Fesoterodine prescription fill patterns and evaluation of the YourWay patient support plan for patients with overactive bladder symptoms and physicians.

BACKGROUND: Adherence with oral medication for overactive bladder syndrome is suboptimal. To improve adherence, the YourWay plan was developed to assist patients and health care providers in defining treatment expectations and facilitating communication. OBJECTIVE: To evaluate medication adherence among patients with overactive bladder syndrome enrolled in the YourWay patient support plan, patient adoption of behavioral interventions, patient satisfaction with the plan, and physician experience with the plan. METHODS: In this 13-week, single-arm, open-label, multicenter, noninterventional study, fesoterodine-naïve patients received a prescription for fesoterodine 4 or 8 mg and a packet including a 14-day fesoterodine sample, educational materials, and progress tracker. Patients registered for the YourWay plan, which included an educational resource kit, interactive voice-response calls, and optional online and mail support. The primary end point was the proportion of patients who filled a prescription for a ≥ 90-day supply of fesoterodine within 90 days of enrollment. Secondary end points were the proportion of patients who filled ≥ 1 prescription and ≥ 2 prescriptions (post hoc), patient evaluation of their experience and satisfaction with the YourWay plan, and differences between prescription fillers and nonfillers in plan adoption and assessment (post hoc). We surveyed an independent sample of physicians to assess their experience with YourWay. RESULTS: Of 500 study completers, 10.4% filled a prescription for a ≥ 90-day supply of fesoterodine. Of those filling a prescription, 26.2% filled ≥ 1 prescription and among those, 61.0% refilled their prescription at least once. Many behavioral recommendations were adopted by 82% to 94% of patients. Fillers were more likely to take fesoterodine as directed, whereas adoption of behavioral recommendations or plan satisfaction did not differ between fillers and nonfillers. Most patients reported that the plan was informative and feasible to implement, and that they were satisfied with various aspects of the plan. Physicians also reported positive experiences. CONCLUSION: Most patients adopted YourWay components and viewed the plan positively, although adherence remained a challenge.

Estimating the quality-of-life impact and cost-effectiveness of alpha-blocker and anti-muscarinic combination treatment in men with lower urinary tract symptoms related to benign prostatic hyperplasia and overactive bladder.

OBJECTIVE: A 12-week clinical trial (TIMES) demonstrated that therapy with tolterodine extended release (TOL) + tamsulosin (TAM) provides clinical benefits vs TOL or TAM monotherapy or placebo (PBO) in men with lower urinary tract symptoms (LUTS) including overactive bladder (OAB). The present analysis estimated the costs and quality-adjusted life-years (QALYs) associated with these therapies from the perspective of the UK healthcare system. METHODS: TIMES cohorts receiving TOL, TAM, TOL + TAM, or PBO were followed from therapy initiation to 12 weeks. A decision-tree model was used to extrapolate the 12-week results to 1 year (including need for surgery owing to treatment failure at 12 weeks) and to track patients' outcomes (symptoms, utility, and costs). Because TIMES did not include costs and QALYs, data from the EpiLUTS epidemiologic survey (12,796 males) were used to model a mathematical relationship between LUTS (daytime and nocturnal frequency, urgency episodes, urgency urinary incontinence episodes, and International Prostate Symptom Score [IPSS]), quality-of-life, and utility. This was used to convert improvements in TIMES patients' LUTS into utility scores and QALYs. The model included drug and surgery procedure costs and hospital length of stay. RESULTS: Incremental QALYs of TOL + TAM vs PBO, TAM, and TOL were 0.042, 0.021, and 0.013, and corresponding incremental costs were £189, £223, and -£70, respectively, resulting in cost-utility ratios for TOL + TAM of £4508/QALY gained compared with PBO and £10,381/QALY gained compared with TAM. TOL + TAM combination therapy was both more effective and cost-saving compared with TOL. Univariate sensitivity analyses showed that patient utility was most responsive to changes in drug efficacy on IPSS and urgency episodes. Changing the percentage of patients undergoing surgery did not substantially affect model outcomes. The main limitation of the study was that the relation between LUTS and patient utility was based on an indirect association. CONCLUSIONS: TOL + TAM combination therapy appears to be cost-effective compared with TOL or TAM monotherapy or PBO in male patients with LUTS.

