Patient Perception of Bladder Condition after Treatment with Solifenacin and Tolterodine in Overactive Bladder Patients.

BACKGROUND: Solefinacin and Tolterodine are new generation antimuscarinics claimed to have bladder specific action and less adverse effect like dry mouth. The objective of the study was to compare the improvement in urinary symptoms among patients using solefinacin and tolterodine with overactive bladder symptoms. METHODS: A hospital based cross-sectional comparative study was done for one year duration. All patients with overactive bladder symptoms were included and in every alternate patient's solefinacin and tolterodine were given after taking note of baseline OAB symptoms, PPBC score and UPS score. Participants were followed up after one month and noted improvement in endpoint OAB symptoms. Comparison of baseline to end-point symptoms changes among each group of participants were analyzed for statistical significance. RESULTS: Among 101 participants included in the study, 49 participants were in solefinacin group and 52 participants were in tolterodine group. The end-point comparison of urgency symptoms were improved by 20.1±6.76 (mean ± SD) units in solefinacin group and by 17.0 ± 9.18 units in tolterodine group. Urgency perception score improved to 2.1±0.66 for patients under solefinacin and 2±0.73 for tolterodine. Patient perception of bladder condition (PPBC) showed improvement in solefinacin group by 3.2±1.26 units and in tolteradine by 2.8±1.54 units (p = 0.165). Comparing the patient's perception of treatment outcome, massive improvement was reported by 81.6% of those receiving Solefinacinand 65.4% receiving tolterodine, though not statistically significant ( p = 0.131). CONCLUSIONS: Solefinacin and Tolterodine showed improvement in urinary symptoms, UPS and PPBC. Both showed comparable efficacy without significant superiority over one another.

Efficacy and Safety of Cathine (Nor-Pseudoephedrine) in the Treatment of Obesity: A Randomized Dose-Finding Study.

OBJECTIVE: To investigate the efficacy and safety of increasing doses of cathine (nor-pseudoephedrine) as a weight-lowering agent in patients with obesity. METHODS: Overweight and obese patients (n = 241, mean BMI 34.6 ± 3.4 kg/m²) were randomly allocated to one of three doses of cathine (16 mg, 32 mg, 53.3 mg) or placebo in addition to a multimodal lifestyle intervention program in a multicenter, double-blind, controlled, dose-finding study for 24 weeks. Primary outcome was weight loss. RESULTS: Treatment with the 3 doses of cathine resulted in a significantly greater weight loss compared to placebo over 24 weeks: 6.5 ± 4.2 kg for 16 mg cathine, 6.2 ± 4.7 kg for 32 mg cathine, and 9.1 ± 5.4 kg for 53.3 mg cathine versus 2.4 ± 4.4 kg for placebo (each p < 0.01, ANCOVA). The percentage of patients losing > 5% / >10% of initial body weight was significantly greater for all doses of cathine than for placebo (each p < 0.01, chi-square test). Heart rate increased dose-dependently (by 1.2 bpm under 16 mg, 5.8 bpm under 32 mg, and 6.2 bpm under 53.3 mg cathine), but no suspected unexpected serious adverse reactions were noted. The overall dropout rate was 24.9%, with the highest rate in the placebo group (42.3%). CONCLUSION: Cathine appears to be an effective weight-lowering agent for adjunct treatment of obesity, but additional clinical studies on its efficacy and safety are required.

Urethral Sphincter Mechanism Incompetence in 163 Neutered Female Dogs: Diagnosis, Treatment, and Relationship of Weight and Age at Neuter to Development of Disease.

