贝那鲁肽对比美泊利珠单抗用于嗜酸性肉芽肿伴多血管炎。
Benralizumab versus Mepolizumab for Eosinophilic Granulomatosis with Polyangiitis.
机构信息
From the Department of Medicine, National Jewish Health, Denver (M.E.W.); McMaster University and St. Joseph's Healthcare, Hamilton, ON, Canada (P.N.); the Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hospital Cochin, and Université Paris Cité, Paris (B.T.), and the Department of Respiratory Diseases, University of Montpellier, Centre Hospitalier Universitaire Montpellier, INSERM, Centre National de la Recherche Scientifique, Montpellier (A.B.) - all in France; the Department of Internal Medicine, Rheumatology, and Immunology, Medius Kliniken, University of Tübingen, Kirchheim-Teck, Germany (B.W.); the Department of Medicine, University of Cambridge (D.R.W.J.), and BioPharmaceuticals Medical (A.S.) and Late-Stage Respiratory and Immunology, BioPharmaceuticals Research and Development (C.W.), AstraZeneca, Cambridge, and Guy's Severe Asthma Centre, School of Immunology and Microbial Sciences, King's College London, London (D.J.J.) - all in the United Kingdom; the Department of Internal Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels (F.R.); Late-Stage Respiratory and Immunology, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (L.B.S., S.N.); Late-Stage Respiratory and Immunology, BioPharmaceuticals Research and Development (Y.F., M.J.), and Translational Science and Experimental Medicine, Early Respiratory and Immunology, BioPharmaceuticals Research and Development (C.M.), AstraZeneca, Gaithersburg, MD; and the Division of Rheumatology, Department of Medicine, and the Division of Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia (P.A.M.).
出版信息
N Engl J Med. 2024 Mar 7;390(10):911-921. doi: 10.1056/NEJMoa2311155. Epub 2024 Feb 23.
BACKGROUND
Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by eosinophilic inflammation. Benralizumab, a monoclonal antibody against the interleukin-5α receptor expressed on eosinophils, may be an option for treating EGPA.
METHODS
We conducted a multicenter, double-blind, phase 3, randomized, active-controlled noninferiority trial to evaluate the efficacy and safety of benralizumab as compared with mepolizumab. Adults with relapsing or refractory EGPA who were receiving standard care were randomly assigned in a 1:1 ratio to receive benralizumab (30 mg) or mepolizumab (300 mg) subcutaneously every 4 weeks for 52 weeks. The primary end point was remission at weeks 36 and 48 (prespecified noninferiority margin, -25 percentage points). Secondary end points included the accrued duration of remission, time to first relapse, oral glucocorticoid use, eosinophil count, and safety.
RESULTS
A total of 140 patients underwent randomization (70 assigned to each group). The adjusted percentage of patients with remission at weeks 36 and 48 was 59% in the benralizumab group and 56% in the mepolizumab group (difference, 3 percentage points; 95% confidence interval [CI], -13 to 18; P = 0.73 for superiority), showing noninferiority but not superiority of benralizumab to mepolizumab. The accrued duration of remission and the time to first relapse were similar in the two groups. Complete withdrawal of oral glucocorticoids during weeks 48 through 52 was achieved in 41% of the patients who received benralizumab and 26% of those who received mepolizumab. The mean (±SD) blood eosinophil count at baseline was 306.0±225.0 per microliter in the benralizumab group and 384.9±563.6 per microliter in the mepolizumab group, decreasing to 32.4±40.8 and 71.8±54.4 per microliter, respectively, at week 52. Adverse events were reported in 90% of the patients in the benralizumab group and 96% of those in the mepolizumab group; serious adverse events were reported in 6% and 13%, respectively.
CONCLUSIONS
Benralizumab was noninferior to mepolizumab for the induction of remission in patients with relapsing or refractory EGPA. (Funded by AstraZeneca; MANDARA ClinicalTrials.gov number, NCT04157348.).
背景
嗜酸性肉芽肿性多血管炎（EGPA）是一种以嗜酸性粒细胞炎症为特征的血管炎。贝那鲁肽是一种针对嗜酸性粒细胞表达的白细胞介素-5α 受体的单克隆抗体，可能是治疗 EGPA 的一种选择。
方法
我们进行了一项多中心、双盲、3 期、随机、活性对照、非劣效性试验，以评估贝那鲁肽与美泊利珠单抗相比的疗效和安全性。正在接受标准治疗的复发或难治性 EGPA 成人患者以 1:1 的比例随机分配，接受贝那鲁肽（30mg）或美泊利珠单抗（300mg）皮下注射，每 4 周 1 次，共 52 周。主要终点为第 36 周和第 48 周的缓解（预设非劣效性边界为-25 个百分点）。次要终点包括缓解持续时间、首次复发时间、口服糖皮质激素使用、嗜酸性粒细胞计数和安全性。
结果
共有 140 名患者接受了随机分组（每组 70 名）。贝那鲁肽组和美泊利珠单抗组在第 36 周和第 48 周的缓解率分别为 59%和 56%（调整后差异为 3 个百分点；95%置信区间[CI]为-13 至 18；P=0.73 用于优势性），表明贝那鲁肽不劣于美泊利珠单抗，但不优于美泊利珠单抗。两组的缓解持续时间和首次复发时间相似。在第 48 周到第 52 周期间，41%接受贝那鲁肽治疗的患者和 26%接受美泊利珠单抗治疗的患者完全停用口服糖皮质激素。贝那鲁肽组基线时平均（±SD）血嗜酸性粒细胞计数为 306.0±225.0 个/微升，美泊利珠单抗组为 384.9±563.6 个/微升，分别降至第 52 周时的 32.4±40.8 和 71.8±54.4 个/微升。贝那鲁肽组和美泊利珠单抗组分别有 90%和 96%的患者报告了不良事件；分别有 6%和 13%的患者报告了严重不良事件。
结论
贝那鲁肽在诱导复发或难治性 EGPA 患者缓解方面不劣于美泊利珠单抗。（由阿斯利康公司资助；MANDARA ClinicalTrials.gov 编号，NCT04157348.）。
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