Characteristics of antimuscarinic responders versus suboptimal responders in a randomized clinical trial of patients with overactive bladder symptoms

Objective: To assess the characteristics of tolterodine extended-release (ER) 4?mg responders and suboptimal responders (≤50% decrease in UUI episodes/24?h) among patients with overactive bladder (OAB), including urgency urinary incontinence (UUI), and identify predictors of a >50% UUI response with fesoterodine 8?mg in tolterodine suboptimal responders.

Methods: Adult patients with OAB symptoms for ≥6 months and ≥8 micturitions, and ≥2 and <15 UUI episodes/24?h at week ?2 received open-label tolterodine ER 4?mg during a 2 week run-in. Suboptimal responders after tolterodine treatment (week 0) were randomized to fesoterodine (4?mg for 1 week, 8?mg for weeks 2–12) or placebo once daily. Post-hoc analyses compared the percentage change from week ?2 to week 0 in UUI episodes/24?h in tolterodine responders versus suboptimal responders and identified significant predictors of a UUI response at week 12 with fesoterodine 8?mg among tolterodine suboptimal responders.

Results: Of 897 patients, 610 (68%) were UUI suboptimal responders during the run-in period. UUI episodes/24?h at week ?2 were similar in tolterodine responders and suboptimal responders (4.2 vs. 4.3), but responders showed a significantly greater median percentage decrease in UUI episodes/24?h after tolterodine treatment at week 0 (80.0% versus 15.3%; p?p?=?.0027). Fesoterodine (vs. placebo), no previous antimuscarinic use before tolterodine run-in, and less UUI severity at baseline were significant predictors of a UUI response.

Conclusions: For patients with OAB, including UUI, who were treated initially with tolterodine and showed a suboptimal UUI response, nearly 70% demonstrated a UUI response with second-line fesoterodine 8?mg. No antimuscarinic use before tolterodine and fewer baseline UUI episodes were significant predictors of a UUI response with fesoterodine.     

Impact of OAB symptoms on work,quality of life and treatment-seeking behavior in Brazil

Abstract

Objective: To evaluate the effect of individual lower urinary tract symptoms (LUTS) and LUTS-specific bother on daily/leisure activities, work productivity and treatment behaviors and satisfaction in a Brazilian population reporting symptoms of the overactive bladder (OAB) syndrome.

Methods: Secondary analysis of Brazil LUTS study data, including individuals ≥40?years old with a possible diagnosis of OAB, based on a score of ≥8 on the OAB-V8 questionnaire. Participants used a 5-point Likert scale to rate occurrence of LUTS during the previous month. Regression models were constructed to analyze association of symptom frequency and bother, controlled for demographics, comorbid conditions, habits and body mass index, to outcomes related to people’s lives and treatment patterns.

Results: This analysis included 5184 individuals (53% female), 24.4% of whom received a possible diagnosis of OAB. There was a greater likelihood of OAB symptoms in men reporting depression/anxiety (2.0 times), diabetes (1.8 times), or constipation (1.9 times) and women reporting depression/anxiety (2.6 times), constipation (1.7 times), and being overweight (1.4 times) or obese (1.8 times). Symptoms of all categories, including voiding, storage, and post-micturition, were associated with a negative impact on individuals’ lives, quality of life and treatment-related outcomes. Treatment seeking for OAB was low among men and women overall (35.1 and 43.6%, respectively), with highest rates among individuals in the 60–69 age group.

Conclusions: LUTS of all categories impacted all domains studied. These results highlight the importance of comprehensive LUTS assessment in OAB patients, including voiding, storage and post-micturition symptoms.     

Effects of tolterodine ER on patient-reported outcomes in sexually active women with overactive bladder and urgency urinary incontinence

ABSTRACT

Objective: To assess the effects of tolterodine extended release (ER) on patient-reported outcomes (PROs) in sexually active women with overactive bladder (OAB) and urgency urinary incontinence (UUI).

