长期每日一次使用思力华能倍乐®在日本有症状哮喘患者中耐受性良好且在52周内维持疗效：一项随机、安慰剂对照研究。
Long-Term Once-Daily Tiotropium Respimat® Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised, Placebo-Controlled Study.
作者信息
Ohta Ken, Ichinose Masakazu, Tohda Yuji, Engel Michael, Moroni-Zentgraf Petra, Kunimitsu Satoko, Sakamoto Wataru, Adachi Mitsuru
机构信息
National Hospital Organization, Tokyo National Hospital, Tokyo, Japan.
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
出版信息
PLoS One. 2015 Apr 20;10(4):e0124109. doi: 10.1371/journal.pone.0124109. eCollection 2015.
BACKGROUND
This study assessed the long-term safety and efficacy of tiotropium Respimat, a long-acting inhaled anticholinergic bronchodilator, in asthma, added on to inhaled corticosteroids (ICS) with or without long-acting β2-agonist (LABA).
METHODS
285 patients with symptomatic asthma, despite treatment with ICS±LABA, were randomised 2:2:1 to once-daily tiotropium 5 μg, tiotropium 2.5 μg or placebo for 52 weeks (via the Respimat SoftMist inhaler) added on to ICS±LABA, in a double-blind, placebo-controlled, parallel-group study (NCT01340209).
PRIMARY OBJECTIVE
to describe the long-term safety profile of tiotropium. Secondary end points included: trough forced expiratory volume in 1 second (FEV1) response; peak expiratory flow rate (PEFR) response; seven-question Asthma Control Questionnaire (ACQ-7) score.
RESULTS
At Week 52, adverse-event (AE) rates with tiotropium 5 μg, 2.5 μg and placebo were 88.6%, 86.8% and 89.5%, respectively. Commonly reported AEs with tiotropium 5 μg, 2.5 μg and placebo were nasopharyngitis (48.2%, 44.7%, 42.1%), asthma (28.9%, 29.8%, 38.6%), decreased PEFR (15.8%, 7.9%, 21.1%), bronchitis (9.6%, 13.2%, 7.0%), pharyngitis (7.9%, 13.2%, 3.5%) and gastroenteritis (10.5%, 3.5%, 5.3%). In the tiotropium 5 μg, 2.5 μg and placebo groups, 8.8%, 5.3% and 5.3% of patients reported drug-related AEs; 3.5%, 3.5% and 15.8% reported serious AEs. Asthma worsening was the only serious AE reported in more than one patient. At Week 52, adjusted mean trough FEV1 and trough PEFR responses were significantly higher with tiotropium 5 μg (but not 2.5 μg) versus placebo. ACQ-7 responder rates were higher with tiotropium 5 μg and 2.5 μg versus placebo at Week 24.
CONCLUSIONS
The long-term tiotropium Respimat safety profile was comparable with that of placebo Respimat, and associated with mild to moderate, non-serious AEs in patients with symptomatic asthma despite ICS±LABA therapy. Compared with placebo, tiotropium 5 μg, but not 2.5 μg, significantly improved lung function and symptoms, supporting the long-term efficacy of the 5 μg dose.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01340209.
背景
本研究评估了噻托溴铵软雾吸入剂（一种长效吸入性抗胆碱能支气管扩张剂）在哮喘治疗中，添加至吸入性糖皮质激素（ICS）联合或不联合长效β2受体激动剂（LABA）治疗方案时的长期安全性和有效性。
方法
在一项双盲、安慰剂对照、平行组研究（NCT01340209）中，285例尽管接受了ICS±LABA治疗但仍有症状的哮喘患者，按2:2:1随机分组，分别接受每日一次的5μg噻托溴铵、2.5μg噻托溴铵或安慰剂治疗，为期52周（通过软雾吸入器给药），添加至ICS±LABA治疗方案中。
主要目的
描述噻托溴铵的长期安全性。次要终点包括：1秒用力呼气容积（FEV1）谷值反应；呼气峰值流速（PEFR）反应；七项哮喘控制问卷（ACQ-7）评分。
结果
在第52周时，5μg噻托溴铵组、2.5μg噻托溴铵组和安慰剂组的不良事件（AE）发生率分别为88.6%、86.8%和89.5%。5μg噻托溴铵组、2.5μg噻托溴铵组和安慰剂组常见报告的AE分别为鼻咽炎（48.2%、44.7%、42.1%）、哮喘（28.9%、29.8%、38.6%）、PEFR降低（15.8%、7.9%、21.1%）、支气管炎（9.6%、13.2%、7.0%）、咽炎（7.9%、13.2%、3.5%）和胃肠炎（10.5%、3.5%、5.3%）。在5μg噻托溴铵组、2.5μg噻托溴铵组和安慰剂组中，分别有8.8%、5.3%和5.3%的患者报告了与药物相关的AE；分别有3.5%、3.5%和15.8%的患者报告了严重AE。哮喘恶化是唯一在不止一名患者中报告的严重AE。在第52周时，与安慰剂相比，5μg噻托溴铵（但不是2.5μg噻托溴铵）调整后的平均FEV1谷值和PEFR谷值反应显著更高。在第24周时，5μg噻托溴铵组和2.5μg噻托溴铵组的ACQ-7缓解率高于安慰剂组。
结论
噻托溴铵软雾吸入剂的长期安全性与安慰剂软雾吸入剂相当，在接受ICS±LABA治疗仍有症状的哮喘患者中，与轻至中度、非严重AE相关。与安慰剂相比，5μg噻托溴铵（而非2.5μg噻托溴铵）显著改善了肺功能和症状，支持了5μg剂量的长期有效性。
试验注册
ClinicalTrials.gov NCT01340209。
Zotero 插件