Effectiveness and Tolerability of 12-Month Brivaracetam in the Real World: EXPERIENCE, an International Pooled Analysis of Individual Patient Records.

BACKGROUND AND OBJECTIVE: Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population. METHODS: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from multiple independent non-interventional studies of patients with epilepsy initiating BRV in Australia, Europe, and the United States. Eligible study cohorts were identified via a literature review and engagement with country lead investigators, clinical experts, and local UCB Pharma scientific/medical teams. Included patients initiated BRV no earlier than January 2016 and no later than December 2019, and had ≥ 6 months of follow-up data. The databases for each cohort were reformatted and standardised to ensure information collected was consistent. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within 3 months before timepoint), continuous seizure freedom (no seizures from baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were considered non-responders/not seizure free. Analyses were performed for all adult patients (≥ 16 years), and for subgroups by seizure type recorded at baseline; by number of prior antiseizure medications (ASMs) at index; by use of BRV as monotherapy versus polytherapy at index; for patients who switched from levetiracetam to BRV versus patients who switched from other ASMs to BRV; and for patients with focal-onset seizures and a BRV dose of ≤ 200 mg/day used as add-on at index. Analysis populations included the full analysis set (FAS; all patients who received at least one BRV dose and had seizure type and age documented at baseline) and the modified FAS (all FAS patients who had at least one seizure recorded during baseline). The FAS was used for all outcomes other than ≥ 50% seizure reduction. All outcomes were summarised using descriptive statistics. RESULTS: Analyses included 1644 adults. At baseline, 72.0% were 16-49 years of age and 92.2% had focal-onset seizures. Patients had a median (Q1, Q3) of 5.0 (2.0, 8.0) prior antiseizure medications at index. At 3, 6, and 12 months, respectively, ≥ 50% seizure reduction was achieved by 32.1% (n = 619), 36.7% (n = 867), and 36.9% (n = 822) of patients; seizure freedom rates were 22.4% (n = 923), 17.9% (n = 1165), and 14.9% (n = 1111); and continuous seizure freedom rates were 22.4% (n = 923), 15.7% (n = 1165), and 11.7% (n = 1111). During the whole study follow-up, 551/1639 (33.6%) patients discontinued BRV. TEAEs since prior visit were reported in 25.6% (n = 1542), 14.2% (n = 1376), and 9.3% (n = 1232) of patients at 3, 6, and 12 months, respectively. CONCLUSIONS: This pooled analysis using data from a variety of real-world settings suggests BRV is effective and well tolerated in routine clinical practice in a highly drug-resistant patient population.

Patient characteristics associated with quality of life in European women seeking treatment for urinary incontinence: results from PURE.

OBJECTIVE: To investigate the association between patient characteristics and disease-specific and generic quality of life (QOL) as well as the degree of bother in women seeking treatment for urinary incontinence (UI). METHODS: The Prospective Urinary Incontinence Research (PURE) was a 6-mo observational study with 1055 physicians from 15 European countries enrolling 9487 women. QOL was assessed at the enrolment visit using the urinary Incontinence Quality of Life questionnaire (I-QOL) and the generic EQ-5D. A single-item instrument was used to measure the degree of bother. UI severity was assessed using the Sandvik Index. UI was categorised into stress (SUI), mixed (MUI), and urge (UUI) urinary incontinence by a patient-administered instrument (Stress and Urge Incontinence Questionnaire [S/UIQ]). Multivariate linear (I-QOL, EQ-5D Visual Analogue Scale) and logistic (bother, EQ-5D health state index) regressions were performed. RESULTS: Mean total I-QOL scores were significantly and independently associated with UI severity, nocturia, age, UI subtype, number of selected concomitant medical conditions, length of suffering from UI before contacting a doctor, smoking status, ongoing use of UI medication, and country. After adjusting for all the covariates, the total I-QOL scores for SUI, MUI, and UUI were 62.7, 53.8 and 60.1, respectively. As with I-QOL, UI severity was also the most important predictor for bother. The number of concomitant medical conditions, together with UI severity, was the variable most strongly associated with EQ-5D. CONCLUSION: In addition to the UI subtypes, severity of UI should be given more importance in treatment algorithms and in treatment decision-making by both the patient and the physician.

Cost-effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in Germany.

Drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) significantly reduced mortality in severe sepsis in the PROWESS trial. We evaluate the cost-effectiveness of drotrecogin alfa (activated) as an adjunct to standard therapy from the German healthcare payer's perspective with respect to patients with 1) severe sepsis and 2) severe sepsis and multiple organ failure the approved European indication. Hospital resource use based on PROWESS was valued using German unit costs. German life-tables and long-term survival assumptions determined life-years gained. European and German healthcare resource use data are examined in the sensitivity analysis. We assumed a unit price of euro;237.50 for drotrecogin alfa (activated). Per patient treated, drotrecogin alfa (activated) increased costs by euro;7,500, and hospital costs by euro;900 for all patients (euro;7,400 and euro;1,500 respectively for the approved indication) and survival by 0.59 life years (0.87 life years respectively for the approved indication). Thus drotrecogin alfa (activated) cost euro;14,100 (euro;17,700 discounting life years at 3%) per life year gained for all patients (euro;10,200 and euro;12,900, respectively, for the approved indication). Testing the unit cost of drotrecogin alfa (activated), pattern of resource use, and survival benefit, demonstrated that cost-effectiveness lies well within the range of other life saving interventions in Germany representing good economic value.

Effect of delavirdine on plasma lipids and lipoproteins in patients receiving antiretroviral therapy.

Plasma lipid and lipoprotein levels were measured at baseline and after 8 weeks of highly active antiretroviral therapy among patients receiving delavirdine with or without a protease inhibitor (PI). In patients receiving nucleoside reverse transcriptase inhibitors (NRTI) plus delavirdine, there was a statistically significant increase in cholesterol and HDL levels, whereas those receiving NRTI plus a PI had no significant change in their HDL levels. When delavirdine was combined with a PI, there was a more dramatic increase in both cholesterol and HDL concentrations.