Department of Urogynecology, King's College Hospital, London, UK.
Curr Med Res Opin. 2010 Feb;26(2):253-61. doi: 10.1185/03007990903438295.
To evaluate short- and long-term safety and efficacy of duloxetine in women with predominant stress urinary incontinence (SUI).
The study was a 6-week, double-blind, randomised, parallel, placebo-controlled study followed by an uncontrolled open-label extension (OLE) run in 342 study centres in 16 European countries. Women with predominant SUI were randomly assigned to placebo (n = 1380) or duloxetine 40 mg twice daily (n = 1378) for 6 weeks. Completers of the acute phase were enrolled in the OLE, which had a minimum duration of 6 weeks and ended, based on the approval status of duloxetine in the participating country.
The primary outcome measure was the change in incontinence episode frequency (IEF) over 6 weeks. Secondary outcome measures were the long-term maintenance of effect on IEF and Patient Global Impression of Improvement (PGI-I), the short- and long-term impact on quality of life using the King's Health Questionnaire (KHQ), and the long-term safety of duloxetine.
After 6 weeks, the decrease in weekly IEF was significantly greater with duloxetine treatment compared to placebo (-50.0 vs. -29.9%; p < 0.001). The percentage of responders (defined as > or =50% decrease in IEF) was significantly higher with duloxetine treatment than with placebo (50.6 vs. 31.2%; p < 0.001). Duloxetine treatment was associated with improvements in weekly pad use (-31.4%), PGI-I ratings (63.6%), and KHQ score (-6.25) compared to placebo (-12.5%, 48.5% and -3.13, respectively, all p < 0.001). Treatment-emergent adverse events were significantly more common during duloxetine treatment (48.3%) than placebo (33.3%), (p < 0.001). Of the 2290 patients continuing into the OLE, 1165 (42.2%) completed the available duration, and 592 (21.5%) discontinued because of an adverse event (percentages relative to total randomised patients). Long-term efficacy in the OLE was assessed over a 72-week period and was maintained over that time. However, the results should be interpreted within the context that better responding patients are more likely to remain on duloxetine, while patients responding poorly are more likely to discontinue over time.
Duloxetine seems to be an efficacious treatment with an acceptable safety profile for women with SUI. Achieved improvement is maintained over the longer term in those women who remain on therapy.
评估度洛西汀治疗以压力性尿失禁（SUI）为主的女性患者的短期和长期安全性和疗效。
这是一项为期 6 周的双盲、随机、平行、安慰剂对照研究，随后在 16 个欧洲国家的 342 个研究中心进行了非控制性开放标签扩展（OLE）。以压力性尿失禁为主的女性患者被随机分配至安慰剂组（n=1380）或度洛西汀 40mg 每日 2 次组（n=1378），治疗 6 周。急性阶段的完成者被纳入 OLE，该阶段的持续时间至少为 6 周，并根据参与国家对度洛西汀的批准状况结束。
主要结局指标为治疗 6 周时失禁发作频率（IEF）的变化。次要结局指标为 IEF 的长期维持疗效和患者总体改善印象（PGI-I）、使用 King's 健康问卷（KHQ）评估的短期和长期生活质量影响，以及度洛西汀的长期安全性。
治疗 6 周后，与安慰剂相比，度洛西汀治疗的每周 IEF 下降显著更大（-50.0 比-29.9%；p<0.001）。与安慰剂相比，度洛西汀治疗的应答者比例（定义为 IEF 下降≥50%）显著更高（50.6%比 31.2%；p<0.001）。与安慰剂组相比，度洛西汀治疗与每周垫使用减少（-31.4%）、PGI-I 评分（63.6%）和 KHQ 评分（-6.25）改善相关（分别为-12.5%、48.5%和-3.13，均 p<0.001）。与安慰剂组（33.3%）相比，度洛西汀治疗（48.3%）的治疗中出现的不良事件更常见（p<0.001）。在进入 OLE 的 2290 名患者中，1165 名（42.2%）完成了可提供的治疗持续时间，592 名（21.5%）因不良事件而停药（相对于总随机患者的百分比）。OLE 中的长期疗效在 72 周的时间内进行了评估，并在该时间内得到维持。然而，结果应在以下背景下进行解释：应答更好的患者更有可能继续接受度洛西汀治疗，而应答较差的患者更有可能随着时间的推移而停药。
度洛西汀似乎是一种有效治疗以压力性尿失禁为主的女性患者的药物，具有可接受的安全性。在那些继续接受治疗的女性中，治疗获得的改善在较长时间内得以维持。
