Temporal analysis of remote electric neuromodulation for the prevention of migraine.

Aim: To evaluate the onset, magnitude and persistence of efficacy of remote electrical neuromodulation (REN) compared with placebo for the preventive treatment of migraine. Materials & methods: Analysis was conducted on data from a prospective, double-blind, placebo-controlled clinical trial, which assessed the efficacy of REN for the prevention of migraine. The number of monthly migraine days (MMD) per group was calculated in 2-week intervals and compared between the groups. Results: Differences between the active (N = 95) and placebo (N = 84) groups reached significance at 2 weeks: therapeutic gain 0.84 MMD; p = 0.036. 4 weeks gain 1.59 MMD; p = 0.025, 6 weeks gain 2.27 MMD; p < 0.001, 8 weeks gain 2.68 MMD; p < 0.001. Conclusion: REN provides rapid and consistent efficacy in preventive treatment of migraine.

Device profile of Nerivio for the acute and preventive treatment of episodic or chronic migraine in patients 12 years and older.

INTRODUCTION: Migraine is a prevalent, inherited and disabling brain disease with multiple symptoms and a variety of treatment options. Nerivio, utilizing remote electrical neuromodulation (REN) a wearable device, offers users good efficacy, tolerability and safety. It is user-friendly, affordable, non-addictive and cleared by the FDA and the European Conformity. AREAS COVERED: The device structure, mechanism of action, indications for use, application instructions, efficacy, adverse events, tolerability, safety, patient satisfaction, associated application and the research highlights are discussed herein. EXPERT OPINION: The device works well for most people living with migraine, often without concomitant medication, is tolerable, safe and causes minimal and mild adverse effects. It expands our migraine treatment options and improves patient adherence to treatment. Nerivio is easy-to-use and can be worn at any time of the day; it provides a non-pharmacologic option for the optimization of migraine treatment without significant adverse events.

Effectiveness comparison of remote electrical neuromodulation and standard-care medications for acute treatment of chronic migraine: a post-hoc analysis.

Aim: The current study compared the effectiveness of remote electrical neuromodulation (REN) to that of standard-care medications for acute treatments of migraine, using a within-subjects design. Materials & methods: Post-hoc within-subject analysis was performed on data from 78 adult chronic migraine patients who participated in a clinical trial with REN, on four end points: single-treatment pain relief, single-treatment pain freedom, consistency of pain relief and consistency of pain freedom. Results: No statistical differences were found between REN and the tested medications, in any of the effectiveness outcomes: single-treatment pain relief p = 0.056, single-treatment pain freedom p = 0.532, consistency of pain relief p = 0.369, consistency of pain freedom p = 1.00. Conclusion: The results suggest that REN may provide an effective non-pharmacological alternative for standard care abortive medications in individuals impacted by chronic migraine.

Due to the high frequency of headaches, patients impacted by chronic migraine are struggling with poor quality of life, as well as elevated risk of medication overuse headache (which might cause migraine chronification). Thus, there is a need for non-pharmacological migraine treatments that are both effective and well tolerated. Remote electrical neuromodulation (REN) is a non-pharmacological abortive migraine treatment, which is US FDA cleared for adults and adolescents with episodic or chronic migraine. The current study compared the effectiveness of REN to that of standard-care medications (i.e., over-the-counter medications and triptans), using data from 78 individuals with chronic migraine who participated in a clinical trial. During the study, each participant treated their attacks with their preferred medication for the first 4 weeks, and then treated their attacks with REN (only) for the following four weeks. The participants rated their pain level prior to each treatment, and 2 h after the beginning of the treatment. The results indicate no statistical difference between the effectiveness of REN and standard care medications and suggest that REN may provide an effective non-pharmacological alternative for standard care abortive medications, for individuals with chronic migraine.

Combining Guided Intervention of Education and Relaxation (GIER) with Remote Electrical Neuromodulation (REN) in the Acute Treatment of Migraine.

