Wagg Adrian, Wyndaele Jean-Jacque, Sieber Paul
Department of Geriatric Medicine, Royal Free and University College School of Medicine, London, United Kingdom.
Am J Geriatr Pharmacother. 2006 Mar;4(1):14-24. doi: 10.1016/j.amjopharm.2006.03.004.
Overactive bladder (OAB) syndrome is characterized by urinary frequency and urgency with or without urge incontinence, and often accompanied by nocturia. The prevalence of OAB increases with aging; it is a particularly common condition among the elderly, affecting at least 25% of people aged > or = 65 years.
The goal of this study was to assess the efficacy and tolerability of solifenacin 5 and 10 mg once daily for treating elderly subjects with OAB.
This was a retrospective analysis of pooled data from 4 studies. Data were analyzed from elderly subjects (aged > or = 65 years) with OAB who were treated with solifenacin in four 12-week, double-blind, Phase III, international, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled studies and from elderly subjects who received solifenacin in a 40-week, open-label, flexible-dose extension trial that enrolled subjects who completed 2 of the double-blind studies. Micturition data were collected from diaries completed during the 3 days before each study visit. Efficacy end points included mean change from baseline for the number of incontinence episodes/24 hours, urgency episodes/24 hours, number of micturitions/24 hours, and volume voided/micturition. The proportion of subjects who became continent or had no urgency episodes at end point was also evaluated.
The mean age of the subjects in the 12-week, double-blind studies (N = 1045; 781 women, 264 men) was 71.9 years; mean age in the 40-week extension trial (N = 509; 359 women, 150 men) was 71.2 years. The majority of subjects (74.7% in the 12-week, double-blind studies and 70.5% in the 40-week extension trial) were female, and >90% of the elderly subjects were white. The duration of OAB ranged from 0 to 66 months, and 43.7% had received previous medical therapy for OAB. The completion rate for elderly subjects was 85.5% for the 12-week, double-blind studies and 80.0% for the 40-week extension trial. Efficacy end points at week 12 of double-blind treatment demonstrated statistically significant improvements in the symptoms of OAB with solifenacin compared with placebo. Mean (SE) changes in number of incontinence episodes/24 hours were -1.5 (0.17) for the 5-mg dose and -1.9 (0.14) for the 10-mg dose compared with -1.0 (0.14) for placebo (P = 0.013 for the 5-mg dose and P < 0.001 for the 10-mg dose, vs placebo); mean (SE) changes in the number of urgency episodes/24 hours were -3.2 (0.27) for the 5-mg dose and -3.2 (0.19) for the 10-mg dose compared with -1.6 (0.18) for placebo (P < 0.001 for both doses vs placebo); mean (SE) changes in the number of micturitions/24 hours were -2.0 (0.17) for the 5-mg dose and -2.5 (0.13) for the 10-mg dose compared with -1.1 (0.13) for placebo (P < 0.001 for both doses vs placebo); mean (SE) changes in the volume voided/micturition were 30.2 (3.24) mL for the 5-mg dose and 46.2 (2.55) mL for the 10-mg dose, compared with 9.1 (2.39) mL for placebo (P < 0.001 for both doses vs placebo). The proportion of subjects with restoration of continence was 49.1% and 47.3% of the 5- and 10-mg treatment groups, respectively, compared with 28.9% of the placebo group (P < 0.001 for both doses vs placebo). The proportion of subjects with resolution of urgency was 34.6% and 24.9% for the 5- and 10-mg treatment groups, respectively, compared with 16.9% of the placebo group (P < 0.001 for the 5-mg dose and P < 0.01 for the 10-mg dose). Improvements in incontinence, urgency, and micturitions were maintained during the 40-week extension trial. The most common adverse events in both the double-blind and extension trials were dry mouth, constipation, and urinary tract infection. Most adverse events were mild to moderate in nature and did not result in treatment discontinuation.
In these pooled analyses, solifenacin 5 and 10 mg once daily were efficacious and well tolerated in the treatment of these elderly subjects with OAB. Solifenacin therapy was also associated with a high level of persistence in a 40-week extension trial.
膀胱过度活动症（OAB）综合征的特征是尿频、尿急，伴或不伴有急迫性尿失禁，且常伴有夜尿症。OAB的患病率随年龄增长而增加；在老年人中这是一种特别常见的病症，至少影响25%年龄≥65岁的人群。
本研究的目的是评估每日一次服用5毫克和10毫克索利那新治疗老年OAB患者的疗效和耐受性。
这是一项对4项研究汇总数据的回顾性分析。分析了来自4项为期12周、双盲、III期、国际、多中心、随机、平行组、固定剂量、安慰剂对照研究中接受索利那新治疗的老年（年龄≥65岁）OAB患者的数据，以及来自一项为期4周、开放标签、灵活剂量延长期试验中接受索利那新治疗的老年患者的数据，该延长期试验纳入了完成2项双盲研究的受试者。排尿数据从每次研究访视前3天完成的日记中收集。疗效终点包括与基线相比，每24小时尿失禁发作次数、尿急发作次数、排尿次数以及每次排尿量的平均变化。还评估了在终点时实现控尿或无尿急发作的受试者比例。
12周双盲研究中受试者的平均年龄（N = 1045；781名女性，264名男性）为71.9岁；40周延长期试验中受试者的平均年龄（N = 509；359名女性，150名男性）为71.2岁。大多数受试者（12周双盲研究中为74.7%，40周延长期试验中为70.5%）为女性，超过90%的老年受试者为白人。OAB的病程为0至66个月，43.7%的患者曾接受过OAB的药物治疗。12周双盲研究中老年受试者的完成率为85.5%，40周延长期试验为80.0%。双盲治疗第12周时的疗效终点显示，与安慰剂相比，索利那新在改善OAB症状方面具有统计学意义。与安慰剂相比，5毫克剂量组每24小时尿失禁发作次数的平均（SE）变化为-1.5（0.17），10毫克剂量组为-1.9（0.14），而安慰剂组为-1.0（0.14）（5毫克剂量组与安慰剂相比P = 0.013，10毫克剂量组P < 0.001）；5毫克剂量组每24小时尿急发作次数的平均（SE）变化为-3.2（0.27），10毫克剂量组为-3.2（0.19），而安慰剂组为-1.6（0.18）（两个剂量组与安慰剂相比P均< 0.001）；5毫克剂量组每24小时排尿次数的平均（SE）变化为-2.0（0.17），10毫克剂量组为-2.5（0.13），而安慰剂组为-1.1（0.13）（两个剂量组与安慰剂相比P均< 0.001）；5毫克剂量组每次排尿量的平均（SE）变化为30.2（3.24）毫升，10毫克剂量组为46.2（2.55）毫升，而安慰剂组为9.1（2.39）毫升（两个剂量组与安慰剂相比P均< 0.001）。5毫克和10毫克治疗组控尿恢复的受试者比例分别为49.1%和47.3%，而安慰剂组为28.9%（两个剂量组与安慰剂相比P均< 0.001）。5毫克和10毫克治疗组尿急缓解的受试者比例分别为34.6%和24.9%，而安慰剂组为16.9%（5毫克剂量组P < 0.001，10毫克剂量组P < 0.01）。在40周延长期试验中，尿失禁、尿急和排尿情况的改善得以维持。双盲试验和延长期试验中最常见的不良事件是口干、便秘和尿路感染。大多数不良事件为轻至中度，未导致治疗中断。
在这些汇总分析中，每日一次服用5毫克和10毫克索利那新治疗这些老年OAB患者有效且耐受性良好。在40周延长期试验中，索利那新治疗的持续性也很高。
