RATIONALE: Published data on refractory partial onset seizures (POS) are limited, especially from real-world settings. The objectives of this study were to estimate the incidence and prevalence of refractory POS and to describe antiepileptic (AED) treatment patterns in this population.
METHODS: Medical and pharmacy claims dated 2004 through 2008 were analyzed to identify patients with refractory POS from a United States (US) population with either commercial or Medicare supplemental insurance. Refractory patients were defined as those with claims for an associated POS diagnosis and at least three different prescribed AEDs. Prevalence of refractory POS was calculated per calendar year and standardized to the US population using census data. Assuming a stable incidence and disease duration, incidence was estimated as prevalence divided by disease duration. The study assumed disease duration ranged between 2 to 10 years to provide an upper and lower bound of the incidence rate. Refractory patients were followed from the first AED dispensed until December 2008 or end of enrollment, during which treatment patterns including the number and sequence of AEDs received were assessed. Add-on treatment was defined as at least a 30-day overlap between two different AEDs; switching was defined as discontinuing the previous AED and starting another AED with overlapping of two AEDs less than 30 days. Among those receiving combination therapies, partial switch was defined as discontinuing one or more AEDs of the combination regimen and starting another AED, complete switch as discontinuing the original combination regimen completely and starting a new regimen, and partial discontinuation as discontinuing one or more AEDs of the combination regimen without starting another AED.
RESULTS: Table 1 presents the standardized prevalence and incidence rates of refractory POS in the US by calendar year. Among prevalence cases of refractory POS (n=10,977), a majority (80.8%) were on monotherapy at the beginning of the follow-up period (Table 2). The most frequently prescribed AEDs as monotherapy were phenytoin (16.7%), levetiracetam (15.3%), carbamazepine (11.9%), oxcarbazepine (10.8%), and lamotrigine (10.5%). These five AEDs were also the most frequently added on to a regimen. Of the 19.2% on multiple AEDs, the most common combination therapies were levetiracetam with other AEDs (phenytoin, lamotrigine, carbamazepine, oxcarbazepine, and topiramate).
CONCLUSIONS: The incidence and prevalence of refractory POS in the U.S. is relatively low. However, treatment for patients with refractory POS was found to be very dynamic, suggesting that seizures are not well-controlled. Refractory POS patients in this US population are most frequently treated using six different AEDs. Describing the economic burden of refractory POS associated with these dynamic treatment patterns requires further research.
