Maspero Jorge F, Nolte Hendrik, Chérrez-Ojeda Iván
Fundacion CIDEA, Allergy/Respiratory Research, Buenos Aires, Argentina.
J Asthma. 2010 Dec;47(10):1106-15. doi: 10.3109/02770903.2010.514634. Epub 2010 Nov 1.
The combination of inhaled corticosteroid (ICS) and long-acting β₂-agonist is recommended for treatment of patients with persistent asthma inadequately controlled on ICS monotherapy. This study was conducted to evaluate the long-term safety of mometasone furoate/formoterol (MF/F) administered through metered-dose inhaler (MDI) in patients with persistent asthma previously on medium- to high-dose ICS.
This was a 52-week, randomized, multicenter, parallel-group, open-label, evaluator-blinded study. At baseline, 404 patients (aged ≥12 years) were stratified according to their previous ICS dose (medium or high), then randomized 2:1 to receive twice-daily treatment of MF/F (200/10 or 400/10 μg) or fluticasone propionate/salmeterol (FP/S; 250/50 or 500/50 μg). The primary endpoint was the number and percentage of patients reporting any adverse event (AE). Additional safety evaluations included plasma cortisol 24-hour area under the curve (AUC(0-24 h)) and ocular changes. Pulmonary function, asthma symptoms, and use of rescue medication were monitored.
The incidence of ≥1 treatment-emergent AE was similar across treatment groups (MF/F 200/10 μg, 77.3% [n= 109]; FP/S 250/50 μg, 82.4% [n= 56]; MF/F 400/10 μg, 79.2% [n= 103]; FP/S 500/50 μg, 76.9% [n= 50]). Rates of treatment-related AEs were also similar across treatment groups (MF/F 200/10 μg, 28.4%; FP/S 250/50 μg, 23.5%; MF/F 400/10 μg, 23.1%; FP/S 500/50 μg, 20.0%). Headache (3.7%) and dysphonia (2.7%) were the most common treatment-related AEs overall. The nature and frequency of AEs and the decreases in plasma cortisol AUC(0-24 h) observed with MF/F treatment were similar to those observed with FP/S treatment. Ocular events were rare (2-6% overall incidence among treatment groups); in particular, no posterior subcapsular cataracts were reported. Only three patients discontinued the study because of treatment-related ocular AEs (two for lens disorders in the MF/F 400/10 μg group; one for reduced visual acuity in the FP/S 250/50 μg group) and no asthma-related deaths occurred. Furthermore, MF/F showed numerical improvement in lung function and clinical benefits by reducing asthma symptoms and rescue medication use.
One-year treatment with the new combination therapies - twice-daily MF/F-MDI 200/10 and 400/10 μg - is safe and well tolerated in patients with persistent asthma.
吸入性糖皮质激素（ICS）与长效β₂受体激动剂联合使用，推荐用于治疗接受ICS单药治疗但控制不佳的持续性哮喘患者。本研究旨在评估通过定量吸入器（MDI）给予糠酸莫米松/福莫特罗（MF/F）对既往使用中高剂量ICS的持续性哮喘患者的长期安全性。
这是一项为期52周的随机、多中心、平行组、开放标签、评估者盲法研究。在基线时，404例年龄≥12岁的患者根据其既往ICS剂量（中或高）进行分层，然后按2:1随机分组，接受每日两次的MF/F（200/10或400/10μg）或丙酸氟替卡松/沙美特罗（FP/S；250/50或500/50μg）治疗。主要终点是报告任何不良事件（AE）的患者数量及百分比。额外的安全性评估包括血浆皮质醇24小时曲线下面积（AUC(0 - 24 h)）和眼部变化。监测肺功能、哮喘症状及急救药物的使用情况。
各治疗组≥1次治疗中出现的AE发生率相似（MF/F 200/10μg组，77.3% [n = 109]；FP/S 250/50μg组，82.4% [n = 56]；MF/F 400/10μg组，79.2% [n = 103]；FP/S 500/50μg组，76.9% [n = 50]）。各治疗组与治疗相关的AE发生率也相似（MF/F 200/10μg组，28.4%；FP/S 250/50μg组，23.5%；MF/F 400/10μg组，23.1%；FP/S 500/50μg组，20.0%）。总体而言，头痛（3.7%）和发音困难（2.7%）是最常见的与治疗相关的AE。MF/F治疗观察到的AE的性质和频率以及血浆皮质醇AUC(0 - 24 h)的降低与FP/S治疗相似。眼部事件罕见（各治疗组总发生率为2 - 6%）；特别是，未报告后囊下白内障。仅3例患者因与治疗相关的眼部AE而停止研究（MF/F 400/10μg组2例因晶状体疾病；FP/S 250/50μg组1例因视力下降），且未发生与哮喘相关的死亡。此外，MF/F在肺功能方面有数值上的改善，并通过减轻哮喘症状和减少急救药物使用而具有临床益处。
对于持续性哮喘患者，每日两次使用新的联合疗法MF/F - MDI 200/10和400/10μg进行一年治疗是安全且耐受性良好的。
