Effects of non-invasive vagus nerve stimulation on attack frequency over time and expanded response rates in patients with chronic cluster headache: a post hoc analysis of the randomised, controlled PREVA study

Charly Gaul,Andreas Straube,Delphine Magis,Eric Liebler

doi:10.1186/s10194-017-0731-4

Abstract

BackgroundIn the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care (nVNS + SoC) than with SoC alone. Given the intensely painful and frequent nature of chronic cluster headache attacks, additional patient-centric outcomes, including the time to and level of therapeutic response, were evaluated in a post hoc analysis of the PREVA study.FindingsAfter a 2-week baseline phase, 97 patients with chronic cluster headache entered a 4-week randomised phase to receive nVNS + SoC (n = 48) or SoC alone (n = 49). All 92 patients who continued into a 4-week extension phase received nVNS + SoC. Compared with SoC alone, nVNS + SoC led to a significantly lower mean weekly attack frequency by week 2 of the randomised phase; the attack frequency remained significantly lower in the nVNS + SoC group through week 3 of the extension phase (P < 0.02). Attack frequencies in the nVNS + SoC group were significantly lower at all study time points than they were at baseline (P < 0.05). Response rates were significantly greater with nVNS + SoC than with SoC alone when response was defined as attack frequency reductions of ≥25%, ≥50%, and ≥75% from baseline (≥25% and ≥50%, P < 0.001; ≥75%, P = 0.009). The 100% response rate was 8% with nVNS + SoC and 0% with SoC alone.ConclusionsProphylactic nVNS led to rapid, significant, and sustained reductions in chronic cluster headache attack frequency within 2 weeks after its addition to SoC and was associated with significantly higher ≥25%, ≥50%, and ≥75% response rates than SoC alone. The rapid decrease in weekly attack frequency justifies a 4-week trial period to identify responders to nVNS, with a high degree of confidence, among patients with chronic cluster headache.

Highlights

In the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care than with SoC alone
Attack frequency The mean weekly attack frequency was significantly lower with non-invasive vagus nerve stimulation (nVNS) + SoC than with SoC alone from week 2 of the randomised phase through week 3 of the extension phase (P < 0.02; Fig. 2)
For the nVNS + SoC group, attack frequencies were significantly reduced from baseline beginning at week 1 of the randomised phase and continuing through week 4 of the extension phase (P < 0.05)

Summary

Introduction

In the PREVention and Acute treatment of chronic cluster headache (PREVA) study, attack frequency reductions from baseline were significantly more pronounced with non-invasive vagus nerve stimulation plus standard of care (nVNS + SoC) than with SoC alone. The PREVention and Acute treatment of chronic cluster headache (PREVA) study of non-invasive vagus nerve stimulation (nVNS) (gammaCore®; electroCore, LLC; Basking Ridge, NJ, USA) used adjunctively with standard of care (SoC) is the largest cCH prophylaxis trial to show significant treatment effects [6, 12]. The primary end point of PREVA was achieved, demonstrating a significantly more pronounced reduction from baseline in weekly attack frequency with nVNS + SoC than with SoC alone and yielding a mean therapeutic benefit of 3.9 fewer attacks per week (P = 0.02) [12]. Economic analyses of PREVA from German and UK perspectives demonstrated that nVNS + SoC was more costeffective when compared with SoC alone [13]

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