AHS Releases Position Statement on CGRP Inhibition Integration Into Clinical Practice

Kathleen Digre, MD, FAHS

The American Headache Society (AHS) recently released its position on the integration of the newly approved preventive migraine therapies into clinical practice, with the goal of providing guidance to the health care professionals who will encounter them.¹

Last year brought the approval of the 3 first-in-class calcitonin gene-related peptide (CGRP) inhibitors—erenumab (Aimovig, Amgen/Novartis), fremanezumab (Ajovy, Teva), and galcanezumab (Emglaity, Eli Lilly)—and another, eptinezumab, is expected to enter the market by mid-2019.

“The Society’s mission is to improve the care and lives of people living with headache disorders,” AHS President Kathleen Digre, MD, FAHS, said in a statement.² “As a headache society that represents neurologists and primary care providers, it was important for us to play an active role in this process.”

Digre told NeurologyLive that the AHS is hopeful that the consensus statement will remind providers of the many treatments that can be used for migraine and "that new and exciting treatments are available—and there are more to come."

The guidance laid out a set of 5 circumstances which must be met in order to use the CGRP monoclonal antibodies, which included that it is prescribed by a licensed medical provider to a patient who is at least 18 years of age with a diagnosis of migraine with or without aura according to the International Classification of Headache Disorders, 3^rd Edition (ICHD-3 ). As well, the patient must have failed 6 weeks of at least 2 therapies and has at least moderate disability, as defined by a Migraine Disability Assessment (MIDA) score of >11 or a Headache Impact Text-6 (HIT-6) score of >50.

For patients with a diagnosis of episodic migraine (8 to 14 monthly headache days), patients must have failed at least 2 previous therapies. Those with chronic migraine (>14 monthly headache days) must have failed either 2 other therapies or have shown an inability to tolerate or inadequate response to 6 months (2 quarterly injections) of treatment with onabotulinumtoxinA.

The guideline included the following as first-line treatments which need to be failed for patients to be administered CGRP inhibitors:

• Topiramate
• Divalproex sodium/valproate sodium
• Beta‐blockers such as metoprolol, propranolol, timolol, atenolol or nadolol
• Tricyclic antidepressants such as amitriptyline or nortriptyline
• Serotonin‐norepinephrine reuptake inhibitors such as venlafaxine or duloxetine
• Another Level A or B treatments according to the American Academy of Neurology/AHS guidelines

“While the principles of preventive therapy for oral preventives generally apply to injectable preventives, there are several notable points of contrast,” the AHS wrote. Those points of contrast, it wrote, include the lack of need for gradual dose escalation, the rapid onset of benefit, and the positive tolerability profiles.

According to the AHS, the response measurements for these therapies will be guided by the same metrics as others, “with emphasis on migraine/headache days, migraine‐related disability, impact, and functional impairment.” It is recommended that 3 months of outcome days for monthly injections and 6 months of follow-up for quarterly treatments are recorded prior to making continuation decisions.

The guidelines state that evidence of treatment can then be assessed by a ≥50% reduction in the average number of monthly headache days or a clinically meaningful improvement in a migraine-specific patient-reported outcome, including MIDAS, the Migraine Physical Function Impact Diary (MPFID), or HIT-6 scores. These are also the AHS criteria for the continuation of a CGRP monoclonal antibody.

Ultimately, the AHS noted that the principles of preventive treatment of migraine maintain the previous values to use evidence‐based treatments when possible and appropriate; begin with a low dose and slow titration; reach a therapeutic dose when possible; allow for an adequate duration in treatment trials; establish expectations of therapeutic response and adverse events; and to maximize adherence. It acknowledged that the newer injectables may work faster and lack a need for titration.

For acute treatment, the suggested code for use includes the use of evidence-based treatments; early, post-migraine-attack onset use; a nonoral route of administration for selected patients; accountability for safety and tolerability; consideration of self‐administered rescue treatments; and avoidance of overuse.

For neuromodulation and biobehavioral therapy, the AHS suggested that it “may be appropriate for preventive and acute treatment, depending on the needs of individual patients.” As well, for those who prefer nonpharmacologic treatment or who have shown poor response, have contraindications, or lack tolerability to available pharmacotherapies.

“I hope that the position statement gives credence and guidance to practitioners treating those who live with migraine,” Digre said. “Ultimately, we advocate for our patients and want them to get the best possible treatment.”

REFERENCES

1. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1-18. doi: 10.1111/head.13456.

2. AHS Launches Position Statement about Integrating New Migraine Treatments Into Clinical Practice [press release]. Mount Royal, NJ: American Headache Society; Published January 9, 2019. americanheadachesociety.org/news/ahs-launches-position-statement-integrating-new-migraine-treatments-into-clinical-practice. Accessed January 14, 2019.