Commercial

Medical Policy

Title:

Remote Electrical Neuromodulation for Migraines

Policy #:

05.00.86

Policy

MEDICALLY NECESSARY

Remote electrical neuromodulation devices (REN [e.g., Nerivio]) for the prevention of migraine may be considered medically necessary in adult individuals when the following criteria are met:

Individual is 18 years of age or older
Headaches meet the International Classification of Headache Disorders (ICHD-3) diagnostic criteria for migraine with or without aura
The REN device will be used in the following clinical scenario:

For the prevention of migraine in individuals with 6 to 24 headache days (defined as a calendar day with headache regardless of severity or duration) per 28-day period in each of the 3 months preceding use of the REN device); AND

One of the following additional criteria must also be met:

Insufficient response, contraindication, or intolerance to two or more guideline-recommended preventive headache medications (e.g., anticonvulsants, antihypertensives, antidepressants, calcitonin gene-related peptide [CGRP] inhibitors)
Pregnancy, breastfeeding, or planning to conceive
At risk for or have a history of medication overuse headache
At risk for drug–drug interactions with medications for comorbid conditions

Remote electrical neuromodulation (REN [e.g. Nerivio]) for the prevention of migraine may be considered medically necessary in pediatric individuals when the following criteria are met:

Individual is 8–17 years of age;
Headaches meet the ICHD-3 diagnostic criteria for migraine with or without aura; AND
The REN device will be used in the following clinical scenario:

For the prevention of migraine in individuals with 6 to 24 headache days (defined as a calendar day with headache regardless of severity or duration) per 28-day period in each of the 3 months preceding use of the REN device).

Continued use of the REN device and/or accessories for the prevention of migraine is considered medically necessary in individuals when the following criteria are met:

Compliance with ongoing use
Documentation of clinical benefit

EXPERIMENTAL/INVESTIGATIONAL

Remote electrical neuromodulation devices for acute migraine is considered experimental/investigational, and therefore, not covered. Remote electrical neuromodulation devices for prevention of migraine outside of the above criteria is considered experimental/investigational, and therefore not covered.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.

Guidelines

BENEFIT APPLICATION

Subject to the applicable benefit contract, remote electrical neuromodulation (REN [e.g. Nerivio]) for the prevention of migraine is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Nerivio Migra™ (Theranica Bio-Electronics Ltd.) was granted a de novo classification by the US Food and Drug Administration (FDA) (class II, special controls, product code: QGT) on May 20, 2019. This new classification applied to this device and substantially equivalent devices of this generic type. Nerivio Migra was initially cleared for treatment of acute migraine in adults who do not have chronic migraine.

Subsequent approval was granted for Nerivio in October 2020, via the 510(k) process (K201824). The FDA determined that this device was substantially equivalent to Nerivio Migra for use in adults. The device name changed to just “Nerivio” and the exclusion of chronic migraine patients was removed. The Nerivio device can provide more treatments than the predicate Nerivio Migra (12 treatments vs. eight treatments) and has a longer shelf life (24 months vs. 9 months). In January 2021, the Nerivio device was cleared for use in patients aged 12 to 17 years. In February 2023, Nerivio's indication was expanded to include preventive treatment of migraine with or without aura in individuals 12 years and age or older and was cleared for marketing through the 510(k) process (K223169). In May 2025, the Nerivio and rechargeable Nerivio Infinity devices were cleared for marketing (K241756) with an expanded indication for acute and/or preventive treatment of migraine with or without aura in patients aged 8 years and older.

REMOTE ELECTRICAL NEUROMODULATION CONTRAINDICATIONS

Nerivio is contraindicated in individuals with uncontrolled epilepsy and individuals with an active implantable medical device, such as a pacemaker, hearing aid implant, or any implanted electronic device. Nerivio has not been evaluated in individuals with congestive heart failure, severe cardiac or cerebrovascular disease, pregnancy, or individuals under the age of 8 years.

CRITERIA FOR MIGRAINE

The International Classification of Headache Disorders (ICDH-3) criteria for migraine with and without aura can be accessed at their website: https://ichd-3.org/1-migraine/.

CLINICAL BENEFIT FOR CONTINUATION OF USE

Documentation of clinical benefit for continuation of use may include a clinician attestation regarding any of the following outcomes:

Improvements in pain relief or freedom, particularly for acute use
Reduction in headache frequency, duration, or severity
Reduction in functional disability
Reduction in absenteeism
Reduction in concomitant headache medications.