BACKGROUND: Evidence indicates that combining behavioral treatments with pharmacological treatments for migraine prevention improves efficacy, but little is known about the outcomes of combining neuromodulation and behavioral interventions for acute treatment of migraine. Remote electrical neuromodulation (REN) is a U.S. Food and Drug Administration (FDA)-cleared nonpharmacological migraine treatment. The present study evaluated the clinical benefits of augmenting REN treatment with a specially tailored behavioral therapy consisting of Guided Intervention of Education and Relaxation (GIER) for the acute treatment of migraine. METHODS: In this two-arm observational study, real-world data were collected from patients across the United States who were using the REN device. Eighty-five migraine patients ≥18 years of age who treated their attacks with REN in parallel with the GIER intervention were individually matched on age and sex with 85 patients who used REN alone. The groups were compared on the proportion of migraine attacks in which they achieved pain relief, pain freedom, improvement of function, and return to normal function, all at 2 hours after treatment. RESULTS: Data from 170 users were analyzed (85 per group). Compared with the REN-only group, the REN+GIER group displayed a statistically significant higher proportion of patients achieving consistent pain relief (P = 0.008), consistent improvement in function (P = 0.014), and consistent return to normal function (P = 0.005), all at 2 hours after treatment. CONCLUSIONS: The results suggest that combining the GIER behavioral intervention with REN treatment can improve the therapeutic efficacy beyond that of REN alone, in terms of both pain level and improvement of disability.

Comparison of Remote Electrical Neuromodulation and Standard-Care Medications for Acute Treatment of Migraine in Adolescents: A Post Hoc Analysis.

OBJECTIVE: There is an unmet need for new, efficacious, well-tolerated, acute treatments for migraine in adolescents. Remote electrical neuromodulation (REN) is a novel, nonpharmacological treatment that provides significant symptom relief with good tolerability. The current post hoc analysis compared the efficacy of REN to that of standard-care medications for the acute treatment of migraine in adolescents. DESIGN: Within-participant post hoc analysis of data from a clinical trial. SETTING: Data from a clinical trial. SUBJECTS: Data from 35 adolescent participants were analyzed. METHODS: Efficacy was compared between a run-in phase, in which attacks were treated with standard-care medications (triptans or over-the-counter medications), and an intervention phase, in which attacks were treated with REN. Efficacy was compared within participants through the use of McNemar's test at four endpoints (2 hours after treatment): single-treatment pain freedom and pain relief, and consistency of pain freedom and pain relief (defined as response in at least 50% of the available first four treatments). RESULTS: At 2 hours after treatment, pain freedom was achieved by 37.1% of the participants with REN, vs 8.6% of the participants with medications (P = 0.004). Pain relief was achieved by 71.4% with REN, vs 57.1% with medications (P = 0.225). Consistency of pain freedom was achieved by 40% with REN, vs 8.6% with medications (P < 0.001). Consistency of pain relief was achieved by 80.0% with REN, vs 57.2% with medications (P = 0.033). CONCLUSIONS: Our results suggest that REN may have higher efficacy than certain standard-care medications for the acute treatment of migraine in adolescents. A larger-scale, blinded comparative-effectiveness and tolerability study is needed.

Safety and efficacy of remote electrical neuromodulation for the acute treatment of chronic migraine: an open-label study.

