Abstracts

RATIONALE: Studies have reported 1-yr remission rates for monotherapy with newer antiepileptic drugs (AEDs) in newly diagnosed epilepsy; fewer still have followed patients to report 2-yr remission rates. Topiramate (TPM) monotherapy was evaluated in adults and children with partial-onset seizures in a double-blind dose-comparison study. Patients completing double-blind treatment could continue TPM in an open-label extension. At data cut-off, patients had been receiving TPM for up to 45 mos, providing information on 1-yr and 2-yr remission.
METHODS: To enter the double-blind dose comparison trial, patients had to have active epilepsy (1-6 seizures in 3-mo retrospective baseline) that had been diagnosed no more than 3 yrs before study entry. For the double-blind study, patients were randomized to treatment with 50 or 500 mg/day TPM (25 or 200 mg/day if body weight [lt]50 kg). After completing double-blind treatment, patients could continue TPM as open-label monotherapy. During a blinded transition, those receiving low-dose TPM during the double-blind study were titrated to 200 or 500 mg/day TPM, depending on weight, or to the maximally tolerated dose. In all patients, TPM dosage could be adjusted to optimize effect.
RESULTS: A total of 164 patients entered the open-label extension. Mean age was 36 yrs (range, 6-85 yrs). At the data cutoff, the median duration of TPM treatment (double-blind and open label) was 28 mos (range, 1-45 mos). The mean TPM dosage during open-label treatment was 367 mg/day. Most (77%, 127/164) patients were seizure-free at least 6 mos when receiving TPM, with 55% (90/164) seizure-free at least 1 yr. Of the 120 patients receiving TPM for at least 1 yr, 90 (75%) experienced a 1-yr seizure remission. Of patients treated at least 2 yrs with TPM, 58% (52/89) achieved a 2-yr seizure remission. Only 10 of the 164 patients discontinued TPM due to ineffective seizure control. These discontinuations were evenly distributed over time: 4/42 treated [lt]6 mos, 1/10 treated 6-12 mos, and 5/90 treated [gt]1 yr. Despite the extended duration of open-label TPM treatment, the incidences of adverse events were generally less than the incidences reported during double-blind treatment. The most common adverse events reported during 26 mos (median) of open-label treatment were upper respiratory tract infection (15%), weight decrease (10%), nausea (10%), injury (10%), depression (10%), and headache (10%); only 15 (9%) patients discontinued due to adverse events.
CONCLUSIONS: As monotherapy in newly/recently diagnosed localization-related epilepsy, TPM is effective and well-tolerated as long-term therapy, with a substantial proportion of patients achieving 1-yr and 2-yr seizure remission. These data reinforce previous observations that the effectiveness of TPM is sustained, i.e., it is not associated with the development of tolerance.
Support: The R.W. Johnson Pharmaceutical Research Institute
Disclosure: Salary - Neto, Pledger, Wu- Pharmaceutical Research Institute Stock - Neto, Pledger, Wu