A Step Forward in Addressing Health Care Inequities in Migraine Management

New research from Harvard Medical School has identified fundamental differences in migraine disease pathology, resulting in a test that can predict who will and won’t respond to anti-calcitonin gene-related peptide (CGRP) migraine therapy. It will be a game changer for migraine sufferers who have great access to care.

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However, if made readily available to primary care providers (PCPs) and combined with consumer-friendly tools to diagnose and effectively treat migraines earlier, it could help reduce the significant treatment deficit that Black, Indigenous, and People of Color (BIPOC) must endure and be a health equity game changer for all migraine sufferers.

Access, diagnosis, and treatment for BIPOC patients suffering from migraines is yet another unflattering reflection of the lack of health equity in the United States. As the Centers for Disease Control and Prevention notes, systemic racism has negatively impacted the health outcomes of communities of color for centuries. As in many therapeutic areas, the disparity statistics for migraines are startling (Figure 1).

To be clear, although a novel precision medicine diagnostic for a migraine therapy is a major step forward, it will not eliminate systemic racism. However, if effective BIPOC-focused awareness and educational campaigns from pharma and patient advocacy groups were added to the mix, and PCPs and emergency department personnel were provided with the resources and training they need to become better at diagnosing and treating migraines, we would have an unprecedented opportunity to address the health disparities associated with migraine treatment and outcomes.

Enabling and Empowering Consumers, Pharmacists, and PCPs to Dx

According to the American Migraine Foundation, 1 in 4 households in the United States has a family member who suffers from migraine. As Figure 1 indicates, the level of suffering is unacceptably magnified in BIPOC communities.

This level of prevalence and disparity combined with a chronic shortage of neurologists clearly qualifies as a health equity mandate for us to empower and enable headache sufferers, pharmacists, and PCPs to become the first line of defense in migraine care. The good news is that the National Headache Foundation has endorsed several tools that make a migraine diagnosis readily accessible to patients, pharmacists, and PCPs no matter where they are on the social determinants of health (SDoH) spectrum.

ID Migraine is an exceptionally easy to administer 3-question migraine screener. Answering yes to 2 out of 3 questions will accurately identify 93% of migraine sufferers. Answering yes to all 3 yields an accurate identification 98% of the time.

1. Has a headache limited your activities for a day or more in the past 3 months?

2. Are you nauseated or sick to your stomach when you have a headache?

3. Does light bother you when you have a headache?

Focusing on the PCP’s role, a more complete work up is enabled by use of the SNOOP criteria for capturing and assessing headache warning signs.

This handy mnemonic device stands for:

• Systemic symptoms such as cancer.
• Neurological abnormalities.
• Onset of rapid escalation of pain within seconds or the so-called thunderclap headache that can be a marker for aneurysm or brain bleed.
• Onset of new headache over the age of 50.
• Prior headache history, where a change in headache history such as increased severity or frequency could be signs of a serious condition.

To be sure, even with these tools, the PCP needs to dedicate an entire office visit to the patient's headache. This is undoubtedly a significant investment of a PCP’s time and resources. However, based on the prevalence of migraines, much more often than not, PCPs will be diagnosing and treating an actual migraine and not a regular headache, so the time is a worthwhile investment.

Given that they are in the best position to proceed in the context of the patient's history and comorbidities, PCPs represent the most significant opportunity to get migraines diagnosed and the treatment underway sooner rather than later. This also means PCPs represent significant untapped potential to bring equitable migraine treatment to BIPOC populations.

Enabling and Empowering PCPs to Tx

So let’s assume:

1. The awareness and education campaigns have worked brilliantly for all patients (both white and BIPOC).

2. PCPs have ID Migraine and the SNOOP criteria in their tool kits and are now actively using them to arrive at a migraine diagnosis with sufficient clinical documentation.

3. The PCP has sufficient awareness of all migraine treatments, including the new anti-CGRP therapies, and are motivated to get patients to the most optimal therapy as soon as possible.

4. And they have determined that 60% of the patients seem to be ideal candidates for expedited access to the anti-CGRP therapies.

The problem is that these therapies are expensive, and approximately 50% of the patients who go on them end up being non-responders. So, does the PCP start with the generic options and work their way toward the new therapies, or work with the payer and patient to determine whether they can justify initiating treatment with one of the newer therapies? This is where the first precision medicine diagnostic for migraines becomes a game changer.