Description

Migraine is a neurologic disease characterized by recurrent moderate to severe headaches with associated symptoms that can include aura, photophobia, nausea, and/or vomiting. Overall migraine prevalence in the United States is about 15% but varies across population groups. Prevalence is higher in women (21%), among American Indian/Alaska Natives (22%), and among 18- to 44-year-old individuals (19%). Migraine can be categorized as episodic or chronic depending on the frequency of attacks. Generally, episodic migraine is characterized by 14 or fewer headache days per month and chronic migraine is characterized by 15 or more headache days per month.

SPECIFIC INTERNATIONAL CLASSIFICATION OF HEADACHE DISORDERS (ICDH-3) DIAGNOSTIC CRITERIA

EPISODIC MIGRAINE

1. Untreated or unsuccessfully treated headache lasting 4 to 72 hours

2. Headache has at least two of the following characteristics:

Unilateral location
Pulsating quality
Moderate or severe pain intensity
Aggravation by or causing avoidance of routine physical activity

3. At least one of the following during headache:

Nausea and/or vomiting
Photophobia or phonophobia

CHRONIC MIGRAINE

1. Migraine-like or tension-type headache on 15 or more days per month for more than 3 months

2. At least five headache attacks without aura meet episodic migraine criteria 1 to 3, and/or at least five headache attacks with aura meet episodic migraine criteria 2 to 3

3. On more than 8 days per month for more than 3 months, fulfilling any of the following criteria:

For migraine without aura, episodic migraine criteria 2 and 3
For migraine with aura, episodic migraine criteria 1 and 2
Believed by the individual to be migraine at onset and relieved by a triptan or ergot derivative

Migraine attacks, whether due to episodic or chronic migraine, require acute management. The goal of acute treatment is to provide pain and symptom relief as quickly as possible while minimizing adverse effects, with the intent of timely return to normal function. Pharmacologic interventions for treatment of acute migraine vary according to migraine severity. First-line therapy for an acute episode of mild or moderate migraine includes oral non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen. Moderate to severe migraine can be treated through the use of triptans or an NSAID–triptan combination. Antiemetics can be added for migraine accompanied by nausea or vomiting, although certain antiemetic medications used as monotherapy can also provide migraine relief. Other pharmacologic interventions used to treat acute migraine include calcitonin-gene related peptide antagonists, which can be used in individuals with an insufficient response or contraindications to triptans, lasmiditan, and dihydroergotamine. Migraine can be managed at home, although acute migraine is a frequently cited reason for primary care and emergency department visits.

Regular use of pharmacologic interventions can result in medication overuse, which in turn could lead to rebound headache and increased risk of progression from episodic to chronic migraine.

Many individuals who suffer from migraine may also benefit from preventive migraine therapy, including those with frequent or long-lasting migraines, migraine attacks that diminish quality of life or cause significant disability despite acute treatment, contraindications to or failure of acute therapies, and risk of medication overuse headache.

The main goals of preventive therapy are to reduce future attack frequency, severity, and duration, improve responsiveness to acute treatments, improve function and reduce disability, and prevent progression of episodic migraine to chronic migraine. For most adults with episodic migraines who may benefit from preventive therapy, initial therapy with an antiepileptic drug (divalproex sodium, sodium valproate, topiramate) or beta-blockers (metoprolol, propranolol, timolol) is recommended. Frovatriptan may be beneficial as initial therapy for prevention of menstrually associated migraine. Antidepressants (amitriptyline, venlafaxine), alternative beta-blockers (atenolol, nadolol), and additional triptans (naratriptan, zolmitriptan for menstrually associated migraine prevention) may be considered if initial therapy is unsuccessful. For preventive treatment of pediatric migraine, many children and adolescents who received placebo in clinical trials improved and most preventive medications were not superior to placebo. Possibly effective preventive treatment options for children and adolescents may include amitriptyline, topiramate, or propranolol.

Remote electrical neuromodulation (REN) may offer an alternative to pharmacologic interventions for individuals with acute migraine or it may decrease the use of abortive or preventive medications and the risk of medication overuse to treat or prevent acute migraines. The only currently available REN device (Nerivio™) cleared for use by the Food and Drug Administration (FDA) is worn on the upper arm and stimulates the peripheral nerves to induce conditioned pain modulation (CPM). The conditioned pain in the arm induced by the Nerivio REN device is believed to reduce the perceived migraine pain intensity.