Research design and methods: This multicenter, double-blind, placebo controlled trial included 411 women aged?≥18 years reporting OAB symptoms for ≥3 months; ≥8 micturitions per 24 hours (including ≥0.6 UUI episodes and ≥3 OAB micturitions) in 5-day bladder diaries at baseline, and being in a sexually active relationship for ≥6 months. Subjects randomized to placebo or tolterodine ER completed validated OAB- or incontinence-specific questionnaires, including the Patient Perception of Bladder Condition (PPBC), Overactive Bladder Questionnaire (OAB-q), Urgency Perception Scale (UPS), and the Incontinence Impact Questionnaire (IIQ) at baseline and week 12, as well as the Perception of Treatment Benefit and Treatment Satisfaction questions at week 12. This study is registered with ClinicalTrials.gov (identifier: NCT00143481)

Results: The mean age of enrolled women was approximately 48 years. Compared with placebo, the tolterodine ER group reported significant baseline to week 12 improvements in PPBC responses (p?=?0.0048); OAB-q Symptom Bother, total Health-Related Quality of Life (HRQL), and HRQL domain scores (all p?<?0.05); IIQ Emotional Health domain scores (p?<?0.05); proportions of subjects reporting treatment benefit (79 vs. 54%; p?<?0.0001) and satisfaction (78 vs. 59%; p?<?0.0001). Improvements on the UPS were not significantly different.

Conclusions: Tolterodine ER treatment was associated with improvements in multiple OAB- and incontinence-specific PROs in a sexually active, relatively young, and racially diverse population of women. The findings provide clinicians with new insights into the impact of OAB and its treatment on HRQL in this population, which has been underrepresented in previous OAB studies. Study limitations include a potential underestimation of the impact of OAB symptoms resulting from the exclusion of women who may not be sexually active because of their urinary symptoms.

Trial registration: ClinicalTrials.gov identifier: NCT00143481.     

Effectiveness and Safety of Intradetrusor OnabotulinumtoxinA Injection for Neurogenic Detrusor Overactivity and Overactive Bladder Patients in Taiwan—A Phase IV Prospective,Interventional, Multiple-Center Study (Restore Study)

We conducted a phase IV, pre/post multi-center study to evaluate the efficacy and safety of intradetrusor onabotulinumtoxinA injection in patients with neurogenic detrusor overactivity (NDO, n = 119) or overactive bladder (OAB, n = 215). Patients received either 200U (i.e., NDO) and 100U (i.e., OAB) of onabotulinumtoxinA injection into the bladder, respectively. The primary endpoint for all patients was the change in the PPBC questionnaire score at week 4 and week 12 post-treatment compared with baseline. The secondary endpoints were the changes in subjective measures (i.e., questionnaires: NBSS for patients with NDO and OABSS for those with OAB) at week 4 and week 12 post-treatment compared with baseline. Adverse events included symptomatic UTI, de novo AUR, gross hematuria and PVR > 350mL were recorded. The results showed that compared with baseline, PPBC (3.4 versus 2.4 and 2.1, p < 0.001) and NBSS (35.4 versus 20.4 and 18.1, p < 0.001) were significantly improved at 4 weeks and 12 weeks in NDO patients. In addition, compared with baseline, PPBC (3.5 versus 2.3 and 2.0, p < 0.001) and OABSS (9.1 versus 6.2 and 5.7, p < 0.001) were significantly improved at 4 weeks and 12 weeks in OAB patients. Eight (6.7%) had symptomatic UTI and 5 (4.2%) had de novo AUR in NDO patients. Twenty (9.3%) had symptomatic UTI but no de novo AUR in OAB patients. In conclusion, we found that intradetrusor onabotulinumtoxinA injections were safe and improved subjective measures related to NDO or OAB in our cohort.     

Adverse Events of Intravesical OnabotulinumtoxinA Injection between Patients with Overactive Bladder and Interstitial Cystitis—Different Mechanisms of Action of Botox on Bladder Dysfunction?

Intravesical onabotulinumtoxinA (BoNT-A) injections have been proposed to treat both overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS) in patients with refractory conditions. We compared adverse events (AEs) after BoNT-A treatment between IC/BPS and OAB in women. IC/BPS patients who failed conventional treatments were enrolled to receive suburothelial injections of BoNT-A (100 U) followed by hydrodistention. Age matched OAB female patients refractory to antimuscarinic agents underwent BoNT-A (100 U) injections. The bladder capacity, maximum flow rate (Qmax), post-void residual (PVR), and voiding efficiency (VE) at baseline, 3 and 6 months, and the post-treatment AEs were analyzed between groups. Finally, 89 IC/BPS and 72 OAB women were included. In the OAB group, the bladder capacity and PVR increased, and VE decreased significantly at three and six months after BoNT-A treatment. In the IC/BPS group, the Qmax increased significantly at six months. There were significant differences in changes of capacity, Qmax, PVR and VE between the two groups. Moreover, OAB patients suffered more frequently from events of hematuria, UTI, and large PVR (>200 mL), but less frequently from events of straining to void. In conclusion, OAB women had higher PVR volume and lower VE than those in IC/BPS after BoNT-A injections. These results imply that the bladder contractility of OAB patients are more susceptible to BoNT-A, which might reflect the different mechanisms of action of Botox on bladder dysfunction. Further investigations to confirm this hypothesis are warranted.     

