Author(s): Diener H.-C.; Goadsby P.J.; Ashina M.; Al-Karagholi M.A.-M.; Sinclair A.; Mitsikostas D.; Magis D.; Pozo-Rosich P.; Sieira P.I.; Lainez M.J.A.; Gaul C.; Silver N.; Hoffmann J.; Liebler E.; Ferrari M.D.
Source: Journal of Headache and Pain; 2018; vol. 19
Publication Date: 2018
Publication Type(s): Conference Abstract
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Abstract:Background: Novel preventive migraine therapies such as noninvasive vagus nerve stimulation (nVNS; gammaCore) would be welcome due to the low adherence, adverse events (AEs), and limited efficacy of traditional options. The aim of the randomised, doubleblind, sham-controlled PREMIUM trial was to evaluate the efficacy, safety, and tolerability of preventive nVNS for episodic migraine. Methods: In PREMIUM, patients from 22 European sites entered a 4- week observational run-in period (no study treatment), a 12-week double-blind period of randomised nVNS or sham, and a 24-week open-label period of nVNS. Patients were instructed to administer two 120-second stimulations bilaterally to the neck 3 times daily (TID). Abortive migraine medication was permitted if needed, but adjunctive preventive migraine medication was not allowed until week 24. The intent-to-treat (ITT) population, defined as enrolled patients who received >=1 treatment in the double-blind period, was the primary analysis set for efficacy. Upon observation of suboptimal rates of adherence to the TID treatment protocol in the ITT population, a modified intent-to-treat (mITT) population was defined as those with >67% adherence per month for evaluation in a post hoc analysis. Safety was evaluated in all enrolled patients. Results: Mean reductions in number of migraine days from the runin period to the last 4 weeks of the double-blind period (primary end point) were -2.26 days (nVNS; n=165) and -1.80 days (sham; n=167) (p=0.146). Percentages of patients with a >=50% reduction in number of migraine days were 31.9% (nVNS) and 25.0% (sham) (p=0.186). Findings were similar for headache and acute medication days. For the mITT population, significant benefits of nVNS (n=138) vs sham (n=140) were seen for reductions in number of migraine days (-2.27 vs -1.53 days; p=0.043), headache days (-2.85 vs -1.99 days; p=0.045), and acute medication days (-1.94 vs -1.14 days; p=0.039). Device-related AEs in the nVNS group were mostly mild, with application site pain being the most common. Conclusions: nVNS demonstrated consistent but nonsignificant preventive benefits over sham in episodic migraine, with sham providing a higher response than anticipated. Patients with >67% adherence experienced statistically significant benefits of nVNS. The role of adherence and the sham response warrants further evaluation to better understand the clinical utility of preventive nVNS for migraine.