Eldred-Evans David, Dasgupta Prokar
Department of Urology, Medical Research Council (MRC) Centre for Transplantation, King's College London, Guy's Hospital, London, UK.
Transl Androl Urol. 2017 Apr;6(2):234-251. doi: 10.21037/tau.2016.12.05.
The use of botulinum toxin A (BoNT-A) has expanded across a range of lower urinary tract conditions. This review provides an overview of the current indications for BoNT-A in the lower urinary tract and critically evaluates the published evidence within each area. The classic application of BoNT-A has been in the management of refractory neurogenic detrusor overactivity (NDO) and overactive bladder (OAB). There is a large volume of high-quality evidence, including numerous randomized placebo-controlled trials, which demonstrate the efficacy of BoNT-A over a long follow-up period. The culmination of this robust evidence-base has led to onabotulinumtoxin A (onaBoNT-A) receiving regulatory approval as a second-line treatment for NDO at a dose of 200 U and OAB at dose of 100 U. Other applications for BoNT-A are used on an off-license basis and include interstitial cystitis/bladder pain syndrome (IC/BPS), benign prostatic hyperplasia (BPH), and detrusor sphincter dyssynergia (DSD). These applications are associated with a less mature evidence-base although the literature is rapidly evolving. At present, the results for painful bladder syndrome (PBS) are promising and BoNT-A injections are recommended as a fourth line option in recent international guidelines, although larger randomized study with longer follow-up are required to confirm the initial findings. As a treatment for DSD, BoNT-A injections have shown potential but only in a small number of trials of limited quality. No definite recommendation can be made based on the current evidence. Finally, the results for the treatment of BPH have been variable and recent high quality randomized controlled trials (RCTs) have suggested no benefit over placebo so at present it cannot be recommended for routine clinical practice. Future advances of BoNT-A include liposome encapsulated formulations which are being developed as an alternative to intravesical injections.
A型肉毒毒素(BoNT-A)在一系列下尿路疾病中的应用不断扩大。本综述概述了BoNT-A在下尿路疾病中的当前适应证,并对每个领域已发表的证据进行了批判性评估。BoNT-A的经典应用一直是治疗难治性神经源性逼尿肌过度活动(NDO)和膀胱过度活动症(OAB)。有大量高质量证据,包括众多随机安慰剂对照试验,证明了BoNT-A在长期随访中的疗效。这一强有力的证据基础最终导致注射用A型肉毒毒素(onaBoNT-A)获得监管批准,作为NDO的二线治疗药物,剂量为200 U,作为OAB的二线治疗药物,剂量为100 U。BoNT-A的其他应用是在未获许可的基础上使用的,包括间质性膀胱炎/膀胱疼痛综合征(IC/BPS)、良性前列腺增生(BPH)和逼尿肌括约肌协同失调(DSD)。这些应用的证据基础不太成熟,尽管相关文献正在迅速发展。目前,疼痛性膀胱综合征(PBS)的治疗结果很有前景,在最近的国际指南中,BoNT-A注射被推荐为第四线选择,不过需要更大规模、随访时间更长的随机研究来证实初步结果。作为DSD的一种治疗方法,BoNT-A注射已显示出潜力,但仅在少数质量有限的试验中。基于目前的证据无法给出明确的推荐。最后,BPH的治疗结果不一,最近的高质量随机对照试验(RCT)表明,与安慰剂相比没有益处,因此目前不推荐用于常规临床实践。BoNT-A的未来进展包括脂质体包裹制剂,正在开发这种制剂以替代膀胱内注射。