INTRODUCTION: Remote electrical neuromodulation (REN) is an acute treatment of migraine. The results from several studies in patients with episodic migraine suggest that REN is an effective and safe acute treatment of migraine. A recent pilot study provided initial support that REN is effective in patients with chronic migraine as well. OBJECTIVES: The current study aimed to validate and provide further evidence for the safety and efficacy of REN in a large sample of patients impacted by chronic migraine. METHODS: In this open-label, single-arm study, patients with chronic migraine treated their headaches with the REN device (Nerivio, Theranica Bio-Electronics Ltd, Israel) for 4 weeks. Participants used an electronic diary to record their symptoms at treatment initiation, 2 hours after treatment, and 24 hours after treatment. The primary end point was the percentage of subjects who achieved pain relief at 2 hours posttreatment. Secondary end points included pain freedom and improvement of associated symptoms and functional disability. RESULTS: One hundred twenty-six subjects were enrolled into the study, of which 91 subjects had an evaluable treatment with REN. Pain relief and pain disappearance at 2 hours were achieved by 59.3% (54/91) and 20.9% (19/91) of modified intent-to-treat subjects, respectively (with worst-case sensitivity analysis indicating 54.5% and 19.2%, respectively). Sustained pain relief at 24 hours was observed in 64.4% (29/45) of those who achieved pain relief at 2 hours (with worst-case sensitivity analysis indicating 45.6%). The findings of the study show that REN has a favorable effect on nausea, photophobia, and phonophobia and improves functional ability. One device-related adverse event was reported. CONCLUSIONS: Remote electrical neuromodulation treatments results in the relief of migraine headaches and associated symptoms, thus offering a drug-free acute treatment option for people with chronic migraine. TRIAL REGISTRATION: ClinicalTrials.gov NCT04194008.

Remote Electrical Neuromodulation (REN) for the Acute Treatment of Menstrual Migraine: a Retrospective Survey Study of Effectiveness and Tolerability.

INTRODUCTION: Migraine is one of the most prevalent neurological disorders worldwide, and estimations are that 60% of women who suffer from migraines experience attacks that are associated with menstruation. Menstrual migraines are typically more debilitating and less responsive to pharmacological treatment. Remote electrical neuromodulation (REN) is a non-pharmacological abortive treatment of migraine headache. The current study evaluated the self-reported effectiveness and tolerability of REN for the acute treatment of menstrual migraine, via a retrospective structured survey that was sent to adult female REN users. METHODS: Women aged 18-55 years who experience menstrually related or pure menstrual migraine and have completed at least four REN treatments, participated in this retrospective, observational survey study. Participants completed a short online survey assessing effectiveness, satisfaction, and safety outcomes. RESULTS: Ninety-one participants qualified for the analysis, out of which 74.7% (68/91) reported that the treatment was at least moderately effective (moderately effective 37.4%, very effective 26.4%, extremely effective 11.0%). Additionally, 45.1% (41/91) reported satisfaction from REN (slightly satisfied 33%, extremely satisfied 12.1%), while 34.1% were neutral and 20.9% (19/91) were not satisfied. Lastly, 100% of the participants reported that the treatment is at least moderately tolerable (moderately tolerable 8.8%, very tolerable 20.9%, extremely tolerable 70.3%), and 13.2% (12/91) of respondents reported mild short-term side effects. CONCLUSIONS: Nearly 75% reported that the treatment was at least moderately effective, 45% reported satisfaction, and 100% of the participants reported that the treatment is at least moderately tolerable. Thirteen percent reported mild short-term side effects. REN was thus reported as effective for menstrual migraine by most participants and was very well tolerated. Therefore, REN may provide a safe, non-pharmacological alternative for the acute treatment of menstrual migraine. CLINICALTRIAL. GOV REGISTRATION NUMBER: NCT04600388.

Remote electrical neuromodulation for acute treatment of migraine in adolescents.

OBJECTIVES: Migraine is a common disabling neurological disorder. Current acute treatments for migraine in adolescents are mostly pharmacological and may have limited effectiveness, can cause side effects, and may lead to medication overuse. There is an unmet need for effective and well-tolerated treatments. Remote electrical neuromodulation (REN) is a novel acute treatment of migraine that stimulates upper arm peripheral nerves to induce conditioned pain modulation (CPM)-an endogenous analgesic mechanism. The REN device (Nerivio® , Theranica Bio-Electronics Ltd., Israel) is a FDA-authorized device for acute treatment of migraine in adults. This study assessed the efficacy and safety of REN in adolescents with migraine. DESIGN AND METHODS: This was an open-label, single-arm, multicenter study in adolescents (ages 12-17 years) with migraine. Participants underwent a 4-week run-in phase. Eligible participants continued to an 8-week treatment phase with the device. Pain severity, associated symptoms, and functional disability were recorded at treatment initiation, and 2 and 24 hours post-treatment. The primary endpoints of this study were related to the safety and tolerability of REN. The secondary endpoints were related to device efficacy and included the proportion of participants who achieved pain relief at 2 hours post-treatment and the proportion of participants who achieved pain freedom at 2 hours. The presented results reflect an interim analysis with subsequent stopping of the rest of the study. RESULTS: Sixty participants were enrolled for the study; of these, 14 failed to meet the run-in criteria and 1 was lost to follow-up. Forty-five participants performed at least one treatment, of which 39 participants completed a test treatment with REN. One device-related adverse event (2%) was reported in which a temporary feeling of pain in the arm was felt. Pain relief and pain-free at 2 hours were achieved by 71% (28/39) and 35% (14/39) participants, respectively. At 2 hours, 69% (23/33) participants experienced improvement in functional ability. CONCLUSIONS: REN may offer a safe and effective non-pharmacological alternative for acute treatment in adolescents.

