Persistence with antimuscarinic therapy in patients with overactive bladder

Overactive bladder (OAB) is a chronic condition, which impacts patients' health and quality of life. The primary symptoms of OAB are distressing and may interfere with work, psychosocial and sexual functioning. OAB also is associated with increased risk of urinary tract infections, fractures from falls, skin infections and depression. Patient's concerns about the effects of incontinence on lifestyle highlight the need to restore continence. The mainstay of treatment is antimuscarinic drug therapy, which may often produce only modest reductions in OAB symptoms and may be accompanied by bothersome adverse effects, leading to poor adherence to prescribed medications. Successful treatment of OAB depends on persistence with the prescribed medication, and efficacy and tolerability are key influencers of persistence. New antimuscarinic agents are now available for treating OAB that significantly improve symptoms of incontinence, urgency and frequency with few adverse effects. An improved efficacy and tolerability profile should result in greater patient satisfaction and persistence with therapy during long-term therapy.     

Mirabegron or tolterodine for the treatment of overactive bladder in Japan: Which drug is more cost‐effective as the first‐line treatment?

Objectives

To assess the cost‐effectiveness of mirabegron 50 mg relative to tolterodine extended release 4 mg for the treatment of overactive bladder if used as the first‐line treatment in Japan.

Methods

A Markov model was developed to simulate the cost‐effectiveness of the mirabegron first‐line treatment (and tolterodine second‐line) versus tolterodine first‐line treatment (and mirabegron second‐line) taken for 5 years from the randomized European‐Australian study (SCORPIO trial) and single technology appraisal assessment report by the National Institute for Health and Care Excellence. The incremental cost‐effectiveness ratio was calculated with utility value by quality‐adjusted life year with cost using the medical fee and the drug price tariff in 2016. For the study of transition of treatment status, our analytical model was established. The transition probabilities of severity states were calculated based on the probabilities for the mean numbers of incontinence episodes/day and micturition episodes/day in mirabegron‐treated and tolterodine‐treated patients in the single technology appraisal assessment report.

Results

The 5‐year expected effect per patient was 3.860 quality‐adjusted life years for first‐line mirabegron and 3.839 quality‐adjusted life years for first‐line tolterodine. The 5‐year expected cost per patient was ¥526 191 for first‐line mirabegron, and ¥472 390 for first‐line tolterodine. The incremental cost‐effectiveness ratio was ¥2 565 927/quality‐adjusted life year. This value was below the willingness‐to‐pay threshold of ¥5 million/quality‐adjusted life year. In more severe states, the incremental cost‐effectiveness ratio exceeded ¥5 million.

Conclusions

First‐line mirabegron appears to be more cost‐effective than first‐line tolterodine. In patients with severe symptoms, first‐line mirabegron is not economically preferable.

     

骶神经磁刺激联合托特罗定治疗老年女性混合性尿失禁的疗效观察

目的 探讨骶神经磁刺激联合托特罗定治疗老年女性混合性尿失禁的临床疗效.方法 选取61例老年女性混合性尿失禁病人,根据就诊顺序分为对照组和观察组,对照组(n=30)服用酒石酸托特罗定缓释片(4mg/粒,1粒/d),共服用2个月;观察组(n=31)在托特罗定基础上联合骶神经磁刺激治疗(2次/周,40 min/次),共治疗2...     

Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder in Japanese patients

AIM: To evaluate the long-term safety, tolerability and efficacy of extended-release (ER) tolterodine in Japanese patients completing 12-week treatment in a randomized, double-blind trial comparing tolterodine ER 4 mg once daily, oxybutynin 3 mg three times daily or placebo in patients with overactive bladder. METHODS: Of 293 Japanese patients completing the 12-week study, 188 continued in the open-label trial and received tolterodine ER 4 mg once daily for 12 months, irrespective of previous treatment. The primary objective was to assess the safety of tolterodine ER for up to 52 weeks of treatment and at post-treatment follow-up. Secondary endpoints included changes in micturition diary variables, patient perception of bladder condition and urgency and treatment benefit. RESULTS: Overall, 77% of patients completed 12 months of open-label treatment. Tolterodine ER was well tolerated and the most common adverse event was dry mouth (33.5%). In general, there was no increase in adverse event frequency with long-term treatment compared with short-term treatment. The efficacy of tolterodine ER was maintained over the 12-month period. The complete analysis showed a median reduction in incontinence episodes/week (-92.9%; mean reduction, -77.2%), a mean reduction in micturitions/24 h (-21.3%) and a mean increase in volume voided per micturition (19.6%). Of patients completing the 12-month study, 78.6% reported improvement in patient perception of bladder condition, 52.4% reported improvement in perception of urgency and 89.7% reported treatment benefit. CONCLUSIONS: Favorable safety, tolerability and efficacy of once-daily tolterodine ER was maintained over 12 months in a Japanese overactive bladder patient population.     