BACKGROUND: Urethral sphincter mechanism incompetence (USMI) is the most common cause of urinary incontinence in neutered bitches and is most common in dogs weighing >20 kg. OBJECTIVES: To describe a population of neutered bitches with USMI and investigate their initial presentation, the relationship between weight and age at neuter, and treatment. ANIMALS: One hundred and sixty-three female dogs with USMI (UI) diagnosed between January 2009 and December 2012, and 193 continent neutered control (C) bitches. METHODS: Retrospective data were collected from neutered female dogs with USMI and healthy, continent neutered females presented between January 2009 and December 2012. RESULTS: Urinary incontinent dogs weighed more than C dogs (P = .003), and there was no difference in age at neuter. The relationship between weight at diagnosis and age at neuter was found to impact the hazard of USMI. A decrease in the hazard of USMI was found in dogs weighing >25 kg for every month delay of neuter in the first year. The hazard did not change for dogs <15 kg. Median time from neuter to development of incontinence was 3.73 years. Phenylpropanolamine was prescribed in 75.5%, diethylstilbestrol in 21.5%, and both in 3.1% of dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Neutering bitches expected to be >25 kg adult weight later in their first year may decrease the hazard of developing USMI, whereas age at neutering of bitches <25 kg may not impact continence. Heavier dogs have increased risk of USMI, and onset occurs within a few years of neuter.

Prominent complaint: a guide to medical therapy of overactive bladder syndrome in older women.

To evaluate Overactive bladder (OAB) with detrusor overactivity (DOA) following oxybutynin or tolterodine treatment in recommended doses at a four-week course. A total of 100 Iranian women 45 years or older with urgency that also showed idiopathic detrusor overactivity (IDO) in the filling phase of their cystometry were included in the current study. In this double-blinded trial two parallel groups were randomized by using two kinds of the antimuscarinic drugs for a four- week course [oxybutinin 5mg, t.d.s. or Tolterodin 2mg, b.i.d.] in the same  packages. Data were collected from three-day frequency volume chart (FVC) one month before and after the treatment course. The effectiveness of each drug was compared using the paired, samples t-test. Patients' improvement regarding urinary urgency, frequency and urge incontinence after treatment in both groups was seen, but mean improvements in the terms of urgency and urge incontinence were larger in patients who were treated by oxybutynin. Night-time frequency was shown to be improved by a significantly larger score by tolterodine. Discontinuation of treatment due to adverse events had no significant difference in two groups. Four-week treatment with oxybutynin was better than tolterodine IR in improving urgency and urge incontinence, but there were not statistically significant difference between them. In planning a course of treatment especially in the elderly, the difference in the group of symptoms that reduce patients' quality of life should be considered. Physicians should consider the patient's prominent symptom in selection of anti-muscarinic drugs for the treatment of overactive bladder syndrome especially in elderly patients.

Drug treatment patterns for the management of men with lower urinary tract symptoms associated with benign prostatic hyperplasia who have both storage and voiding symptoms: a study using the health improvement network UK primary care data.

BACKGROUND: Real-world data on the pharmacological management of men who have lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) are limited. OBJECTIVE: To characterize men with LUTS/BPH who had both storage and voiding symptoms and to evaluate treatment patterns in UK primary care. DESIGN, SETTING AND PARTICIPANTS: This was an observational study of men aged ≥45 years with a diagnosis, symptoms or therapies indicative of LUTS/BPH with both storage and voiding components. These men were identified from the large Health Improvement Network (THIN) database between 1 January 2004 and 30 September 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Drug prescriptions and switching/discontinuation patterns for α1-blockers and antimuscarinics. RESULTS AND LIMITATIONS: We identified 8694 men with a median age of 66.0 (interquartile range [IQR], 59.0-74.0) years. Most (7850; 90.3%) received an α1-blocker, and 2167 (24.9%) received antimuscarinic therapy over a median of 2.1 years. The most commonly prescribed α1-blocker was tamsulosin (81.8%); most frequent antimuscarinics were tolterodine (41.0%), oxybutynin (37.2%) and solifenacin (35.7%). Concomitant prescription of α1-blocker and antimuscarinic therapy (within 30 days of each other) was received by 1160 men (14.8% of α1-blocker-treated men). Of α1-blocker recipients, 3024 (38.5%) discontinued during follow-up, while 1149 (53.0%) discontinued antimuscarinic therapy. Of 2167 men who received an antimuscarinic, 476 (22.0%) switched to another antimuscarinic. Of the three most commonly prescribed antimuscarinics, solifenacin had the lowest proportions of discontinuations (43.0%) and switches (15.3%), and the longest median duration of therapy (90 days, IQR 30-300). General practice consultations accounted for most resource use (5307.9 per 1000 patient-years). CONCLUSIONS: This study presents real-world management of men with LUTS/BPH who have both storage and voiding symptoms. The low proportion of men who received concomitant α1-blocker and antimuscarinic therapy suggests that some patients are sub-optimally treated in routine clinical practice.