Predictors of discontinuing overactive bladder medications.

OBJECTIVE: To identify predictors of self-reported discontinuation of overactive bladder (OAB) medication using a three-phase survey. PATIENTS AND METHODS: In January 2005, a phase 1 survey was sent to 260 000 households in the USA to assess the prevalence of OAB symptom bother, treatment patterns and healthcare consulting behaviour. In July 2005, a detailed phase 2 follow-up survey was sent to 6577 phase 1 respondents who had used one or more OAB medications within the 12 months before phase 1; the phase 2 survey included questions about respondents' sociodemographic characteristics, general health status, OAB symptom bother, healthcare consulting behaviour, beliefs about OAB and treatment options, and medication usage. Six months later, a phase 3 survey was sent to 3387 phase-2 respondents who were persistent with OAB medication or had discontinued within <18 months of phase 2; the phase 3 survey measured the same variables as phase 2. Only phase 3 respondents who were persistent with OAB medication at phase 2 were included in the analyses reported here. Assessed were the proportions of respondents who were still persistent with OAB medication at phase 3 and who discontinued OAB medication between phases 2 and 3. The variables measured during the phase 2 survey were screened as potential predictors of discontinuation at phase 3 using univariate analysis and then assessed using multivariate logistic regression. RESULTS: Among 2838 respondents at phase 3 (84% response rate), 1194 had recently discontinued and 1644 were persistent with medication at phase 2. Among phase-3 respondents who were persistent at phase 2, 1040 (66%) continued to be persistent at phase 3, 280 (18%) had discontinued between phases 2 and 3, and 261 (17%) had switched medication between phases 2 and 3; 63 respondents had missing prescription information at phase 3. Predictors of discontinuing at phase 3 included smoking (odds ratio 1.80; 95% confidence interval 1.15-2.83; P = 0.010), not knowing whether treating bladder problems requires multiple daily doses of medication (1.71, 1.10-2.67; P = 0.018), believing (2.11, 1.34-3.33; P = 0.001) or not knowing (1.76, 1.23-2.52; P = 0.002) whether adverse effects of OAB medications are often severe, and being bothered 'quite a bit or more' by a sudden urge to urinate (1.54, 1.05-2.26; P = 0.028). Respondents taking two or more medications were less likely to discontinue (odds ratio 0.45-0.58; P < 0.05). CONCLUSION: Persistence with OAB medications might be improved by addressing predictors of discontinuation in the management of OAB, by proactively informing patients about the severity of antimuscarinic adverse effects, and dosing regimens. Bother associated with the key OAB symptom, urgency, is a predictor of discontinuation of treatment.

Patient-reported reasons for discontinuing overactive bladder medication.

OBJECTIVE: To evaluate patient-reported reasons for discontinuing antimuscarinic prescription medications for overactive bladder (OAB). PATIENTS AND METHODS: A phase 1 screening survey was sent to a representative sample of 260 000 households in the USA to identify patients using antimuscarinic agents for OAB. A detailed phase-2 follow-up survey was sent to 6577 respondents with one or more antimuscarinic prescriptions for OAB in the 12 months before the phase 1 survey. The follow-up survey included questions about demographics, clinical characteristics, antimuscarinic use, beliefs about OAB, treatment expectations, OAB symptom bother, and pre-coded reasons for discontinuation. Patients who reported discontinuing one or more OAB medication during the 12 months before phase 2 were grouped by reason, using latent class analysis (LCA); the Lo-Mendell-Rubin likelihood statistical test was used to determine the number of classes. Conditional probabilities of reasons for discontinuation were calculated for each class. Multivariable logistic regression was used to assess the influence of demographic and clinical characteristics on class assignment. RESULTS: In all, 162 906 (63%) and 5392 (82%) useable responses were returned in phases 1 and 2, respectively; the demographics were similar in respondents and nonrespondents in both phases. In all, 1322 phase 2 respondents (24.5%) reported discontinuing one or more antimuscarinic drugs during the 12 months before phase 2. LCA identified two classes (Lo-Mendell-Rubin statistic, P = 0.01) based on reasons for discontinuation. Most respondents (89%) reported discontinuing OAB medication primarily due to unmet treatment expectations and/or tolerability; many respondents in this class switched to a new antimuscarinic agent. A smaller group (11%) indicated a general aversion to taking medication. Age, sex, race, income, and history of incontinence were not predictive of class assignment. CONCLUSIONS: Expectations about treatment efficacy and side-effects are the most important considerations in discontinuing OAB medications for most patients. Interventions to promote realistic expectations about treatment efficacy and side-effects might enhance adherence.

