Abstract
BackgroundSome antiepileptic drugs (AEDs) induce expression of hepatic enzymes. This can contribute to comorbidities via interference with metabolic pathways and concomitant drug metabolization, thereby increasing the likelihood of health care interventions. Using medical records, we compared the direct health care cost in patients initiating epilepsy therapy with enzyme-inducing AEDs (EIAEDs) vs non-enzyme-active AEDs (nEAAEDs) over up to 12 years.MethodsPatients with untreated epilepsy were indexed in the UK Clinical Practice Research Datalink and Hospital Episode Statistics database when prescribed a new EIAED or nEAAED between January 2001 and December 2010. Propensity score matching reduced confounding factors between cohorts. Patients were followed until cohort treatment failure or data cut-off. The primary outcome was the median standardized monthly direct health care cost during follow-up in 2014 £GBP, calculated using published reference costs and compared using a Mann–Whitney U test.ResultsThe unmatched EIAED cohort (n = 2752) was older (54 vs 46 years), more likely to be male, had more comorbidities, and higher health care resource use/cost during the 1-year pre-index period (median £3014 vs £2516) than the nEAAED cohort (n = 2,137). The most common index EIAED and nEAAED were carbamazepine (63.3%) and lamotrigine (58.0%), respectively. After matching, cohorts had similar features (n = 951 each). Over up to 12 years of follow-up, the median standardized monthly direct health care cost was £229 for the EIAED and £188 for the nEAAED cohorts (p = 0.0091). The median cost was higher for the EIAED cohort in every year of follow-up. In the two cohorts, 25.1% and 20.1% of total mean cost during follow-up was epilepsy-related, with approximately 4.6% and 3.0% for AED acquisition, respectively. The median time to cohort treatment failure was shorter in the matched EIAED cohort (468 vs 1194 days).ConclusionsPatients in the UK who initiated epilepsy therapy with an EIAED appeared to be at higher risk of complications associated with enzyme induction. In long-term matched cohort analyses, the median total direct health care cost associated with EIAED therapy was higher than with nEAAEDs. Changing current treatment practices could potentially improve patient outcomes and reduce costs.
Highlights
Some antiepileptic drugs (AEDs) induce expression of hepatic enzymes
NEAAED cohort entry steadily increased over the selection period, peaking in 2010 (17.8%; Table 2)
Our results suggest that the higher cost observed for the enzyme-inducing antiepileptic drug (EIAED) cohort was related to higher health care utilization in general
Summary
Some antiepileptic drugs (AEDs) induce expression of hepatic enzymes. This can contribute to comorbidities via interference with metabolic pathways and concomitant drug metabolization, thereby increasing the likelihood of health care interventions. We compared the direct health care cost in patients initiating epilepsy therapy with enzyme-inducing AEDs (EIAEDs) vs non-enzyme-active AEDs (nEAAEDs) over up to 12 years. Epilepsy is a chronic disorder that requires long-term antiepileptic drug (AED) therapy. Enzyme-inducing AEDs (EIAEDs), such as carbamazepine and phenytoin, stimulate the synthesis of endogenous cytochrome P450 (CYP450) enzymes as an off-target effect. Treatment with enzyme-inducing drugs can potentially lead to altered metabolization of some concomitant drugs, and requires a distinct set of treatment considerations [2,3,4]. Other AEDs, such as oxcarbazepine and topiramate (mild EIAEDs), induce only a few CYP450 enzymes, while valproate is a CYP450 inhibitor [2, 5]
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