Cost effectiveness of mirabegron compared with tolterodine extended release for the treatment of adults with overactive bladder in the United Kingdom.

BACKGROUND: Overactive bladder (OAB) is highly prevalent and is associated with considerable morbidity and reduced health-related quality of life. ß3-adrenergic receptor (ß3-AR) stimulation is a novel alternative to antimuscarinic therapy for OAB. OBJECTIVE: The objective of this analysis was to assess the cost effectiveness of the ß3-AR agonist mirabegron relative to tolterodine extended release (ER) in patients with OAB from a UK National Health Service (NHS) perspective. METHODS: A Markov model was developed to simulate the management, course of disease, and effect of complications in OAB patients over a period of 5 years. Transition probabilities for symptom severity levels and probabilities of adverse events were estimated from the results of the randomised, double-blind SCORPIO trial in 1,987 patients with OAB. Other model inputs were derived from the literature and on assumptions based on clinical experience. RESULTS: Total 5-year costs per patient were £1,645.62 for mirabegron 50 mg/day and £1,607.75 for tolterodine ER 4 mg/day. Mirabegron was associated with a gain of 0.009 quality-adjusted life-years (QALYs) with an additional cost of £37.88. The resulting incremental cost-effectiveness ratio (ICER) was £4,386/QALY gained. In deterministic sensitivity analyses in the general OAB population and several subgroups, ICERs remained below the generally accepted willingness-to-pay (WTP) threshold of £20,000/QALY gained. The probability of mirabegron 50 mg being cost effective relative to tolterodine ER 4 mg was 89.4 % at the same WTP threshold. CONCLUSIONS: Mirabegron 50 mg/day is likely to be cost effective compared with tolterodine ER 4 mg/day for adult patients with OAB from a UK NHS perspective.

Tolterodine extended release in the treatment of male OAB/storage LUTS: a systematic review.

BACKGROUND: Overactive bladder (OAB)/ storage lower urinary tract symptoms (LUTS) have a high prevalence affecting up to 90% of men over 80 years. The role of sufficient therapies appears crucial. In the present review, we analyzed the mechanism of action of tolterodine extended-release (ER) with the aim to clarify its efficacy and safety profile, as compared to other active treatments of OAB/storage LUTS. METHODS: A wide Medline search was performed including the combination of following words: "LUTS", "BPH", "OAB", "antimuscarinic", "tolterodine", "tolterodine ER". IPSS, IPSS storage sub-score and IPSS QoL (International Prostate Symptom Score) were the validated efficacy outcomes. In addition, the numbers of urgency episodes/24 h, urgency incontinence episodes/24 h, incontinence episodes/24 h and pad use were considered. We also evaluated the most common adverse events (AEs) reported for tolterodine ER. RESULTS: Of 128 retrieved articles, 109 were excluded. The efficacy and tolerability of tolterodine ER Vs. tolterodine IR have been evaluated in a multicenter, double-blind, randomized placebo controlled study in 1529 patients with OAB. A 71% mean reduction in urgency incontinence episodes was found in the tolterodine ER group compared to a 60% reduction in the tolterodine IR (p < 0.05). Few studies evaluated the clinical efficacy of α-blocker/tolterodine combination therapy. In patients with large prostates (prostate volume >29 cc) only the combination therapy significantly reduced 24-h voiding frequency (2.8 vs. 1.7 with tamsulosin, 1.4 with tolterodine, or 1.6 with placebo). A recent meta-analysis evaluating tolterodine in comparison with other antimuscarinic drugs demonstrated that tolterodine ER was significantly more effective than placebo in reducing micturition/24 h, urinary leakage episodes/24 h, urgency episodes/24 h, and urgency incontinence episodes/24 h. With regard to adverse events, tolterodine ER was associated with a good adverse event profile resulting in the third most favorable antimuscarinic. Antimuscarinic drugs are the mainstay of pharmacological therapy for OAB / storage LUTS; several studies have demonstrated that tolterodine ER is an effective and well tolerated formulation of this class of treatment. CONCLUSION: Tolterodine ER resulted effective in reducing frequency urgency and nocturia and urinary leakage in male patients with OAB/storage LUTS. Dry mouth and constipation are the most frequently reported adverse events.

