Marie-Hélène Lafeuille

Generic antiepileptic drugs and associated medical resource utilization in the United States

Objective: To evaluate whether generic substitution was associated with any difference in medical resource utilization for 5 widely used antiepileptic drugs (AEDs) in the United States. Methods: Health insurance claims from PharMetrics Database, representing over 90 health plans between January 2000 and October 2007, were analyzed. Adult patients with epilepsy, continuously treated with carbamazepine, gabapentin, phenytoin, primidone, or zonisamide, were selected. An open-cohort design was used to classify patients into mutually exclusive periods of brand vs generic use of AEDs. Pharmacy and medical utilization were compared between the 2 periods with multivariate regression analyses. Results were stratified into epilepsy-related medical services, and stable (≤2 outpatient visits per year and no emergency room visit) vs unstable epilepsy. Time-to-event analyses were also performed for all services and epilepsy-related endpoints. Results: A total of 18,125 patients were observed in the stable group and 15,500 patients in the unstable group. After adjustment of covariates, periods of generic AED treatment were associated with increased use of all prescription drugs (incidence rate ratio [IRR] [95% confidence interval (CI)] = 1.13 [1.13–1.14]) and higher epilepsy-related medical utilization rates (hospitalizations: IRR [95% CI] = 1.24 [1.19–1.30]; outpatient visits: IRR [95% CI] = 1.14 [1.13–1.16]; lengths of hospital stays: IRR [95% CI] = 1.29 [1.27–1.32]). Generic-use periods were associated with increased utilization rates in stable and unstable patients and with 20% increased risk of injury, compared to periods with brand use of AEDs. Conclusions: Generic antiepileptic drug use was associated with significantly greater medical utilization and risk of epilepsy-related medical events, compared to brand use. This relationship was observed even in patients characterized as stable. AED = antiepileptic drug; CI = confidence interval; ER = emergency room; HR = hazard ratio; ICD = International Classification of Diseases; IRR = incidence rate ratio.

Initial Combination Therapy Reduces the Risk of Cardiovascular Events in Hypertensive Patients: A Matched Cohort Study

This study evaluated the effects of initial versus delayed treatment with a drug combination on blood pressure (BP) control and the risk of cardiovascular (CV) events in hypertensive patients. Clinical trials suggest that the time to BP control is an important determinant of long-term outcomes, but real-world evidence is scarce. Using electronic medical charts (2005–2009), we retrospectively analyzed 1762 adult patients with BP elevation initiating combination therapy matched 1:1 with similar patients initiating monotherapy and later switched to combination therapy. Incidence rate ratios of CV events (myocardial infarction, stroke/transient ischemic attack, or hospitalization for heart failure) or all-cause death and Kaplan-Meier analyses of time to BP control were compared between cohorts. Hazard ratios indicating the effects of initial treatment on CV events and BP control were estimated using time-varying Cox proportional hazard models. Initial combination therapy was associated with a significant reduction in the risk of CV events or death (incidence rate ratio, 0.66 [95% confidence interval, 0.52–0.84]; P=0.0008). After 6 months of therapy, 40.3% and 32.6% of patients with initial versus delayed combination treatment reached BP control, respectively. Achieving target BP was associated with a statistically significant risk reduction of 23% for CV events or death (hazard ratio, 0.77 [95% confidence interval, 0.61–0.96]; P=0.0223); the residual effect of initial combination therapy did not reach statistical significance (hazard ratio, 0.84 [95% confidence interval, 0.68–1.03]; P=0.0935). Initial combination therapy was associated with a significant risk reduction of cardiovascular events. More rapid achievement of target BP was found to be the main contributor to the estimated risk reduction.

Burden of uncontrolled epilepsy in patients requiring an emergency room visit or hospitalization

Objective: To quantify the clinical and economic burden of uncontrolled epilepsy in patients requiring emergency department (ED) visit or hospitalization. Methods: Health insurance claims from a 5-state Medicaid database (1997Q1–2009Q2) and 55 self-insured US companies (“employer,” 1999Q1 and 2008Q4) were analyzed. Adult patients with epilepsy receiving antiepileptic drugs (AED) were selected. Using a retrospective matched-cohort design, patients were categorized into cohorts of “uncontrolled” (≥2 changes in AED therapy, then ≥1 epilepsy-related ED visit/hospitalization within 1 year) and “well-controlled” (no AED change, no epilepsy-related ED visit/hospitalization) epilepsy. Matched cohorts were compared for health care resource utilization and costs using multivariate conditional regression models and nonparametric methods. Results: From 110,312 (Medicaid) and 36,529 (employer) eligible patients, 3,454 and 602 with uncontrolled epilepsy were matched 1:1 to patients with well-controlled epilepsy, respectively. In both populations, uncontrolled epilepsy cohorts presented about 2 times more fractures and head injuries (all p values < 0.0001) and higher health care resource utilization (ranges of adjusted incidence rate ratios [IRRs] [all-cause utilization]: AEDs = 1.8–1.9, non-AEDs = 1.3–1.5, hospitalizations = 5.4–6.7, length of hospital stays = 7.3–7.7, ED visits = 3.7–5.0, outpatient visits = 1.4–1.7, neurologist visits = 2.3–3.1; all p values < 0.0001) than well-controlled groups. Total direct health care costs were higher in patients with uncontrolled epilepsy (adjusted cost difference [95% confidence interval (CI)] Medicaid =

Incremental direct and indirect costs of untreated vasomotor symptoms.

12,258 [

Impact of omalizumab on emergency-department visits, hospitalizations, and corticosteroid use among patients with uncontrolled asthma

10,482–

Systematic review of long-acting injectables versus oral atypical antipsychotics on hospitalization in schizophrenia

14,083]; employer =

Clinical predictors of survival in men with castration-resistant prostate cancer: evidence that Gleason score 6 cancer can evolve to lethal disease.

14,582 [

Risk of Hepatotoxicity‐Related Hospitalizations among Patients Treated with Opioid/Acetaminophen Combination Prescription Pain Medications

12,019–

Patterns of relapse and associated cost burden in schizophrenia patients receiving atypical antipsychotics

17,097]) vs well-controlled patients. Privately insured employees with uncontrolled epilepsy lost 2.5 times more work days, with associated indirect costs of

Resource utilization and costs following hospitalization of patients with chronic heart failure in the US

2,857 (95% CI