Efficacy and safety of tamsulosin 0.4 mg single pills for treatment of Asian patients with symptomatic benign prostatic hyperplasia with lower urinary tract symptoms: a randomized,double-blind,phase 3 trial

Objective: To verify the efficacy and safety of tamsulosin 0.4?mg and tamsulosin 0.2?mg compared with those of placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).

Methods: A total of 494 patients from multiple centers participated in this double-blind, randomized, phase 3 trial. Eligible patients were randomly assigned to the tamsulosin 0.4?mg group, tamsulosin 0.2?mg group or placebo group. The International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual (PVR) urine volume, blood pressure, heart rate and adverse events were compared among the three groups at 4, 8 and 12 weeks.

Results: A total of 494 BPH patients were analyzed. There were no differences in the baseline characteristics among the three groups. After 12 weeks of treatment, total IPSS was improved in the 0.2?mg and 0.4?mg tamsulosin groups; however, the extent of improvement was greater in the 0.4?mg group than in the 0.2?mg group (0.4?mg: ?9.59 vs. 0.2?mg: ?5.61; least-squares mean difference [95% confidence interval]: ?3.95 [?5.01, ?2.89], p?p?Qmax and PVR were improved in the 0.4?mg and 0.2?mg groups; however, the differences were not statistically significant between treatment groups. No patients experienced any serious adverse effects in any of the three groups.

Conclusions: Tamsulosin 0.4?mg and 0.2?mg appear to be superior to placebo treatment, and tamsulosin 0.4?mg is more effective than 0.2?mg in terms of total IPSS improvement. Tamsulosin 0.4?mg has favorable efficacy and tolerability in Asian men with symptomatic BPH.

ClinicalTrials.gov Identifier: NCT02390882.     

Efficacy and Safety of Intravesical OnabotulinumtoxinA Injection in Patients with Detrusor Hyperactivity and Impaired Contractility

We investigated the efficacy and safety of intravesical onabotulinumtoxinA injection in patients with detrusor hyperactivity and impaired contractility (DHIC). Twenty-one patients with urodynamically proven DHIC and 21 age-matched patients with overactive bladder (OAB) with urodynamic detrusor overactivity were treated with intravesical injections of 100 U of onabotulinumtoxinA. The overactive bladder symptom score, urgency severity score, patient perception of bladder condition, global response assessment, voiding diary, and procedure-related adverse events (AE) at baseline, two weeks, one, three, and six months after treatment were assessed. The results showed that the subjective symptom scores improved significantly in both groups, and the scores did not differ between the groups. The decrease in urgency episodes and urgency urinary incontinence were noted in OAB patients but not in DHIC patients. Although the incidence of AEs was comparable between the groups, the therapeutic efficacy lasted for a mean of 4.9 ± 4.8 months in DHIC patients and 7.2 ± 3.3 months in OAB patients (p = 0.03). We concluded that the efficacy of intravesical onabotulinumtoxinA injection for DHIC patients was limited and short-term. Nevertheless, AEs did not increase in DHIC. Intravesical onabotulinumtoxinA might not be a good indication in patients with DHIC and high post-voiding residual urine. Physicians should inform patients of the potential benefits and risks of onabotulinumtoxinA injection for treatment of DHIC.     

Long-term darifenacin treatment for overactive bladder in patients aged 65 years and older: analysis of results from a 2-year,open-label extension study

ABSTRACT

Objectives: This analysis evaluated the long-term safety, tolerability and efficacy of darifenacin, a muscarinic M₃ selective receptor antagonist, in the treatment of overactive bladder (OAB) in patients ≥ 65 years of age.

Methods: Patients who completed one of two 12-week, placebo-controlled, double-blind, feeder studies received once-daily (o.d.) treatment with darifenacin 7.5?mg for the first 2 weeks of the 2-year, open-label extension study. The dose could be subsequently adjusted (7.5 or 15?mg o.d.) according to need. Safety and tolerability were assessed, and efficacy variables/endpoints were evaluated from patient diary data.

