Expanding Access to CGRP Medications as First-Line Treatments: Thoughts and Implications

Stephen Samples, MD

Preventive treatment, defined as an intervention to reduce migraine attack frequency, intensity, duration, and disability, is a core principle in the treatment of migraine. Traditionally, medications considered to be first-line approaches for the prevention of migraine include therapies from the classes of antihyperintensives, antiseizure medications, antidepressants, and onabotulinumtoxinA specifically for chronic migraine. Over the years, the toolbox of options for migraine has expanded significantly with the introduction of calcitonin gene-related peptide (CGRP)-targeting agents, which offer greater efficacy and safety than off-label options.

Recently, for the first time ever, the American Headache Society (AHS) published a statement paper calling for the use of CGRP-targeting agents as first-line options for patients, a complete contrast to the standard process. In the previous AHS consensus statements, it was noted that patients must try at least 2 classes of previous first-line medications for at least 8 weeks before being considered for these therapies. Overall, the mounting evidence that has established CGRP as a fundamental mechanism of migraine and CGRP-targeting therapies as "migraine-specific" helped lead to the organization’s position statement.

Additional factors that led to the paper included the wide evidence base favoring CGRP-targeting therapies on categories of responder rates, efficacy in patients with multiple prior treatment failures, efficacy in those with acute medication overuse, and those who do and do not have aura. Furthermore, nearly all of these medications are FDA-approved for the preventive treatment of both episodic and chronic migraine, which may simplify decision-making in patients who simultaneously transition back and forth along the continuum of episodic and chronic migraine.

Following the news, NeurologyLive^® reached out to migraine expert Stephen Samples, MD, to get his thoughts on the paper and the significance it holds for patients with migraine and those who treat the condition. Samples, chair of Allegheny Health Network’s department of neurology, provided commentary on the treatment possibilities of having CGRP-targeting therapies as first-line options and how this may lead to further personalized approaches. Additionally, he stressed the need to continue to educate the patient community on the treatment options available and the ways to lower rates of chronic migraine.

What was your initial reaction to the AHS’s statement regarding CGRPs to be used as first-line medications?

On May 17th, 2018 the 1st monoclonal antibody therapy targeting CGRP receptor was approved by FDA for preventative treatment of episodic and chronic migraine headaches.Patient had to have 4 or more migraine headache days per month to receive this innovative treatment. My disappointment at that point was that insurance companies were asking migraine patients to try conventional preventative group of medications 1st for at least 4-6 weeks, showing lack of efficacy or tolerability, prior starting calcitonin gene related peptide antagonist pathway treatments. As you know conventional preventative therapy for migraines includes beta-blockers, treatments used to control blood pressure, antiepileptic medication, treatments used to control epilepsy and antidepressant therapy used for anxiety and depression. Although those therapies showed efficacy, they are not migraine specific treatments and associated with myriad of side effects. For the 1st time in the history of headache medicine, migraine was seen as a true neurological and extraordinary prevalent disorder, for which patient had an opportunity to start with migraine specific treatments, designed and developed specifically for migraine management. However, patients and providers encountered different rules and regulations from the insurance companies, preventing the use of calcitonin gene related peptide antagonist as a 1st line of treatment.

If CGRPs were to be used as first-line treatments, what benefits/opportunities does this bring?

This month of May marks 6 years of release of the paradigm treatments for migraines, with enough clinical data supporting low profile of side effects (less than 5%), accounting for safety for these treatments and significant efficacy showing 50% to 100% response rate to control migraine frequency, severity, quality of pain and improvement in migraine disability. Those medications used as a first-line not only can benefits the patient from exposure to unnecessary side effects, but also will prevent medication overuse due to lack of efficacy of conventional treatments, a condition that leads to ED visits. As you know every 10 seconds, somebody in U.S. goes to the emergency room complaining of head pain, and approximately 1.2 million visits are for acute migraine attacks due to lack of targeted and specific management. We are entering in the new era of migraine management, supported by pathophysiology behind this complex disease, targeting pathways that can reverse the burden of the 3rd most prevalent illness in the world and the 6th most disabling.

Of the therapies approved, are there any specific medications that may be more applicable as a first-line treatment?

There are 2 lines of calcitonin gene related peptide treatment currently approved by FDA.One is related to monoclonal antibody treatment biologic injectable once a month, or IV infusion in quarterly basis which helps prevents migraine headaches. Another line is related to small molecules or Gepants, orally or intranasally administered and can be use not only as a preventive but also as acute treatment for migraine attacks. Depending on the patient presentation, or migraine disability patient will benefit from either monoclonal antibody or small molecule. The best way to differentiate if the patient has episodic migraine headache, associating with low-grade of disability and can benefit from just acute management. Those who have episodic migraine headache with severe disability, and migraine attack lasting for more than 24 hours, or chronic migraine headache patient is who will benefit from preventative therapy.

How can we continue to advance the care and treatment for patients with migraine?

Patient education is pivotal. It is important for them to understand that migraine is a true neurological disorder and needs to be treated accordingly. Headache medicine providers should be an advocates for their field and provide compassionate care by assessing patient's migraine disease impact and instructing the importance of not only treating acute migraine attack as soon as possible, but also to prevent chonification of this disabling condition. Chronic migraine headache affects more than 4,000,000 Americans, with at least 15 migraine days per month and more than 90% of suffers are unable to work or function normally during the migraine. Adequate diagnosis and treatment can help significantly to reduce migraine disability and bring patient back to normal life activities and work duties.

Are there ways to effectively test previously approved medications to gain even more insights on treatment personalization/optimization?

The next step in the pivotal clinical trials should be head-to-head studies comparing the efficacy and safety of conventional nonspecific medication use for migraine treatment and the new migraine specific innovative treatments. Comparison data can help understand the importance of developing further migraine specific treatments which will be based on the complex pathophysiology of migraine brain, and ascertain new paths that can prevent hyperexcitability leading to central neurogenic inflammatory process, presenting with diverse symptoms not only as pain, but also as multisystem hyper excitability, such as anxiety, depression, IBS, fibromyalgia, abnormality of circadian rhythms leading to insomnia, and cognitive dysfunction among others.