Remote Electrical Neuromodulation for the Acute Treatment of Migraine in Patients with Chronic Migraine: An Open-Label Pilot Study.

INTRODUCTION: Remote electrical neuromodulation (REN) is a novel acute treatment of migraine. Upper arm peripheral nerves are stimulated to induce conditioned pain modulation (CPM)-an endogenous analgesic mechanism in which conditioning stimulation inhibits pain in remote body regions. The REN device (Nerivio®, Theranica Bio-Electronics LTD., Israel) is FDA-authorized for acute treatment of migraine in adults who do not have chronic migraine. The current study assessed the consistency of response over multiple migraine attacks in people with chronic migraine who are typically characterized with severe pain intensity, high disability, and less robust response to triptans. METHODS: This was an open-label, single-arm, dual-center study conducted on adults with chronic migraine. Participants underwent a 4-week treatment phase in which they treated their migraine headaches with the device for 45 min within 1 h of attack onset. Pain levels were recorded at baseline, 2 h, and 24 h post-treatment. Efficacy outcomes (pain relief and pain-free responses at 2 h, sustained pain relief and sustained pain-free responses at 24 h) focused on intra-individual consistency of response across multiple attacks, which was defined as response in at least 50% of the treatments. RESULTS: Forty-two participants were enrolled, and 38 participants were evaluable for analyses; 73.7% (28/38) achieved pain relief at 2 h, 26.3% (10/38) were pain-free at 2 h, 84.4% (27/32) had sustained pain relief response at 24 h and 45.0% (9/20) had sustained pain relief response at 24 h in at least 50% of their treated attacks. The effects of REN on associated symptoms and improvement in function were also consistent. The incidence of device-related adverse events was low (1.8%). CONCLUSIONS: REN used for a series of migraine attacks was effective and well tolerated across attacks. REN may offer a safe and effective non-pharmacological alternative for acute treatment in patients with chronic migraine. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04161807. Retrospectively registered on November 13, 2019.

Device profile of the Nerivio™ for acute migraine treatment: overview of its efficacy and safety.

Introduction: Noninvasive neuromodulation devices represent an emerging field in the acute treatment of migraine. High efficacy, favorable safety profile, good tolerability and low cost are important factors for the desired shift to non-pharmacological treatments. This will have the potential to improve the quality of life of people with migraine and reduce the risk for adverse events and medication overuse headache (MOH).Areas covered: Nerivio™ (Theranica Bio-Electronics, Israel) is a novel FDA-cleared remote electrical neuromodulation (REN) device for acute treatment of migraine. This review highlights the mechanism of action of REN and summarizes the clinical data. Nerivio™ has been studied in two randomized trials which provide support for the efficacy and safety of the device. Post-hoc analyses suggest that the efficacy of REN is non-inferior to usual care in general and to acute pharmacological treatments specifically.Expert commentary: Nerivo™ integrates clinically meaningful efficacy with a high safety profile, satisfying a great unmet need in migraine acute care. The unique mechanism of action, in which the electrical stimulation is applied to peripheral nerves in the upper arm, permits the introduction of an innovative device with high efficacy and superior and improved usability aspects compared with acute pharmacological treatments and other approved devices.