| 哮喘加剧与患者的发病率和死亡率呈正相关，预防哮喘加剧是治疗哮喘的重要目标。有研究显示，气道嗜酸性炎症与哮喘的加剧相关。美泊利单抗（Mepolizumab）是一种人源性抗白介素5单克隆抗体，选择性抑制嗜酸性炎症，具有潜在治疗难治性嗜酸细胞性哮喘的作用。 为了研究美泊利单抗对嗜酸细胞性哮喘的疗效，英国进行了一项随机、双盲、安慰剂平行对照试验。61位既往有哮喘严重加剧的难治性嗜酸细胞性哮喘患者被随机分为两组，每月一次输注美泊利单抗（n=29）或安慰剂（n=32），疗程为一年。主要观察指标为哮喘严重加剧的发生率；次要观察指标包括哮喘症状的改善、哮喘生活质量调查表评分、1秒用力呼吸量、气道高反应性及全血与血清嗜酸细胞计数等。 结果显示，与安慰剂相比，美泊利单抗显著降低哮喘严重加剧的发生率，并显著提高哮喘生活质量调查表评分，降低全血及血清嗜酸细胞计数，对难治性嗜酸细胞性哮喘有效。
"Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources," write Pranabashis Haldar, MRCP, from University Hospitals of Leicester National Health Service Trust, United Kingdom, and colleagues. "Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations." In a double-blind, parallel-group study, 61 patients with refractory eosinophilic asthma and a history of recurrent severe exacerbations were randomly assigned to receive monthly infusions of either mepolizumab (n = 29) or placebo (n = 32) for 1 year. The main study endpoint was the number of severe exacerbations per subject during the 50-week treatment phase. Secondary endpoints were change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, scored from 1 [most severe impairment] to 7, with a change of 0.5 unit considered clinically important), postbronchodilator forced expiratory volume in 1 second (FEV1), airway hyperresponsiveness, and blood and sputum eosinophil counts. During the 50-week study, mepolizumab was associated with significantly fewer severe exacerbations compared with placebo (2.0 vs 3.4 mean exacerbations per subject; relative risk [RR], 0.57; 95% confidence interval [CI], 0.32 – 0.92; P = .02) and with a significant improvement in AQLQ score (mean increase from baseline, 0.55 vs 0.19; mean difference between groups, 0.35; 95% CI, 0.08 – 0.62; P = .02). Blood (P < .001) and sputum (P = .002) eosinophil counts were significantly lower with mepolizumab, but symptoms, FEV1 after bronchodilator use and airway hyperresponsiveness were not significantly different between groups. Hospitalizations for acute severe asthma were the only serious adverse events reported. "Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma," the study authors write. "The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population." Limitations of this study include its lack of generalizability to patient groups with other clinical characteristics and its inability to determine the mechanisms underlying heterogeneity in the biologic response to mepolizumab and the relative resistance of eosinophils in tissue to anti-interleukin-5. "Eosinophilic inflammation, which may be a consequence of interleukin-5 action, is a characteristic feature of some forms of asthma," write Parameswaran Nair, MD, PhD, from McMaster University in Hamilton, Ontario, Canada, and colleagues from the second study. "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." The secondary goal of this study was to assess the effect of mepolizumab on the number of eosinophils in sputum and blood, symptoms, and airflow limitation. In this double-blind, parallel-group trial, 9 patients with persistent sputum eosinophilia and symptoms despite prednisone treatment were randomly assigned to receive mepolizumab (5 monthly infusions of 750 mg each), and 11 patients were randomly assigned to receive placebo. There were 12 asthma exacerbations in 10 participants assigned to placebo, of whom 9 had sputum eosinophilia during their exacerbation. In contrast, only 1 patient assigned to mepolizumab had an asthma exacerbation, and this was not characterized by sputum eosinophilia (P = .002). Prednisone dose could be reduced by a mean of 83.8% ± 33.4% of maximum possible dose in the mepolizumab group vs 47.7% ± 40.5% in the placebo group (P = .04). The number of sputum and blood eosinophils also decreased significantly with mepolizumab. Improvements in eosinophil numbers, asthma control, and FEV1 were maintained for 8 weeks after the last infusion, and no serious adverse events were reported. "Mepolizumab reduced the number of blood and sputum eosinophils and allowed prednisone sparing in patients who had asthma with sputum eosinophilia despite prednisone treatment," the study authors write. "Our small pilot study is potentially clinically directive and highlights the importance of selecting patients with airway eosinophilia for the study of the use of anti-eosinophil drugs in asthma." The authors acknowledge substantial limitations of this study, including a higher sputum eosinophil count at baseline in the mepolizumab group; no significant difference between groups in the final prednisone doses; reliance on past objective evidence of asthma, as indicated by variable airflow limitation; lack of generalizability to most patients with asthma; incomplete blinding; and small sample size. "These studies clearly confirm that in a subgroup of patients with eosinophilic asthma, eosinophils play a role in exacerbations," Sally E. Wenzel, MD, from the University of Pittsburgh, Pennsylvania, writes in accompanying editorial. "These particular eosinophils contribute to the pathobiology of asthma, and in this small subgroup, mepolizumab therapy had some clinical benefit. However, many patients with asthma do not have eosinophilia, and even in patients with eosinophilic asthma, mepolizumab had no effect on other physiological and clinical factors." GlaxoSmithKline supported the first study, employs 2 of its authors, and has various financial relationships with 4 other authors of the first study. Some of the authors of the first study also report various financial arrangements with AstraZeneca, MedImmune, Merck, Aerocrine, and/or Wyeth. The second study was supported by GlaxoSmithKline, which also provided the mepolizumab. Some of the authors report various financial arrangements with GlaxoSmithKline, Merck, Sepracor, Ception, Schering-Plough, Amgen, AstraZeneca, Novartis, Nycomed, Methapharm, Biolipox, Resistentia, Topigen, Wyeth, Chiesi, Ono Pharmaceutical, Alexion, Genentech, Medimmune, and/or Schering. Dr. Nair and 2 other authors report being listed on a patent application for a sputum-filtration device. Dr. Wenzel reports receiving consulting fees from GlaxoSmithKline, Novartis, Genentech, Wyeth, Amgen, MedImmune, Johnson & Johnson, Amira, Epigenesis, and Altair; lecture fees from Merck; and grant support from Ception, MedImmune, and GlaxoSmithKline. N Engl J Med. 2009;360:973–984, 985–993, 1026–1028. |
美泊利单抗治疗难治性嗜酸细胞性哮喘有效简介：
哮喘加剧与患者的发病率和死亡率呈正相关，预防哮喘加剧是治疗哮喘的重要目标。有研究显示，气道嗜酸性炎症与哮喘的加剧相关。美泊利单抗（Mepolizumab）是一种人源性抗白介素5单克隆抗体，选择性抑制嗜酸 ... 责任编辑：admin
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