感染以及其他对症治疗措施，故而治疗效果有限。现主流观点认为异常激活的免疫系统，包括异常升高的TNF-α、IL-17、IL-12、IL-23等细胞因子，可能在其发病过程中发挥着重要作用。随着对化脓性汗腺炎病理生理过程的了解，以及对于并发其他炎症性疾病的患者进行生物治疗有效性的观察，对化脓性汗腺炎的生物治疗获得了广泛的关注。基于多项临床试验的结果，美国FDA批准了抗TNF-α单克隆抗体阿达木单抗作为治疗化脓性汗腺炎的唯一生物制剂。同时，以上述炎症细胞因子为靶标的其他生物制剂也在中重度化脓性汗腺炎的治疗中显示了良好的疗效和安全性。本文在简单介绍化脓性汗腺炎的基础上，主要对化脓性汗腺炎所涉及的免疫因子的靶向生物治疗进展作一综述。Abstract: Hidradenitis suppurativa is a chronic recurrent inflammatory skin disease, which occurs in the skin folds of axillary, inguinal, gluteal and perianal areas. The disease is often seen in young females, which is characterised by inflammatory nodules, abscesses, fistulae and scars. Patients with hidradenitis suppurativa have a long disease history and a reduced quality of life. Although its pathogenesis is still unclear, hidradenitis suppurativa is considered as a result of interactions between genetic factors and other environmental factors. At present, the therapeutic options are limited to antibiotics and other symptom-relieving measures. Aberrant immune responses, including increased cytokines, such as TNF-α, IL-17, IL-12 and IL-23, may play an important role. Considering that the pathogenetic mechanisms are understood, and observations are made when patients with concurrent hidradenitis suppurativa are treated with biological agents, biological treatment has gained considerable attention. Adalimumab, an anti-TNF-α monoclonal antibody, is currently the only biological agent approved by the US FDA based on the results of several clinical trials, which can treat hidradenitis suppurativa, but other biological agents targeting these inflammatory cytokines have also shown good efficacy and safety in the treatment of moderate-to-severe hidradenitis suppurativa. Based on a brief introduction to hidradenitis suppurativa, this review summarises advances in the biological therapy targeting immune factors involved in hidradenitis suppurativa.
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Key words:
- Hidradenitis suppurativa /
- Therapy /
- Biological agents
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表 1 应用于HS的生物制剂和小分子抑制剂
药物名称 靶标 性质 最高临床研究等级 阿达木单抗 TNF-α 全人源化IgG1单克隆抗体 Ⅲ期随机双盲对照 英夫利昔单抗 TNF-α 人鼠嵌合IgG1单克隆抗体 随机双盲对照 依那西普 TNF-α受体 二聚TNF- α受体拮抗剂 随机双盲对照 阿那白滞素 IL-1受体 人重组形式的IL-1受体拮抗剂 随机双盲对照 Bermekimab(MABp1) IL-1α 人源化IgG1单克隆抗体 随机双盲对照 Canakinumab IL-1β 人源化IgG1单克隆抗体 病例系列 司库奇尤单抗 IL-17A 全人源化IgG1单克隆抗体 开放标签试验 依奇珠单抗 IL-17A 人源化IgG4单克隆抗体 病例系列 布罗达单抗 IL-17RA 人源化IgG2单克隆抗体 队列研究 乌司奴单抗 IL-12/IL-23p40 全人源化IgG1单克隆抗体 队列研究 古塞奇尤单抗 IL-23 全人源化IgG1单克隆抗体 病例系列 IFX-1 补体C5a IgG4单克隆抗体 Ⅱa临床试验 
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