Latest Review Date: October 2024

Category: Medical                                          

POLICY:

For dates of service December 16, 2023, and after:

Remote electrical neuromodulation for acute migraine or prevention of migraine is considered investigational.

For dates of service prior to December 16, 2023:

Remote electrical neuromodulation for acute migraine is considered investigational.

DESCRIPTION OF PROCEDURE OR SERVICE:

Migraine attacks due to episodic or chronic migraine require acute management. Some individuals may also require preventive migraine therapy. Current first-line therapy for treatment and prevention of acute migraine involves use of various pharmacologic interventions. Regular use of pharmacologic interventions can result in medication overuse and increased risk of progression from episodic to chronic migraine. Nonpharmacologic remote electrical neuromodulation (REN) may offer an alternative to pharmacologic interventions for individuals with migraine.

Migraine

Migraine is a neurologic disease categorized by recurrent moderate to severe headaches with associated symptoms that can consist of aura, photophobia, nausea and/or vomiting. Overall migraine prevalence in the United States is about 15 percent but varies according to population group. Prevalence is higher in women (21%), among American Indian/Alaska Natives (22%) and among 18- to 44-year-olds (19%). Social determinants including low education level (18%), use of Medicaid (27%), high poverty level (23%) and being unemployed (22%) are also associated with higher rates of migraine.

Migraine is 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 days or more headache days per month. Specific International Classification of Headache Disorders diagnostic criteria is as follows:

• Episodic migraine:
  1. Untreated or unsuccessfully treated headache lasting 4 to 72 hours
  2. Headache has at least two of the following characteristics:
     1. Unilateral location
     2. Pulsating quality
     3. Moderate or severe pain intensity
     4. Aggravation by or causing avoidance of routine physical activity
  3. At least one of the following during headache:
     1. Nausea and/or vomiting
     2. 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 5 headache attacks without aura meet episodic migraine criteria 1-3, and/or at least 5 headache attacks with aura meet episodic migraine criteria 2-3
  3. On more than 8 days per month for more than 3 months, fulfilling any of the following criteria:
     1. For migraine without aura, episodic migraine criteria 2 and 3
     2. For migraine with aura, episodic migraine criteria 1 and 2
     3.  Believed by the patient to be migraine at onset and relieved by
        a triptan or ergot derivative

Migraine attacks, whether due to episodic or chronic migraine, call for 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 with triptans or an NSAID-triptan combination. Antiemetic’s can be added for migraine accompanied by nausea or vomiting, though 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 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 ifinitial 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

Remote electrical neuromodulation (REN) may possibly offer an alternative to pharmacologic interventions for individuals with acute migraine or it may reduce 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 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 decrease the perceived migraine pain intensity. Control of the REN device is accomplished through Bluetooth communication between the device and the patient's smartphone or tablet. For acute treatment, at onset of migraine or aura and no later than within one 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. Patient-controlled stimulation intensity ranges from 0% to 100%, corresponding to 0 to 40 mill amperes (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 specifies that the device can be used instead of or in combination with medication.

KEY POINTS:

This evidence review was created in March 2022 with a search of the PubMed database. The most recent literature update was performed through August 9, 2024.

SUMMARY OF EVIDENCE

For individuals with acute migraine due to episodic or chronic migraine who receive remote electrical neuromodulation (REN), the evidence includes 2 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 small (total N=212) RCTs with numerous relevance limitations. Based on the existing evidence, it is unclear how Nerivio would fit into the current acute migraine management pathways. The specific intended-use (e.g., treatment naive, those with contraindications to medication, or those who have failed pharmacologic treatment); and associated empirically documented recommended REN regimen(s) (e.g., a clinically relevant effective device intensity threshold) must be specified in order to adequately evaluate net health benefit. Additionally, functional outcomes and quality of life must be evaluated in well-designed and well-conducted studies in well-defined populations using well-defined and documented Nerivio regimens. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome. 

For 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 1 RCT and 1 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 1 small (N=248) RCT with numerous relevance limitations. Prospective, observational data in 2 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 insufficient to determine that the technology results in an improvement in the net health outcome.

Practice Guidelines and Position Statements

American Academy of Neurology/American Headache Society

A 2012 joint guideline by the American Academy of Neurology (AAN) and the American Headache Society (AHS) on pharmacologic treatment for episodic migraine prevention in adults was published prior to the approval of Nerivio in the US and did not address the use of remote electrical neuromodulation (REN) or other nonpharmacologic treatments. Similarly, 2019 joint guidelines issued by AAN and AHS on the treatment of acute migraine and prevention of migraine in children and adolescents did not address the use of REN or other nonpharmacologic treatments.

American Headache Society

In 2021, the American Headache Society (AHS) issued guidance on the integration of new migraine treatments, including REN, into clinical practice. The AHS addressed the use of neuromodulatory devices as a group that included electrical trigeminal nerve stimulation, noninvasive vagus nerve stimulation, single-pulse transcranial magnetic stimulation and REN; no guidance specific to REN use was issued.