Combination of sacral neuromodulation and tolterodine for treatment of idiopathic overactive bladder in women: a clinical trial.

PURPOSE: To evaluate the efficacy of intermittent percutaneous needle sacral nerve stimulation (IPN-SNS) in women with idiopathic overactive bladder (IOAB) treated with tolterodine. MATERIALS AND METHODS: A total of 240 female patients diagnosed with IOAB were randomized to receive tolterodine only treatment (group 1, n = 120) or tolterodine combined with IPN-SNS (group 2, n = 120). Each group included 120 participants, who were divided into subgroups depending on whether they had dry OAB (urinary frequency and urgency) or wet OAB (urinary frequency and urgency with urgency incontinence). In the treatment group, patients received percutaneous IPN-SNS plus tolterodine (2 mg once daily), while in the control group, only tolterodine (2 mg once daily) was administered for 3 months. The voiding diary and urodynamic parameters were monitored, and patients' psychological depression and anxiety scores were recorded before and after treatment. RESULTS: There were significantly greater improvements in the conditions of first desire to void (FDV), max­imum cystometric capacity (MCC), and daily average volumes, as well as the daily single maximum voided volumes in group 2 (P = .001) than in group 1. In addition, there were significantly greater decreases in self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores in group 2 compared with group 1 (P < .001). CONCLUSION: Combined treatment with tolterodine plus IPN-SNS can not only improve the symptoms of voiding dysfunction but can also reduce the concomitant depression and anxiety in women with IOAB, there­by improving patients' quality of life.

Are we shortchanging frail older people when it comes to the pharmacological treatment of urgency urinary incontinence?

Overactive bladder and urgency incontinence are common and distressing conditions in older people, for which the first-line pharmacological treatment is a bladder antimuscarinic agent. Of these, oxybutynin is often recommended in guidelines, but is associated with a higher incidence of adverse drug effects, and in particular has been suggested to have deleterious cognitive effects. Despite this, guidelines often suggest oxybutynin as first-line treatment, and insurance based healthcare systems often require oxybutynin to be used as a first-line therapy and fail before reimbursement for the cost of newer anticholinergics is authorised. We reviewed the literature of bladder antimuscarinics in older adults, using the headings overactive bladder, urinary frequency, urgency, urge, oxybutynin, antimuscarinic, older, older people, and frail. In general, oxybutynin had a similar efficacy to other anticholinergic drugs, but a higher incidence of adverse drug events, in particular significant yet unnoticed cognitive impairment. We conclude that oxybutynin should not be used in frail older people.

Mirabegron 50 mg once-daily for the treatment of symptoms of overactive bladder: an overview of efficacy and tolerability over 12 weeks and 1 year.

