Abstracts

Rationale: Pregabalin (150-600mg/day) has been shown to be an effective and well tolerated add-on therapy for epilepsy patients with refractory partial-onset seizures in a series of double-blind (DB) controlled clinical trials. The purpose of this study was to evaluate efficacy of long-term (LT) treatment with pregabalin in 6 open-label (OL) trials.Methods: Data were gathered from 6 LT studies that followed the DB trials. 2061 patients received OL pregabalin administered BID or TID as add-on therapy for treatment refractory partial-onset epilepsy. Inclusion criteria included; male or female patients ≥ 12 years old, diagnosis of epilepsy with partial-onset seizures with or without secondary generalization, pre-screening frequency of ≥3 seizures/month while receiving between 1 and 3 standard AEDs. The primary efficacy parameter was the percentage of patients with ≥50% reduction in the frequency of all partial seizures during the OL phase compared with the baseline period for the double-blind (DB) cohort. Only patients (N=1467) with prospective baseline seizure counts were included in the efficacy analyses on responder rates. Other efficacy parameters included seizure freedom. All spontaneous reported or observed adverse events were recorded.Results: The median average of baseline seizures was approximately 9/28 days. Overall, 79.1% of patients had been exposed to pregabalin for ≥6 months, 61.2% for ≥1 year, 33.5% for ≥2 years, and 14.2% for ≥3 years for a total exposure to pregabalin of 3877 person-years. A total of 576 patients completed one of the 6 OL studies. 33.2% of patients withdrew due to lack of efficacy. The percentages of patients completing at least 52 weeks was similar for all six of the OL studies. Most patients (71.5%) were receiving at least 2 concomitant AEs during OL pregabalin treatment. During the first 3 months of the OL trials, the responder rate for all patients with prospective baseline seizure counts (n=1467) was 39.2%. Responder rates were 43.2% during the last 12 weeks of OL treatment. For patients treated with pregabalin during DB studies and who were ≥50% responders (N=346), the responder rates during the first three months of open-label treatment were 63.9%. For those not responding to pregabalin at the end of the DB studies (n=588) (no ≥50% reduction of seizure compared to baseline), the responder rate during the first three months of open label was 21.4%. At 3, 6, and 12 month seizure-free periods at any time during treatment, 24%, 12%, and 6% of patients were seizure-free, respectively. Dizziness and somnolence were the most common AEs – which mild or moderate in intensity and tended to be transient in nature. Conclusions: Add-on treatment with pregabalin showed sustained and significant efficacy in controlling partial-onset seizures in a highly refractory population during long term follow up. Pregabalin was well tolerated and no new safety concerns were identified with long-term treatment