Efficacy and safety of solifenacin plus tamsulosin oral controlled absorption system in men with lower urinary tract symptoms: a meta-analysis

We performed a meta-analysis to compare treatment with a combination of solifenacin plus tamsulosin oral controlled absorption system (TOCAS) with placebo or TOCAS monotherapy. The aim of the meta-analysis was to clarify the efficacy and safety of the combination treatments method for lower urinary tract symptoms (LUTS). We searched for trials of men with LUTS that were randomized to combination treatment compared with TOCAS monotherapy or placebo. We pooled data from three placebo-controlled trials meeting inclusion criteria. Primary outcomes of interest included changes in International Prostate Symptom Score (IPSS) and urinary frequency. We also assessed postvoid residual, maximum urinary flow rate, incidence of urinary retention (UR), adverse events. Data were pooled using random or fixed effect models for continuous outcomes and the Mantel–Haenszel method to generate risk ratio. Reductions in IPSS storage subscore and total urgency and frequency score (TUFS) were observed with solifenacin 6 mg plus TOCAS compared with placebo (P < 0.0001 and P < 0.0001, respectively). Reductions in IPSS storage subscore and TUFS were observed with solifenacin 9 mg plus TOCAS compared with placebo (P = 0.003 and P = 0.0006, respectively). Reductions in TUFS was observed with solifenacin 6 mg plus TOCAS compared with TOCAS (P = 0.01). Both combination treatments were well tolerated, with low incidence of UR. Solifenacin 6 mg plus TOCAS significantly improved total IPSS, storage and voiding symptoms compared with placebo. Solifenacin 6 mg plus TOCAS also improved storage symptoms compared with TOCAS alone. There was no additional benefit of solifenacin 9 mg compared with 6 mg when used in combination with TOCAS.     

琥珀酸索利那新在控制经尿道膀胱肿瘤电切术后膀胱刺激症状中的价值

目的 探讨索利那新在控制经尿道膀胱肿瘤电切术后膀胱刺激症状中的价值.方法 116例诊断为非肌层浸润性膀胱癌的患者纳入本研究,患者被随机分为试验组和对照组.所有患者均接受经尿道膀胱肿瘤电切术和术后即刻表柔比星灌注治疗;试验组患者于术前6h和术后连续3d每天口服索利那新5mg,对照组患者口服安慰剂;于术后6、12、24、48和72 h分别记录膀胱刺激症状评分.结果 膀胱刺激症状的发生率从93.1％(对照组)下降到67.2％(试验组)(P=0.001);在各个观测时间点对照组膀胱刺激症状的严重性均高于试验组(P＜0.05或P＜0.01).结论 索利那新可有效改善经尿道膀胱肿瘤电切术后膀胱刺激症状.     

Mirabegron causes vesical and urethral relaxation in rats with spinal cord injury

The effects of solifenacin and mirabegron on vesical and urethral function were compared in rats with or without spinal cord injury (SCI). Isovolumetric cystometry and urethral pressure recording were initially performed in intact rats. Then, the bladder neck was ligated under urethane anesthesia, after which a catheter was inserted through the bladder dome for isovolumetric cystometry and another catheter was inserted into the urethra to measure urethral pressure. Solifenacin (0.03–3 mg/kg) or mirabegron (0.03–3 mg/kg) was injected intravenously, and bladder and urethral activity were recorded. To create rats with SCI, the spinal cord was transected at the lower thoracic level under isoflurane anesthesia. After 2 weeks, a catheter was inserted through the bladder dome for single cystometry and bladder activity was recorded without anesthesia following intravenous injection of solifenacin or mirabegron. Isovolumetric cystometry revealed a larger decrease in maximum bladder contraction pressure after injection of solifenacin, whereas prolongation of the interval between bladder contractions was greater with mirabegron. In SCI rats, single cystometry showed that solifenacin and mirabegron both increased bladder volume at the first non‐voiding bladder contraction and decreased the maximum bladder contraction pressure. Mirabegron also increased the voided volume and decreased the percentage residual volume without altering bladder capacity. Solifenacin and mirabegron both inhibited bladder contractility, and mirabegron possibly also induced urethral relaxation. Mirabegron may be suitable for patients with overactive bladder and residual urine.     

