哮喘治疗中选择性PDE4抑制剂的随机、安慰剂对照研究
2009/03/18
背景：磷酸二酯酶-4（PDE4）抑制剂可能是改善哮喘和慢性阻塞性肺疾病（COPD）患者症状和肺功能的一种新的治疗方法。MK-0359是PDE4的选择性、强效、口服的抑制剂，本研究评价了慢性哮喘中MK-0359的安全性和有效性。
方法：哮喘病史≥1年、FEV1为50%～80%预计值的成人患者（N=88）随机分配进行双盲试验，分别服用MK-0359（15 mg/天）或安慰剂，服用14天后，再分别服用安慰剂或MK-0359（15 mg/天），服用14天。主要终点为在每次为期2周的治疗结束时，与基线水平相比FEV1的变化。次要终点和其他终点包括与基线水平相比，日间哮喘症状评分、夜间哮喘症状评分、总的每天β激动剂的使用情况（喷/天）、上下午的呼气峰流量（PEF）和总的哮喘患者的生活质量的变化。通过临床不良反应情况评估安全性和耐受性。
结果：MK-0359显著改善了主要终点（与安慰剂相比）：与基线水平相比，FEV1改变的最小二乘均数为0.9 L（95% CI为0.01-0.18）。日间哮喘症状评分、夜间哮喘症状评分、总的每天β激动剂的使用情况、上午的PEF、下午的PEF和生活质量也显著改善。服用MK-0359的19名患者（24.1%）和服用安慰剂的8名患者（10.4%）主诉临床上有胃肠道不良反应。还有3名服用MK-0359的患者有严重的胃肠道不良反应。
结论：口服PDE4抑制剂MK-0359服用14天后，可以改善慢性哮喘患者较低的通气功能、症状并减少药物的使用，尽管患者会出现胃肠道不良反应。
结论：口服PDE4抑制剂MK-0359服用14天后，可以改善慢性哮喘患者较低的通气功能、症状并减少药物的使用，尽管患者会出现胃肠道不良反应。
（苏楠 审校）
Lu S, et al. Respir Med. 2009 Jan 7. [Epub ahead of print]
Lu S, et al. Respir Med. 2009 Jan 7. [Epub ahead of print]
Randomized, placebo-controlled study of a selective PDE4 inhibitor in the treatment of asthma.
BACKGROUND: Phosphodiesterase-4 (PDE4) inhibitors have potential utility as a new therapeutic approach to improving symptoms and pulmonary function in asthma and COPD. This study evaluated the efficacy and safety of MK-0359, a selective and potent oral PDE4 inhibitor, in chronic asthma.
METHODS: Adults (N=88) with >/=1 year asthma history and an FEV(1) 50-80% predicted were randomized to double-blind treatment with MK-0359 (15mg/day) or placebo for 14 days, then crossed-over to the other treatment for 14 days. The primary endpoint was the change from baseline in FEV(1) at the end of each 2-week treatment period. Secondary and other endpoints included the changes from baseline in Daytime asthma symptom score, Nighttime asthma symptom score, Total daily beta-agonist use (puffs/day), AM and PM peak expiratory flow (PEF) and overall asthma-specific quality-of-life. Safety and tolerability were assessed by clinical adverse experiences.
RESULTS: MK-0359 significantly improved the primary endpoint (versus placebo): the least-squares mean difference in change from baseline in FEV(1) (L) was 0.09L (95% CI 0.01, 0.18). Endpoints of Daytime asthma symptom score, Nighttime asthma symptom score, Total daily beta-agonist use, AM PEF, PM PEF, and quality-of-life were also significantly improved. Nineteen patients (24.1%) on MK-0359 and 8 patients (10.4%) on placebo reported gastrointestinal clinical adverse experiences. Serious gastrointestinal clinical adverse experiences were reported in 3 patients while receiving MK-0359.
CONCLUSION: Over a 14-day treatment period, the oral PDE4 inhibitor MK-0359 improved lower airway function, symptoms and rescue medication use in chronic asthma, although at the expense of gastrointestinal adverse experiences.
METHODS: Adults (N=88) with >/=1 year asthma history and an FEV(1) 50-80% predicted were randomized to double-blind treatment with MK-0359 (15mg/day) or placebo for 14 days, then crossed-over to the other treatment for 14 days. The primary endpoint was the change from baseline in FEV(1) at the end of each 2-week treatment period. Secondary and other endpoints included the changes from baseline in Daytime asthma symptom score, Nighttime asthma symptom score, Total daily beta-agonist use (puffs/day), AM and PM peak expiratory flow (PEF) and overall asthma-specific quality-of-life. Safety and tolerability were assessed by clinical adverse experiences.
RESULTS: MK-0359 significantly improved the primary endpoint (versus placebo): the least-squares mean difference in change from baseline in FEV(1) (L) was 0.09L (95% CI 0.01, 0.18). Endpoints of Daytime asthma symptom score, Nighttime asthma symptom score, Total daily beta-agonist use, AM PEF, PM PEF, and quality-of-life were also significantly improved. Nineteen patients (24.1%) on MK-0359 and 8 patients (10.4%) on placebo reported gastrointestinal clinical adverse experiences. Serious gastrointestinal clinical adverse experiences were reported in 3 patients while receiving MK-0359.
CONCLUSION: Over a 14-day treatment period, the oral PDE4 inhibitor MK-0359 improved lower airway function, symptoms and rescue medication use in chronic asthma, although at the expense of gastrointestinal adverse experiences.
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