Challenges for managing overactive bladder and guidance for patient support.

OBJECTIVE: Describe challenges to improving management of overactive bladder (OAB) outcomes and summarize research findings on critical success factors for supporting OAB treatment. STUDY DESIGN: A multidisciplinary team collected primary and secondary data, including an OAB-specific survey; a literature review; and an expert panel discussion. METHODS: A US survey of patients who were prescribed antimuscarinics included topics related to OAB, such as reasons for medication discontinuation. The PubMed database was searched for articles published in the past 10 years on OAB treatment and adherence, and additional publications were reviewed related to health behavior change models. An expert panel reviewed findings and provided perspective. RESULTS: The survey (n = 5392) showed that, among patients discontinuing OAB medications, 45.4% reported unmet treatment expectations as the reason for discontinuation. Literature review findings supported intervention at the beginning of OAB treatment, specific messages to increase treatment adherence, and involving the healthcare stakeholders most trusted by patients. Implications of OAB patient support were drawn from reviews of the Transtheoretical Model, the Health Belief Model, and social learning theory. The expert panel highlighted desirable attributes of OAB patient education delivered in the medical care setting. CONCLUSION: Challenges to improving OAB symptom burden and outcomes include underdiagnosis, undertreatment, and patient nonadherence with medications. Patient support of medication adherence may be enhanced by simultaneously supporting the use of nonpharmaceutical lifestyle modifications and behavioral interventions. Healthcare providers acknowledge the need for patient education but lack the time and resources to deliver interventions or monitor patients' progress outside the medical office. Patient support may be achieved through external programs that complement patient-physician interactions.

IL-15 as memory T-cell adjuvant for topical HIV-1 DermaVir vaccine.

IL-7 and IL-15 are key cytokines involved in the generation and maintenance of memory CD8+ T-cells. We evaluated these cytokines as molecular adjuvants for topical HIV-1 DermaVir vaccine. We found that mice receiving DermaVir formulated with HIV-1 Gag plasmid in the presence of IL-7- or IL-15-encoding plasmid significantly enhanced Gag-specific central memory T-cells, as measured by a peptide-based cultured IFN-gamma ELISPOT. Additionally, IL-15 significantly improved DermaVir-induced Gag-specific effector memory CD8+ T-cell responses, measured by standard IFN-gamma ELISPOT. In a DermaVir prime/vaccinia vector boost regimen, the inclusion of IL-15 together with DermaVir significantly improved Gag-specific effector memory T-cell responses. Our study demonstrates that IL-15 is more potent than IL-7 in enhancing HIV-1-specific central memory T-cells induced by topical DermaVir. IL-15 adjuvanted DermaVir might be an alternative prime in a prophylactic vaccine regimen.

HIV-1 prophylactic vaccine comprised of topical DermaVir prime and protein boost elicits cellular immune responses and controls pathogenic R5 SHIV162P3.

Topical DNA vaccination (DermaVir) facilitates antigen presentation to naive T cells. DermaVir immunization in mice, using HIV-1 Env and Gag, elicited cellular immune responses. Boosting with HIV-1 gp120 Env and p41 Gag augmented Th1 cytokine levels. Intramuscular DNA administration was less efficient in priming antigen-specific cytokine production and memory T cells. In rhesus macaques, DermaVir immunization induced Gag- and Env-specific Th1 and Th2 cytokines and generation of memory T cells. Boosting of DermaVir-primed serum antibody levels was noted following gp140(SHIV89.6P)/p27(SIV) immunization. Rectal challenge with pathogenic R5-tropic SHIV162P3 resulted in control of plasma viremia (4/5 animals) that was reflected in jejunum, colon and mesenteric lymph nodes. An inverse correlation was found between Gag- and Env-specific central memory T cell responses on the day of challenge and plasma viremia at set point. Overall, the topical DermaVir/protein vaccination yields central memory T cell responses and facilitates control of pathogenic SHIV infection.