嗜酸性食管炎的单克隆抗体治疗：对吞咽困难、组织学应答及内镜结局影响的叙述性综述

文献信息

中文摘要

背景： 嗜酸性食管炎（EoE）是一种慢性免疫介导的炎症性疾病，以食管嗜酸性粒细胞浸润和食管功能障碍症状为特征，最突出的是吞咽困难和食物嵌塞。过去20年EoE患病率显著增加，该病现已被认为是成人和青少年食管疾病的重要原因。尽管质子泵抑制剂、吞咽型局部糖皮质激素、饮食排除策略和内镜下扩张仍是治疗的基石，但相当比例的患者仍存在持续症状、疾病复发或治疗相关限制。对EoE免疫发病机制认识的进展已确定2型炎症通路是疾病活动的核心驱动因素，从而促进了靶向单克隆抗体疗法的发展。针对白细胞介素-4、白细胞介素-5、白细胞介素-13和Siglec-8的几种单克隆抗体已在随机对照试验中接受评估，显示出对临床症状、组织学缓解和内镜疾病严重程度的不同影响。本综述综合了青少年和成人EoE单克隆抗体治疗的当前证据，重点阐述其机制依据、临床疗效和局限性。特别关注症状改善与组织学或内镜应答之间经常观察到的不一致。还讨论了当前指南推荐、监管考虑和未来研究方向。

英文摘要

Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder characterized by esophageal eosinophilic infiltration and symptoms of esophageal dysfunction, most notably dysphagia and food impaction. The prevalence of EoE has increased substantially over the past 2 decades, and the disease is now recognized as a major cause of esophageal morbidity in both adults and adolescents. Although proton pump inhibitors, swallowed topical corticosteroids, dietary elimination strategies, and endoscopic dilation remain the cornerstone of therapy, a considerable proportion of patients experience persistent symptoms, disease recurrence, or treatment-related limitations. Advances in understanding the immunopathogenesis of EoE have identified type 2 inflammatory pathways as central drivers of disease activity, leading to the development of targeted monoclonal antibody therapies. Several monoclonal antibodies directed against interleukin-4, interleukin-5, interleukin-13, and Siglec-8 have been evaluated in randomized controlled trials, demonstrating variable effects on clinical symptoms, histologic remission, and endoscopic disease severity. This review synthesizes current evidence on monoclonal antibody therapy for EoE in adolescents and adults, with emphasis on their mechanistic rationale, clinical efficacy, and limitations. Particular attention is given to the frequently observed discordance between symptomatic improvement and histologic or endoscopic response. Current guideline recommendations, regulatory considerations, and future research directions are also discussed.