Authors :
Presenting Author: Kathryn Nichol, PhD – LivaNova PLC (or a subsidiary)
Patrick Kwan, BMedSci, BM, BChir, FRACP, PhD, FAHMS – Monash Institute of Medical Engineering, Monash Univeristy
Gaia Giannicola, PhD – LivaNova PLC (or a subsidiary)
Saleh Salim Baeesa, MD, FRCSC – King Faisal Specialist Hospital and Research Centre
Xiangping Zhou, MD, PhD – SUNY Upstate
Seijiro Shimada, MD, PhD – University Hospital Medical Network
George Morris, MD, MPH, DIC – Ascension Wisconsin, St. Mary's Hospital, Milwaukee, WI, USA
Gholam Motamedi, MD – Georgetown University
Kenneth Myers, MD, PhD – McGill University Health Centre
Maxine Dibue, PhD – LivaNova PLC (or a subsidiary)
Ryan Verner, PhD – LivaNova PLC (or a subsidiary)
Charles Gordon, PhD – LivaNova PLC (or a subsidiary)
Arjune Sen, PhD – Oxford NIHR Biomedical Research Centre, John Radcliffe Hospital
Rationale:
Since approval in 1997, VNS Therapy has been recognized as an effective non-pharmacological option for drug-resistant epilepsy (DRE), especially in cases where surgical resection or ablation is not feasible. Despite broad use and a well-characterized safety profile, delays in access to VNS Therapy continue as people with a diagnosis of DRE are prescribed additional anti-seizure medications (ASMs). In this analysis the effectiveness of VNS Therapy following failure of various numbers of ASMs is described.
Methods:
People with DRE enrolled in the CORE-VNS (NCT03529045) study were categorized and grouped by the number of failed ASMs: ≤3, 4-6, 7-10, 11-16, or >16. Clinical outcomes were assessed across seizure-related (frequency) and non-seizure (Quality of Life) domains at 3, 6-, 12-, 24-, and 36-months post-implantation.
Results:
The CORE-VNS study included 531 people with no prior exposure to VNS Therapy. Of these, 62 had failed 2 or 3 ASMs before VNS Therapy implantation, 222 failed 4-6, 182 failed 7-10, 62 failed 11-16, and only 3 had failed greater than 16 ASMs. People treated after fewer failed ASMs had a significantly greater likelihood of response than those treated after more failed ASMs, when adjusted for covariates including participant age and duration of epilepsy (p< 0.05). Participants implanted after only 2-3 failed ASMs experienced a median change from baseline in seizure frequency at 36 months after VNS Therapy implant of -94.4% (95CI -100% to -80.1%) with 80.4% of patients responding (≥50% reduction in seizure frequency), while those implanted after 11-16 failed ASMs experienced a median change in seizure frequency of -57.4% (95CI -71.1% to -2.6%) with 54.4% of patients responding. Onset of clinical response was similar between subgroups, with seizure reduction occurring as early as the first study visit. Participants in the 11-16 failed ASMs group were most likely to report a quality of life improvement by 36 months (59.6% improved from baseline). The safety profile of VNS was consistent with historical studies and generally similar between subgroups.
Conclusions:
The benefits of VNS Therapy on seizure outcomes are more pronounced when initiated promptly upon clinical indication. Continued trials of additional ASMs may limit the extent to which people can benefit from early implantation following diagnosis of DRE.
Funding: The CORE-VNS Study was supported by LivaNova PLC.