Division of Pulmonary, Critical Care, and Sleep Medicine, National Jewish Health, The NJH Cohen Family Asthma Institute, Denver, Colo.
Division of Pulmonary Diseases, Critical Care & Environmental Medicine, Tulane University, New Orleans, La.
J Allergy Clin Immunol Pract. 2021 Mar;9(3):1186-1193.e1. doi: 10.1016/j.jaip.2020.09.054. Epub 2020 Oct 14.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis associated with significant morbidity and mortality that has historically been treated with systemic corticosteroids and immunosuppressants. The IL-5 antagonist mepolizumab was Food and Drug Administration approved in 2017 after demonstrating safety and efficacy in EGPA. We hypothesized that benralizumab, an IL-5 receptor antagonist approved for eosinophilic asthma, would demonstrate safety and efficacy in EGPA.
To determine the safety and efficacy of benralizumab in EGPA as measured by reduction in oral corticosteroid dose and EGPA exacerbations.
We conducted a prospective 40-week open-label pilot study of benralizumab 30 mg administered subcutaneously in 10 patients with EGPA. Adverse events, oral corticosteroid dosing, exacerbations, and lung function were evaluated before, during, and after benralizumab treatment. Paired tests and tests derived from longitudinal models were used to compare outcome variables between phases or visits.
Benralizumab was well tolerated and resulted in reduction of median corticosteroid dose from 15 mg at the start to 2 mg at the end of treatment. Geometric mean corticosteroid dose was reduced from 11.6 mg during pretreatment to 6.3 mg during treatment phase. Five patients were able to achieve a dose of 0 mg. Mean annualized exacerbation rate was lowest during the treatment (1.5) compared with the pre- and posttreatment phases (4.6, P = .008 for treatment vs pre- and postphases combined).
Benralizumab was well tolerated, facilitated oral corticosteroid reduction, and reduced exacerbations in EGPA. Larger controlled trials are warranted to further evaluate the role of benralizumab in EGPA.
嗜酸性肉芽肿伴多血管炎（EGPA）是一种与较高发病率和死亡率相关的血管炎，既往常采用全身性皮质类固醇和免疫抑制剂进行治疗。白细胞介素-5（IL-5）拮抗剂美泊利珠单抗于 2017 年获得美国食品和药物管理局（FDA）批准，在 EGPA 中证实其安全性和疗效后得以应用。我们假设，用于治疗嗜酸性粒细胞性哮喘的 IL-5 受体拮抗剂贝那利珠单抗在 EGPA 中也具有安全性和疗效。
通过减少口服皮质类固醇剂量和 EGPA 恶化情况来确定贝那利珠单抗在 EGPA 中的安全性和疗效。
我们进行了一项前瞻性、40 周、开放标签的贝那利珠单抗 30 mg 皮下注射治疗 10 例 EGPA 患者的试点研究。在贝那利珠单抗治疗前后及期间评估不良事件、口服皮质类固醇剂量、恶化情况和肺功能。采用配对检验和来自纵向模型的检验比较各阶段或访视之间的结局变量。
贝那利珠单抗耐受性良好，可降低中位皮质类固醇剂量，从治疗开始时的 15 mg 降至治疗结束时的 2 mg。皮质类固醇剂量的几何均数从预处理时的 11.6 mg 降低到治疗阶段的 6.3 mg。5 例患者能够实现 0 mg 的剂量。与治疗前和治疗后阶段相比，治疗期间的平均年化恶化率最低（1.5，P<0.008，治疗与治疗前和治疗后阶段合并比较）。
贝那利珠单抗耐受性良好，可促进口服皮质类固醇剂量减少，并降低 EGPA 恶化率。需要进行更大规模的对照试验来进一步评估贝那利珠单抗在 EGPA 中的作用。