Control of the REN device is accomplished through Bluetooth communication between the device and the individual's smartphone or tablet. For acute treatment, at onset of migraine or aura and no later than within 1 hour of onset, the user initiates use of the device through their mobile application. When used for preventive treatment, the device should be used every other day, controlled by the individual through their smartphone or tablet application. User-controlled stimulation intensity ranges from 0% to 100%, corresponding to 0 to 40 milliamperes (mA) of electrical current. Individuals are instructed to set the device to the strongest stimulation intensity that is just below their perceived pain level. The device provides stimulation for up to 45 minutes before turning off automatically. The Nerivio manufacturer indicates that the device can be used instead of or in addition to medication.

Use of REN for the treatment of migraine has been assessed in two randomized controlled trials (RCTs) (Yarnitsky et al., 2017 and 2019) comparing an active REN device (Nerivio Migra) with a sham device in individuals with an acute migraine attack due to episodic migraine.

A pilot crossover trial conducted by Yarnitsky et al. (2017) included data from 71 (of 86 randomized) individuals who received active or sham REN. All individuals were given an identical REN device that was preprogrammed to deliver in random order four active treatment sessions ranging from 80 to 120 hertz (Hz), corresponding to pulse widths of 50 to 200 milliseconds, and one sham session of 0.1 Hz (45-millsecond pulse width). Both active and sham treatments were programmed for a duration of 20 minutes each. Most participants were women (80%) in their mid-40s (mean age, 46 years), with a mean of five migraine attacks per month with a mean pain intensity of 8.8, corresponding to severe pain. Race and/or ethnicity were not reported. In the trial, treatment with active REN was more frequently associated with reduction in, and freedom from, migraine pain than sham REN at 2-hour follow-up. When the device was programmed to deliver an active treatment session, it was most effective at reducing pain when used within 20 minutes of migraine onset. Treatment response to active REN diminished over time of initiation following migraine onset, and no active REN participants reported complete pain relief if the device was initiated more than 1 hour from onset. No adverse events were reported, although individuals were more likely to rate their treatment perception of the active REN sessions as painful (11%) or unpleasant (28%) compared with sham REN sessions (1% painful; 13% unpleasant). Other outcomes were not reported in this study.

A second, larger (N=252) RCT was conducted by Yarnitsky et al. in 2019. The mean age of study participants was 43 years; 81% were female. Most participants were White (88%); 7% were Black and fewer than 1% were Asian. Time since migraine diagnosis was not reported; participants experienced a mean of 7 migraine days per month. Seventy-one percent of participants managed their migraines with the use of acute medication, but important details about type and dosage were not provided. At baseline, 50% of participants reported that light sensitivity was their most bothersome symptom apart from migraine pain, followed by nausea (27%) and sound sensitivity (19%). After a 2- to 4-week run-in during which study participants kept a headache diary, participants were randomly assigned to 4 to 6 weeks of at-home active or sham REN. The frequency was 100 to 120 Hz for the active device and less than 0.1 Hz for the sham device. The pulse width was 400 microseconds for the active device and ranged from 40 to 550 microseconds for the sham device, with the intent of mimicking a similar sensation as that delivered by the active device. At the time of randomization, participants were instructed on how to determine their optimal REN intensity, but this was unclearly defined as a threshold that was "perceptible not painful" (e.g., no specific measure of intensity was described) and no data on the actual intensities used during the study were reported. Participants were instructed to treat their migraine with the REN device as soon as possible following migraine onset, and no later than within 1 hour of onset. Participants who initiated device use more than 1 hour following onset were excluded from the outcome analyses. Individuals treated with active REN were more likely to report freedom from pain and pain relief at 2-hour follow-up, and sustained freedom from pain and pain relief at 48-hour follow-up compared with the sham REN group.

There was no statistical between-group difference in the proportions of individuals reporting freedom from their most bothersome symptom (MBS) at 2-hour follow-up, but a greater proportion of active REN users reported MBS relief at 2 hours relative to sham REN. Device-related adverse events were reported in 5% of active REN and 2% of sham REN participants (P=0.49). At the conclusion of the study, participants were asked whether they believed they had received active or sham treatment as a measure of blinding. Half as many active participants correctly identified their device as did sham participants (23% in the active group vs. 50% in the sham group), although statistical analyses determined the treatment outcome differences between groups were not affected by participants' perceived treatment group. Notable limitations include an unclearly defined intended use population, a nonempirically determined optimum treatment regimen, and no assessment of functional or quality of life outcomes.