The AHS determined that initiation of a neuromodulatory device is appropriate when all of the following criteria are met:

• Prescribed/recommended by a licensed clinician
• Individual is at least 18 years of age (the guidance noted that 3 devices, including REN, are approved for use in individuals aged 12 to 17 years)
• Diagnosis of ICHD-3 migraine with aura, migraine without aura, or chronic migraine
• Either of the following:
  • Contraindications to or inability to tolerate triptans
  • Inadequate response to two or more oral triptans, as determined by EITHER of the following:
    • Validated acute treatment patient-reported outcome questionnaire (Migraine Treatment Optimization Questionnaire, Patient Perception of Migraine Questionnaire-Revised, Functional Impairment Scale, Patient Global Impression of Change)
    • Clinician attestation

Department of Veterans Affairs/ Department of Defense

The U.S Department of Veterans Affairs/Department of Defense (VA/DoD) 2023 guidelines for the management of headache state that "there is insufficient evidence to recommend for or against any form of neuromodulation for the treatment and/or prevention of migraine"; examples of neuromodulation treatments mentioned include remote electrical neurostimulation.

U.S. Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

smartphone-controlled wireless transcutaneous electrical nerve stimulation device; Nerivio Migra; remote TENS unit; Remote electrical neuromodulation (REN); conditioned pain modulation (CPM); REN device; Nerivio®; Acute migraine treatment; Chronic migraine; Headache

APPROVED BY GOVERNING BODIES:

In May 2019, Nerivio Migra™ (Theranica Bio-Electronics Ltd.) was granted a de novo classification by the FDA (class II, special controls, product code: QGT). 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.

In October, 2020, Nerivio was cleared for marketing by the FDA through the 510(k) process (K201824). 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. 8 treatments) and has a longer shelf life (24 months vs. 9 months). In January, 2021, the Nerivio device was cleared for use in individuals 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).

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Covered if covered by the Participating Home Plan

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING:

HCPCS:

PREVIOUS CODING:

REFERENCES:

1. 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.
2. Ailani J, Burch RC, Robbins MS. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. Jul 2021; 61(7): 1021-1039.
3. 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. Jan 2015; 55(1): 21-34.
4. 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. Jan 2021; 61(1): 60-68.
5. 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. May 2019; 39(6): 687-710.
6. 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. Nov-Dec 2021; 6(4): e966.
7. 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. Apr 08 2022; 23(4): 815-820.
8. Hershey AD, Lin T, Gruper Y, et al. Remote electrical neuromodulation for acute treatment of migraine in adolescents. Headache. Feb 2021; 61(2): 310-317.
9. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
10. Management of Headache Work Group. VA/DoD Clinical Practice Guideline.Washington, DC. September 2023. www.healthquality.va.gov/guidelines/pain/headache/VA-DoD-CPG-Headache-Full-CPG.pdf
11. 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.
12. 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.
13. 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. Dec 2020; 9(2): 531-543.
14. 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. Dec 2021; 10(2):1245-1253.
15. Nierenburg H, Stark-Inbar A. Nerivio (R) remote electrical neuromodulation for acute treatment of chronic migraine. Pain Manag. Apr 2022; 12(3): 267-281.
16. 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. Sep 2019; 59(8): 1158-1173.
17. 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. Sep 10 2019; 93(11): 500-509.
18. 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. Jul 22 2019; 20(1): 83.
19. 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. Apr 24 2012; 78(17): 1337-45.
20. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. Sep 26 2000; 55(6): 754-62.
21. Singh RBH, VanderPluym JH, Morrow AS, et al. Acute Treatments for Episodic Migraine. Rockville (MD): Agency for Healthcare Research and Quality (US); December 2020. 
22. 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. Oct 2021; 41(11-12): 1135-1151.
23. Tepper SJ, Lin T, Montal T, et al. Real-world Experience with Remote Electrical Neuromodulation in the Acute Treatment of Migraine. Pain Med. Dec 25 2020; 21(12): 3522-3529.
24. Tepper SJ, Rabany L, Cowan RP, et al. Remote electrical neuromodulation for migraine prevention: A double-blind, randomized, placebo-controlled clinical trial. Headache. Mar 2023; 63(3): 377-389.
25. U.S. Food and Drug Administration. 510(k) Summary (K223169): Nerivio Approval for Preventative Treatment.
26. U.S. Food and Drug Administration. De Novo Classification Request for Nerivio Migra. 
27. U.S. Food and Drug Administration. 510(k) Summary: Nerivio Approval in Adolescents.
28. U.S. Food and Drug Administration. 510(k) Summary (K223169): Nerivio Approval for Preventative Treatment.
29. VanderPluym JH, Halker Singh RB, Urtecho M, et al. Acute Treatments for Episodic Migraine in Adults: A Systematic Review and Meta-analysis. JAMA. Jun 15 2021; 325(23): 2357-2369.
30. Yarnitsky D, Dodick DW, Grosberg BM, et al. Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Headache. Sep 2019; 59(8): 1240-1252.
31. Yarnitsky D, Volokh L, Ironi A, et al. Nonpainful remote electrical stimulation alleviates episodic migraine pain. Neurology. Mar 28 2017; 88(13): 1250-1255.

POLICY HISTORY:

Medical Policy Panel, May 2022

Medical Policy Group, May 2022 (3): New medical policy. Policy created with literature review through March 22, 2022. Remote electrical neuromodulation for acute migraine is considered investigational. Available for comment June 1, 2022 through July 15, 2022.

Medical Policy Administration Committee, June 2022

Medical Policy Panel, October 2023

Medical Policy Group, October 2023 (6): Updates to Policy statement to include non-covered indication of migraine prevention, Description, Key Points, Governing Bodies, Practice Guidelines, Benefit Application and References. Policy on Draft November 1, 2023-December 16, 2023.

Medical Policy Group, December 2023: 2024 Annual HCPCS Coding update. Added HCPCS A4540. K1023 moved to Previous Coding section.

Medical Policy Panel, October 2024

Medical Policy Group, October 2024 (9): Updates to Key Points and References. No change to policy statement.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.