坦索罗辛联合索利那新在治疗轻中度良性前列腺增生合并膀胱过度活动症中的疗效分析

目的:探讨坦索罗辛联合索利那新在治疗轻中度BPH合并膀胱过度活动症(OAB)中的有效性及安全性。方法:选取在我院诊治的轻中度良性BPH合并OAB患者166例,分为轻度梗阻症状组(88例)(联合用药组48例及坦索罗辛组40例)和中度梗阻症状组(78例)(联合用药组36例及坦索罗辛组42例)。坦索罗辛组均服用坦索罗辛0.2mg,每日1次。联合用药组均口服坦索罗辛0.2mg,每日1次,索利那新5mg,每日1次,共12周。比较两组治疗前后国际前列腺症状评分(IPSS)、排尿期症状评分、储尿期症状评分、最大尿流率(Qmax)、残余尿量、膀胱过度活动症症状评分(OABSS)、尿常规检查、不良事件等。结果:在轻度梗阻症状组中,联合用药组治疗后在IPSS、储尿期症状评分、Qmax、OABSS明显优于治疗前(P0.05),而残余尿无明显变化(P0.05),坦索罗辛组治疗后仅IPSS较治疗前有所改善,而其他方面无明显变化(P0.05);而治疗后联合用药组IPSS[(9.7±3.0)分vs(15.8±3.3)分]、储尿期症状评分[(8.1±1.7)分vs(12.3±3.1)分]、Qmax[(18.6±4.1)ml/s vs(14.2±2.3)ml/s]、OABSS[(5.3±1.3)分vs(9.7±2.7)分]等方面明显优于坦索罗辛组(P均0.05),而残余尿、尿常规检查及不良事件无明显差异(P0.05);在中度梗阻症状组,联合用药组治疗后IPSS、排尿期症状评分、Qmax、OABSS明显优于治疗前,而残余尿无明显差异;坦索罗辛组治疗后IPSS、排尿期症状评分、Qmax、OABSS及残余尿较治疗前改善明显;联合用药组的OABSS优于坦索罗辛组[(4.8±1.5)分vs(6.5±2.5)分,P0.05],而在IPSS、Qmax、排尿期症状评分、尿常规检查及不良事件等方面与坦索罗辛组无明显差异(P均0.05)。结论:坦索罗辛联合索利那新在治疗BPH轻中度梗阻症状合并OAB均有明显疗效,其疗效优于单用坦索罗辛,而不良反应无明显增加。     

Solifenacin appears effective and well tolerated in patients with symptomatic idiopathic detrusor overactivity in a placebo- and tolterodine-controlled phase 2 dose-finding study

OBJECTIVES: To evaluate the dose-response relationship and safety/tolerability of solifenacin succinate (YM905) in the treatment of overactive bladder (OAB), and to compare its efficacy and safety/tolerability with tolterodine 2 mg twice daily. PATIENTS AND METHODS: This multicentre study included a 2-week single-blind placebo run-in, a 4-week double-blind placebo-controlled active treatment phase, and a 2-week follow-up. Men and women with an OAB and urodynamic evidence of detrusor overactivity were randomized to placebo or solifenacin 2.5, 5, 10 or 20 mg once daily, or tolterodine 2 mg twice daily. RESULTS: Of 265 patients enrolled, 225 were randomized and 192 completed the study. Solifenacin 5, 10 and 20 mg produced statistically significant (P < 0.05) improvements in voids/24 h vs placebo, whereas tolterodine did not; the mean change with tolterodine was between those with solifenacin 2.5 and 5 mg. The outcome was similar for the mean change from baseline to endpoint in mean volume voided/void. For incontinence and urgency episodes/24 h the solifenacin dose groups showed numerically superior changes vs placebo; the mean effects with tolterodine were generally smaller than with solifenacin. Most of the efficacy effect of solifenacin was evident at 2 weeks. Quality-of-life outcomes supported the efficacy results. Solifenacin 5 and 10 mg were well tolerated; there were no serious treatment-related adverse events. The incidence of dry mouth was 14% for solifenacin 5 and 10 mg, 2.6% for placebo and 24% for tolterodine. CONCLUSION: In this study, the 5- and 10-mg doses of solifenacin appeared to be the most clinically effective for treating OAB, considering the balance between efficacy, quality of life and tolerability. From the results of this study solifenacin 5 and 10 mg were selected for further evaluation in large-scale phase 3 studies.     

Fistula Secondary to Unoperated Benign Gastroduodenal Ulcer

The physician must be prepared to recognize bizarre fistulas complicating benign gastroduodenal ulcer and occurring without previous gastric surgery. A benign, often subclinical ulcer crater may suddenly perforate any hollow structure in the upper abdomen or lower chest. The consequences may be remarkably benign or immediately calamitous, depending on the anatomy of the resulting fistula.     

Patient‐reported outcomes from SYNERGY,a randomized,double‐blind,multicenter study evaluating combinations of mirabegron and solifenacin compared with monotherapy and placebo in OAB patients

Aims

To evaluate patient‐reported outcomes (PROs) of combinations of solifenacin and mirabegron compared with solifenacin and mirabegron monotherapy and with placebo in patients with overactive bladder (OAB) from the SYNERGY trial.