A post-hoc analysis of the Yarnitsky et al. 2019 RCT retrospectively compared the effectiveness of acute migraine treatment with the Nerivio device with usual care (i.e., pharmacologic acute migraine management) used during the 2- to 4-week run-in phase of the trial. Pharmacologic treatment used during the run-in phase consisted of NSAIDs, acetaminophen (alone, or in combination with aspirin and caffeine) or triptans. In analysis of a subset of 99 trial participants, the rate of freedom from pain was similar for Nerivio (37.4% [37/99]) and usual care (26.3% [26/99]; P=0.099) at 2-hour follow-up. Results were similar for achievement of pain relief (66.7% [66/99] vs. 52.5% [52/99]; P=0.034). RCTs directly comparing REN with pharmacologic management are needed to confirm these pain findings and to compare the effect of REN versus pharmacologic management on other outcomes.

Avoiding medication overuse has been postulated as a potential benefit of REN treatment of acute migraine. Marmura et al. (2020) reported the results of an observational 8-week open-label extension study following the double-blind phase of the Yarnitsky et al. 2019 trial. The Marmura et al. study compared within-subject data (N=117) from the trial run-in phase with data from the open-label phase, finding that a higher proportion of individuals avoided medication use during the open-label phase (when the REN device was available for use; 89.7%) than in the run-in phase (when the REN device was not available for use; 15.4%). Although these results suggest that use of the REN device could result in less medication use and therefore reduce the risk of medication overuse, confirmatory studies designed to directly assess the role of REN in populations at risk of medication overuse are needed.

The FDA 510(k) summary for the 2024 expanded approval of acute use of REN in pediatric individuals (ages 8–11) was based on a retrospective real-world analysis of 293 children, aged between 6 and 11 years at their first use of the device. Median age was 11 (73.7% female). Safety data were primarily collected via self-reported customer service complaints, which indicated no adverse events. Effectiveness was assessed in participants who completed voluntary pre- and posttreatment surveys. Available efficacy data were only available in 18 participants, of which consistent headache relief was reported by 72.2% (13/18), consistent freedom from headache by 83.3% (15/18), and consistent functional disability freedom by 38.9% (7/18). Additional appropriated sized, controlled studies are required to confirm efficacy in this population. Participants in this population used REN as a stand-alone treatment, with over-the-counter medications, and with prescribed headache medications, in 45.4%, 34.4%, and 20.9% of treatments, respectively.

In 2024, Hershey et al. published the results of a survey of 332 students aged between 7 and 17 years (80.4% female). After being prescribed REN, the percentage of students reporting having their headaches treated at school increased by 11.5%. The most common reasons given for preferring REN treatment at school are the ability to avoid going to the nurse's office (42.5%) and the ability to treat discreetly (39.2%). Barriers to treatment included concerns about standing out (42.2%), and permission to use a smartphone in class to control the REN device (22.9%).

In 2025, Synowiec et al. published the outcomes of a real-world postmarketing coverage with evidence development study. Participants aged between 12 and 75 years who were diagnosed with migraine were prescribed REN. Eligibility criteria included 1) at least one standard-of-care acute migraine therapy had failed for one or more of the following reasons: contraindication, lack of sufficient efficacy, or intolerability of adverse effects; 2) individual at risk of drug–drug interaction with other medications; 3) individual was a pregnant woman, woman trying to conceive, or breastfeeding woman; 4) had chronic migraine and at risk of or diagnosed with medication overuse headache (MOH); or 5) were younger than 18 years. Efficacy was assessed by change in Migraine Disability Assessment (MIDAS) score from baseline to 3 months of treatment and by prospective pain and disability reports 2 hours posttreatment. Device utilization was assessed through prescription fulfillment rates. Three hundred eighty-one participants (mean age, 40.5; 91.1% female) participated in the study. Change in MIDAS score was calculated for all participants who answered the questionnaire twice (n=116), indicating a statistically and clinically meaningful improvement of −12.1 point (P=0.014). Pain relief, pain freedom, functional disability relief, and functional disability freedom were reported in 77.8%, 33.3%, 70.6%, and 50.0% of participants, respectively. Three minor adverse events were reported and participants used a mean of 4.0 (SD, 3.1) devices annually. Generalizability of outcomes is limited due to lack of a control group and high degree of missing data (70%).

Acute Migraine due to Episodic or Chronic Migraine Summary

Evidence from TWO small RCTs found REN with the Nerivio device was more effective than a sham device for measures of pain and symptom relief at 2 hours post-treatment. Participants treated with the Nerivio device were also more likely than those treated with a sham device to report 48-hour freedom from pain and pain relief based on one RCT. Outcomes related to functional disability and quality of life were not reported. No significant between-group difference in functional disability or quality of life was noted in a post-hoc analysis of the pivotal RCT. The remaining evidence from post-hoc and nonrandomized studies suggests that REN with the Nerivio device may provide improvements in acute pain and symptomatology.

