Shiomi Mayu, Watanabe Ryu, Ishihara Ryuhei, Tanaka Sayaka, Nakazawa Takashi, Hashimoto Motomu
Department of Rheumatology, Osaka Saiseikai Nakatsu Hospital, Osaka 530-0012, Japan.
Department of Clinical Immunology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3, Asahi-machi, Abeno-Ku, Osaka 545-8585, Japan.
Biomolecules. 2025 Apr 8;15(4):544. doi: 10.3390/biom15040544.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing vasculitis characterized by extravascular granulomas and eosinophilia in both blood and tissues. Eosinophils, which play a critical role in the pathophysiology of EGPA, require interleukin (IL)-5 for maturation in the bone marrow and migration to tissues. Glucocorticoids and immunosuppressants have been the cornerstone of treatment; however, their side effects have imposed a significant burden on many patients. Mepolizumab, an antibody that binds to and neutralizes IL-5, demonstrated efficacy in controlling disease activity in EGPA in the MIRRA trial conducted in 2017. In 2024, benralizumab, an IL-5 receptor alpha antagonist, was shown to be non-inferior to mepolizumab in efficacy against EGPA in the MANDARA trial. Both drugs were originally used for severe asthma and have benefited EGPA by reducing eosinophil counts. Due to differences in pharmacological structure and pharmacokinetics, the degree of eosinophil suppression varies between the two agents, and recent studies suggest that they may also affect inflammatory and homeostatic eosinophils differently. This review summarizes the latest insights into the pathophysiology of EGPA, highlights the similarities and differences between the two drugs, and discusses future treatment strategies for EGPA based on current clinical unmet needs, including drug selection.
嗜酸性肉芽肿性多血管炎（EGPA）是一种坏死性血管炎，其特征为血管外肉芽肿以及血液和组织中的嗜酸性粒细胞增多。嗜酸性粒细胞在EGPA的病理生理学中起关键作用，其在骨髓中成熟并迁移至组织需要白细胞介素（IL）-5。糖皮质激素和免疫抑制剂一直是治疗的基石；然而，它们的副作用给许多患者带来了沉重负担。美泊利珠单抗是一种可结合并中和IL-5的抗体，在2017年进行的MIRRA试验中显示出控制EGPA疾病活动的疗效。2024年，在MANDARA试验中，IL-5受体α拮抗剂贝那利珠单抗在治疗EGPA的疗效上被证明不劣于美泊利珠单抗。这两种药物最初都用于治疗重度哮喘，通过降低嗜酸性粒细胞计数使EGPA患者受益。由于药理结构和药代动力学的差异，两种药物对嗜酸性粒细胞的抑制程度有所不同，最近的研究表明它们对炎症性和稳态嗜酸性粒细胞的影响可能也有所不同。本综述总结了对EGPA病理生理学的最新见解，强调了这两种药物的异同，并根据当前临床未满足的需求，包括药物选择，讨论了EGPA未来的治疗策略。