The aim of the present review article was to summarize the efficacy and tolerability for mirabegron 50 mg over 12 weeks and 1 year versus placebo (SCORPIO) or tolterodine ER 4 mg (SCORPIO and TAURUS). After a 2-week placebo run-in, adults with overactive bladder symptoms for ≥3 months were randomized if, during a 3-day micturition diary period before baseline, they had an average of ≥8 micturitions/24 h and ≥3 urgency episodes. Efficacy end-points were change from baseline to each study visit and final visit in incontinence, micturitions, volume voided/micturition, urgency incontinence, urgency (grades 3 or 4), level of urgency and nocturia. Additional secondary efficacy variables included patient-reported outcomes. Safety variables included changes in treatment-emergent adverse events and vital signs. For SCORPIO, statistically significant improvements from baseline in efficacy variables and patient-reported outcomes were seen with mirabegron versus placebo from week 4, and were maintained over time. For TAURUS, numerical improvements in efficacy were evident from month 1, and were maintained throughout 12 months. Treatment-emergent adverse events incidence was similar between groups, except for dry mouth, which was reported by fourfold (SCORPIO) and threefold (TAURUS) more patients taking tolterodine than mirabegron. Mirabegron 50 mg for 12 weeks was associated with statistically significant improvements in objective measures of efficacy and patient-reported outcomes. At final visit, improvements with mirabegron 50 mg were statistically greater versus placebo. The efficacy profile of mirabegron 50 mg appears to be maintained over 12 months.

The role of mirabegron in overactive bladder: a systematic review and meta-analysis.

OBJECTIVE: To present a systematic review assessing the efficacy and safety of mirabegron for overactive bladder (OAB). MATERIALS AND METHODS: A literature search was performed using the Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded. The literature reviewed included meta-analyses, randomized and nonrandomized prospective studies. We utilized mean difference (MD) to measure the mean number of incontinence episodes and the mean number of micturitions, and OAB questionnaire (OAB-q) and odds ratio (OR) to measure adverse events rates. We used the Cochrane Collaboration's Review Manager 5.1 software for statistical analysis. RESULTS: We identified six publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that mirabegron was more effective than placebo in treating OAB despite different drug dosages in the efficacy end points: mean number of incontinence episodes per 24 h (MD -0.54; 95% CI -0.63, -0.45; p = 0.001), mean number of micturitions per 24 h (MD -0.55; 95% CI -0.63, -0.47; p = 0.001), OAB-q (MD -4.49; 95% CI -6.27, -2.71; p = 0.001) and adverse events (OR 0.99; 95% CI 0.83, 1.19; p = 0.92). When compared to tolterodine, mirabegron was more effective in terms of mean number of incontinence episodes per 24 h (MD -0.25; 95% CI -0.43, -0.06; p = 0.009). However, there were no differences between mirabegron and tolterodine in mean number of micturitions per 24 h (MD -0.17; 95% CI -0.35, 0.01; p = 0.07) and OAB-q (MD -1.09; 95% CI -2.51, 0.33; p = 0.13). Mirabegron also had a lower adverse reaction rate (OR 0.9; 95% CI 0.8, 1.0; p = 0.04). CONCLUSIONS: In this diverse population, mirabegron was an effective and safe pharmacologic therapy for OAB.

Drug development for pediatric neurogenic bladder dysfunction: dosing, endpoints, and study design.

Pediatric drug development is challenging when a product is studied for a pediatric disease that has a different underlying etiology and pathophysiology compared to the adult disease. Neurogenic bladder dysfunction (NBD) is such a therapeutic area with multiple unsuccessful development programs. The objective of this study was to critically evaluate clinical trial design elements that may have contributed to unsuccessful drug development programs for pediatric NBD. Trial design elements of drugs tested for pediatric NBD were identified from trials submitted to the U.S. Food and Drug Administration. Data were extracted from publically available FDA reviews and labeling and included trial design, primary endpoints, enrollment eligibilities, and pharmacokinetic data. A total of four products were identified. Although all four programs potentially provided clinically useful information, only one drug (oxybutynin) demonstrated efficacy in children with NBD. The lack of demonstrable efficacy for the remainder of the products illustrates that future trials should give careful attention to testing a range of doses, using objectively measured, clinically meaningful endpoints, and selecting clinical trial designs that are both interpretable and feasible. Compiling the drug development experience with pediatric NBD will facilitate an improved approach for future drug development for this, and perhaps other, therapeutic areas.

Effect of electroacupuncture combined with tolterodine on treating female mixed urinary incontinence.

