Abstracts

Rationale: Approximately 20% of all epilepsy patients have Idiopathic Generalised Epilepsy (IGE). Juvenile Absence Epilepsy (JAE), Juvenile Myoclonic Epilepsy (JME) and epilepsy with GTCS upon awakening are among the most frequent epilepsy syndromes and most commonly develop during adolescence. Levetiracetam (LEV) has been licensed in the US and EU as adjunctive therapy of myoclonic seizures in JME and of tonic-clonic seizures in adults and adolescents with IGE based on 2 separate double-blind, placebo-controlled, randomised studies. The purpose of this supplementary analysis was to assess the efficacy and tolerability of adjunctive LEV specifically by IGE syndrome, i.e. JAE, JME and GTCS upon awakening.Methods: Data were obtained from the 2 studies mentioned above. Efficacy analysis was based on seizure days/week (combining all seizure types), and expressed as 50% responder rate (percentage of patients achieving at least a 50% reduction in seizure days during treatment (titration and maintenance periods combined)) and seizure freedom rate (maintenance period; only patients completing this period could be considered seizure-free). Tolerability was assessed by evaluating adverse events (AEs).Results: 27 of 243 patients (11.1%) were diagnosed with JAE, 167 (68.7%) with JME and 49 (20.2%) with GTCS upon awakening. After an 8 week baseline period during which all patients had to have a minimum number of seizures in accordance with the 2 study protocols, they were randomised to either LEV 3000 mg/day (60 mg/kg/day in children) (n=115; 15 JAE, 78 JME, 22 GTCS) or placebo (n=128; 12 JAE, 89 JME, 27 GTCS). Study treatment was taken for 16-24 weeks, including a 4 week titration period, in addition to 1-2 concomitant antiepileptic drugs (AEDs). Most frequently used concomitant AEDs were valproate and lamotrigine. The 50% responder rate was significantly higher for LEV vs. placebo for JAE (53.3% vs. 25.0%; p=0.004), JME (61.0% vs. 24.7%; p<0.001) and GTCS upon awakening (61.9% vs. 29.6%; p=0.024). Seizure freedom rates were significantly higher for LEV vs. placebo in JME patients (20.8% vs. 3.4%; p=0.002), the subgroup representing the majority of patients. While differences in seizure freedom rates for the 2 other syndromes appeared to be clinically relevant, they did not reach statistical significance: 33.3% (LEV) vs. 8.3% (placebo; p=0.148) for JAE and 23.8% (LEV) vs. 11.1% (placebo; p=0.446) for GTCS upon awakening. The most frequently reported AEs were headache (LEV 16.8%; placebo 14.8%) and somnolence (LEV 9.7%; placebo 3.9%). AEs led to permanent drug discontinuation in 3 (2.7%) LEV patients and 4 (3.1%) placebo patients.Conclusions: This analysis demonstrates that adjunctive LEV provided effective seizure control over 16 to 24 weeks in patients with insufficiently controlled JAE, JME and GTCS upon awakening, further supporting LEV’s broad spectrum of activity. UCB Funded.