For individuals with acute migraine due to episodic or chronic migraine who receive remote electrical neuromodulation (REN), the evidence includes two RCTs and nonrandomized, uncontrolled studies. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Use of an active REN device resulted in more participants with improved pain and symptoms at 2-hour follow-up compared with a sham device based on two RCTs (N=212) with numerous relevance limitations.

Based on the existing evidence, it is unclear how Nerivio would fit into the current acute migraine management pathway. The specific intended use and associated empirically documented recommended regimen(s) must be specified in order to adequately evaluate the net health benefit. Additionally, functional outcomes and quality of life must be evaluated in well-designed and conducted studies in defined populations using documented Nerivio regimens. No significant between-group difference in functional disability or quality of life was noted in a post-hoc analysis of the pivotal RCT. The remaining evidence from post-hoc and nonrandomized studies suggests that REN with the Nerivio device may provide improvements in acute pain and symptomatology. Additionally, controlled studies in adolescent and pediatric populations are lacking. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For adult individuals who may benefit from preventive migraine therapy, including those with frequent or long-lasting episodic or chronic migraines, migraine attacks that diminish quality of life or cause significant disability despite acute treatment, contraindications to or failure of acute therapies, and risk of medication overuse headache, who receive REN, the evidence includes one RCT and one prospective, observational study. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Use of an active REN device resulted in more adults with decreased migraine days per month, regardless of episodic or chronic subtype, when used every other day for 8 weeks compared with a sham device based on one RCT(N=248). Prospective, observational data in two real-world evidence studies using the device for acute treatment of migraine demonstrated a significant reduction in migraine headache days from baseline to months 2 and 3 with device use in adolescent individuals.

Based on the existing evidence, it is unclear how Nerivio would fit into the current migraine prevention pathway, although it could provide benefit for those who do not receive adequate benefit from pharmacologic first- or second-line therapies, or who may have a contraindication to pharmacologic therapies. The specific intended use and associated empirically documented recommended regimen(s) must be specified in order to adequately evaluate the net health benefit. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

For adolescent individuals who may benefit from preventive migraine therapy who receive REN, the evidence includes data from the summary submitted in the FDA approval packet and one real-world evidence analysis. The data in the FDA summary were collected from adolescents who used the device for acute migraine treatment, but use was equivalent to the suggested preventive use (10 times per month or higher). There was substantial reduction from baseline during months 2 and 3 of device use. These data are limited by a lack of comparator and no description of medications or alternative interventions that participants were additionally using. A prospective, real-world evidence analysis investigated the use of Nerivio in adolescents over a 3-month period. There was a statistically significant monthly reduction in mean monthly migraine treatment days. Well-defined, controlled studies are required to confirm benefit in this population. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For children who may benefit from preventive migraine therapy who receive REN, the evidence includes the FDA summary for the expanded approval of preventive use of Nerivio in pediatric individuals (between ages 8 and 11 years) based on a retrospective real-world analysis. Preventive use of the device was assumed by analyzing individuals whose frequency of use in month one was suggestive of preventive treatments. No specific data on proportion of participants in whom preventive use was assumed or efficacy outcomes in the assumed preventive use population were reported. Additional well-defined, controlled studies are warranted to confirm benefit in this population.

The FDA 510(k) summary for the 2024 expanded approval of acute use of Nerivio in pediatric individuals (between ages 8 and 11 years) was based on a retrospective real-world analysis of 293 children, aged between 6 and 11 years at their first use of the device. Median age was 11 years (73.7% female). Safety data were primarily collected via self-reported customer service complaints, which indicated no adverse events. Effectiveness was assessed in individuals who completed voluntary pre- and posttreatment surveys.

Available efficacy data were only available in 18 participants, among which consistent headache relief was reported by 72.2% (13/18), consistent freedom from headache by 83.3% (15/18), and consistent functional disability freedom by 38.9% (7/18). Additional controlled studies are required to confirm efficacy in this population. Participants in this population used REN as a stand-alone treatment, with over-the-counter medications, and with prescribed headache medications, in 45.4%, 34.4%, and 20.9% of treatments, respectively.

In 2024, Hershey et al. published the results of a survey of 332 students aged between 7 and 17 years (80.4% female). After being prescribed REN, the percentage of students reporting having their headaches treated at school increased by 11.5%. The most common reasons given for preferring REN treatment at school are the ability to avoid going to the nurse's office (42.5%) and the ability to treat discreetly (39.2%). Barriers to treatment included concerns about standing out (42.2%) and permission to use a smartphone in class to control the REN device (22.9%).