PURPOSE: To examine the effectiveness of combination therapy of electroacupuncture and tolterodine in treating female patients with mixed urinary incontinence. MATERIALS AND METHODS: Seventy-one women with mixed urinary incontinence were recruited to receive electroacupuncture therapy or combination therapy with electroacupuncture and tolterodine 2 mg orally twice a day for 8 weeks. In electroacupuncture therapy, the acupoints, including BL32 (Ci Liao), BL35 (Hui Yang), SP6 (San Yin Jiao), and ST36 (Zu San Li), were selected with the stimulation of a low-frequency (20 Hz) disperse-dense wave. The International Consultation on Incontinence Questionnaire score, the number of incontinence episodes, and urine leakage were measured before and after the treatment to evaluate the effect. RESULTS: Response rates were 73.5% and 78.4% in electroacupuncture therapy group and in the combination therapy group respectively. No significant differences were found when group outcomes were compared. The International Consultation on Incontinence Questionnaire score, the number of incontinence episodes, and urine leakage improved significantly (P < .001) after 8 weeks compared with baseline values in both groups. Significantly more patients in the combination therapy group experienced more than 50% reduction in the number of incontinent episodes than in the electroacupuncture group (75.7% vs 58.8%, P < .01). They also had significantly less urine leakage than those in electroacupuncture therapy group (11.2 ± 7.6 g vs 15 ± 9.1 g) (P < .05). CONCLUSIONS: The effect of electroacupuncture for female mixed urinary incontinence may be enhanced by tolterodine.

Web-based trial to evaluate the efficacy and safety of tolterodine ER 4 mg in participants with overactive bladder: REMOTE trial.

INTRODUCTION: Participatory patient-centered, web-based methods could streamline and improve the convenience of clinical trial participation. We used an entirely web-based approach to conduct a randomized, placebo-controlled, Phase 4 (REMOTE) trial under an Investigational New Drug (IND) application to evaluate tolterodine extended release (ER) 4 mg for overactive bladder. METHODS: The trial was designed to replicate previous clinic-based trials of tolterodine ER but was conducted via the web from one clinical site overseen by physicians. Participants were recruited via the web, screened for eligibility using web-based questionnaires, had laboratory testing in their community, and entered a run-in phase requiring bladder e-diaries. Informed consent was obtained using an interactive web-based method with physician countersignature. Study medication was shipped directly to participants. RESULTS: With a goal of 283 randomized participants, 5157 registered on the trial website. Of 456 who passed initial screening, identification verification, and signed consent, 237 passed additional medical screening and were countersigned by the investigator. After laboratory testing, 118 entered the placebo run-in; only 18 passed e-diary assessments and were randomized to treatment. At week 12, the mean change from the baseline in micturitions/24 hours (primary endpoint) was -2.4 for tolterodine ER versus -0.8 for placebo [treatment difference (95% CI): -1.6 (-3.9, 0.6)]. CONCLUSION: The REMOTE trial is the first entirely web-based trial conducted under an IND application. The efficacy observed was consistent with results from conventional trials. With simplification of multi-step screening and testing, web-based trials or their component parts should provide a participant-friendly approach to many clinical trials.

Do patient characteristics predict responsiveness to treatment of overactive bladder with antimuscarinic agents?

