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.

An economic evaluation of short-acting opioids for treatment of breakthrough pain in patients with cancer.

OBJECTIVE: Breakthrough cancer pain (BTCP) represents a considerable economic burden. A decision-analysis model was developed to evaluate the cost-effectiveness of intranasal fentanyl spray (INFS) compared with oral transmucosal fentanyl citrate (OTFC) and fentanyl buccal tablet (FBT) for the treatment of BTCP. METHODS: The model was parameterized for Sweden to estimate the costs and benefits associated with treatments. Expected reductions in pain intensity (PI; measured on a numeric rating scale ranging from 0 to 10) per BTCP episodes were translated into resource use and quality-adjusted life years (QALYs). Relative analgesic efficacy of interventions was derived from a mixed treatment comparison of six randomized controlled trials. The relationship between PI and utility was obtained from a time-trade off study in the general population. Resource use and unit cost data were obtained from the literature and validated by Swedish clinical experts. The base case scenario assumed three BTCP episodes/day, a background PI of 2, and a time horizon of 180 days. Prices of INFS and OTFC were assumed to be equal with FBT ∼14% less. Uncertainty in the source data was incorporated by probabilistic sensitivity analyses and different scenario analyses. RESULTS: With INFS, 55% of BTCP (95% uncertainty interval [UI]: 46-68%) was avoided, which is greater than expected with OTFC (29%; UI 22-38%) or FBT (31%; UI 25-39%). INFS was dominating OTFC (resulting in 0.046 QALY gain and saving 174 Euros with a time horizon of 180 days) and cost-effective versus FBT (incremental cost-effectiveness ratio 12203 Euros/QALY). Despite uncertainty in the source data, there is a >99% probability that INFS is the most cost-effective intervention. CONCLUSION: Given inherent limitations of modelling studies, the greater efficacy of INFS translates to cost and QALY advantages over competing interventions in the treatment for BTCP in Sweden.

Inappropriate prescribing for elderly Americans in a large outpatient population.

BACKGROUND: We sought to determine the extent of potentially inappropriate outpatient prescribing for elderly patients, as defined by the Beers revised list of drugs to be avoided in elderly populations. METHODS: We conducted a retrospective cohort study using the outpatient prescription claims database of a large, national pharmaceutical benefit manager. The cohort included 765,423 subjects 65 years or older, who were covered by a pharmaceutical benefit manager and filed 1 or more prescription drug claims during 1999. Main outcome measures were the proportion of subjects who filled a prescription for 1 or more drugs of concern and the proportion of subjects who filled prescriptions for 2 or more of the drugs. RESULTS: A total of 162,370 subjects (21%) filled a prescription for 1 or more drugs of concern. Amitriptyline and doxepin accounted for 23% of all claims for Beers list drugs, and 51% of those claims were for drugs with the potential for severe adverse effects. More than 15% of subjects filled prescriptions for 2 drugs of concern, and 4% filled prescriptions for 3 or more of the drugs within the same year. The most commonly prescribed classes were psychotropic drugs and neuromuscular agents. CONCLUSIONS: The common use of potentially inappropriate drugs should serve as a reminder to monitor their use closely. Pharmaceutical claims databases can be important tools for accomplishing this task, though clinical and laboratory data are needed to improve the sensitivity and specificity of patient-specific alerts.

Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients.

Many drugs prolong the QT interval and increase the risk of torsade de pointes. Concurrent use of two or more of these drugs can further increase the risk, but the prevalence of concurrent prescription of QT-prolonging drugs is not known. Using the administrative claims database of a national pharmaceutical benefit manager, we conducted a retrospective cohort study in 4,825,345 subjects aged 18 years or older. After identifying 50 drugs with QT-prolonging potential, and an additional 26 drugs that inhibit the metabolic clearance of QT-prolonging drugs, we measured the frequency of overlapping prescriptions for two or more of these drugs in the outpatient setting in 1999. Nearly 1.1 million subjects (22.8%) filled 4.4 million prescriptions for QT-prolonging drugs. Of these, 103,119 subjects (9.4%) filled overlapping prescriptions for two or more of the drugs or for a QT-prolonging drug and another drug that inhibits its clearance; 7249 subjects (0.7%) filled overlapping prescriptions for three or more of these drugs. Twenty-two percent of subjects who filled overlapping prescriptions were aged 65 or older; 74% were women. Antidepressants were involved in nearly 50% of the cases. Concurrent prescription of QT-prolonging drugs is common in the outpatient setting, and antidepressants are involved in half of these cases. Large pharmaceutical claims databases are useful for detecting potentially harmful prescribing behaviors, but better clinical evidence on medication safety is needed before such a system can be implemented fully.

Toward estimating the impact of changes in immigrants' insurance eligibility on hospital expenditures for uncompensated care.

BACKGROUND: The Personal Responsibility and Work Opportunity Reconciliation Act (PRWORA) of 1996 gave states the option to withdraw Medicaid coverage of nonemergency care from most legal immigrants. Our goal was to assess the effect of PRWORA on hospital uncompensated care in the United States. METHODS: We collected the following state-level data for the period from 1994 through 1999: foreign-born, noncitizen population and health uninsurance rates (US Census Current Population Survey); percentage of teaching hospitals (American Hospital Association Annual Survey of Hospitals); and each state's decision whether to implement the PRWORA Medicaid bar for legal permanent residents or to continue offering nonemergency Medicaid coverage using state-only funds (Urban Institute). We modeled uncompensated care expenditures by state (also from the Annual Survey of Hospitals) in both univariate and multivariable regression analyses. RESULTS: When measured at the state level, there was no significant relationship between uncompensated care expenditures and states' percentage of noncitizen immigrants. Uninsurance rates were the only significant factor in predicting uncompensated hospital care expenditures by state. CONCLUSIONS: Reducing the number of uninsured patients would most surely reduce hospital expenditures for uncompensated care. However, data limitations hampered our efforts to obtain a monetary estimate of hospitals' financial losses due specifically to the immigrant eligibility changes in PRWORA. Quantifying the impact of these provisions on hospitals will require better data sources.