Use of REN for the prevention of migraine has been assessed in one double-blind, multicenter RCT by Tepper et al. (2023). This study compared an active REN device (Nerivio) used every other day (n=128) with a sham device in adult individuals (n=120) with at least a 6-month history of headaches that meet the ICHD-3 criteria and 6 to 24 headache days per 28-day period in the past 3 months. The researchers included participants who either did not use preventive medicine or were on a stable dose of a single migraine preventive medication during the 2 months before enrollment and throughout the study. Prior to initiation of REN, all enrollees participated in a 4-week baseline phase, where they were instructed to continue their regular medications when needed, and document daily reports, regardless of whether or not they had a headache that day, to rate symptoms using a four-point scale. Symptoms that were collected included pain, functional disability, presence or absence of nausea and/or vomiting, photophobia and phonophobia, and acute medication usage.

To be eligible for the intervention phase, individuals had to have had 6 to 24 headache days during the 28-day baseline period, with at least 4 headache days fulfilling ICHD-3 criteria for migraine, and had at least 80% compliance on completing their daily record of symptoms. The intervention phase was 8 weeks long and included participants who were randomly assigned 1:1 to active REN or sham REN. The active and sham devices were visually identical, so staff and participants were blinded to their randomized group. Participants were directed to complete a full 45-minute treatment with REN every other day and to complete a daily diary. If acute treatment was needed, participants were instructed to use their usual acute treatments. The primary outcome was the mean change in number of migraine days per month in the 4-week baseline phase compared to the last 4 weeks of treatment phase (weeks 9–12). Overall, participants treated with the active REN device had statistically significantly fewer migraine days during the intervention period compared to baseline compared to those treated with sham. This was also demonstrated in subanalyses based on episodic or chronic migraines. Of the participants, 40.8% used a preventive medication in combination with REN. Half of the medication users were on first-line preventive medications (e.g., amitriptyline, topiramate), while the other half were on second-line agents (e.g., anti-calcitonin gene-related peptide monoclonal antibodies, on abotulinumtoxin A, gepants). There were two non-device-related serious adverse events, both in the REN arm. There was a single device-related adverse event in the sham group and no device-related adverse events in the active group. There were no differences in quality of life questionnaires or Headache Impact Tests, a tool used to capture the impact of headache on functional health and well-being, between groups at any time period. These results are limited by the 8-week duration, shorter than the recommended 12-week duration by the International Headache Society guidelines for neuromodulation devices, and lack of medical history reporting previous preventive medications used by participants. No significant difference between REN and sham groups was noted for mean change in the Headache Impact Test Short Form (HIT-6) or Migraine Specific Quality of Life Questionnaire - Function Domain (MSQ).

Evidence from a small RCT found REN with the Nerivio device was more effective than a sham device for decreasing migraine days per month, regardless of episodic or chronic subgroup, when used every other day for 8 weeks. Participants treated with the Nerivio device were also more likely than those treated with sham to have reduced moderate to severe headache days, reduced headache days in general, and at least a 50% reduction from their baseline in overall headache days. Approximately half of the participants included in this study were also taking preventive pharmacologic therapy. There were no differences in quality of life or functional health patient-reported outcomes between groups at any time point. Prospective, observational data in two real-world evidence studies using the device for acute treatment of migraine demonstrated a significant reduction in migraine headache days from baseline to months 2 and 3 with device use in adolescent individuals.

Based on the existing evidence, it is unclear how Nerivio would fit into the current migraine prevention pathway, although it could provide benefit for those who do not receive adequate benefit from pharmacologic first- or second-line therapies, or who may have a contraindication to pharmacologic therapies. Study limitations include a high-degree of missing data and choice of imputation method. Controlled data in pediatric populations is lacking.

Summary

For individuals with acute migraine due to episodic or chronic migraine who receive REN, the evidence includes two RCTs and nonrandomized, uncontrolled studies. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Use of an active REN device resulted in more individuals with improved pain and symptoms at 2-hour follow-up compared with a sham device based on two RCTs (N=212) with numerous relevance limitations. Based on the existing evidence, it is unclear how Nerivio would fit into the current acute migraine management pathway. No significant between-group difference in functional disability or quality of life was noted in a post-hoc

