Philip George, Villarán César, Shah Shailen R, Vandormael Kristel, Smugar Steven S, Reiss Theodore F
Clinical Research, Merck & Co., Inc., Whitehouse Station, NJ 19454, USA.
J Asthma. 2011 Jun;48(5):495-502. doi: 10.3109/02770903.2011.573042. Epub 2011 May 5.
The efficacy of oral montelukast in chronic asthma is well established. Montelukast is also an effective adjunctive therapy to inhaled corticosteroids (ICS) in asthma uncontrolled on ICS alone. Inhaled montelukast was recently shown to provide significant bronchodilation compared with placebo in patients with chronic asthma. The purpose of this study was to evaluate the efficacy of inhaled montelukast added to inhaled mometasone.
This was an 8-week, multicenter, randomized, double-blind, placebo-controlled study comparing once-daily inhaled montelukast 1 mg plus inhaled mometasone 220 μg (delivered by separate dry powder inhalers) with placebo plus inhaled mometasone 220 μg. Men and women aged 15-85 years with chronic asthma, forced expiratory volume in 1 second (FEV(1)) 50-80% of the predicted value, and β-agonist reversibility ≥12% were eligible. Patients were required to meet a minimum symptom threshold while receiving open-label inhaled mometasone during a 3-week prestudy/run-in period. Patients received blinded (montelukast vs. placebo) treatment for 2 weeks, entered a 1-week washout period, then crossed over to the other treatment for 2 weeks. The primary endpoint was the average change from baseline in FEV(1) over the 2-week treatment period. Secondary endpoints included daytime and nighttime symptom scores. Other endpoints included short-acting β-agonist (SABA) use, asthma exacerbations, asthma control, peak expiratory flow (PEF), and blood eosinophil count.
A total of 134 patients were randomized. For the primary endpoint, change from baseline in FEV(1), inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone (least squares mean 0.22 L vs. 0.17 L; p = .033 [two-sided at α = 0.05]). Inhaled montelukast plus inhaled mometasone was also significantly more effective than placebo plus inhaled mometasone in improving daytime asthma symptom scores (p = .005) and nighttime asthma symptom scores (p = .015), increasing the percentage of days with asthma control (p = .004), decreasing the percentage of days with asthma exacerbations (p ≤ .001), and decreasing the blood eosinophil count (p = .013). Differences were not significant on AM or PM PEF or SABA use, although the latter approached significance (p = .073). Both treatments were well tolerated.
Inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone in improving FEV(1), symptoms, asthma control, and blood eosinophil count.
口服孟鲁司特在慢性哮喘治疗中的疗效已得到充分证实。孟鲁司特也是一种有效的辅助治疗药物，用于单独使用吸入性糖皮质激素（ICS）控制不佳的哮喘患者。最近研究表明，与安慰剂相比，吸入孟鲁司特可使慢性哮喘患者的支气管显著扩张。本研究旨在评估吸入孟鲁司特联合吸入莫米松的疗效。
这是一项为期8周的多中心、随机、双盲、安慰剂对照研究，比较每日一次吸入1mg孟鲁司特加220μg吸入莫米松（通过单独的干粉吸入器给药）与安慰剂加220μg吸入莫米松。年龄在15 - 85岁的慢性哮喘患者，其1秒用力呼气容积（FEV₁）为预测值的50 - 80%，且β受体激动剂可逆性≥12%者符合入选标准。患者在为期3周的预研究/导入期接受开放标签的吸入莫米松治疗时，需达到最低症状阈值。患者接受双盲（孟鲁司特与安慰剂）治疗2周，进入1周的洗脱期，然后交叉接受另一种治疗2周。主要终点是2周治疗期内FEV₁相对于基线的平均变化。次要终点包括白天和夜间症状评分。其他终点包括短效β受体激动剂（SABA）的使用、哮喘急性发作、哮喘控制情况、呼气峰值流速（PEF）和血液嗜酸性粒细胞计数。
共134例患者被随机分组。对于主要终点，即FEV₁相对于基线的变化，吸入孟鲁司特加吸入莫米松比安慰剂加吸入莫米松显著更有效（最小二乘均值0.22L对0.17L；p = 0.033[α = 0.05时双侧检验]）。吸入孟鲁司特加吸入莫米松在改善白天哮喘症状评分（p = 0.005）和夜间哮喘症状评分（p = 0.015）、提高哮喘控制天数百分比（p = 0.004）、降低哮喘急性发作天数百分比（p≤0.001）以及降低血液嗜酸性粒细胞计数（p = 0.013）方面也比安慰剂加吸入莫米松显著更有效。在上午或下午的PEF或SABA使用方面差异不显著，尽管后者接近显著水平（p = 0.073）。两种治疗耐受性均良好。
吸入孟鲁司特加吸入莫米松在改善FEV₁、症状、哮喘控制和血液嗜酸性粒细胞计数方面比安慰剂加吸入莫米松显著更有效。