OBJECTIVE: To determine clinical and demographic characteristics associated with antimuscarinic treatment response using a regression model. METHODS: Adults with overactive bladder (OAB) symptoms for >3 months and ≥ 1 urgency urinary incontinence (UUI) episode and ≥ 8 micturitions per 24 hours at baseline were randomized to fesoterodine (8 mg), tolterodine extended-release (4 mg), or placebo in two 12-week, double-blind, head-to-head studies. Fesoterodine-treated patients received 4 mg/d during the first week and 8 mg/d thereafter. Patients completed 3-day bladder diaries and the Overactive Bladder Questionnaire at baseline and week 12. Pooled data for changes from baseline to week 12 in winsorized UUI episodes, micturitions, and urgency episodes per 24 hours and Overactive Bladder Questionnaire Symptom Bother and health-related quality of life scores were analyzed posthoc using a regression model that selects outcome predictors from baseline values and patient characteristics while retaining baseline values and treatment, with stepwise inclusion of significant covariates and assessment of treatment interactions. Logistic regression was used for analysis of diary-dry rates. RESULTS: Younger age, lack of previous antimuscarinic treatment, shorter duration of OAB diagnosis, and female gender were common predictors of larger changes in outcomes from baseline to week 12. Baseline measures often interacted with treatment, such that poorer baseline outcomes were predictive of larger treatment differences. Longer duration since OAB diagnosis predicted greater treatment differences for UUI episodes and in diary-dry rate, and increased age predicted greater treatment differences for micturitions. CONCLUSION: Symptom severity and duration, age, gender, and previous antimuscarinic pharmacotherapy impact the response to antimuscarinic treatment.

Cost effectiveness of fesoterodine and tolterodine for the treatment of overactive bladder with urge urinary incontinence in Spain and Finland.

BACKGROUND: Overactive bladder is a prevalent condition worldwide that is associated with a considerable burden, both on the patient and on society. OBJECTIVE: Our objective was to assess the economic value of fesoterodine compared with tolterodine extended release (ER) for the treatment of overactive bladder (OAB) with urge urinary incontinence (UUI) in Spain and Finland. METHODS: A decision-tree economic model estimated the 52-week costs and quality-adjusted life-years (QALYs) of OAB/UUI patients initiating treatment with fesoterodine 4 mg/day or tolterodine ER. Individuals were evaluated for treatment response (UUI fewer than one episode/day) and persistence at weeks 4, 12, and 24. Titration from fesoterodine 4 mg/day to 8 mg/day was permitted at week 4. At week 12, non-responders discontinued treatment permanently. Efficacy, discontinuation, and utility data were derived from four clinical trials of fesoterodine. OAB-related costs, including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections, depression, and nursing home) were also included. RESULTS: A total of 19.5 % and 18.0 % of fesoterodine and tolterodine ER patients remained on treatment until week 52, respectively. QALYs were higher with fesoterodine than tolterodine ER (0.762 vs. 0.760). In Spain, fesoterodine treatment had higher total costs than (generic) tolterodine ER (€6,697 vs. 6,597), resulting in a cost of €15,633/QALY gained. In Finland, fesoterodine was cost saving relative to (non-generic) tolterodine ER (€7,885 vs. 8,024). Sensitivity analysis confirmed that these findings were robust to the expected price decrease for generic tolterodine ER in Finland. CONCLUSION: Fesoterodine is cost effective or cost saving relative to tolterodine ER for the treatment of OAB with UUI in two European countries. Payers and prescribers should consider a broad scope of costs to make informed cost-conscious choices of antimuscarinic treatment.

Phase II study on the efficacy and safety of the EP1 receptor antagonist ONO-8539 for nonneurogenic overactive bladder syndrome.

PURPOSE: We evaluated the efficacy, safety and tolerability of the EP1 receptor antagonist ONO-8539 in patients with overactive bladder syndrome. MATERIALS AND METHODS: This was a 12-week, randomized, double-blind, placebo controlled, parallel group, multicenter study with a 2-week single blind placebo run-in phase. The 435 patients were randomized to receive twice daily ONO-8539 (30, 100 or 300 mg), placebo or once daily tolterodine (4 mg). RESULTS: At the end of the 12-week treatment no statistically significant difference was found between ONO-8539 and placebo in the change from baseline in the number of micturitions per 24 hours. The primary end points for 30, 100 and 300 mg ONO-8539, and placebo were -1.02, -1.53, -1.31 and -1.40, respectively. There was no statistically significant difference between any ONO-8539 group and placebo in the change from baseline in the number of urgency or urinary urgency incontinence episodes per 24 hours, or the mean volume voided per micturition, which were secondary end points. Statistically significant differences for tolterodine vs placebo were observed in the change from baseline in the number of micturitions (p = 0.045), urgency episodes (p = 0.04) and mean volume voided per micturition (p <0.001). The incidence of adverse events was 54.1% in the placebo group, 43.0% to 54.0% in the ONO-8539 groups and 46.6% in the tolterodine group. The intensity of adverse events was similar among the treatment groups. Similar to other treatments, the most frequently reported adverse events after ONO-8539 were nasopharyngitis and diarrhea. CONCLUSIONS: The results of this study, which to our knowledge represents the first evaluation of ONO-8539 in patients with overactive bladder, suggest a minimal role for EP1 receptor antagonism in the management of overactive bladder syndrome.