Efficacy of extended‐release tolterodine for the treatment of neurogenic detrusor overactivity and/or low‐compliance bladder

Objective: To evaluate the efficacy of extended‐release (ER) tolterodine 4 mg/day for the treatment of neurogenic detrusor overactivity (NDO) and/or low‐compliance bladder by assessing urodynamic parameters. Methods: Forty‐six patients (25 male, 21 female; mean age 57.6 ± 20.7 years) with NDO (n = 39) and/or low‐compliance bladder (n = 7) were included in this 12‐week single‐arm study. Twenty‐one patients (46%) were on clean intermittent catheterization and other patients could void on their own. A video urodynamic study was performed before and at 3 months after treatment. Changes in Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Questionnaire–Short Form (ICIQ‐SF), and King's Health Questionnaire (KHQ) as well as changes in number of voids, amount of each void, and number of leaks in 24 h according to the 3‐day voiding diary were also evaluated before treatment and at weeks 4 and 12 after treatment. Results: Bladder capacity at first sensation and maximum cystometric capacity increased significantly, by an average of 36.8 mL (P = 0.0402) and 82.3 mL (P < 0.0001), respectively. Maximum cystometric capacity increased by more than 50 mL in 19 patients (49%) following treatment. Detrusor overactivity disappeared in three of 32 patients (9%), bladder capacity at first involuntary contraction increased significantly (P = 0.0009), and amplitude of detrusor overactivity decreased significantly (P = 0.0025). In patients with low‐compliance bladder, bladder compliance increased significantly (P = 0.0156). Overactive bladder symptom score, International Consultation on Incontinence Questionnaire–Short Form score, number of voids (per 24 h and night‐time), number of urgency episodes in 24 h, number and amount of leaks in 24 h, and amount of mean and maximum voided volumes all decreased significantly after treatment. Conclusion: Tolterodine is effective and well tolerated for the treatment of NDO and/or low‐compliance bladder in patients with neurogenic bladder.     

随机单盲对照研究观察托特罗定治疗留置尿管相关膀胱不适的疗效

目的探讨托特罗定治疗留置尿管后导致膀胱不适的疗效。方法观察2005年10月至2010年8月由于各种原因留置尿管的患者,对比托特罗定治疗和安慰剂治疗的疗效,采用随机分组选择患者为治疗组或安慰剂组,治疗组口服托特罗定,每次2 mg,每天2次至拔管。结果尿道手术组完成的63例中,治疗组36例发生膀胱不适1例,安慰剂组27例发生膀胱不适7例;前列腺电切组完成的271例中,治疗组164例发生膀胱不适7例,安慰剂组107例发生膀胱不适43例;膀胱肿瘤电切组完成的76例中,治疗组34例均未发生膀胱不适,安慰剂组42例发生膀胱不适9例;输尿管镜组完成的363例中,治疗组217例发生膀胱不适9例,安慰剂组146例发生膀胱不适41例;经皮肾镜组167例中,治疗组72例发生膀胱不适2例,安慰剂组95例发生膀胱不适25例;腔内未操作组完成的88例中,治疗组47例发生膀胱不适4例,安慰剂组41例发生膀胱不适10例。结论托特罗定能够有效控制各种原因留置尿管后引起的膀胱不适症状。     

Evidence for the efficacy and safety of tolterodine in the treatment of overactive bladder

Overactive bladder (OAB) is a chronic and prevalent condition, the symptoms of which (urinary frequency and urgency, with or without urge incontinence) can exert a profound negative effect on a person’s daily life activities. Tolterodine (Detrol^® in North America and Detrusitol^® in the rest of the world, Pharmacia), a competitive muscarinic antagonist, is the first agent of this class to be specifically developed for the treatment of OAB. This agent displays in vivo functional selectivity for the bladder over other tissues that contain muscarinic receptors (e.g., salivary glands, eye), which translates into good efficacy and tolerability in patients with OAB (including the elderly). Comparative, randomised, double-blind studies show that tolterodine (administered as immediate-release [IR] tablets 2 mg b.i.d.) is as effective as oxybutynin (5 mg t.i.d.) in improving all of the troublesome symptoms of OAB but with a significantly lower incidence and severity of dry mouth. The advent of a new extended-release (ER) capsule formulation of tolterodine (4 mg) for convenient once-daily treatment builds upon these findings, with significantly improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth relative to the existing IR tablet (2 mg b.i.d.). Tolterodine can therefore be considered a valuable, well-tolerated treatment option for patients with OAB, providing improvements in symptoms that are both clinically meaningful to patients and sustained during long-term treatment.     

