Three years of remote electrical neuromodulation (REN) acute treatment for migraine shows consistent effectiveness...

The current study aimed to evaluate the remote electrical neuromodulation (REN) wearable device over 3 years, assessing the potential for tachyphylaxis, consistent effectiveness, overall utilization patterns, and safety.

Migraine is a highly prevalent chronic neurological disease, especially during peak years of productivity, requiring ongoing management to prevent and reduce its disability. Traditional treatments often face challenges with long-term adherence due to waning efficacy, side effects, and medication interactions. REN offers a nonpharmacological approach for acute and preventive migraine treatment.

This prospective real-world cohort study analyzed data from 224 patients with migraine in the United States who consistently treated their migraine attacks with the REN wearable device for 3 years between December 2019 and September 2024. The primary endpoint was defined as lack of tachyphylaxis, aka an increase of no more than 2.5 intensity units on a scale of 100 units between 2 consecutive years, representing a nonclinically meaningful change in treatment intensity over 3 years. Secondary endpoints were consistent effectiveness in at least 50% of treatments and consistent utilization, compared over 3 years. The safety outcome assessed the proportion of users with device-related adverse events (dAEs) and the severity and seriousness of the dAEs.

Over 3 years, there was no clinically meaningful change in treatment intensity, and the average (± standard deviation, SD) change between 2 consecutive years was no more than 2.5 intensity units (1.8 ± 5.5 between years 1 and 2, and 1.4 ± 5.3 between years 2 and 3; p = 0.120, McNemar test for two related dichotomous variables), indicating no tachyphylaxis. Effectiveness endpoints remained consistent over 3 years of treated attacks (generalized linear mixed model of repeated measures categorical data) with no significant differences over the 3 years: 72.1%-76.8% of users reporting pain relief (p = 0.846), 26.8%-28.7% pain freedom (p = 0.966), 65.3%-70.8% functional disability relief (p = 0.749), 31.4%-38.9% functional disability freedom (p = 0.680), 29.0%-37.0% freedom from photophobia (p = 0.590), 37.9%-49.4% freedom from phonophobia (p = 0.534), and 57.1%-66.7% freedom from nausea/vomiting (p = 0.753). Monthly utilization was consistent, ranging between 8.0 and 8.8 treatments per month, suggesting sustained adherence to therapy (p = 0.337, generalized linear model of repeated measures). Only two (0.9%) expected, nonserious dAEs were reported (mild or moderate localized skin reactions), neither leading to treatment discontinuation.

This study demonstrates the long-term safety, consistent utilization, and acute treatment effectiveness, with no tachyphylaxis, in patients with migraine consistently treating with REN for 3 years. This suggests that REN offers an effective, well-tolerated, safe, and sustainable long-term treatment option for individuals with migraine.