Large-Scale Study Demonstrates Benefits of Early Nerivio REN Use for Migraine Treatmentne Treatment

A large-scale, real-world evidence study by Theranica found that early acute treatment with remote electrical neuromodulation (REN), or Nerivio, significantly reduced migraine outcomes. The study, titled The Effect of Treatment Onset Time on Acute Efficacy in Migraine Patients Treating with Remote Electrical Neuromodulation (REN), showed that initiating treatment within one hour of migraine onset using the Nerivio® REN wearable can enhance efficacy outcomes by up to twofold compared with later treatment initiation.¹

Published in Cephalalgia, the study aimed to evaluate how treatment onset timing affected Nerivio’s effectiveness for acute migraine management. The study included 55,261 patients (mean age, 37.9 [SD, 18.5] years; 83.4% female) who performed 586,981 treatments with the REN wearable.² Treatments initiated within 1 hour of migraine attack onset (headache or aura) were classified as early, while patients who initiated after one hour were classified as late. The study assessed 7 prospective acute treatment efficacy outcomes: pain relief, pain freedom, functional disability relief, functional disability freedom, and freedom from migraine associated symptoms (photophobia, phonophobia, and nausea/vomiting).

“While the value of early acute treatment makes a lot of sense and has been known to healthcare providers, this is the first time that its advantage is demonstrated rigorously, in a non-pharmacological treatment", said Jessica Ailani, MD, lead study author and director of the MedStar Georgetown Headache Center, in a statement.¹ “What's especially impressive about this study is the huge sample size, which makes it the largest prospective study in migraine, ever.”

All told, the study found that early initiation of Nerivio treatments yielded higher responder-rates than later treatments (P < 0.001, significant following Bonferroni correction for multiple comparisons). The symptoms monitored and compared included pain relief (65.1% vs. 46.6%; Δ = 18.5%), pain freedom (28.8% vs. 14.5%; Δ = 14.3%), functional disability relief (58.1% vs. 49.3%; Δ = 8.8%), functional disability freedom (35.4% vs. 20.9%; Δ = 14.5%), freedom from photophobia (26.9% vs. 19.0%; Δ = 7.9%), phonophobia (34.0% vs. 25.9%; Δ = 8.1%) and nausea/vomiting (51.5% vs. 38.7%; Δ = 12.8%).

Of the total treatments administered, 56.5% (n = 331,760) were considered early. The number of treatments that meet the criteria for efficacy analysis varied between 6413 and 35,581 for the different efficacy outcomes. Participants who administered 50% or more of their treatments early, considered early treaters, were slightly older (38.5 [±16.3] vs. 36.0 [±22.3]; P < 0.001) and included more females (% of females: 85.4% vs. 84.1%; P < 0.001) than those who administered early treatments in less than 50% of their treatments.

The Nerivio REN wearable is an acute and preventive prescription migraine treatment that works without drugs, needles, or invasive procedures. Since receiving its initial FDA De Novo clearance for adults in 2019, Nerivio’s approved use has continued to expand, with the most recent clearance in 2024 extending access to children as young as 8. Controlled by a smartphone app, the wearable uses electrical pulses on the arm to activate the brain's natural pain regulation system, relieving migraine symptoms during an attack and reducing the frequency and burden of future episodes when used preventively.

"The study further iterates that timely acute treatment is key in optimizing clinical results and reducing the overall burden of migraine, including the impact on quality of life, medication overuse headache, and disease chronification," said Alit Stark-Inbar, PhD, Vice President of Medical Information and Research at Theranica, in a statement.¹ "Moreover, timely intervention is expected to increase treatment adherence, as patients who treat early and experience meaningful relief are more likely to continue using the REN wearable as part of their care plan."

REFERENCES
1. Theranica's Nerivio® REN Wearable Validated in Landmark 55,000-Patient Study Published in Cephalalgia. Theranica. News Release. October 28, 2025. Accessed November 4, 2025. https://www.prnewswire.com/news-releases/theranicas-nerivio-ren-wearable-validated-in-landmark-55-000-patient-study-published-in-cephalalgia-302596007.html
2. Ailani J, Tomaschek I, Stark-Inbar A, Shmuely S, Ironi A, Lax DN. The effect of treatment onset time on acute efficacy in migraine patients treating with remote electrical neuromodulation (REN). Cephalalgia. 2025;45(10). doi:10.1177/03331024251370696