Results: 214 patients (65–89 years) entered and 137 (64.0%) completed the 2-year extension study, amounting to 308 patient-years’ drug exposure. Darifenacin was well tolerated with no new safety concerns. The most common adverse events (AEs) were dry mouth and constipation, which infrequently resulted in discontinuation (2.3% and 4.2%, respectively). Darifenacin produced significant improvements in OAB symptoms that were maintained over the 2-year period (median reduction from feeder-study baseline to 2 years: –11.0 [–83.7%] for incontinence episodes/week and –1.2 [–12.4%] for micturitions/day, both p < 0.05), with 44.4% patients achieving ≥ 90% reduction in incontinence episodes at 2 years.

Conclusions: Darifenacin demonstrated good tolerability and safety in older patients with OAB. The improvement in OAB symptoms was sustained throughout the 2-year extension, resulting in high treatment persistence rates. Results were comparable with those in the overall OAB population from this study, indicating that darifenacin treatment is effective and well tolerated irrespective of age.     

Real-world characteristics of elderly patients with overactive bladder in the United States

Objectives: Although much has been published about the demographic and clinical characteristics of elderly patients with overactive bladder (OAB) who were enrolled in clinical trials, very little is known about the general population of elderly Americans with OAB. We update this gap in the literature by using real-world data to describe this population.

Methods: We used Medicare claims and the Medicare Current Beneficiary Surveys from 2006 to 2011 to identify patients with OAB. We describe the demographic characteristics, functional impairment and physical limitations, concurrent medical conditions, Charlson Comorbidity Index (CCI) scores, and concomitant medication use of patients with OAB; these characteristics are also described by sex and age group (65–74 vs. ≥75 years). We also compare the characteristics of OAB with non-OAB patients.

Results: We identified 415 elderly patients with OAB (average age 79 years; 71% female) and 6868 without OAB (average age 77 years; 62% female). Patients with OAB reported high levels of functional impairment as measured by the Activities of Daily Living (44% vs. 33% for non-OAB patients), Instrumental ADL (53% vs. 40% for non-OAB patients), and physical functioning limitation (90% vs. 81% for non-OAB patients) scales. Elderly patients with OAB also experienced high levels of comorbidity burden, as measured by the number of medical conditions (18 vs. 11 for non-OAB patients), CCI (2.1 vs. 1.4 for non-OAB patients), and number of non-OAB-related concomitant medications used (11 vs. 8 for non-OAB patients).

Conclusions: Elderly patients with OAB in the general population have high levels of functional impairment and physical limitations, comorbidity, and concomitant medication use. These characteristics should be taken into consideration when managing OAB symptoms and designing future clinical studies. These results, which are representative of elderly patients with OAB in the general US population, should, however, be interpreted in light of the key limitations of the data we used: patients may have been misclassified and medical conditions overestimated due to artifacts of diagnosis coding and our results can only be generalized to patients who were enrolled in Medicare Parts A, B, and D for at least 12 continuous months.     

Prevalence of probable overactive bladder in a private obstetrics and gynecology group practice

ABSTRACT

Objective: To examine the prevalence of probable overactive bladder (OAB) in black, Hispanic, and white women.

Research design and methods: This was a cross-sectional survey of women (aged ≥ 18 years) presenting to a private obstetrics and gynecology group practice. The survey consisted of the Overactive Bladder-Validated 8 (OAB-V8) and other questions related to ethnicity, health history, desire for treatment, and reason for visit.

Main outcome measure: The OAB-V8 is a validated, eight-item, self-administered questionnaire that assesses the degree of bother associated with OAB symptoms. Subjects scoring ≥ 8 on the OAB-V8 were considered to have probable OAB.

Results: A total of 947 women completed the OAB-V8: 82% were black, 10% were white, and 4% were Hispanic. The prevalence of probable OAB was similar among different races/ethnicities, with 35% of black, 36% of Hispanic, and 30% of white women scoring ≥ 8 on the OAB-V8. Micturition frequency, nocturia, and waking up at night were the most bothersome symptoms. History of constipation, history of urinary tract infection, and number of pregnancies were independent risk factors for probable OAB. Thirty-five percent of patients with probable OAB and 5% of those without OAB desired information about OAB treatment options; however, only 5% of patients reported visiting their doctor for reasons related to their bladder symptoms.

