CORE-VNS: Dosing and titration of VNS therapy in contemporary clinical practice

Abstract

In this analysis of dosing and titration in the CORE-VNS study, we aimed to replicate previously published findings related to dosing and titration of VNS Therapy and describe the impact of Scheduled Programming (SP).Participants who received their first VNS Therapy device during the CORE-VNS study and who attended at least one of either the 6- or 12-month follow-ups were selected for this analysis. Various statistical models (generalized linear mixed models, weighted Cox regression, Kaplan-Meier, and Poisson regression) were used to assess the relationship between VNS titration and clinical response. Participants who were predominantly manually titrated were compared to those who were predominantly titrated using SP. 526 participants met the inclusion criteria for this analysis. The majority were titrated manually (n = 364), compared with the SP feature (n = 162). We found a strong relationship between speed of titration and onset of clinical response but did not find SP use to significantly impact time-to-dose. The mean time-to-response in the SP group was 7.8 months, compared to a mean time-to-response of 10.7 months for manually titrated patients but this effect was not significant in the Cox regression. Patients who were titrated using SP were able to complete their titration phase with fewer required in-office visits than manually titrated patients (p < 0.0001). We replicate prior findings that titration speed of VNS impacts the time to response. Scheduled Programming does not appear to strongly impact titration speed but aids the clinical workflow and reduces patient burden by reducing the frequency of required in-office titration visits.