特应性皮炎生物制剂治疗研究进展

Advances in Biologic Therapy for Atopic Dermatitis

摘要: 特应性皮炎(atopic dermatitis, AD)是一种以反复湿疹样皮损、剧烈瘙痒和慢性复发为主要特征的炎症性皮肤病，其发生发展涉及表皮屏障受损、2型免疫偏移、神经免疫异常及微生态失衡。传统外用治疗和系统免疫抑制剂在中重度AD中存在疗效不足、长期安全性或依从性受限等问题。随着对AD免疫内表型认识的深入，以单克隆抗体为代表的生物制剂逐渐成为中重度AD系统治疗的重要组成部分。本文围绕IL-4/IL-13共同通路、选择性IL-13通路、IL-31瘙痒通路以及OX40/OX40L T细胞共刺激通路，对dupilumab、tralokinumab、lebrikizumab、nemolizumab、rocatinlimab及amlitelimab等代表性药物的临床证据进行分类综述，并重点分析既往研究在直接头对头比较、长期真实世界安全性、特殊人群外推、结局指标一致性、疗效预测标志物、停药与换药策略以及成本可及性方面的不足。以综合获益–精准治疗为分析框架，多维度对比不同靶点生物制剂的临床特征，梳理可行的患者分层路径，结合网络Meta分析量化结果、真实世界数据与RCT试验数据开展对照解析，剖析当前临床决策现实困境。现有证据表明，AD生物制剂已由单一2型免疫阻断进入多靶点、分层治疗阶段，但“哪一种药最适合哪一类患者、何时调整以及能否获得长期疾病控制”仍缺乏充分证据。本文据此提出以不同靶点生物制剂的综合获益及个体化长期治疗决策为核心的研究问题，以期为后续临床研究和精准治疗提供依据。

Abstract: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease characterized by eczematous lesions and intense pruritus. Its pathogenesis involves epidermal barrier dysfunction, type 2 immune activation, neuroimmune dysregulation, and microbial imbalance. Conventional topical therapy and systemic immunosuppressants may be limited by inadequate efficacy, long-term safety concerns, or poor adherence in patients with moderate-to-severe disease. With advances in understanding AD endotypes, monoclonal antibody-based biologic therapies have become an important component of systemic treatment. This review summarizes clinical evidence for representative biologics targeting the shared IL-4/IL-13 pathway, selective IL-13 signaling, the IL-31 itch pathway, and the OX40/OX40L T-cell co-stimulatory axis, including dupilumab, tralokinumab, lebrikizumab, nemolizumab, rocatinlimab, and amlitelimab. Particular attention is given to limitations of previous studies, including a lack of direct head-to-head comparisons, uneven long-term and real-world safety data, limited evidence in special populations, heterogeneity of outcome measures, insufficient validated predictive biomarkers, uncertainty regarding switching or discontinuation strategies, and inadequate health-economic evidence. Taking “comprehensive benefit-precision treatment” as the analytical framework, this paper compares the clinical characteristics of biologics with different targets from multiple dimensions, sorts out feasible patient stratification pathways, conducts comparative analysis combined with quantitative results of network meta-analysis, real-world data and RCT data, and analyzes the practical dilemmas of current clinical decision-making. Current findings indicate that biologic therapy for AD is moving from broad type 2 blockade toward multi-target and stratified treatment. However, robust evidence remains insufficient to determine which biologic is optimal for a given patient and how treatment should be adjusted to achieve durable disease control. Accordingly, this review formulates a central research question focused on the comparative overall benefit of biologics with different targets and the evidence required to support individualized long-term treatment decisions.