Abstracts

Rationale: VNS Therapy® was approved for use for drug-resistant epilepsy (DRE) in 2010 in Japan. We conducted a multi-center, open-label, long-term prospective study to evaluate clinical efficacy and safety of VNS in Japan using a complete-enumeration registry of adult and pediatric patients who underwent VNS Therapy for the first three years after the approval. We present complete data from the first two-years of the study.Methods: Indication for VNS Therapy was DRE of all ages and seizure types. Patients expected to benefit from neurosurgical intervention were excluded. The implantation surgery was performed by board-certified epilepsy surgeons in the standard manner. The treating physicians adjusted medications and VNS parameters as clinically indicated. Data were collected using study-specific Case Report Forms prior to implantation and at 3, 6, 12, 24, and 36 months after start of VNS Therapy, including seizure frequency in each seizure type, antiepileptic drugs, quality of life, and adverse events. Clinical efficacy at each time point was evaluated using changes in seizure frequency and responder rate defined as the rate of patients with seizure reduction > 50%. Since levetiracetam (LEV) and rufinamide (RFN) were newly approved in Japan during this study period, we analyzed the difference in seizure reduction and responder rate among those who started these drugs prior to VNS, those who started these drugs after receiving VNS, and who did not use these drugs.Results: The registry included 385 patients aged 12 months to 72 years at time of VNS implantation (mean: 24.0 years), including 19% who were <12 years of age at implant. Age at seizure onset was 9.2 + 11.6 years (median: 5). Duration of epilepsy prior to VNS was 15.6 + 11.1 years (median: 13). Seizure frequency per week prior to VNS was 106 + 764 (median: 10). Numbers of AEDs on and tried prior to VNS were 3.4 + 1.1 (median: 3) and 5.7 + 3.2 (median: 5), respectively. Ninety seven and 82 patients underwent prior resective surgery and callosotomy, respectively. Epilepsy classification was structural-metabolic in 65.9%, unknown in 28.5% and genetic in 5.5% of the total patients. Responder rates at 6, 12, and 24 months after VNS Therapy were, respectively, 46.6%, 56.0% and 58.6% for all seizure types, 49.8%, 55.6% and 59.3% for partial seizures and 55.0%, 63.7% and 68.2% for generalized seizures, including secondarily generalized seizures. There were no differences in seizure reduction and responder rates among those patients who started LEV and RFN prior to VNS (n=154), those who started these drugs during VNS (n=63), and those who did not use these drugs (n=104). No new safety signals were identified.Conclusions: Similar to the published literature, clinical outcomes of the first, long-term, prospective registry in Japan support the safe and effective use of VNS Therapy in this severely ill and difficult to treat Japanese patient population with drug-resistant epilepsy. The efficacy seemed independent from addition of newly approved AEDs.