analysis of the pivotal RCT. Additionally, controlled studies in adolescent and pediatric populations are lacking. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For adult individuals who may benefit from preventive migraine therapy, including those with frequent or long-lasting episodic or chronic migraines, migraine attacks that diminish quality of life or cause significant disability despite acute treatment, contraindications to or failure of acute therapies, and risk of medication overuse headache, who receive REN, the evidence includes one RCT and one prospective, observational study. Relevant outcomes are symptoms, functional outcomes, quality of life, and treatment-related morbidity. Use of an active REN device resulted in more adults with decreased migraine days per month, regardless of episodic or chronic subtype, when used every other day for 8 weeks compared with a sham device based on one RCT (N=248). Prospective, observational data in two real-world evidence studies using the device for acute treatment of migraine demonstrated a significant reduction in migraine headache days from baseline to months 2 and 3 with device use in adolescent individuals. Based on the existing evidence, it is unclear how Nerivio would fit into the current migraine prevention pathway, although it could provide benefit for those who do not receive adequate benefit from pharmacologic first- or second-line therapies, or who may have a contraindication to pharmacologic therapies. The evidence is sufficient to determine that the technology results in an improvement in the net health outcome.

References

Ailani J, Rabany L, Tamir S, et al. Real-World Analysis of Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine. Front Pain Res (Lausanne). 2021;2:753736.

Ailani J, Burch RC, Robbins MS. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039.

Burch RC, Loder S, Loder E, et al. The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache. 2015;55(1):21-34.

Burch R, Rizzoli P, Loder E. The prevalence and impact of migraine and severe headache in the United States: Updated age, sex, and socioeconomic-specific estimates from government health surveys. Headache. 2021;61(1):60-68.

Diener HC, Tassorelli C, Dodick DW, et al. Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition. Cephalalgia. 2019;39(6):687-710.

Grosberg B, Rabany L, Lin T, et al. Safety and efficacy of remote electrical neuromodulation for the acute treatment of chronic migraine: an open-label study. Pain Rep. 2021;6(4):e966.

Hershey AD, Irwin S, Rabany L, et al. Comparison of Remote Electrical Neuromodulation and Standard-Care Medications for Acute Treatment of Migraine in Adolescents: A Post Hoc Analysis. Pain Med. 2022;23(4):815-820.

Hershey AD, Lin T, Gruper Y, et al. Remote electrical neuromodulation for acute treatment of migraine in adolescents. Headache. 2021;61(2):310-317.

Hershey AD, Shmuely S, Stark-Inbar A, et al. Patterns, Barriers, and Preferences of Treating Migraine Within the School Setting: A Survey Study of Students. Children (Basel). 2024;11(11):1286.

Management of Headache Work Group. VA/DoD Clinical Practice Guideline.Washington, DC. September 2023. Accessed August 13, 2024. Available at: https://www.healthquality.va.gov/guidelines/pain/headache/VA-DoD-CPG-Headache-Full-CPG.pdf. Accessed on June 12, 2026.

Marmura MJ, Lin T, Harris D, et al. Incorporating Remote Electrical Neuromodulation (REN) Into Usual Care Reduces Acute Migraine Medication Use: An Open-Label Extension Study. Front Neurol. 2020;11:226.

Monteith TS, Stark-Inbar A, Shmuely S, et al. Remote electrical neuromodulation (REN) wearable device for adolescents with migraine: a real-world study of high-frequency abortive treatment suggests preventive effects. Front Pain Res (Lausanne). 2023;4:1247313.

Nierenburg H, Rabany L, Lin T, et al. Remote Electrical Neuromodulation (REN) for the Acute Treatment of Menstrual Migraine: a Retrospective Survey Study of Effectiveness and Tolerability. Pain Ther. 2021;10(2):1245-1253.

Nierenburg H, Vieira JR, Lev N, et al. Remote Electrical Neuromodulation for the Acute Treatment of Migraine in Patients with Chronic Migraine: An Open-Label Pilot Study. Pain Ther. 2020;9(2):531-543.

Nierenburg H, Stark-Inbar A. Nerivio® remote electrical neuromodulation for acute treatment of chronic migraine. Pain Manag. 2022;12(3):267-281.

Oskoui M, Pringsheim T, Billinghurst L, et al. Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2019;93(11):500-509.

Oskoui M, Pringsheim T, Holler-Managan Y, et al. Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society. Headache. 2019;59(8):1158-1173.

Rapoport AM, Bonner JH, Lin T, et al. Remote electrical neuromodulation (REN) in the acute treatment of migraine: a comparison with usual care and acute migraine medications. J Headache Pain. 2019;20(1):83.

Rastogi RG, Santiago JA, Chang A, et al. A Real-World Evidence Study on US Patients Demonstrating Safety of High-Frequency Use of the Remote Electrical Neuromodulation (REN) Wearable Device for Migraine Treatment. Pain Ther. 2026 Jun;15(3):711-720.

Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review) [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000;55(6):754-762.

Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78(17):1337-1345.

Singh RBH, VanderPluym JH, Morrow AS, et al. Acute Treatments for Episodic Migraine. Rockville (MD): Agency for Healthcare Research and Quality (US); December 2020. Accessed on June 12, 2026..

Synowiec A, Stark-Inbar A, Santamaria DD, et al. Coverage with evidence development study shows benefits in patients with migraine treated with remote electrical neuromodulation. Am J Manag Care. 2025;31(11):e315-e321.

Tassorelli C, Diener HC, Silberstein SD, et al. Guidelines of the International Headache Society for clinical trials with neuromodulation devices for the treatment of migraine. Cephalalgia. 2021;41(11-12):1135-1151.

Tepper SJ, Rabany L, Cowan RP, et al. Remote electrical neuromodulation for migraine prevention: A double-blind, randomized, placebo-controlled clinical trial. Headache. 2023;63(3):377-389.

Tepper SJ, Lin T, Montal T, et al. Real-world Experience with Remote Electrical Neuromodulation in the Acute Treatment of Migraine. Pain Med. 2020;21(12):3522-3529.

U.S. Food and Drug Administration. De Novo Classification Request for Nerivio Migra. Accessed October 23, 2025.

U.S. Food and Drug Administration. 501(k) Summary: Theranica Bio-Electronics LTDs Nerivio. K203181. Accessed June 12, 2026.

U.S. Food and Drug Administration. 510(k) Summary: Nerivio Approval in Adolescents. K203181. Accessed June 12, 2026.

U.S. Food and Drug Administration. 510(k) Summary (K223169): Nerivio Approval for Preventative Treatment. Accessed June 12, 2026..

U.S Food and Drug Administration (FDA). 510(k) Summary. Theranica Bio-Electronics LTD.'s NerivioInfinity and Nerivio (K241756). October 8, 2024. Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf24/K241756.pdf. Accessed June 12, 2026.

VanderPluym JH, Halker Singh RB, Urtecho M, et al. Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis. JAMA. 2021;325(23):2357-2369.

Werner K, Gerson T, Stark-Inbar, A, et al. Acute treatment of migraine in children aged 6-11: Real-world analysis of remote electrical neuromodulation (REN). Annals of the Child Neurology Society. 2024;2(2):135-145.

Yarnitsky D, Volokh L, Ironi A, et al. Nonpainful remote electrical stimulation alleviates episodic migraine pain. Neurology. 2017;88(13):1250-1255.

Yarnitsky D, Dodick DW, Grosberg BM, et al. Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Headache. 2019;59(8):1240-1252.

Yuan H, Orr SL, Al-Karagholi MAM, et al. International Headache society evidence-based guidelines on the use of non-invasive neuromodulation devices for the acute and preventive treatment of migraine. Cephalalgia. 2025 Oct;45(10):3331024251388377.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

G43.001 Migraine without aura, not intractable, with status migrainosus

G43.009 Migraine without aura, not intractable, without status migrainosus

G43.011 Migraine without aura, intractable, with status migrainosus

G43.019 Migraine without aura, intractable, without status migrainosus

G43.101 Migraine with aura, not intractable, with status migrainosus

G43.109 Migraine with aura, not intractable, without status migrainosus

G43.111 Migraine with aura, intractable, with status migrainosus

G43.119 Migraine with aura, intractable, without status migrainosus

G43.501 Persistent migraine aura without cerebral infarction, not intractable, with status migrainosus

G43.509 Persistent migraine aura without cerebral infarction, not intractable, without status migrainosus

G43.511 Persistent migraine aura without cerebral infarction, intractable, with status migrainosus

G43.519 Persistent migraine aura without cerebral infarction, intractable, without status migrainosus

G43.701 Chronic migraine without aura, not intractable, with status migrainosus

G43.709 Chronic migraine without aura, not intractable, without status migrainosus

G43.711 Chronic migraine without aura, intractable, with status migrainosus

G43.719 Chronic migraine without aura, intractable, without status migrainosus

HCPCS Level II Code Number(s)

A4540 Distal transcutaneous electrical nerve stimulator, stimulates peripheral nerves of the upper arm

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From 05.00.86:

09/16/2026	This policy has been reissued in accordance with the Company's annual review process.
01/01/2026	This new policy will become effective 01/01/2026. This new policy has been issued to communicate the Company's coverage position from Experimental/Investigational to Medically Necessary for remote electrical neuromodulation for migraines.

Version Effective Date:

1/1/2026

Version Issued Date:

1/2/2026

Version Reissued Date:

9/16/2026