Suissa S, Dennis R, Ernst P, Sheehy O, Wood-Dauphinee S
Royal Victoria Hospital, Montreal, Quebec, Canada.
Ann Intern Med. 1997 Feb 1;126(3):177-83. doi: 10.7326/0003-4819-126-3-199702010-00001.
The increasing costs of managing asthma are due in part to the introduction of new medications, such as leukotriene receptor antagonists. These antagonists interfere with the action of leukotrienes, which are implicated in bronchoconstriction and the formation of airway edema in patients with asthma. Leukotriene receptor antagonists must be shown to be clinically and economically effective for their clinical use to be justified.
To assess the clinical and economic effectiveness of zafirlukast, a leukotriene receptor antagonist, in patients with mild-to-moderate asthma who might benefit from regular anti-inflammatory therapy.
Randomized, double-blind, multicenter, placebo-controlled trial.
28 outpatient clinics.
146 patients with mild-to-moderate asthma who were 12 years of age or older, had not smoked cigarettes in the previous 6 months, had a smoking history of less than 10 pack-years, had an FEV1 at least 55% of the predicted value with no upper limit, had demonstrated bronchial hyperresponsiveness, and were symptomatic during the 7-day run-in period. All patients were seen every 2 to 3 weeks for 13 weeks.
103 patients received zafirlukast (20 mg twice daily), and 43 patients received placebo (twice daily). All patients received inhaled beta-agonists as needed.
Data were obtained from medical examinations, patient questionnaires, and daily diaries. The clinical effectiveness outcomes were days per month without asthma symptoms, limitation of activity, use of beta-agonists, sleep disturbance, and episodes of asthma (the latter was a composite measure made up of the first four outcomes plus the occurrence of adverse events). The economic effectiveness outcomes were frequency and type of unscheduled health care contacts, use of beta-agonist inhalers, consumption of nonasthma medications, and days of absence from work or school.
The zafirlukast group had 89% more days without symptoms (adjusted rates, 7.0 compared with 3.7 days per month; P = 0.03), 89% more days without use of beta-agonists (adjusted rates, 11.3 compared with 6.0 days per month; P = 0.001), and 98% more days without episodes of asthma (adjusted rates, 10.1 compared with 5.1 days per month; P = 0.003). They also had 55% (95% CI, 19% to 74%) fewer health care contacts (18.5 compared with 40.7 per 100 per month; P = 0.007) and 55% (CI, 3% to 79%) fewer days of absence from work or school (15.6 compared with 35.0 per 100 per month; P = 0.04). They used 17% fewer canisters of inhaled beta-agonists (P = 0.17) and 19% less nonasthma medication (P < 0.2).
A daily regimen of zafirlukast added to as-needed inhaled beta-agonists is more effective than beta-agonists alone in treating mild-to-moderate asthma. The clinical and economic effectiveness of zafirlukast, a potential alternative to inhaled corticosteroids, provides further impetus to use regular "preventive" therapy in patients with mild-to-moderate asthma.
哮喘管理成本的不断增加部分归因于新药物的引入，如白三烯受体拮抗剂。这些拮抗剂干扰白三烯的作用，而白三烯与哮喘患者的支气管收缩和气道水肿形成有关。白三烯受体拮抗剂必须在临床和经济上被证明是有效的，其临床应用才合理。
评估白三烯受体拮抗剂扎鲁司特对可能从常规抗炎治疗中获益的轻至中度哮喘患者的临床和经济效果。
随机、双盲、多中心、安慰剂对照试验。
28个门诊诊所。
146例年龄在12岁及以上的轻至中度哮喘患者，在过去6个月内未吸烟，吸烟史少于10包年，第一秒用力呼气容积（FEV1）至少为预测值的55%且无上限，已证明有支气管高反应性，且在7天导入期内有症状。所有患者每2至3周就诊一次为期13周。
103例患者接受扎鲁司特（每日2次，每次20毫克），43例患者接受安慰剂（每日2次）。所有患者根据需要吸入β受体激动剂。
数据来自医学检查患者问卷和每日日记。临床效果指标包括每月无哮喘症状的天数、活动受限情况、β受体激动剂的使用、睡眠障碍和哮喘发作次数（后者是由前四项指标加上不良事件的发生情况组成的综合指标）。经济效果指标包括非计划医疗接触的频率和类型、β受体激动剂吸入器的使用、非哮喘药物的消耗以及缺勤或缺课天数。
扎鲁司特组无症状天数多89%（校正率：每月7.0天对比3.7天；P = 0.0），未使用β受体激动剂的天数多89%（校正率：每月11.3天对比6.0天；P = 0.001），无哮喘发作天数多98%（校正率：每月10.1天对比5.1天；P = 0.003）。他们的医疗接触次数少55%（95%可信区间，19%至74%）（每月每100人18.5次对比40.7次；P = 0.007），缺勤或缺课天数少55%（可信区间，3%至79%）（每月每100人15.6天对比35.0天；P = 0.04）。他们使用的吸入β受体激动剂药罐少17%（P = 0.17），非哮喘药物少19%（P < 0.2）。
在按需吸入β受体激动剂基础上加用每日一次的扎鲁司特治疗轻至中度哮喘比单用β受体激动剂更有效。扎鲁司特作为吸入性糖皮质激素的潜在替代药物，其临床和经济效果为在轻至中度哮喘患者中使用常规“预防性”治疗提供了进一步的推动力。
