在人工合成的抗白介素5抗体美泊利单的研究中发现,对于频繁反复发作、有持续嗜酸性粒细胞炎症并且激素治疗效果不佳的哮喘患者,静脉注射或皮下注射美泊利单抗均能明显减少哮喘发作,并与改善哮喘控制的指标有关。

—2014925日《新英格兰医学杂志》

 

中文翻译


 

【题目】美泊利单抗治疗严重的嗜酸性粒细胞哮喘

【译文】

背景:部分严重哮喘病人频繁的反复发作与持续的嗜酸性粒细胞炎症有关,尽管他们已持续使用了高剂量的吸入激素,联合或不联合口服激素治疗。

方法:在本随机双盲双模拟研究中,我们纳入了576个病人,他们使用高剂量吸入激素后仍反复发作哮喘,并证实有嗜酸性粒细胞炎症。美泊利单抗是一种人工合成的抗白介素5抗体。全部病人分成3组,静脉注射75mg美泊利单抗组,皮下注射100mg美泊利单抗组,以及安慰剂组;每4周给药1次,持续32周。主要观察结局是哮喘发作率。其他观察结局包括1秒用力呼气容积(FEV1)、圣乔治呼吸问卷(SGRQ)和5项哮喘控制问卷(ACQ-5),并且评价了药物安全性。

结果:与安慰剂组比较,静脉注射组哮喘发作率减少了47%95%CI29-61),皮下注射组减少了53%95%CI:37-65),差别有显著性(P<0.001)。在静脉注射组,哮喘发作需急诊治疗或住院的情况减少了32%,皮下注射组减少了61%。在第32周,与对照组相比,静脉注射组FEV1平均升高值多100mlP=0.02),皮下注射组多98mlP=0.03)。在静脉注射组和皮下注射组,SGRQ评分提高的分数较安慰剂组(最小临床重要变化,4分)分别增加6.4分和7.0分;ACQ-5评分提高的分数较安慰剂组分别增加0.42分和0.44分(最小临床重要变化,0.5分)(P<0.001)。美泊利单抗的安全性与安慰剂类似。

结论:静脉注射或皮下注射美泊利单抗均能明显减少哮喘发作,并与改善哮喘控制的指标有关。

 

英文原稿


 

[Title] Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma

[Authors] Hector G. Ortega, M.D., Sc.D., Mark C. Liu, M.D., Ian D. Pavord, D.M., Guy G. Brusselle, M.D.,
J. Mark FitzGerald, M.D., Alfredo Chetta, M.D., Marc Humbert, M.D., Ph.D., Lynn E. Katz, Pharm.D.,
Oliver N. Keene, M.Sc., Steven W. Yancey, M.Sc., and Pascal Chanez, M.D., Ph.D.

[Abstract]

BACKGROUND: Some patients with severe asthma have frequent exacerbations associated with persistent
eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or
without oral glucocorticoids.

METHODS: In this randomized, double-blind, double-dummy study, we assigned 576 patients with
recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of
inhaled glucocorticoids to one of three study groups. Patients were assigned to receive mepolizumab,
a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg
intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. The
primary outcome was the rate of exacerbations. Other outcomes included the forced expiratory
volume in 1 second (FEV1) and scores on the St. George’s Respiratory Questionnaire (SGRQ)
and the 5-item Asthma Control Questionnaire (ACQ-5). Safety was also assessed.

RESULTS: The rate of exacerbations was reduced by 47% (95% confidence interval [CI], 29 to 61)
among patients receiving intravenous mepolizumab and by 53% (95% CI, 37 to 65) among those
receiving subcutaneous mepolizumab, as compared with those receiving placebo (P<0.001 for both
comparisons). Exacerbations necessitating an emergency department visit or hospitalization were
reduced by 32% in the group receiving intravenous mepolizumab and by 61% in the group receiving
subcutaneous mepolizumab. At week 32, the mean increase from baseline in FEV1 was 100 ml greater
in patients receiving intravenous mepolizumab than in those receiving placebo (P=0.02) and 98 ml
greater in patients receiving subcutaneous mepolizumab than in those receiving placebo (P=0.03).
The improvement from baseline in the SGRQ score was 6.4 points and 7.0 points greater in the
intravenous and subcutaneous mepolizumab groups, respectively, than in the placebo group (minimal
clinically important change, 4 points), and the improvement in the ACQ-5 score was 0.42 points and
0.44 points greater in the two mepolizumab groups, respectively, than in the placebo group (minimal
clinically important change, 0.5 points) (P<0.001 for all comparisons). The safety profile of
mepolizumab was similar to that of placebo.

CONCLUSIONS: Mepolizumab administered either intravenously or subcutaneously significantly reduced
asthma exacerbations and was associated with improvements in markers of asthma control.

 

原文地址

http://www.nejm.org/doi/full/10.1056/NEJMoa1403290?query=featured_home

 

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