生物制剂在大疱性类天疱疮中的应用进展——生物制剂应用进展

Advances in the Application of Biologics for Bullous Pemphigoid—Advances in the Application of Biologics

摘要: 大疱性类天疱疮(Bullous Pemphigoid, BP)是一种主要发生于老年人的自身免疫性表皮下大疱性疾病，临床特征为紧张性大疱伴剧烈瘙痒。随着人口老龄化加剧，BP的发病率呈现逐年上升趋势，最新流行病学数据显示其年发病率约5例/10万人，随人口老龄化呈上升趋势(部分国家发病率增长2~5倍)。该病的发病机制主要与抗BP180 (BPAG2)和BP230 (BPAG1)的自身抗体介导的表皮–真皮分离有关，涉及复杂的免疫学级联反应。传统治疗方案以系统性糖皮质激素联合免疫抑制剂为主，但长期使用常导致感染、糖尿病、骨质疏松等严重不良反应，老年患者的治疗相关死亡率显著升高(1年内达20%~41%)。近年来，随着对BP发病机制的深入理解，多种靶向B细胞、IgE、嗜酸性粒细胞、补体系统及特定细胞因子的生物制剂逐渐应用于临床。本文通过系统分析近年来的临床研究数据，详细评估了各类生物制剂的疗效、安全性及成本效益，并基于最新基础研究进展，提出了未来的研究方向，包括新型靶点开发、生物标志物指导的个体化治疗等，以期为临床实践提供循证依据。

Abstract: Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease that mainly occurs in the elderly, characterized by tense blisters accompanied by severe pruritus. With the intensification of population aging, the incidence of BP has been increasing year by year. The latest epidemiological data show that its annual incidence rate is about 5 cases per 100,000 people, and it is on the rise with population aging (the incidence rate has increased by 2 to 5 times in some countries). The pathogenesis of this disease is mainly related to the separation of the epidermis and dermis mediated by autoantibodies against BP180 (BPAG2) and BP230 (BPAG1), involving complex immunological cascade reactions. The traditional treatment plan mainly consists of systemic glucocorticoids combined with immunosuppressants, but long-term use often leads to serious adverse reactions such as infection, diabetes, and osteoporosis, and the treatment-related mortality rate of elderly patients is significantly increased (reaching 20%~41% within one year). In recent years, with the in-depth understanding of the pathogenesis of BP, various biological agents targeting B cells, IgE, eosinophils, complement systems, and specific cytokines have gradually been applied in clinical practice. This article systematically analyzes the clinical research data in recent years, evaluates the efficacy, safety, and cost-effectiveness of various biological agents in detail, and based on the latest basic research progress, proposes future research directions, including the development of new targets and biomarker-guided individualized treatment, in order to provide evidence-based support for clinical practice.