Flexible dosing with fesoterodine 4 and 8 mg: a systematic review of data from clinical trials.

AIMS: To systematically review dose-escalation data from flexible-dose studies of fesoterodine and summarise factors associated with dose-escalation decisions. METHODS: A PubMed search was conducted using the terms (fesoterodine AND flexible dose), with no limits. Articles were included if they contained fesoterodine dose-escalation data for efficacy or safety outcomes or factors associated with dose-escalation decisions. RESULTS: Of 13 articles identified by the search, 10 articles (six clinical studies) met inclusion criteria. In flexible-dose trials of fesoterodine, 51-63% of subjects initially receiving fesoterodine 4 mg opted for dose escalation to fesoterodine 8 mg. Escalators generally reported significantly more severe overactive bladder (OAB) symptoms, greater OAB symptom bother and worse health-related quality of life at baseline than non-escalators. Escalators demonstrated less treatment benefit with fesoterodine 4 mg than non-escalators. Non-escalators generally had a higher rate of dry mouth and constipation with fesoterodine 4 mg than escalators. The decision to escalate appeared to be determined by the efficacy/tolerability responses; fesoterodine escalators demonstrated a lower sensitivity (less efficacy and fewer adverse events) before their decision to escalate. By study end (8-11 weeks after escalation decision), the efficacy and tolerability profiles were similar in escalators and non-escalators. CONCLUSIONS: Data from flexible-dose studies provide strong evidence that fesoterodine provides treatment benefit to individual subjects with OAB because of its true dose-response effect. In clinical practice, it can be worthwhile to escalate to fesoterodine 8 mg in individual subjects who require additional efficacy benefit.

An observational study of patient satisfaction with fesoterodine in the treatment of overactive bladder: effects of additional educational material.

AIM: To compare the effects of additional educational material on treatment satisfaction of overactive bladder (OAB) patients treated with a muscarinic receptor antagonist. METHODS: In an observational study of OAB patients being treated by their physician with fesoterodine for 4 months (FAKTEN study), sites were randomised to providing standard treatment or additional educational material including the SAGA tool. Patient satisfaction was assessed by three validated patient-reported outcomes including the Treatment Satisfaction Question. Because of premature discontinuation of the study, descriptive statistical analysis was performed. RESULTS: A total of 431 and 342 patients received standard treatment or additional educational material, respectively. At study end, 76.1% [95% CI = 71.3, 80.4] of patients with standard care and 79.6% [95% CI = 74.4, 84.1] with additional SAGA tool were satisfied with treatment (primary end-point). Comparable outcomes with and without the additional educational material were also found in various patient subgroups, at the 1-month time point, and for the other patient-reported outcomes. A notable exception was the subgroup of treatment-naïve patients in which the percentage of satisfied patients was 77.2% vs. 89.5% with standard treatment and additional SAGA tool, respectively (post hoc analysis). DISCUSSION AND CONCLUSIONS: In an observational study, most overactive bladder patients were satisfied with fesoterodine treatment. Because of the small sample size, the study does not support or refute the hypothesis that adding the SAGA tool will improve patient satisfaction with treatment. The potential effect of additional educational material in treatment-naïve patients warrants further dedicated studies.

Efficacy and safety of fesoterodine 8 mg in subjects with overactive bladder after a suboptimal response to tolterodine ER.

AIMS: To assess fesoterodine 8 mg efficacy over time and vs. placebo in subjects with overactive bladder (OAB) who responded suboptimally to tolterodine extended release (ER) 4 mg. METHODS: In a 12-week, double-blind trial, subjects with self-reported OAB symptoms for ≥ 6 months, mean of ≥ 8 micturitions and ≥ 2 to < 15 urgency urinary incontinence (UUI) episodes/24 h, and suboptimal response to tolterodine ER 4 mg (defined as ≤ 50% reduction in UUI episodes during 2-week run-in) were randomised to fesoterodine (4 mg for 1 week, 8 mg for 11 weeks) or placebo once daily. Change from baseline to week 12 in UUI episodes (primary end-point) was analysed in step-wise fashion: first, baseline vs. week 12 for fesoterodine; if significant, then change from baseline to week 12 for fesoterodine vs. placebo. RESULTS: By week 12, subjects receiving fesoterodine 8 mg had significantly greater improvement from baseline vs. placebo in UUI episodes, urgency episodes and scores on the Patient Perception of Bladder Control, Urgency Perception Scale and OAB Questionnaire Symptom Bother and Health-Related Quality of Life scales and domains (all p < 0.05). 50% and 70% UUI responder rates were also significantly higher with fesoterodine 8 mg vs. placebo at week 12 (p < 0.05). Dry mouth (placebo, 4%, 12/301; fesoterodine, 16.6%, 51/308) and constipation (placebo, 1.3%, 4/301; fesoterodine, 3.9%, 12/308) were the most frequent adverse events. CONCLUSIONS: Subjects who responded suboptimally to tolterodine ER 4 mg showed significant improvements in UUI and other OAB symptoms and patient-reported outcomes, with good tolerability, during treatment with fesoterodine 8 mg vs. placebo.