Conclusions: OAB is prevalent among black, white, and Hispanic women. Using a simple OAB awareness tool, such as the OAB-V8, can help clinicians identify patients with bothersome OAB symptoms who could benefit from treatment. The survey results may have been limited by incorrect self-reported responses, the demographics of the population, and incomplete surveys.     

Safety profiles of non-small cell lung cancer patients treated with pemetrexed plus carboplatin: a real-world retrospective,observational, cohort study

Objective: Pemetrexed plus carboplatin (PCb) is a frequently used first-line treatment in advanced non-small cell lung cancer (NSCLC). This study examined the characteristics and safety profile of a NSCLC population treated with PCb area under the concentration-time curve 5 (PCb5) or 6?mg/mL?min (PCb6) under real-world conditions.

Research design and methods: A retrospective, observational, cohort study was conducted, utilizing data from the IMS Oncology US clinic-based, longitudinal, patient-level electronic medical records (EMR), including patients with NSCLC on PCb5 or PCb6 regimens initiated concomitantly on or after the diagnosis of lung cancer during 2004–2014. Patient characteristics and incidence of adverse events (AEs) were described for each cohort. Propensity scores were calculated based on baseline demographic and clinical factors. Propensity score stratification was used to further adjust for cohort differences.

Results: In total, 636 NSCLC patients receiving PCb5 (37% aged ≥70 years) and 184 patients receiving PCb6 (34% aged ≥70 years) who met the inclusion criteria were identified in the EMR. Patients with more comorbidities were more likely to have received PCb5. Overall incidence rates (IRs) per 100 person-years were similar for neutropenia in both cohorts, were numerically higher for anemia (IR?=?43.6 vs 101.0) and thrombocytopenia (IR?=?1.5 vs 17.9), and were numerically lower for nausea (IR?=?14.4 vs 9.9) in the PCb6 vs PCb5 cohort. Within the PCb6 cohort, the IR per 100 person-years was higher for neutropenia for ≥70 year-old patients (IR?=?41.1) compared to <70 year-old patients (IR?=?14.5). After propensity score stratification, adjusted IRs showed similar patterns.

Limitations: Limitations included lack of power for AEs other than anemia, given the nature of EMR.

Conclusions: Results from this real-world analysis add to existing evidence from randomized clinical trials about PCb safety profiles in the overall NSCLC population and in elderly patients. These results may guide physicians when making treatment decisions.     

Real-world effectiveness of daily teriparatide in Japanese patients with osteoporosis at high risk for fracture: final results from the 24-month Japan Fracture Observational Study (JFOS)

Objective: The Japan Fracture Observational Study (JFOS), a prospective observational study, investigated the real-world effectiveness of daily teriparatide to reduce clinical fracture risk in osteoporotic patients.

Methods: In routine clinical practice, Japanese patients initiated on teriparatide 20?μg/day by subcutaneous injection were enrolled. The primary end-point was the rate of clinical fractures at 6-month intervals over 24 months. Bone mineral density (BMD), procollagen type 1 aminoterminal propeptide (P1NP), back pain, and health-related quality-of-life (HRQoL) information was collected.

Results: Of 1,996 patients at baseline, 90.1% were female, and mean age was 76.9 years. Teriparatide persistence at 12 and 24 months was 68.0% and 51.6%, respectively. Compared to the first 6-month treatment interval, the odds ratio of fractures decreased by 56.4% during 6–12 months, 51.6% during 12–18 months, and 58.8% during 18–24 months (all p?Conclusions: JFOS demonstrated effectiveness of teriparatide 20?μg/day to reduce the risk of clinical fractures in Japanese patients in a real-world setting.     

Oral pharmacotherapy for overactive bladder in older patients: mirabegron as a potential alternative to antimuscarinics

Objective Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and β₃-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice.

Methods Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described.

Results Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4?mg than with mirabegron 25?mg or 50?mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50?mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years.

Conclusions Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.     

Comparison of a step-down dose of once-daily ciclesonide with a continued dose of twice-daily fluticasone propionate in maintaining control of asthma

ABSTRACT

Objective: To compare a step-down approach in well-controlled asthma patients, as recommended by treatment guidelines, from fluticasone propionate 250?μg twice daily (FP250 BID), or equivalent, to ciclesonide 160?μg once daily (CIC160 OD) with continued FP250 BID treatment.