Therapeutic benefit in patients switching tolterodine to other novel antimuscarinic agents.

OBJECTIVES: To explore in the daily clinical practice setting that antimuscarinic, Fesoterodine or Solifenacin, provides a greater clinical benefit after changing their prior Overactive Bladder (OAB) therapy with tolterodine extended-release (ER) to other novel antimuscarinic agents. MATERIAL AND METHODS: A post-hoc analysis of data from an observational multicenter, cross-sectional, retrospective study. Adult patients of both sexes, with OAB and OAB-V8 score≥8, who switched to fesoterodine or solifenacin within the 3-4 months before study visit from their prior tolterodine-ER-based therapy due to poor response were included. 92 patients were selected for each treatment group, matched (1:1) according to conditioned probability using the propensity score. Benefit of treatment change perceived by the physician and patient was evaluated by means of the Clinical Global Impression of Improvement subscale (CGI-I) and Treatment Benefit Scale (TBS), respectively. Degree of worry, bother and interference with daily living activities due to urinary symptoms, level of satisfaction, and preference for current treatment were also assessed. RESULTS: Fesoterodine provided a significantly greater improvement than solifenacina in terms of therapeutic benefit perceived by the physician according to ICG-I. 96.7% of the patients on fesoterodine treatment vs. 81.6% of the solifenacin group showed a score of improvement in TBS (P<.05). Fesoterodine was also better rated than solifenacin with regard to satisfaction and preference for the new treatment (93.4 vs. 78.2% P<.05). CONCLUSIONS: In daily clinical practice the switch from tolterodine LP to fesoterodine seems to provide greater benefits both from the physician's and the patient's point of view compared with those provided by solifenacin.

Gonadotropin-releasing hormone immunization for the treatment of urethral sphincter mechanism incompetence in ovariectomized bitches.

We have investigated GnRH immunization for the treatment of urethral sphincter mechanism incompetence in ovariectomized bitches. It has been reported that decreasing LH secretion through the use of GnRH agonists temporarily restores continence in some bitches. Therefore, decreasing the circulating LH concentrations by immunizing against GnRH might temporarily maintain continence in incontinent dogs. Sixteen incontinent dogs given phenylpropanolamine (PPA) to control incontinence were recruited for this study. Eleven dogs were immunized against GnRH (novel treatment group) at week 0, and nine dogs were vaccinated again 4 weeks later. Five dogs (standard treatment group) were vaccinated with a placebo twice at 4-week intervals. PPA was discontinued in the novel treatment group 2 weeks after revaccination, and standard-treatment dogs were given PPA for the duration of the study. Blood samples were collected before each treatment and at 6, 8, 10, 12, 16, 20, and 24 weeks and owners recorded episodes of incontinence throughout the study. Ten of the eleven dogs in the novel treatment group experienced side effects as a result of vaccination; two of these dogs experienced more severe side effects after the first vaccination and were withdrawn from the study as a result. Of the nine dogs that completed the vaccination series, four dogs remained continent after PPA was discontinued. For these four dogs, there was no difference in incontinent episodes when they were given PPA versus treatment with the vaccine. All nine novel-treatment dogs developed a GnRH antibody titer and experienced a significant decrease in circulating LH concentrations. In conclusion, GnRH immunization was effective in maintaining continence in four of the nine incontinent ovariectomized dogs, and in these dogs, treatment with the vaccine was comparable with treatment with PPA.