Proof of Concept Trial of Tanezumab for the Treatment of Symptoms Associated With Interstitial Cystitis
Proof of Concept Trial of Tanezumab for the Treatment of Symptoms Associated With Interstitial Cystitis
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DOI：
10.1016/j.juro.2010.12.088
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发表时间：
2011-05-01
影响因子：
6.6
通讯作者：
Scholfield, D.
中科院分区：
文献类型：
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作者：
Evans, R. J.;Moldwin, R. M.;Scholfield, D.
目的：在这项随机、双盲、安慰剂对照的2期研究中，我们研究了tanezumab，一种特异性抑制神经生长因子的人源化单克隆抗体，用于治疗间质性膀胱炎疼痛。材料和方法：间质性膀胱炎患者接受单次静脉注射剂量为200 μ g/kg的tanezumab或安慰剂。患者在参加研究访问前7天记录每日疼痛评分（11分数值评定量表），并在其中3天完成泌尿症状日记。患者还完成了间质性膀胱炎症状指数问卷调查和全球反应评估。主要终点是从基线到第6周平均每日数值评定量表疼痛评分的变化。次要终点包括总体反应评估、间质性膀胱炎症状指数评分、每24小时排尿次数和尿急次数，以及每次排尿的平均排尿量。对不良事件的发生率也进行了评估。结果：共有34例患者接受tanezumab治疗，30例患者接受安慰剂治疗。在第6周，与安慰剂相比，tanezumab的平均每日疼痛评分较基线显著降低（治疗差异[LS平均值，90% CI]为-1.4[-2.2,-0.5]）。与安慰剂相比，服用tanezumab的患者在总体反应评估中有显著提高的比例，并且tanezumab也显著降低了紧急事件发生的频率。Tanezumab对间质性膀胱炎症状指数评分、排尿频率或每次排尿的平均排尿量没有显著影响。最常见的不良事件是头痛（tanezumab 20.6%，安慰剂16.7%）和感觉异常（tanezumab 17.6%，安慰剂3.3%）。结论：Tanezumab在治疗间质性膀胱炎相关疼痛方面显示出初步疗效。
Purpose: In this randomized, double-blind, placebo controlled phase 2 study we investigated tanezumab, a humanized monoclonal antibody that specifically inhibits nerve growth factor as a treatment for interstitial cystitis pain.Materials and Methods: Patients with interstitial cystitis received a single intravenous dose of 200 mu g/kg tanezumab or placebo. Patients recorded daily pain scores (on an 11-point numerical rating scale) 7 days before attending study visits and completed a urinary symptom diary for 3 of those days. Patients also completed the Interstitial Cystitis Symptom Index questionnaire and a global response assessment. The primary end point was change in average daily numerical rating scale pain score from baseline to week 6. Secondary end points included global response assessment, Interstitial Cystitis Symptom Index score, micturition and urgency episode frequency per 24 hours, and mean voided volume per micturition. The incidence of adverse events was also assessed.Results: A total of 34 patients received tanezumab and 30 received placebo. At week 6 tanezumab produced a significant reduction from baseline in average daily pain score vs placebo (treatment difference [LS mean, 90% CI] was -1.4 [-2.2, -0.5]). A significantly higher proportion of patients on tanezumab responded as improved in the global response assessment and tanezumab also significantly reduced urgency episode frequency vs placebo. Tanezumab had no significant effect on Interstitial Cystitis Symptom Index score, micturition frequency or mean voided volume per micturition. The most common adverse events were headache (tanezumab 20.6%, placebo 16.7%) and paresthesia (tanezumab 17.6%, placebo 3.3%).Conclusions: Tanezumab has shown preliminary efficacy in the treatment of pain associated with interstitial cystitis.