Association Between Adverse Events and Discontinuation of Antiepileptic Drugs Among Drug-Naïve Adults with Epilepsy

BACKGROUND: Adherence to antiepileptic drugs (AEDs) remains the primary management tool to prevent recurrent seizures in patients with epilepsy. Adverse events associated with AEDs could have an impact on adherence and result in treatment failures. OBJECTIVE: The goal of this study was to assess the association between adverse events and discontinuation of AEDs for AED-naïve patients with epilepsy. Our second objective was to estimate the economic burden of AED discontinuation. METHODS: We retrospectively analyzed IBM MarketScan administrative data from 2014 to 2017. The cohort consisted of new users of AEDs with an epilepsy diagnosis and with two or more subsequent AED claims. Outpatient and inpatient cohorts were analyzed separately. Adverse events were identified by injury codes (E-CODES) or by International Classification of Diseases, Ninth/Tenth Edition (ICD-9/10) codes for disease manifestations reported in the literature or product inserts (LADE). Discontinuation of AEDs was defined as a gap of ≥ 60 days without a refill. All cost comparisons were based on 1:1 propensity-score matching. Associations between adverse events and discontinuation were estimated using logistic regression, adjusting for predefined covariates such as age, sex, Charlson Comorbidity Index, insurance type, and AED type. RESULTS: The overall discontinuation rate was 9% (E-CODES rate was 0.1% and LADE rate was 27%). The discontinued group was older (56.1 vs. 52.8 years; p < 0.0001). Adults aged ≥ 65 years had the highest discontinuation rate (11%). Patients who discontinued had fewer AED claims (6.8 vs. 9.2; p < 0.0001), more outpatient claims (19.3 vs. 17.8; p < 0.0001), and longer hospital stays (6.6 vs. 5.3 days; p < 0.0001). Differences in daily outpatient costs between patients with and without adverse events were statistically significant (E-CODES $US213 vs. 105; p = 0.001; LADE $US188 vs. 161; p < 0.0001). Additionally, total cost of AEDs in the outpatient cohort was higher for patients with adverse events (E-CODES and LADE). There was no association between E-CODES and AED discontinuation; however, there was a positive association between LADE and discontinuation in the outpatient cohort but a negative association in the inpatient cohort. CONCLUSION: We found that total costs of prescriptions claimed and total costs of outpatient visits among the outpatient cohort were higher for those with adverse drug events than for those without. An association between adverse events and discontinuation was inconclusive because it depended on the target population and how the adverse events were identified.