Three years of remote electrical neuromodulation (REN) acute treatment for migraine shows consistent effectiveness and no tachyphylaxis phenomenon

Objective 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. Background 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. Methods 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. Results 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. Conclusion 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.