Quality of life assessment of cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial.

BACKGROUND: The CELESTIAL trial (NCT01908426) demonstrated overall survival benefit for cabozantinib versus placebo in patients with advanced hepatocellular carcinoma (aHCC) who had received prior sorafenib treatment. This analysis of CELESTIAL compared the impact of cabozantinib versus placebo on health-related quality of life (HRQoL). MATERIALS AND METHODS: Health status was assessed using the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire over the 800-day follow-up period. EQ-5D-5L health states were mapped to health utility scores using reference values for the UK population. Quality-adjusted life years (QALYs) were calculated for each treatment group as the area under the curve for the plot of health utility score over time. The between-treatment group difference in restricted mean QALYs was calculated by generalized linear models and adjusted for baseline differences. A difference of 0.08 in health utility score (or in QALY) was deemed a minimally important difference and to be clinically significant. RESULTS: At week 5, the difference in mean health utility score between cabozantinib and placebo was -0.097 (95% confidence interval [95% CI]: -0.126, -0.067; p ≤ 0.001). Between-group differences in health utility scores diminished over time and were generally non-significant. The cabozantinib group accrued more QALYs than the placebo group over follow-up. Differences in mean QALYs (cabozantinib minus placebo) were statistically and clinically significant, ranging from +0.092 (95% CI: 0.016, 0.169) to +0.185 (95% CI: 0.126, 0.243) in favour of cabozantinib, depending on the reference value set used. CONCLUSIONS: These HRQoL findings support a positive benefit-risk profile for cabozantinib in previously treated patients with aHCC.

Economic burden of comorbidities in psoriasis patients in the United States: results from a retrospective U.S. database.

BACKGROUND: Psoriasis is a multifactorial, inflammatory, skin disease associated with various comorbidities. The cost of those comorbidities is not well characterized. The present study assesses the incremental burden of comorbidities on healthcare resource utilization, direct costs and indirect costs associated with short-term disabilities among patients with psoriasis in the United States. METHODS: A retrospective, U.S. cohort analysis was conducted using a large claims database. Adult psoriasis patients with at least two diagnoses of psoriasis during the years 2010 and 2011 (one psoriasis diagnosis had to happen in the year 2010) and with continuous enrollment of medical and pharmacy benefits in the years 2010 and 2011 were included. Psoriasis patients were categorized and compared according to the presence or absence of pre-selected comorbidities in the year 2010. Adjusted annual direct (costs associated with outpatient, emergency room, and inpatient claims, and outpatient pharmacy claims) and indirect costs (short-term disabilities) was assessed in patients with and without comorbidities using a regression analysis, controlling for age, gender, and psoriasis severity in year 2010. RESULTS: In total, 56,406 patients (mean [SD]) age, 51.6 [14.6] years) were included in the analysis. The most prevalent comorbidities were hypertension (34.3%), hyperlipidemia (33.5%), cardiovascular disease (17.7%), diabetes (14.2%), and psoriatic arthritis (9.9%). Psoriasis patients with comorbidities used more healthcare resources than those without comorbidities. The incidence rate ratio (IRR) (95% CI) for patients with cardiovascular disease was 1.5 (1.4 - 1.5) for outpatient visits, 2.6 (2.4 - 2.8) for hospitalizations, and 2.3 (2.2 - 2.5) for ER visits, showing higher IRRs across all three types of resource use. The mean annual adjusted direct cost differences (i.e., incremental adjusted costs) in psoriasis patients with and without comorbidities were $9914.3, $8386.5, and $8275.1 for psoriatic arthritis, peripheral vascular disease, and cardiovascular disease, respectively. The mean annual incremental adjusted indirect costs of short-term disabilities were $1333, $1195, $994.9, and $996.6 for cerebrovascular disease, obesity, peripheral vascular disease, and depression, respectively. CONCLUSION: The presence of comorbidities was associated with higher healthcare resource utilization and costs among patients with psoriasis.