Oral anticoagulant treatment in atrial fibrillation: the AFIRMA real-world study using natural language processing and machine learning.

INTRODUCTION: Oral anticoagulation (OAC) is key in atrial fibrillation (AF) thromboprophylaxis, but Spain lacks substantial real-world evidence. We aimed to analyze the prevalence, clinical characteristics, and treatment patterns among patients with AF undertaking OAC, using natural language processing (NLP) and machine learning (ML). MATERIALS AND METHODS: This retrospective study included AF patients on OAC from 15 Spanish hospitals (2014-2020). Using EHRead® (including NLP and ML), and SNOMED_CT, we extracted and analyzed patient demographics, comorbidities, and OAC treatment from electronic health records. AF prevalence was estimated, and a descriptive analysis was conducted. RESULTS: Among 4,664,224 patients in our cohort, AF prevalence ranged from 1.9% to 2.9%. A total of 57,190 patients on OAC therapy were included, 80.7% receiving Vitamin K antagonists (VKA) and 19.3% Direct-acting OAC (DOAC). The median age was 78 and 76 years respectively, with males constituting 53% of the cohort. Comorbidities like hypertension (76.3%), diabetes (48.0%), heart failure (42.2%), and renal disease (18.7%) were common, and more frequent in VKA users. Over 50% had a high CHA2DS2-VASc score. The most frequent treatment switch was from DOAC to acenocoumarol (58.6% to 70.2%). In switches from VKA to DOAC, apixaban was the most chosen (35.2%). CONCLUSIONS: Utilizing NLP and ML to extract RWD, we established the most comprehensive Spanish cohort of AF patients with OAC to date. Analysis revealed a high AF prevalence, patient complexity, and a marked VKA preference over DOAC. Importantly, in VKA to DOAC transitions, apixaban was the favored option.

Why are antithrombotic drugs not prescribed to octogenarian patients with atrial fibrillation at risk of stroke?

OBJECTIVE: In non-valvular atrial fibrillation (NVAF) patients at risk of stroke, anticoagulant drugs are less likely to be received by older patients than younger patients. In this study, an attempt is made to discover whether the reasons reported by physicians for denying anticoagulant drugs prescription differ between older and younger atrial fibrillation patients. MATERIALS AND METHODS: A retrospective, cross-sectional, multicentre study was conducted from October 2014 to July 2015. The study comprised patients aged ≥18 years diagnosed with NVAF, with a moderate to high stroke risk (CHADS2 score ≥2). Patients were stratified according to age (<80 and ≥80 years). RESULTS: A total of 1309 NVAF patients were evaluated, of whom 40.1% were ≥80 years old. Older patients were predominantly women with higher mean time since diagnosis of AF, with a higher rate of permanent NVAF, and with higher thromboembolic risk. In patients for whom physicians decided not to prescribe any anticoagulant agents, the following reasons were significantly more frequent in patients aged ≥80 years compared to younger patients: cognitive impairment, perceived high bleeding risk, falls, difficult access to monitoring, non-neoplastic terminal illness, and perceived low thromboembolic risk. Uncontrolled hypertension was a significantly more frequent reason for non-prescription of anticoagulant agents in patients aged <80 year. CONCLUSIONS: Octogenarian patients with NVAF and a moderate to high risk of stroke had a different as regards reasons for not being prescribed anticoagulant agents, which should be taken into account in order to improve.

Impact of daily number of urgency urinary incontinence episodes on overactive bladder patient reported outcomes.

