Abstracts

Rationale: Adjunctive VNS Therapy has been available for nearly three decades for the management of drug-resistant epilepsy (DRE). Real-world evidence of contemporary VNS device use obtained from prospective studies in pediatric patients with different seizure presentations is important to evaluate benefits and risks and inform the healthcare community. In this analysis, VNS Therapy after 24 months of use in children with DRE and focal onset seizures during the baseline assessment period is evaluated.

Methods: Participants were enrolled into a prospective, multicenter, multinational observational study- CORE-VNS (NCT03529045). The real-world study collected data on seizure and non-seizure outcomes before and following treatment with VNS across all age groups. This subgroup analysis studied neuromodulation implant naïve (NIN) children with focal onset seizures (FOS) at baseline, between 4 and 18 years of age receiving VNS Therapy. Baseline seizure frequency data and patient-reported outcome measures, such as quality of life and quality of sleep were collected at baseline, 3, 6, 12, 24, and 36 months. Here, the 24-month outcomes are presented.

Results: 150 participants in the CORE-VNS study were between the ages of 4-18 years, had FOS at baseline, and were NIN. 41% of these patients lived in Europe, 28% in the Americas, and 26% in the Western Pacific. The median age at first implant was 10.4 years (range 4.05 to 17.99), with a median duration between epilepsy diagnosis and informed consent of 6.5 years.  A median of 6 anti-seizure medications (ASMs) (range 2 to 17) had been tried in this group, and over 58% had at least moderate cognitive impairment. The responder rate (≥50% reduction in seizure frequency over the previous 3 months compared to baseline) at 24 months was 59.2% (all focal seizures). Approximately 40% of children had a > 80% seizure response, and 22% were seizure free (over the previous 3 months) at 24 months. The median seizure frequency reduction at 24 months was 64% for focal seizures (CI= -79.2 to -50). The median time to target dose (optimal combination of output current and pulse width) for VNS Therapy was 6 months from initial implant. Quality of life improvement was observed for over half of the children, with 31.4% reporting no change. There was no significant change in overall sleep quality. Greater than 89% of children with FOS received a responsive VNS device (i.e., SenTiva, AspireSR). VNS was well-tolerated, 24.7% of children reported at least 1 treatment-emergent adverse event. The most common AEs were cough (5.3%) and dysphonia (7.3%)., and other respiratory, thoracic, and mediastinal events (10.7%).

Conclusions: Children with DRE who received adjunctive VNS Therapy with a contemporary VNS device  had a significant decrease in FOS at  2 years. Quality of life also improved in over half of the study participants. VNS is well tolerated and effective for this sub-group and results were sustained and/or continued to improve at 24 months.

Funding: LivaNova PLC