Research design and methods: Patients with well-controlled asthma prior to study entry were included in two identical, randomized, double-blind, double-dummy, parallel-group studies. After a 2-week run-in period with FP250 BID, patients were randomized to CIC160 OD (n = 58) or FP250 BID (n = 53) for 12 weeks. Primary endpoints were percentage of days with asthma control, asthma symptom-free days, rescue medication-free days and nocturnal awakening-free days. Secondary endpoints included lung function variables, asthma symptom scores, rescue medication use and asthma exacerbations. Safety variables were also recorded.

Results: Patients had ≥ 97% of days with asthma control, 98% asthma symptom-free days and 100% of days free from rescue medication use and nocturnal awakenings in both treatment groups (median values). There were no significant between-treatment differences for any of the primary or secondary efficacy variables. Overall, 42 treatment-emergent adverse events (TEAEs) were reported in the CIC160 OD group and 49 TEAEs were reported in the FP250 BID group. There were no clinically relevant changes from baseline in the safety variables in either treatment group.

Conclusions: Patients well controlled on FP250 BID, or equivalent, who were stepped down to CIC160 OD, maintained similar asthma control compared with patients who received continued treatment standardized to FP250 BID.     

Safety and efficacy of fesoterodine fumarate in patients with overactive bladder: results of a post-marketing surveillance study in Korea

Objectives: The aim of this study was to evaluate the safety and efficacy of fesoterodine fumarate (fesoterodine; Toviaz) in Korean patients with overactive bladder (OAB) in routine clinical practice. Methods: This was an open-label, non-interventional, prospective, post-marketing surveillance study submitted to the Korean Ministry of Food and Drug Safety. A total of 3109 patients aged ≥18 years with OAB symptoms were prescribed flexible doses of fesoterodine at the investigator’s discretion. Safety was assessed based upon the reporting of adverse events (AEs). Efficacy was evaluated on the basis of patient self-assessment using a bladder diary as well as on the basis of investigator assessment in terms of overall clinical efficacy.

Results: A final analysis was performed on 3107 (99.9%) and 2978 (95.8%) patients for safety and efficacy analysis, respectively. The mean treatment duration of fesoterodine was 83.2 days. The incidence of AEs was 8.5% (265/3107). Common AEs that accounted for more than 1.0% of the total AE incidence included dry mouth (5.4%, 168/3107), constipation (1.5%, 48/3107) and micturition disorder (1.1%, 35/3107). Mean episodes of urinary frequency, urgency, and urgency urinary incontinence (UUI) per 24?hours decreased by 4.0, 2.4, and 0.8, respectively (all p?<?0.001). At the final follow-up visit, the investigators found improvement in clinical efficacy for the majority of patients (90.1%, 2684/2978). Limitations of this study include the observational study design and the relatively short treatment duration.

Conclusion: These results suggest that fesoterodine is a well tolerated and effective treatment for Korean patients with OAB in routine clinical practice.     

Onset of efficacy of tolterodine extended release in patients with overactive bladder*

ABSTRACT

Objective: To assess the onset of efficacy of tolterodine extended release (ER) in patients with overactive bladder (OAB).

Research design and methods: A post hoc analysis was conducted using 3-day bladder diary data from a 12?week, multicenter, prospective, open-label study of tolterodine ER (4?mg qd) in patients (aged ≥ 18 years) with urinary frequency (≥ 8 micturitions/24?h) and urgency (strong and sudden desire to urinate) with or without urgency urinary incontinence (UUI).

Main outcome measures: Changes in micturition frequency, urgency, and UUI episodes/24?h were evaluated for treatment Days 5, 6, and 7. The percentages of patients who achieved normal micturition frequency (< 8/day) and 50%, 70%, 90%, and 100% reductions in urgency and UUI episodes (i.e., responders) were determined at Days 5, 6, and 7. Week 12 data are presented as a referent for the magnitude of treatment efficacy during Week 1.

Results: This analysis included 698 patients. On Day 5, there were significant reductions in all three diary variables (all p < 0.0001), and improvements continued on Days 6 and 7. More than half of the patients reported ≥ 50% reductions in urgency or UUI episodes on Day 5. Responder rates for all three symptoms increased through Week 12.

Conclusions: Patients with OAB experienced significant reductions in OAB symptoms as early as Day 5 of treatment with tolterodine ER. These data extend the findings of a previous analysis, in which all 3 days of the bladder diary were pooled, that demonstrated improvements in micturition frequency, urgency episodes, and UUI episodes in patients with OAB after 1 week of treatment with tolterodine ER. Limitations are that efficacy was not assessed before Day 5, this was a post hoc analysis, and the study was not placebo-controlled.