Efficacy and tolerability of tolterodine extended-release in men with overactive bladder and urgency urinary incontinence

A group of authors from the USA evaluated the efficacy and tolerability of tolterodine extended-release on objective and subjective endpoints in men with an overactive bladder. They found that it significantly reduced incontinent episodes and improved patient perception of treatment benefit in men with an overactive bladder OBJECTIVE: To evaluate the efficacy and tolerability of tolterodine extended-release (ER) on objective and subjective endpoints in men with overactive bladder (OAB) and urgency urinary incontinence (UI). PATIENTS AND METHODS This was a post hoc analysis of data collected from men with OAB enrolled in a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once daily; tolterodine ER registration trial) and included men with urinary frequency (> or =8 micturitions/24 h) and urgency UI (> or =5 episodes/week). UI episodes were assessed using 7-day bladder diaries. Patient perception of treatment benefit was evaluated after 12 weeks. Adverse events (AEs) were recorded throughout the study. RESULTS: In all, 163 men with OAB (placebo, 86; tolterodine ER, 77; mean age 65 years) were evaluated. Baseline demographics and clinical characteristics were similar for the two treatment groups. Compared with placebo, tolterodine ER significantly reduced weekly UI episodes (median % change, -71% vs - 40%, P < 0.05; mean numeric change, - 11.9 vs -5.9, P = 0.02). Men receiving tolterodine ER had fewer micturitions/24 h, but this was not a significant difference from placebo (median % change, -12% vs - 4%, P = 0.22). Significantly more men treated with tolterodine-ER (63%) than placebo-treated men (46%) reported a benefit of treatment after 12 weeks (P = 0.04). The most commonly reported AEs associated with tolterodine-ER vs placebo were dry mouth (16% vs 7%), constipation (4% vs 9%), dyspepsia (4% vs 1%), dizziness (5% vs 1%), and somnolence (3% vs 1%). One of the men receiving tolterodine ER had symptoms suggestive of urinary retention that led to his withdrawal from the study. None of the men had acute urinary retention requiring catheterization. CONCLUSION: In men with OAB and urgency UI, tolterodine ER was well tolerated and significantly reduced episodes of urgency UI, and improved patient perception of treatment benefit.     

Efficacy and tolerability of tolterodine extended-release in continent patients with overactive bladder and nocturia

OBJECTIVE: To evaluate the clinical efficacy and tolerability of tolterodine extended-release (ER) in continent patients with overactive bladder (OAB) and nocturia. PATIENTS AND METHODS: A post hoc analysis was conducted of data from a 12-week, double-blind study of 850 patients randomized to tolterodine ER (4 mg once daily) or placebo, taken within 4 h of going to bed. Patients with a mean of > or = 8 voids/24 h were enrolled, including a mean of > or = 2.5 voids/night. Patients completed 7-day voiding diaries, and for each void an urgency rating was assessed using a 5-point scale (1, none; 5, urgency incontinence); 24-h voids were categorized by urgency rating: total (1-5), non-OAB (1-2), OAB (3-4), and severe OAB (4-5) voids. All adverse events were recorded. RESULTS: The post hoc analysis included 513 patients (243 placebo; 270 tolterodine ER; 58% men) who were continent at baseline; 47% of 24-h voids were classed as non-OAB, and 12% as severe OAB. After 12 weeks of treatment, tolterodine ER significantly reduced mean urgency rating and 24-h OAB, severe OAB, and total voids vs placebo. Tolterodine ER did not affect normal, non-OAB voids, and there were no significant adverse events related to voiding. Other than dry mouth (tolterodine ER, 9% vs placebo, 2%), all the adverse events were reported in <3% of patients; <2% of patients receiving tolterodine ER withdrew because of adverse events. CONCLUSIONS: In continent patients with OAB, tolterodine ER significantly improved urgency rating and reduced 24-h OAB, severe OAB, and total voids, suggesting that it is an effective and well-tolerated treatment option for this subpopulation. More studies are needed to better understand the clinical efficacy of tolterodine ER in this under evaluated group of OAB patients without incontinence.