Aubier M, Pieters W R, Schlösser N J, Steinmetz K O
Unit de Pneumologie-8é Sud, Hospital Bichat, Paris, France.
Respir Med. 1999 Dec;93(12):876-84. doi: 10.1016/s0954-6111(99)90053-7.
This multicentre double-blind, double-dummy study compared the safety and efficacy of a new combination Diskus inhaler containing both salmeterol 50 microg and fluticasone propionate 500 microg (Seretide, GlaxoWellcome, France) with the same doses of the two drugs delivered via separate Diskus inhalers and with the same dose of fluticasone propionate alone. Patients were eligible for study entry if they had received an inhaled corticosteroid continuously for 12 weeks prior to run-in, and had received treatment with beclomethasone dipropionate or budesonide 1500-2000 microg day(-1) or fluticasone propionate 750-1000 microg day(-1) for at least 4 weeks prior to run-in. In total, 503 patients receiving inhaled corticosteroids were randomized to 28 weeks' treatment with either salmeterol/fluticasone propionate (50/500 microg) via a single Diskus inhaler (combination) and placebo, or salmeterol 50 microg and fluticasone propionate 500 microg administered via separate Diskus inhalers (concurrent), or fluticasone propionate 500 microg and placebo. All treatments were administered twice daily, mean morning peak expiratory flow rate (PEFR) and asthma symptoms were measured for the first 12 weeks and safety data were collected throughout the 28-week study. Over weeks 1 to 12, improvement in adjusted mean morning PEFR was 35 and 33 l min(-1), respectively, in the combination and concurrent therapy treatment groups (12 and 10% increase from baseline, respectively). The mean difference between treatments was -3 l min(-1) (90% confidence interval -10.4 l min(-1)) which was within the criteria for clinical equivalence. However, the combination therapy was statistically significantly superior to fluticasone propionate alone for mean morning PEFR (P<0.001) and other measures of lung function, whilst clinical equivalence of the combination and concurrent therapies was observed. All three treatments were well tolerated. In addition, there were no differences between the three treatments in either the c.hange in serum cortisol or urinary cortisol concentrations, which, for each treatment group, were no significantly different from baseline at the end of the treatment period. Thus, the combination of salmeterol and fluticasone propionate in a single inhaler is as well tolerated and effective in achieving asthma control in steroid-dependent patients as the separate administration of the two drugs, and both combination and concurrent therapy are superior to administration of the same dose of corticosteroid alone.
这项多中心双盲、双模拟研究比较了一种新的联合使用的碟式吸入器（含50微克沙美特罗和500微克丙酸氟替卡松，商品名舒利迭，法国葛兰素威康公司生产）与通过单独的碟式吸入器分别递送相同剂量的两种药物以及单独使用相同剂量丙酸氟替卡松的安全性和有效性。如果患者在导入期前连续吸入皮质类固醇12周，且在导入期前至少4周接受过丙酸倍氯米松或布地奈德1500 - 2000微克/天或丙酸氟替卡松750 - 1000微克/天的治疗，则有资格进入本研究。共有503名接受吸入皮质类固醇治疗的患者被随机分配接受为期28周的治疗，治疗方式分别为通过单一碟式吸入器吸入沙美特罗/丙酸氟替卡松（50/500微克）（联合治疗组）并使用安慰剂，或通过单独的碟式吸入器分别吸入50微克沙美特罗和500微克丙酸氟替卡松（同时治疗组），或吸入500微克丙酸氟替卡松并使用安慰剂。所有治疗均每日给药两次，在最初的12周测量平均晨起呼气峰值流速（PEFR）和哮喘症状，并在整个28周的研究过程中收集安全性数据。在第1至12周期间，联合治疗组和同时治疗组调整后的平均晨起PEFR分别改善了35升/分钟和33升/分钟（分别较基线增加12%和10%）。治疗组之间的平均差异为-3升/分钟（90%置信区间为-10.4升/分钟），这在临床等效标准范围内。然而，联合治疗在平均晨起PEFR（P<0.001）和其他肺功能指标方面在统计学上显著优于单独使用丙酸氟替卡松，同时观察到联合治疗和同时治疗具有临床等效性。所有三种治疗的耐受性均良好。此外，三种治疗在血清皮质醇或尿皮质醇浓度变化方面均无差异，对于每个治疗组，在治疗期结束时与基线相比均无显著差异。因此，在单一吸入器中联合使用沙美特罗和丙酸氟替卡松在依赖类固醇的患者中实现哮喘控制方面与分别使用这两种药物具有同样良好的耐受性和有效性，并且联合治疗和同时治疗均优于单独使用相同剂量的皮质类固醇。
