Nair Parameswaran, Pizzichini Marcia M M, Kjarsgaard Melanie, Inman Mark D, Efthimiadis Ann, Pizzichini Emilio, Hargreave Frederick E, O'Byrne Paul M
Firestone Institute for Respiratory Health, St. Joseph's Healthcare and Department of Medicine, McMaster University, Hamilton, ON, Canada.
N Engl J Med. 2009 Mar 5;360(10):985-93. doi: 10.1056/NEJMoa0805435.
Eosinophilic inflammation, which may be a consequence of interleukin-5 action, is a characteristic feature of some forms of asthma. However, in three previous clinical trials involving patients with asthma, blockade of this cytokine did not result in a significant improvement in outcomes. We studied the prednisone-sparing effect of mepolizumab, a monoclonal antibody against interleukin-5, in a rare subgroup of patients who have sputum eosinophilia and airway symptoms despite continued treatment with prednisone. Secondary objectives were to examine its effect on the number of eosinophils in sputum and blood, symptoms, and airflow limitation.
In this randomized, double-blind, parallel-group trial involving patients with persistent sputum eosinophilia and symptoms despite prednisone treatment, we assigned 9 patients to receive mepolizumab (administered in five monthly infusions of 750 mg each) and 11 patients to receive placebo.
There were 12 asthma exacerbations in 10 patients who received placebo, 9 of whom had sputum eosinophilia at the time of exacerbation. In comparison, only one patient who received mepolizumab had an asthma exacerbation, and this episode was not associated with sputum eosinophilia (P=0.002). Patients who received mepolizumab were able to reduce their prednisone dose by a mean (+/-SD) of 83.8+/-33.4% of their maximum possible dose, as compared with 47.7+/-40.5% in the placebo group (P=0.04). The use of mepolizumab was associated with a significant decrease in the number of sputum and blood eosinophils. Improvements in eosinophil numbers, asthma control, and forced expiratory volume in 1 second were maintained for 8 weeks after the last infusion. There were no serious adverse events.
Mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with sputum eosinophilia despite prednisone treatment. (ClinicalTrials.gov number, NCT00292877.)
嗜酸性粒细胞炎症可能是白细胞介素-5作用的结果，是某些形式哮喘的特征性表现。然而，在之前三项涉及哮喘患者的临床试验中，阻断这种细胞因子并未使治疗结果得到显著改善。我们研究了美泊利单抗（一种抗白细胞介素-5单克隆抗体）在一小部分尽管持续使用泼尼松治疗仍有痰嗜酸性粒细胞增多和气道症状的罕见患者亚组中的泼尼松减量效果。次要目标是检查其对痰液和血液中嗜酸性粒细胞数量、症状及气流受限的影响。
在这项随机、双盲、平行组试验中，纳入尽管接受泼尼松治疗仍有持续性痰嗜酸性粒细胞增多和症状的患者，我们将9例患者分配接受美泊利单抗（每月输注1次，每次750mg，共5次），11例患者分配接受安慰剂。
接受安慰剂的10例患者中有12次哮喘发作，其中9例在发作时伴有痰嗜酸性粒细胞增多。相比之下，接受美泊利单抗的患者中只有1例出现哮喘发作，且此次发作与痰嗜酸性粒细胞增多无关（P = 0.002）。接受美泊利单抗的患者能够将泼尼松剂量平均（±标准差）减少至其最大可能剂量的83.8±33.4%，而安慰剂组为47.7±40.5%（P = 0.04）。使用美泊利单抗与痰液和血液中嗜酸性粒细胞数量显著减少相关。在最后一次输注后8周，嗜酸性粒细胞数量、哮喘控制及第一秒用力呼气量仍保持改善。未发生严重不良事件。
美泊利单抗减少了血液和痰液中嗜酸性粒细胞的数量，并使尽管接受泼尼松治疗仍有痰嗜酸性粒细胞增多的哮喘患者能够减少泼尼松用量。（临床试验注册号，NCT00292877。）