OBJECTIVE: To explore the impact of urgency urinary incontinence (UUI) on well-being in non-institutionalized patients with overactive bladder (OAB) in a community sample. METHODS: A cross-sectional web-based study was conducted in the general population, including males and females, >18 years of age. Patients with probable OAB were identified using a validated algorithm together with a score ≥8 on the OAB-V8 scale. Presence of coping behavior was considered determinant for the clinical diagnosis of OAB. Individual well-being was determined through a battery of patient-reported outcomes (PRO) measurements including assessment of health-related quality of life (EQ-5D), sleep disturbances (MOS Sleep), and life satisfaction (LISAT-8). Patients were grouped according to the number of daily UUI episodes (UUI severity): 0 (dry OAB),1, 2-3, or ≥4. Multivariate analysis to evaluate factors independently affecting quality of life was undertaken. RESULTS: A total of 396 patients (52.5% women, mean age: 55.3 [11.1] years, OAB-V8 mean score: 14.5 [7.9]) out of 2035 subjects participating from the general population met the criteria for OAB: 203 (51.3%) with 0episodes, 119 (30.1%) with 1, 52 (13.1%) with 2 or 3, and 22 (5.6%) with ≥4 episodes. A statistically significant linear adjusted association was found between number of UUI episodes and PRO scores. Participants with more episodes had poorer health profiles and self-evaluated quality of life, worse life satisfaction, and more sleep disturbances and fewer hours of sleep per night. Number of incontinence episodes was independent factor to affect quality of life using both LISAT-8 and MOS questionnaires. CONCLUSION: Severity of UUI was significantly associated with poorer individual well-being in subjects with OAB in a community sample in Spain.

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.

The effect of hyperactive bladder severity on healthcare utilization and labor productivity.

OBJECTIVE: To explore the relationship between the severity of urinary urge incontinence (UUI) on healthcare resources utilization (HRU) and loss of labor productivity of subjects with overactive bladder (OAB) in the general population in Spain. METHODS: Secondary analysis of a cross-sectional web-based study conducted in the general population >18 years, through a battery of HRU questions asked using an online method. Probable OAB subjects were identified using a previously validated algorithm and a score >8 in the OAB-V8 questionnaire. HRU questions included an assessment of concomitant medication used as a consequence of OAB/UUI, pad utilization, and medical office visits. Patients were grouped according to the number of UUI episodes into 0, 1, 2-3 or 4+ episodes. RESULTS: Of a total of 2,035 subjects participating from the general population, 396 patients [52.5% women, mean age: 55.3 (11.1) years, OAB-V8 mean score: 14.5 (7.9)] were analyzed; 203 (51.3%) with 0 episodes, 119 (30.1%) with 1, 52 (13.1%) with 2 or 3, and 22 (5.6%) with 4 or more episodes. A linear and significant adjusted association was observed between the number of UUI episodes and HRU; the higher the number of daily episodes the higher the HRU. Subjects with more episodes had medical visits more frequently at the primary care (P = .001) and specialist (P = .009) level as well. Consumption of day (P < .001) and night (P < .001) urinary absorbents, anxiolytic medicines (P = .021) and antibiotics (P = .05) was higher in patients with more UUI episodes. CONCLUSION: The severity of OAB in terms of frequency of daily urge incontinence episodes was significantly and linearly associated with higher healthcare resources utilization and a decrease in labor productivity in subjects with probable OAB in Spain.

[Assessment of reasons for overactive bladder treatment change]. / Evaluación de los motivos del cambio de tratamiento para la vejiga hiperactiva.

OBJECTIVES: although efficacious, some patients do not respond optimally to overactive bladder (OAB) treatment. The objective of this study was to identify the reasons why some patients do not respond and to look for reasons for changes in treatment and patient satisfaction with the new treatment. MATERIALS AND METHODS: epidemiological, cross-sectional, non-interventional study to determine the reasons for OAB treatment switching and satisfaction with such OAB treatment switch. OAB patients (OAB-V8≥8), 18 years or more, who had modified their treatment during the previous 3-4 months, were recruited. Demographic data, symptoms, previous, current and concomitant treatments, reasons for treatment switch, clinical global impression (CGI) on disease severity and symptom improvement, Morinsky Green questionnaire, satisfaction with treatment, treatment preference and treatment benefit scale (TBS) were compared. RESULTS: out of 3,365 successive patients, 2,038 (61%) were eligible (61.1±11.2 years; 77% women). The physician decided to switch in 69% of the cases and 31% of patients asked for a change in treatment. Reasons for switching were lack of clinical benefit (60%), side effects (24%), patients' request (8%), non-compliance (6%) and other (2%). 52% of patients complied with new treatment. According to the CGI, 65.4% showed improvement with respect to their previous treatment. 60% were quite/very satisfied with current treatment, 91% preferred it to their previous treatment and 93% reported that their symptoms had improved. CONCLUSIONS: the lack of clinical benefit is the main reason for changing OAB treatment. Most of the patients that switched prefer their new treatment.