Abstracts

Five large, double-blind, randomized monotherapy comparative studies were conducted with oxcarbazepine that included patients with partial seizures as well as with generalized tonic-clonic seizures. A meta-analysis of these studies was conducted to evaluate the efficacy and tolerability of oxcarbazepine monotherapy in patients with generalized tonic-clonic seizures (GTCS).
Data from five multicenter, double-blind, randomized studies comparing oxcarbazepine monotherapy with other AEDs (phenytoin, valproic acid, carbamazepine or phenobarbital) were analyzed. All these studies included adults and children with previously treated or untreated epilepsy. Patients received double-blind treatment for 11-14 months. Outcome measures included time to first occurrence of GTCS, weekly GTCS rate, and rate and time to discontinuation for lack of therapeutic control or adverse events. The primary efficacy result is expressed as the hazard ratio of GTCS first occurrence, oxcarbazepine to active controls (95% confidence values). Homogeneity of study treatment effect being confirmed, meta-analysis was legitimate.
For patients with at least one baseline GTCS (N=273; oxcarbazepine n=150, other AEDs n=123), there were 102 patients with GTC first seizure events during the double-blind phase of the studies (oxcarbazepine n=59, other AEDs n=43). The combined hazard ratio for time to first occurrence of a GTC seizure was 1.15 (95% CI 0.77-1.71), with no significant study variation in the hazard ratios. The estimated 1-year GTC seizure-free rates were not significantly different (oxcarbazepine 56.8% [plusmn] 4.3% vs other AEDs 62.3 [plusmn] 4.6%). Time to discontinuation rates due to lack of therapeutic control were similar within study arms and across studies, with a 1-year adequate control rate of 93.3% ([plusmn]1.3%). Similar numbers of patients in both groups completed the studies (oxcarbazepine 54.9% vs other AEDs 53.4%). For adverse event discontinuation rates, however, a considerable between study variation was noted. This was attributed to significantly fewer discontinuations due to adverse events with oxcarbazepine than with phenytoin.
In addition to the well-documented efficacy, safety, and tolerability of oxcarbazepine monotherapy in patients with partial seizures versus standard AEDs, this meta-analysis supports the efficacy of oxcarbazepine in the treatment of GTCS. Oxcarbazepine monotherapy was similar to phenytoin, valproic acid, carbamazepine or phenobarbital in controlling seizures in patients with a history of GTCS.
[Supported by: Novartis Pharma]