Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: a post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial

Abstract

Background: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication.

Methods: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation.

Results: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037).

Conclusions: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events.

Trial registration: ClinicalTrials.gov identifier: NCT02686034 .

Keywords: Migraine; Neuromodulation; Pain intensity; Post hoc analysis; Rescue medication; Vagus nerve stimulation.

Conflict of interest statement

L. Grazzi has received consultancy and advisory fees from Allergan S.p.A. and electroCore, Inc. C. Tassorelli has consulted for Allergan S.p.A.; electroCore, Inc.; Eli Lilly and Company; and Novartis AG and has received research grants from the European Commission and the Italian Ministry of Health. She is also a principal investigator or collaborator for RCTs sponsored by Alder BioPharmaceuticals Inc.; Eli Lilly and Company; and Teva Pharmaceutical Industries Ltd. M. de Tommaso has received advisory fees from Allergan S.p.A.; Neopharmed; and Pfizer Inc. G. Pierangeli has nothing to disclose. P. Martelletti has received research grants, advisory board fees, or travel fees from ACRAF; Allergan S.p.A.; Amgen Inc.; electroCore, Inc.; Novartis AG; and Teva Pharmaceutical Industries Ltd. I. Rainero has received consultancy fees from electroCore, Inc., and Mylan N.V. and research grants from the European Commission -- Horizon 2020. He is also a principal investigator for RCTs sponsored by Axovant Sciences Ltd. and TauRx Pharmaceuticals Ltd. P. Geppetti has received consultancy fees from Allergan S.p.A.; electroCore, Inc.; Evidera; Novartis AG; Pfizer Inc.; and Sanofi S.p.A. and research grants from Chiesi Farmaceutici S.p.A. He is also a principal investigator for RCTs sponsored by Eli Lilly and Company; Novartis AG; and Teva Pharmaceutical Industries Ltd. A. Ambrosini has received consultancy fees from Almirall, S.A., and travel grants from Allergan S.p.A.; Almirall, S.A.; and Novartis AG. P. Sarchielli has received clinical study fees from Allergan S.p.A. E. Liebler is an employee of electroCore, Inc., and receives stock ownership. P. Barbanti has received consultancy fees from Allergan S.p.A.; electroCore, Inc.; Janssen Pharmaceuticals, Inc.; Lusofarmaco; and Visufarma and advisory fees from Abbott Laboratories and Merck & Co., Inc.

Figures

Fig. 1

The Non-invasive Vagus Nerve Stimulation Device. Note: A previous model of the nVNS device was used by patients in the PRospectivE Study of nVNS for the acute Treatment Of migraine (PRESTO) trial. Image provided courtesy of electroCore, Inc. Abbreviation: nVNS, non-invasive vagus nerve stimulation

Fig. 2

PRESTO Treatment Paradigm. Abbreviations: L, left; nVNS, non-invasive vagus nerve stimulation; R, right; Stim, stimulation

Fig. 3

≥1-Point Reduction in Pain Intensity at 30, 60, and 120 Minutes for (a) First Attack and (b) All Attacks. Models are adjusted for the patients' baseline pain score, use of preventive therapies, and presence of aura; data for number of patients are unadjusted numbers. Abbreviation: nVNS, non-invasive vagus nerve stimulation

Fig. 4

Rescue Medication Use. Models are adjusted for the patients’ baseline pain score, use of preventive therapies, and presence of aura; data for number of patients are unadjusted numbers. Abbreviation: nVNS, non-invasive vagus nerve stimulation

Fig. 5

Pain-free Rates at 30, 60, and 120 Minutes for (a) First Attack and (b) All Attacks. Abbreviation: nVNS, non-invasive vagus nerve stimulation