Ito Ayaka, Miyoshi Shoki, Toyota Hikaru, Suzuki Yuki, Uehara Yuki, Hattori Saya, Takeshita Yuri, Sakasegawa Hirokazu, Kuramochi Michio, Kobayashi Konomi, Sugimoto Naoya, Nagase Hiroyuki
Division of Respiratory Medicine and Allergology, Department of Medicine, Teikyo University School of Medicine.
Arerugi. 2022;71(3):210-220. doi: 10.15036/arerugi.71.210.
Biologics are an important treatment option for patients with severe asthma. Four biologics are available in Japan, and an overlapping eligibility has been observed. The eligibility and availability of drugs depend on the local regulations of different countries. However, there is no precise information about the eligibility for biologics, including dupilumab, in Japan. The aim of the study was to investigate the overlapping eligibility and to analyze the phenotypes of patients with multiple eligibility.
In this observational study, a retrospective chart review of patients was performed. The eligibility criteria for omalizumab were IgE 30-1500IU/mL and positive IgE for perennial aeroallergen. The eligibility criteria for IL-5-targeted biologics (mepolizumab and benralizumab) were eosinophil counts (Eos) > 150μL, while those for dupilumab were Eos > 150μL or fraction of exhaled nitric oxide (FeNO) > 150ppb or IgE > 167IU/mL. Severe asthma was defined by the severity criteria under treatment based on Japanese guidelines for adult asthma.
One hundred patients with severe asthma were identified. The eligibility for omalizumab, IL-5-targeted therapies, and dupilumab was 43%, 69%, and 82%, respectively. Thirty percent of the patients were eligible for all the four biologics and showed the lowest FEV1, frequent exacerbation history, and the highest levels of Eos, FeNO, and serum periostin. Only 11% of the patients were not indicated for any biologics.
A considerable portion of patients was eligible for all the biologics. Asthma control was poor, and type 2 inflammation was prominent in such patients.
生物制剂是重度哮喘患者的重要治疗选择。日本有四种生物制剂可供使用，且已观察到存在重叠的适用资格情况。药物的适用资格和可获得性取决于不同国家的当地法规。然而，在日本，关于包括度普利尤单抗在内的生物制剂的适用资格尚无确切信息。本研究的目的是调查重叠的适用资格情况，并分析具有多种适用资格的患者的表型。
在这项观察性研究中，对患者进行了回顾性病历审查。奥马珠单抗的适用标准为免疫球蛋白E（IgE）30 - 1500IU/mL且对常年性气传变应原IgE呈阳性。白细胞介素-5靶向生物制剂（美泊利单抗和贝那利珠单抗）的适用标准为嗜酸性粒细胞计数（Eos）>150μL，而度普利尤单抗的适用标准为Eos>150μL或呼出一氧化氮分数（FeNO）>150ppb或IgE>167IU/mL。重度哮喘根据日本成人哮喘指南中治疗时的严重程度标准来定义。
共确定了100例重度哮喘患者。奥马珠单抗、白细胞介素-5靶向疗法和度普利尤单抗的适用率分别为43%、69%和82%。30%的患者符合所有四种生物制剂的适用标准，且其第一秒用力呼气容积（FEV1）最低，有频繁的加重病史，嗜酸性粒细胞、FeNO和血清骨膜蛋白水平最高。仅11%的患者未被推荐使用任何生物制剂。
相当一部分患者符合所有生物制剂的适用标准。这些患者的哮喘控制不佳，且2型炎症突出。