Being able to identify, with ease and precision, the patients who will respond to these new therapies puts payers and PCPs in an unprecedented position to create equitable access to all migraine sufferers and have the confidence that those patients will have the highest probability of an optimal response. In this scenario, the PCP has been fully enabled with a diagnostic tool that helps reduce time and suffering wasted on suboptimal therapies, time off work, and the need to wait for a specialist.

The converse is also meaningful—not spending time, money, and additional migraine days suffering on treatments that are not likely to work makes for a sound clinical and financial proposition.

Putting employers, payers, and providers in position to address the unique human suffering and productivity disparities associated with migraines in BIPOC communities, more often and earlier, represents a significant step in the right direction for health equity. This is the epitome of value-based care and a model that should be replicated for other high disparity therapeutic areas.

A Quick Primer on Anti-CGRP Therapy and the World’s First Neurology Dx

Anti-CGRP therapy was the biggest therapeutic advance in migraine treatment in 30 years when the first was launched in 2018. These advanced medications work by neutralizing the CGRP peptide or by blocking CGRP receptors in the dura, which is a part of the meningeal membrane that protects the brain and spinal cord. Successful blockade of CGRP signaling in the meninges prevents dilation of blood vessels, as well as activation and sensitization of pain fibers that mediate the headache phase of migraine.

Their efficacy is well documented, more than halving monthly headache days for many of the worst affected patients in a way that traditional generic medicines cannot. The big challenge is that because anti-CGRP drugs are too large to cross the blood-brain barrier, they can only prevent migraine in patients whose headache is triggered by CGRP signaling outside the brain—as such, approximately 50% of migraine patients do not respond to anti-CGRP therapy.

It used to be impossible to know which 50% would or would not respond before taking the drug. However, for the first time, a patient-friendly test has prospectively demonstrated in a clinical trial, published in Cephalalgia, the ability to accurately predict anti-CGRP response before initiation of treatment with 86% accuracy, which could potentially transform migraine management.

Results from the study demonstrated that non-ictal cephalic allodynia, a certain kind of pain sensitivity experienced during a specific period of time, determined before interventional treatment is a statistically significant predictor of response to anti-CGRP therapy being present in 84% of the 19 non-responders, but absent in 79% of the 24 responders, for an overall accuracy rate of 86% (p<0.0001). Importantly, the test achieved these results irrespective of the demographic background of the patients tested.

The Harvard team, led by Rami Burstein, PhD, professor of Anesthesia at Harvard Medical School and president-elect of the International Headache Society (IHS), along with co-author Dr. Sait Ashina, state in their paper: “Key fundamental differences in the disease pathology of responders and non-responders have been identified, providing a quick, affordable, non-invasive, and patient-friendly way to prospectively distinguish between responders and non-responders to the prophylactic treatment of chronic and high-frequency episodic migraine with drugs that reduce CGRP signaling.”

The Cephalalgia study used a novel proprietary Quantitative Sensory Testing (QST) algorithm to determine the presence or absence of cephalic allodynia during the "non-ictal" phase of migraine (>12 hours after a migraine attack and >12 hours before the next attack). Importantly, the study also confirmed that manifestation of non-ictal extracephalic (peripherally governed) allodynia was less successful in identifying non-responders, and that non-ictal cephalic allodynia was consistently predictive of response across the chronic migraine (CM) as well as high frequency episodic migraine (HFEM) groups.

David Greeley, MD, FAAN, who leads the Northwest Neurological clinical practice in Spokane, is excited by the prospects of having access to this precision medicine tool, describing it as a potential game-changer.

“Migraine is a huge burden for neurologists and pain and headache specialists. The result is a massive underdiagnosis—especially in the BIPOC community who are not being diagnosed and even less likely to see a specialist,” he said. “Bringing PCPs into the battle will make an enormous difference and there is no reason why PCPs should not be able to manage migraines, especially if they have access to a simple patient-friendly test that makes confidently prescribing effective therapy a relative walk in the park. This will bring treatment to a patient population that is significantly under diagnosed and under treated.”

Greeley added that support for reducing disparities across the health care landscape will be crucial in addressing this important issue.

“The science supports it and the unacceptable racial disparities compel it,” he said. “My hope is that industry, payers, and PBMs do all they can to allow doctors to use this promising technology to equitably help all patients. It would be a win-win-win for all involved.”