体重调整的静脉注射瑞利珠单抗治疗对固定剂量皮下美泊利珠单抗应答不足的重症哮喘。
Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab.
机构信息
Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
出版信息
Am J Respir Crit Care Med. 2018 Jan 1;197(1):38-46. doi: 10.1164/rccm.201707-1323OC.
RATIONALE
Clinical benefits of fixed-dose 100-mg subcutaneous (SC) mepolizumab in prednisone-dependent patients are modest when sputum eosinophilia is not adequately controlled.
OBJECTIVES
This study compared treatment response of weight-adjusted intravenous (IV) reslizumab in patients previously treated with 100-mg SC mepolizumab.
METHODS
Ten prednisone-dependent patients with asthma (sputum eosinophils >3% and blood eosinophils >300 cells/μl), who had previously received mepolizumab (100 mg SC dosed every 4 wk [Q4W]) for at least 1 year, received two infusions of placebo (Q4W) followed by four infusions of 3.0 mg/kg reslizumab Q4W in a single-blind, placebo-controlled sequential trial. Primary outcomes were reduction of eosinophils in sputum and blood. Additional outcomes included FEV, asthma control questionnaire, eosinophil peroxidase, IL-5, sputum and blood innate lymphoid cells group 2, eosinophil progenitor cells, and autoimmune responses.
MEASUREMENTS AND MAIN RESULTS
IV reslizumab attenuated sputum eosinophils by 91.2% (P = 0.002), blood eosinophil counts by 87.4% (P = 0.004), and sputum eosinophil peroxidase levels by 65.5% (P = 0.03) compared with placebo. Attenuation of both local and systemic eosinophilia was associated with statistically significant improvements in FEV (P = 0.004) and asthma control questionnaire five-question instrument scores (P = 0.006). Decrease in percent sputum eosinophil was greater with reslizumab (by 42.7%) compared with mepolizumab (by 5.0%) and this was associated with greater improvement in asthma control questionnaire (P = 0.01; analysis of covariance of Δ between before and after treatment, mepolizumab vs. reslizumab, adjusted for baseline prednisone). Changes in sputum IL-5 and anti-eosinophil peroxidase IgG after anti-IL-5 therapy were predictors of response.
CONCLUSIONS
Weight-adjusted IV reslizumab was superior to fixed-dose SC mepolizumab in attenuating airway eosinophilia in prednisone-dependent patients with asthma, with associated improvement in asthma control. Clinical trial registered with www.clinicaltrials.gov (NCT 02559791).
背景
对于痰嗜酸性粒细胞未得到充分控制的依赖于皮质类固醇的患者，固定剂量的皮下注射美泊利珠单抗（100mg）的临床获益有限。
目的
本研究比较了体重调整的静脉注射（IV）瑞利珠单抗治疗先前接受过 100mg 皮下注射美泊利珠单抗（每 4 周[Q4W]）治疗的患者的治疗反应。
方法
10 例依赖于皮质类固醇的哮喘患者（痰嗜酸性粒细胞>3%，血液嗜酸性粒细胞>300 个/μl），此前至少接受过 1 年的美泊利珠单抗（100mg SC，Q4W）治疗，在单盲、安慰剂对照的序贯试验中，他们先接受两次安慰剂（Q4W）治疗，然后再接受四次 3.0mg/kg 瑞利珠单抗 Q4W 治疗。主要结局是痰和血液中嗜酸性粒细胞的减少。其他结局包括 FEV1、哮喘控制问卷、过氧化物酶、IL-5、痰和血液固有淋巴细胞 2 组、嗜酸性粒细胞祖细胞和自身免疫反应。
测量和主要结果
与安慰剂相比，IV 瑞利珠单抗可使痰嗜酸性粒细胞减少 91.2%（P=0.002），血液嗜酸性粒细胞计数减少 87.4%（P=0.004），痰过氧化物酶水平减少 65.5%（P=0.03）。局部和全身嗜酸性粒细胞的减少与 FEV1（P=0.004）和哮喘控制问卷五分量表评分（P=0.006）的统计学显著改善相关。瑞利珠单抗引起的痰嗜酸性粒细胞百分比下降（42.7%）明显大于美泊利珠单抗（5.0%），这与哮喘控制问卷的改善更大有关（P=0.01；协方差分析的治疗前后变化，美泊利珠单抗与瑞利珠单抗，调整基线皮质类固醇）。抗 IL-5 治疗后痰 IL-5 和抗过氧化物酶 IgG 的变化是反应的预测因素。
结论
体重调整的 IV 瑞利珠单抗在减轻依赖于皮质类固醇的哮喘患者气道嗜酸性粒细胞方面优于固定剂量的皮下注射美泊利珠单抗，同时改善哮喘控制。该临床试验已在 www.clinicaltrials.gov 上注册（NCT 02559791）。
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