Abstracts

Rationale: Generic substitution may be problematic for antiepileptic drugs (AEDs). Recent population-based evidence has found negative patient outcomes and steeper health care costs associated with the use of generic AEDs. Multiple generic substitutions of AEDs may affect efficacy and/or tolerability because of variability in bioequivalence, leading to worsened health and economic effects. The objective was to investigate clinical and economic outcomes associated with switching of 1 vs multiple generics of topiramate (Topamax®). Methods: Medical and pharmacy claims data of Régie de l’assurance-maladie du Québec (RAMQ) from 01/2006-10/2007 were used (Findings from TPM-OUT-30). Patients with epilepsy (ICD-9 345 or 780.3) treated with topiramate (Canadian patent expired 01/2006) were selected. An open-cohort person-time design was used to classify the observation period into mutually exclusive periods of brand, single-generic, and multiple-generic use. One-year switching rates of brand-to-generic and switchback-to-brand were computed using Kaplan-Meier estimation. Medical resource utilization (frequency per person per year [p/y]) and total costs (C$2006 per p/y; medical and pharmacy costs) were compared among the 3 periods using multivariate regressions adjusted for demographics, treatment characteristics, and comorbidities. Results: 948 topiramate patients (brand only: 518; brand-to-generic: 352; start-on-generic: 78) were observed during 1105 p/y of brand use, 233 p/y of single-generic use, and 91 p/y of multiple-generic use. Among 430 patients who used generic topiramate, 23% (n=99) received at least 2 different generic versions. Multiple-generic use of topiramate was associated with increased pharmacy utilization (both AEDs and non-AEDs) compared to brand (incidence rate ratios [RR]=1.27; 95% CI=1.24-1.31) and single-generic use (RR=1.21; 95% CI=1.19-1.23) after covariate adjustment. Compared to brand use, multiple-generic use was associated with a higher hospitalization rate (0.48 vs 0.83 visit/p/y; RR=1.65; 95% CI=1.28-2.13) and a longer length of stay (2.6 vs 3.9 days/p/y; RR=1.43; 95% CI=1.27-1.60), but the effect was less pronounced in single-generic use (hospitalization: RR=1.08, 95% CI=0.88-1.34; length of stay: RR=1.12, 95% CI=1.03-1.23). The risk of head injury or fracture was nearly 3 times higher (hazard ratio [HR]=2.84; 95% CI=1.24-6.48) following a generic-to-generic switch compared to brand use, while the risk of hospitalization was also increased (HR=1.62; 95% CI=1.05-2.50). Total per-patient costs were higher in the multiple-generic use vs brand periods by C$1,716 (adjusted cost ratio=1.21; p=0.0420). Conclusions: Compared to brand use, multiple generic substitutions were associated with significantly higher hospitalization rates, longer length of stay, and increased risk of fracture or head injury. In addition to poor outcomes, total costs were higher for patients using multiple generics compared to the brand group. Higher total costs may outweigh the benefit of pharmacy cost savings of topiramate generic substitution.