Abstracts

Rationale: The long-term safety and tolerability of a new antiepileptic drug (AED) in the market should be adequately assessed in large patient populations long enough to continuously evaluate the current safety profile and/or detect any potential new adverse reactions. The purpose of this study was to evaluate the safety and tolerability of long-term pregabalin as add-on treatment for patients with treatment refractory partial-onset seizures.Methods: Data were combined from 6 long-term studies involving 2061 patients receiving open-label (OL) pregabalin administered BID or TID as add-on therapy for partial-onset epilepsy. Male or female patients ≥ 12 years old, with a diagnosis of epilepsy with partial-onset seizures with or without secondary generalization and who were highly refractory to existing treatment with a pre-screening frequency of ≥3 seizures/month while receiving between 1 and 3 standard AEDs were eligible for inclusion. All spontaneous reported or observed adverse events were recorded.Results: A total of 576 patients completed one of the 6 OL studies. Overall, at the completion date, 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. The percentages of patients completing at least 52 weeks was similar for all six of the OL studies. Out of 2061 patients who received OL pregabalin, 1891 (91.7%) experienced at least 1 AE and 1590 (77.1%) experienced a treatment-related AE. A total of 262 patients (12.5%) withdrew due to AEs and for 217 patients (10.5%), the AEs leading to withdrawal were considered related to treatment. The most common AEs by frequency were dizziness (30.0%), accidental injury (25.3%), somnolence (22.8%), weight gain (20.8%), infection (20.2%) headache (18.2%), asthenia (17.6%), pain (14.6%), ataxia (12.1%), amblyopia (11.0%) and diplopia (10.0%). Those were mild to moderate in intensity. The most common AEs causing patients to discontinue from the studies were somnolence (2.0%), dizziness (1.6%), weight gain (1.4%), and asthenia (1.3%). The most common AEs were observed within the first few months of OL pregabalin treatment and tended to be transient in nature. The most frequent serious adverse events reported were accidental injury (68 patients, 3.3%), pneumonia (21 patients, 1.02%), overdose (14 patients, 0.68%), depression (12 patients, 0.58%) and psychosis (10 patients, 0.48%). A total of 28 patients died, none of which were considered related to pregabalin.Conclusions: Add on treatment with pregabalin has proven to provide sustained efficacy in patients with refractory partial onset seizures and was well tolerated during long-term treatment. No new safety concerns were identified with long-term treatment. Study funded by Pfizer, Inc