Abstracts

Open-label extension (OLE) studies provide effectiveness and tolerability information that are closer to experiences observed in actual clinical settings. The OLE phases of three conversion to monotherapy studies were analyzed in order to evaluate the long-term effectiveness and safety of oxcarbazepine (OXC) in patients with refractory seizures. Pooled data from patients who participated in the OLE phase of one of three studies were analyzed. The dosage of OXC and concomitant antiepileptic drugs (AEDs) was flexible (lowest dose that achieved seizure control or maximum tolerated dose). OXC was administered on a bid schedule with a maximum allowable dose of 3000 mg/day. Three subpopulations were defined: [lsquo]true[rsquo] monotherapy (oxcarbazepine monotherapy throughout), [lsquo]adjunctive[rsquo] therapy (adjunctive AED during at least 1 of their last 3 visits), and [lsquo]late[rsquo] monotherapy (adjunctive therapy at any visit before reverting back to monotherapy for at least their last 3 visits). Long-term patient outcomes over 4 years were analyzed, including the median number of seizures/28 days at 1-year intervals and retention rates (estimated using Kaplan-Meier analysis of time to discontinuation for any reason). A total of 266 patients provided seizure information in the combined OLEs: 53 patients in [lsquo]true[rsquo] monotherapy, 167 in [lsquo]adjunctive[rsquo] therapy, and 46 in [lsquo]late[rsquo] monotherapy. The adjusted mean dose of oxcarbazepine ranged from 2170 mg/day to 2527 mg/day across all 4 years and treatment groups. For all three treatment groups, the 28-day seizure rate was reduced by the fourth year of the OLE compared with the first year. The overall OLE median 28-day seizure rates were 1.99 in the [lsquo]true[rsquo] monotherapy group, 1.74 in the [lsquo]late[rsquo] monotherapy group, and 3.70 in the [lsquo]adjunctive[rsquo] therapy group. Retention rates were especially sustained over time in the [lsquo]late[rsquo] monotherapy group (87% first year; 77% fourth year), and decreased from 62% to 43% in the [lsquo]true[rsquo] monotherapy group and from 60% to 27% in the [lsquo]adjunctive[rsquo] therapy group. Based on this pooled analysis of the long-term extension phases of three pivotal studies, OXC monotherapy demonstrated sustained effectiveness for up to 4 years, with a [gt]75% retention rate in patients reverting back to oxcarbazepine monotherapy after adjunctive therapy with another AED. These data suggest that converting patients treated with adjunctive therapy back to oxcarbazepine monotherapy may be beneficial in certain patients. (Supported by Novartis Pharmaceuticals)