Acute Migraine Agent Rimegepant Appears Safe With CGRP Monoclonal Antibodies

August 22, 2020

The data support and extend the safe use of combination treatment with rimegepant and CGRP monoclonal antibodies in migraine that was initially reported in 2 earlier cases.

Gary Berman, MD

New safety data published in Headache suggest that rimegepant (Nurtec ODT; Biohaven), a recently FDA-approved agent for the acute treatment of migraine, can be safely administered in tandem with the preventive monoclonal antibodies against calcitonin gene-related peptide (CGRP).1

At least 1 on-treatment adverse event (AE) was reported by 38% (n = 5), after a mean 4-week exposure of 7.8 doses (standard deviation [SD], 5.5; total, 224 doses). Of those, 15% (n = 2) of the patients had mild or moderate nasopharyngitis; no other AEs occurred in ≥2 patients. Possible treatment-related AEs of mild to moderate severity— viral gastroenteritis, first‐degree atrioventricular block, and dizziness—occurred in 23% (n = 3) of patients.

Notably, no patients had serious AEs, AEs leading to discontinuation, or aminotransferase levels >3 times the upper limit of normal. Of the 12 patients with liver function test data, 1 patient had an AST level that was above normal (45 U/L; 1.1× ULN).

“Rimegepant was well tolerated, with minimal side effects reported, for the acute treatment of migraine in 13 safety‐evaluable patients receiving concomitant preventive treatment with an injectable CGRP monoclonal antibody over 12 weeks,” study author Gary Berman, MD, adjunct assistant professor of medicine, Division of Pulmonary, Allergy, and Critical Care, University of Minnesota, and colleagues wrote. “These data support and extend the safe use of combination treatment initially reported in 2 earlier cases. Research in a larger patient population is needed to further confirm and extend these results.”

The data were pulled from a substudy within a multicenter, open-label, long-term safety assessment of adults with episodic migraine (2—14 days per month) of moderate to severe pain intensity (NCT03266588). A subgroup of patients experiencing 2–8 monthly attacks and taking a stable dose of a CGRP monoclonal antibody also took 75-mg rimegepant as needed up to once daily for acute treatment for 12 weeks.

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In total, 13 patients (mean age, 49.9 years) were enrolled who were being treated with a CGRP agent, including erenumab (Aimovig, Amgen; n = 7), fremanezumab (Ajovy, Teva; n = 4), or galcanezumab (Emgality, Eli Lilly; n = 2).

“Although not specifically studied, the mechanism(s) that might underlie the therapeutic benefit of oral rimegepant acute treatment combined with injectable CGRP monoclonal antibody preventive therapy are of interest,” Berman and colleagues noted, adding that the belief that monoclonal antibodies completely block peripheral CGRP signaling is incorrect.

As Berman et al. alluded to, prior research this year from 2 patients experiencing suboptimal response to medication suggested that concomitant use of rimegepant and erenumab could effectively treat refractory migraine. That work, conducted by Kathleen Mullin, MD, and colleagues, was the first clinical report documenting that 2 CGRP therapies could be used this way.

Patient 1 used rimegepant for 6 months prior to initiating 70 mg erenumab monthly. She responded to preventive treatment, and additional as-needed use of rimegepant successfully quelled 100% (n = 7) of her acute attacks. Additionally, it eliminated regular, frequent use of ibuprofen and a caffeinated analgesic. Patient 2 had used rimegepant for 60 days before beginning 140 mg erenumab monthly. Similarly, 100% (n = 9) of her acute attacks treated with rimegepant were successful. She halted “near-daily” use of injectable ketorolac and diphenhydramine as well.2

“There's something to be said—if you think about it, these are patients that respond to the monoclonal antibodies as their preventative,” Mullin told NeurologyLive at the time. “If these patients that we put on CGRP monoclonal antibodies have a successful reduction in the monthly migraine days—what we call CGRP responders—then why wouldn't something that sort of further suppresses that pathway in an acute way be effective for them to abort their migraines as they come?”

These data join a growing body of literature around the use of CGRP monoclonal antibodies in combination with other preventive and acute medications. At the American Headache Society (AHS) Virtual Annual Scientific Meeting on June 13, 2020, Fred Cohen, MD, and colleagues, presented findings that suggest patients with chronic migraine receiving treatment with onabotulinumtoxinA can do so safely and effectively with an add-on CGRP monoclonal antibody.3

REFERENCES

1. Berman G, Croop R, Kudrow D, et al. Safety of Rimegepant, an Oral CGRP Receptor Antagonist, Plus CGRP Monoclonal Antibodies for Migraine. Headache. Published online August 16, 2020. doi: 10.1111/head.13930.

2. Mullin K, Kudrow D, Croop R, et al. Potential for treatment benefit of small molecule CGRP receptor antagonist plus monoclonal antibody in migraine therapy. Neurology. 2020;00:1-5. doi:10.1212/WNL.0000000000008944.

3. Cohen F, Armand C, Vollbracht S. Efficacy and Tolerability of CGRP Monoclonal Antibody Medications in Patients with Chronic Migraine Undergoing Treatment with OnabotulinumtoxinA. Headache. 2020;60(S1 suppl). 1-156. doi: 10.1111/head.13854.