No Pain, No 'Graine: Strategies for Optimized Use of New Migraine Therapies

Angela Luong, PharmD, RPh
September 12, 2022

Migraines represent the world’s third most prevalent illness. A new class of drugs called calcitonin gene-related peptide (CGRP) inhibitors entered the market in 2018. Since then, CGRPs have shifted the treatment paradigm for migraine treatments, bringing welcome relief to migraine patients while also increasing spend for plan sponsors. As was reported in the Artemetrx State of Specialty Spend and Trend report, within our book of business we observed a 40% increase in migraine medication costs from 2020 to 2021.

Treatment for migraines is separated into two categories:

  • Treatment of acute migraine attacks
  • Prevention or prophylaxis of migraines

Injectable and infused CGRP inhibitors are used primarily to prevent migraines, whereas oral CGRP inhibitors could be used to prevent or treat migraines. Oral CGRP inhibitors are higher in cost for migraine treatment, whether used for acute treatment or prevention of migraines.



What do we need to know about CGRP inhibitors for migraine treatments?

Anyone who has suffered a migraine or been with someone who has will recognize that providing relief for those whose disease has not been well controlled with existing therapies is a great innovation in the market. However, this is a therapy class with many options across the affordability continuum. Consequently, plans need to understand migraine trends and treatment options.

Acute migraine treatments have many options available through the pharmacy benefit. Preventative treatments for migraines, however, span across medical and pharmacy benefits. Although CGRP inhibitors offer a novel mechanism of action and pain relief for migraine patients, cost considerations and market basket evaluations across both benefits are critical for plans to implement a comprehensive strategy for migraine management.



Recommended strategies for management

The prevalence of migraine patients will be an important consideration when implementing cost management strategies. Many will want to ensure access for the many patients who will benefit from the new treatments. However, due to high prevalence of migraines with varying degree of control, most payers will need to balance access with appropriateness of care.

The good news is that with access to the right information – both from data and clinical best-practice – plans can confidently implement migraine management strategies that accomplish the goals of member access with cost containment. A few key strategies we are recommending for our clients are as follows:


1.  Ensure the use of lower-cost alternatives before starting therapy on CGRP inhibitors.

As referenced in the Artemetrx State of Specialty Spend and Trend Report, therapies such as Botox that have been on the market for some time are still effective at treating migraines for many patients. The American Headache Society has outlined criteria for migraine management and cost-effective decisions.


2.  Employ integrated management of preventative migraine treatments with available therapies.

Integrated data provides a full view of the appropriateness and use of migraine medicines within a population. An important data point is diagnosis and medication history to verify the utilization of lower-cost therapies.


3.  Limiting overutilization with multiple agents simultaneously and day supply allowances.

Once again, data is key to accomplishing this goal. As noted above, preventative treatments for migraines cross both pharmacy and medical; therefore, suboptimal management can be common. An example of this is the use of multiple, duplicative agents simultaneously. Also, our analytics have revealed a common occurrence where patients start a 90-day supply of one medicine only to start a new therapy within the next 2-4 weeks. Consequently, we recommend limiting day supply for new starts.


4.  Consider published treatment guidelines to align treatment strategies with disease severity.

The American Headache Society released an updated consensus statement for integrated recommendations for migraine treatments. A few key recommendations from the report are as follows:

  • Proper migraine diagnosis could be refined based on the frequency of monthly migraine days and monthly headache days. Chronic migraines require ≥15 migraine days per month, lasting for greater than 3 months.
  • First line therapy for acute treatments is as follows:
    • Mild to moderate attacks: NSAIDs, non opioid analgesics, acetaminophen or caffeinated analgesic combinations
    • Moderate to severe: triptans, dihydroergotamine, CGRPs agonists, selective serotonin receptor agonists
  • Inadequate response to two or more oral triptans is verified before novel agents (including Nurtec ODT and Ubrelvy) or intolerance or contraindication to triptans to achieve cost-effective care while ensuring access to those most appropriate for acute treatment. Additionally, to determine efficacy and tolerability, at least 3 attacks should be treated, and response should be evaluated
  • Considerations for preventative migraine treatments include:
    • Degree of disability based on migraine attacks that interfere with patient’s daily routines despite acute treatment
    • Frequency of migraine attacks
    • contraindications to, failure or overuse of acute treatments
    • adverse events with acute treatments
    • patient preference
    • uncommon migraine subtypes (e.g., hemiplegic migraines, migraine with brainstem aura)
  • Treatments Considerations
    • Identification and minimization of migraine triggers, including proper nutrition, regular exercise, adequate hydration, proper sleep, stress management
    • Oral treatments with established efficacy: candesartan, divalproex sodium, frovatriptan, metoprolol, propranolol, timolol, topiramate, valproate
      • Adequate trial for oral treatments should be assessed at a minimum of 8 weeks at the target dose
    • Parental/injectable agents with established efficacy: Aimovig, Ajovy, Botox, Emgality, Vyepti
      • Adequate trial for injectable CGRPs should be assessed after at least 3 months of treatment
      • Adequate trial for drugs administered quarterly should be assessed after 6 months
  • Recommended criteria for initiating therapy with CGRP inhibitors:
    • Diagnosis of migraine
    • Disability considerations
    • Inability to tolerate or inadequate response to 8 week trial of two or more of the following:
      • Topiramate
      • Divalproex sodium or valproate sodium
      • Beta blocks (metoprolol, propranolol, timolol, atenolol, nadolol
      • Tricyclic antidepressants (amitriptyline, nortriptyline)
      • SNRI (venlafaxine, duloxetine)
    • Inability to tolerate or inadequate response to a minimum of 2 quarterly injections (6 months) of Botox 




Ailani, J., Burch, R. C., & Robbins, M. S. (2021). The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. The American Headache Society Consensus Statement: Update on Integrating New Migraine Treatments into Clinical Practice, 61(7).




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Angela has over 12 years of experience in managed care following her doctorate of pharmacy training from the University of Michigan College of Pharmacy. Angela completed a PGY-1, managed care residency focusing on data analytics, consulting and specialty medication management. Following her career, Angela has extensive experience in various positions through out the pharmacy benefit management realm, including benefit operations, Medicare Part D clinical utilization management programs, commercial utilization management programs, commercial and Medicare Part B medical policy strategies, Specialty trend management and clinical programs, specialty pharmacy network management, and manufacture clinical engagement.