New York University Urology Associates, New York, New York.
Vanderbilt University, Nashville, Tennessee.
J Urol. 2017 Feb;197(2S):S216-S223. doi: 10.1016/j.juro.2016.10.109. Epub 2016 Dec 22.
Overactive bladder affects 12% to 17% of the general population and almost a third experience urinary incontinence, which may severely impact health related quality of life. Oral anticholinergics are the mainstay of pharmacological treatment but they are limited by inadequate efficacy or side effects, leading to a high discontinuation rate. We report the results of the first large (557 patients), phase 3, placebo controlled trial of onabotulinumtoxinA in patients with overactive bladder and urinary incontinence inadequately managed with anticholinergics.
Eligible patients with overactive bladder, 3 or more urgency urinary incontinence episodes in 3 days and 8 or more micturitions per day were randomized 1:1 to receive intradetrusor injection of onabotulinumtoxinA 100 U or placebo. Co-primary end points were the change from baseline in the number of urinary incontinence episodes per day and the proportion of patients with a positive response on the treatment benefit scale at posttreatment week 12. Secondary end points included other overactive bladder symptoms and health related quality of life. Adverse events were assessed.
OnabotulinumtoxinA significantly decreased the daily frequency of urinary incontinence episodes vs placebo (-2.65 vs -0.87, p <0.001) and 22.9% vs 6.5% of patients became completely continent. A larger proportion of onabotulinumtoxinA than placebo treated patients reported a positive response on the treatment benefit scale (60.8% vs 29.2%, p <0.001). All other overactive bladder symptoms improved vs placebo (p ≤0.05). OnabotulinumtoxinA improved patient health related quality of life across multiple measures (p <0.001). Uncomplicated urinary tract infection was the most common adverse event. A 5.4% rate of urinary retention was observed.
OnabotulinumtoxinA 100 U showed significant, clinically relevant improvement in all overactive bladder symptoms and health related quality of life in patients inadequately treated with anticholinergics and was well tolerated.
膀胱过度活动症影响 12%至 17%的普通人群，近三分之一的患者患有尿失禁，这可能严重影响健康相关的生活质量。口服抗胆碱能药物是药物治疗的主要手段，但由于疗效不足或副作用，导致停药率很高。我们报告了首个大型（557 例患者）、安慰剂对照、3 期临床试验的结果，该试验评估了在抗胆碱能药物治疗效果不佳的膀胱过度活动症伴尿失禁患者中应用奥昔布宁毒素 A 的效果。
符合条件的膀胱过度活动症患者，3 天内有 3 次或以上尿急性尿失禁发作，每天排尿 8 次或以上，按 1:1 随机分配接受膀胱内注射奥昔布宁毒素 A（100U）或安慰剂。主要共同终点为治疗后 12 周时每日尿失禁发作次数的基线变化和治疗受益量表上阳性反应的患者比例。次要终点包括其他膀胱过度活动症症状和健康相关生活质量。评估不良事件。
奥昔布宁毒素 A 与安慰剂相比显著减少了每日尿失禁发作次数（-2.65 次 vs -0.87 次，p<0.001），22.9%的患者完全缓解。奥昔布宁毒素 A 治疗组患者比安慰剂组更倾向于报告治疗受益量表上的阳性反应（60.8% vs 29.2%，p<0.001）。与安慰剂相比，所有其他膀胱过度活动症症状均有改善（p≤0.05）。奥昔布宁毒素 A 改善了多项患者健康相关生活质量指标（p<0.001）。单纯性尿路感染是最常见的不良事件。观察到 5.4%的尿潴留发生率。
奥昔布宁毒素 A 100U 显著改善了抗胆碱能药物治疗效果不佳的膀胱过度活动症患者的所有症状和健康相关生活质量，且耐受性良好。