Methods

Following a 4‐week placebo run‐in, period patients (≥18 years) with OAB were randomized 2:2:1:1:1:1 to receive solifenacin 5 mg + mirabegron 25 mg (combination 5 + 25 mg), solifenacin 5 mg + mirabegron 50 mg, (combination 5 + 50 mg), solifenacin 5 mg, mirabegron 25 mg, mirabegron 50 mg or placebo for 12 weeks, followed by a 2‐week washout period. At each visit, PROs related to quality of life, symptom bother, and treatment satisfaction were assessed, including OAB‐q Symptom Bother score, health‐related quality of life (HRQOL) Total score, treatment satisfaction‐visual analogue scale (TS‐VAS), and patient perception of bladder condition (PPBC) questionnaires.

Results

Overall, 3527 patients were randomized into the study, with 3494 receiving double‐blind treatment. At end of treatment (EoT), both combination groups showed greater improvements in OAB‐q Symptom Bother score compared with the monotherapy groups (nominal P < 0.001). Statistically significant improvements in HRQOL Total scores were observed in the combination groups versus monotherapy groups (P ≤ 0.002). For both combination groups, the OAB‐q Symptom Bother score responder rates at EoT were statistically significantly higher versus mirabegron monotherapy (P < 0.05). The mean adjusted changes from baseline to EoT for PPBC were greater in the combination groups compared with monotherapy groups.

Conclusions

PROs showed that combination therapy provided clear improvements and an additive effect for many HRQOL parameters, including OAB‐q Symptom Bother score, HRQOL Total score, and PPBC.     

Comparative efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents in overactive bladder: A systematic literature review and network meta‐analysis

Aims

To compare efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents for the treatment of overactive bladder (OAB).

Methods

Literature searches of MEDLINE, Embase, and the Cochrane Library were undertaken to identify randomized controlled trials in OAB (2000‐2015) for antimuscarinic agents. A network meta‐analysis (NMA) was performed to estimate efficacy and tolerability outcomes for solifenacin 5 mg/day relative to other antimuscarinics.

Results

The NMA included 53 eligible trials (published, n = 48; unpublished on search date, n = 5). Solifenacin 5 mg/day was significantly more effective than tolterodine 4 mg/day for reducing incontinence and urgency urinary incontinence (UUI) episodes, but significantly less effective than solifenacin 10 mg/day for micturition; no other statistically significant differences were noted for efficacy. Solifenacin 5 mg/day had a statistically significant lower risk of dry mouth compared with darifenacin 15 mg/day, fesoterodine 8 mg/day, oxybutynin extended‐release 10 mg/day, oxybutynin immediate‐release (IR) 9‐15 mg/day, tolterodine IR 4 mg/day, propiverine 20 mg/day, and solifenacin 10 mg/day. There were no significant differences between solifenacin 5 mg/day and other antimuscarinics for risk of blurred vision, or for 11 of 17 active comparators for risk of constipation.

Conclusions

This NMA suggests that the efficacy of solifenacin 5 mg/day is at least similar to other common antimuscarinics across the spectrum of OAB symptoms analyzed, and is more effective than tolterodine 4 mg/day in reducing incontinence and UUI episodes. Solifenacin 5 mg/day has a lower risk of dry mouth compared with several agents.

     

坦索罗辛联合索利那新治疗BPH伴膀胱过度活动症的临床观察

目的:探讨坦索罗辛联合索利那新治疗BPH伴膀胱过度活动症(OAB)患者的临床疗效及安全性。方法:2009年12月～2011年6月期间收集BPH伴有OAB患者262例,随机分成试验组(134例)和对照组(128例)。试验组患者口服坦索罗辛0.2mg,每天一次,同时口服索利那新5mg,每天一次;对照组患者仅口服坦索罗辛,用量用法同实验组。两组患者均药物治疗4周。观察两组患者治疗前后主观指标IPSS评分、OABSS评分及QOL评分和客观指标最大尿流率(Qmax)、24h排尿次数、尿急次数、急迫性尿失禁次数、夜尿次数、每次排尿量的变化,评估治疗后BPH患者OAB症状的改善情况及其安全性。结果:两组患者主观指标和客观指标治疗前后组内对比,差异均有统计学意义(P<0.05)。试验组治疗前后的主观指标和客观指标变化值与对照组相比,除Qmax和每次排尿量外,差异均有统计学意义(P<0.05)。两组患者的Qmax和每次排尿量治疗前后的变化值相比,差异均无统计学意义(P>0.05)。试验组和对照组不良事件总发生率较低,分别为4.58%和2.47%,无严重不良事件发生。结论:坦索罗辛联合索利那新治疗BPH伴有OAB患者的疗效,较单用坦索罗辛的疗效显著,且安全性好。