吸入式阿朴吗啡治疗“开-关”波动患者的随机、双盲、安慰剂对照、诊所和家庭为基础的平行分组研究。
Inhaled apomorphine in patients with 'on-off' fluctuations: a randomized, double-blind, placebo-controlled, clinic and home based, parallel-group study.
机构信息
Department of Neurology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK.
出版信息
J Parkinsons Dis. 2013;3(1):31-7. doi: 10.3233/JPD-120142.
BACKGROUND
In later stages of Parkinson's disease, treatment of 'off' periods with subcutaneous apomorphine is helpful but requires injection; inhaled apomorphine would be potentially more convenient.
OBJECTIVES
To identify optimal efficacy, safety and tolerability for inhaled apomorphine in reversing Parkinson's disease 'off' periods.
METHODS
A randomized, double-blind, 2:1 active:placebo, parallel-group, ascending dose titration study was conducted at 16 centres in 3 countries. Inhaled apomorphine was administered under observation, at escalating fine particle doses of 1.5, 2.5, 3.5 and 4.5 mg. This was followed by at-home patient self-treatment for 2 to 4 weeks, assessed from 'on-off' diaries.
RESULTS
In 55 patients, mean age 65.6 years (range 47-79), mean disease duration 12 years (range 5-22), the mean improvement in the unified PD rating scale part 3 (UPDRS 3) was significantly greater for apomorphine (mean dose 2.3 mg) at 19.5 (standard deviation 13.6) than for placebo at 9.9 (9.6), least squares mean difference 8.4 (95% confidence interval 1.2 to 15.5, p = 0.023). During at-home testing, mean 'off' time per day was reduced by 139.8 minutes (standard deviation 149.6) for apomorphine versus 68.0 (108.6) minutes for placebo, least squares mean difference not significant at 100.5 minutes (95% confidence interval -12.0 to 212.9, p = 0.078). The onset of action was faster for apomorphine (mean 8.1 SD 6.2 minutes) than placebo (mean 13.1 SD 6.6 minutes) (p < 0.0001). Reversal of 'off' episodes was significantly more likely for episodes treated with apomorphine than those treated with placebo: apomorphine 64.6% SD 32.3 of episodes versus placebo 11.1% SD 15.3 (p < 0.0001). During at-home treatment, 36% of apomorphine and 20% of placebo patients experienced adverse events.
CONCLUSIONS
Inhaled apomorphine in the dose range 1.5 to 4.5 mg, significantly improved UPDRS 3 scores in the clinic, and aborted a greater proportion of 'off' periods at-home, compared to placebo. However, daily 'off' time was not significantly reduced by the use of inhaled apomorphine.
背景
在帕金森病的晚期，皮下给予阿朴吗啡治疗“关闭”期是有帮助的，但需要注射；吸入阿朴吗啡可能更方便。
目的
确定吸入阿朴吗啡逆转帕金森病“关闭”期的最佳疗效、安全性和耐受性。
方法
在三个国家的 16 个中心进行了一项随机、双盲、2:1 活性药物：安慰剂、平行组、递增剂量滴定研究。在观察下，以递增的细颗粒剂量 1.5、2.5、3.5 和 4.5mg 给予吸入阿朴吗啡。随后，患者在家中自行治疗 2 至 4 周，通过“开/关”日记进行评估。
结果
在 55 名患者中，平均年龄 65.6 岁（范围 47-79），平均病程 12 年（范围 5-22），与安慰剂相比，阿朴吗啡（平均剂量 2.3mg）在统一帕金森病评定量表第 3 部分（UPDRS 3）的平均改善显著更大，为 19.5（标准差 13.6），而安慰剂为 9.9（9.6），最小二乘均数差异 8.4（95%置信区间 1.2 至 15.5，p=0.023）。在家中测试期间，阿朴吗啡的平均每日“关闭”时间减少了 139.8 分钟（标准差 149.6），而安慰剂减少了 68.0 分钟（标准差 108.6），最小二乘均数差异无统计学意义，为 100.5 分钟（95%置信区间-12.0 至 212.9，p=0.078）。阿朴吗啡的作用开始时间（平均 8.1，标准差 6.2 分钟）快于安慰剂（平均 13.1，标准差 6.6 分钟）（p<0.0001）。与安慰剂相比，阿朴吗啡治疗的“关闭”发作更有可能逆转：阿朴吗啡 64.6%（标准差 32.3）的发作，安慰剂 11.1%（标准差 15.3）（p<0.0001）。在家庭治疗期间，36%的阿朴吗啡患者和 20%的安慰剂患者出现不良反应。
结论
在 1.5 至 4.5mg 的剂量范围内，吸入阿朴吗啡可显著改善诊所的 UPDRS 3 评分，并在家中更有效地终止“关闭”期，与安慰剂相比。然而，使用吸入阿朴吗啡并没有显著减少每日“关闭”时间。
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