Clinical outcomes, health resource use, and cost in patients with early versus late dual or triple anti-platelet treatment for acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) guidelines recommend early dual anti-platelet therapy (thienopyridines + acetylsalicylic acid [aspirin]). However, triple therapy (thienopyridines + aspirin + glycoprotein IIb/IIIa receptor inhibitors [GRIs]) has shown benefit in clinical trials. OBJECTIVE: This study assessed real-world ACS treatment patterns and outcomes in the acute care setting. STUDY DESIGN: A retrospective analysis of patients admitted to hospital with ACS (index event) from January 2007 to December 2009 was conducted (Thomson's MarketScan Hospital Drug Database). PATIENTS: Eligible patients were ≥18 years of age, of either sex, and had primary admission and discharge diagnoses of ACS. OUTCOME MEASURES: Cohorts were defined by anti-platelet treatment and then by the timing of treatment initiation (early initiation: within ≤2 days of admission; late initiation: ≥2 days post-admission). Patient characteristics, clinical outcomes, resource utilization, and costs were assessed using descriptive statistics. RESULTS: A total of 249,907 eligible patients were placed into four treatment cohorts (aspirin assumed for all patients): aspirin only; clopidogrel only (dual therapy); GRI only (dual therapy); and clopidogrel + GRI (triple therapy). Patients in the 'clopidogrel-only' cohort were more likely to be older, female, and have more co-morbidities than those in other cohorts; stroke (6.2 %) and re-hospitalization (15.4 %) rates were higher than in the 'GRI-only' and 'triple therapy' cohorts. The GRI-only cohort had higher major bleeding rates (3.3 %), mortality (7.6 %), and costs ($US21,975 [year 2010 values]) than the clopidogrel-only and triple-therapy cohorts. Late initiation cohorts were more likely to be older, female, and have more co-morbidities than early initiation cohorts. Major bleeding was more likely with GRI-only patients (regardless of initiation timing) than with other cohorts. Late-treated clopidogrel-only patients had higher rates of stroke (6.9 %), ACS-related re-admissions (6.1 %), and all-cause re-admissions (15.9 %) than other cohorts. Late treatment was associated with longer length of stay and significantly higher costs. CONCLUSIONS: Real-world anti-platelet treatment patterns are consistent with ACS guidelines recommending early initiation and selective GRI use. In contrast to recommendations, some outcomes were improved with triple therapy compared with dual therapy.

A microsimulation of the cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals.

PURPOSE: Maraviroc (MVC) is the first approved CCR5 antagonist. The aim of this study was to explore the cost-effectiveness of MVC in treatment-experienced or treatment-resistant HIV-infected adults. METHODS: The validated HIV microsimulation model ARAMIS was used to predict clinical and economic outcomes of treating patients with optimized background therapy (OBT) alone, as compared to a strategy of testing for the patient's viral tropism and treating with OBT with or without (+/-) MVC in a cohort corresponding to the MOTIVATE screening cohort. RESULTS: Compared to treatment with OBT alone, a treatment strategy of OBT +/- MVC (twice daily) according to tropism test result was predicted to increase CD4+ cell count after 5 years (from mean 249 to 360 cells/microL), undiscounted life expectancy (7.6 to 8.9 years), and quality-adjusted life years (QALYs; from 4.99 to 5.71) for an additional $40,500, giving an incremental cost-effectiveness ratio of $56,400 per QALY gained. The result was relatively insensitive to alternative clinical and cost assumptions within reasonable ranges, but for individuals with HIV susceptible to only two or fewer components of OBT, the ICER decreased to $52,000 per QALY gained. CONCLUSION: MVC is cost-effective, especially among individuals with few remaining options for active antiretroviral therapy.

Implications of recent epidemiology studies for the clinical management of lower urinary tract symptoms.

Lower urinary tract symptoms (LUTS) include storage, voiding, and postmicturition symptoms, and occur commonly in both men and women. Findings from two recent epidemiological studies, the Epidemiology of LUTS study and the Boston Area Community Health survey, further extend the understanding of the prevalence of individual LUTS, the overlap of LUTS in men and women, the associations of LUTS with other comorbid conditions, the impact of LUTS on health-related quality of life (HRQL), and the relationships between frequency and bother of LUTS and treatment-seeking behaviour. Examining the clinical implications of these findings might provide directions to physicians for managing their patients with LUTS. For example, common findings of separate patient groups spanning a spectrum from those with typically one urinary symptom of mild to moderate severity to those with multiple more severe LUTS and frequent comorbidities might further encourage the diagnosis and treatment of comorbid conditions as a standard part of the management of patients with LUTS. Likewise, understanding that the impact of LUTS on HRQL and the degree of bother, rather than the frequency of LUTS, are significant drivers for treatment seeking might aid in assisting patients to make decisions about treatment.

Urological symptom clusters and health-related quality-of-life: results from the Boston Area Community Health Survey.

OBJECTIVE To determine whether urological symptom clusters, as identified in previous studies, were associated with health-related quality-of-life (HRQoL) and use of healthcare. SUBJECTS AND METHODS The Boston Area Community Health Survey is a population-based epidemiological study of 2301 male and 3201 female residents of Boston, MA, USA, aged 30-79 years. Baseline data collected from 2002 to 2005 were used in this analysis. Data on 14 urological symptoms were used for the cluster analysis, and five derived symptom clusters among men and four among women were used in multivariate linear regression models (adjusted for age group, race/ethnicity, and comorbidity) to determine their association with physical (PCS-12) and mental health component scores (MCS-12) calculated from the Medical Outcomes Study 12-item Short Form Survey. RESULTS For both men and women, being in the most symptomatic cluster was associated with decrements in the PCS-12 score (men, cluster 5, -10.42; women, cluster 4, -9.80; both P < 0.001) and the MCS-12 score (men, cluster 5, -9.35; women, cluster 4, -6.24; both P < 0.001) compared with the asymptomatic groups. Both men and women in these most symptomatic clusters appeared to have adequate access to healthcare. CONCLUSION For men and women, those with the most urological symptoms reported poorer HRQoL in two domains after adjusting for age and comorbidity, and despite adequate access to care.