Rimegepant Displays Safety and Efficacy in Study of Adolescents With Migraine

In a small, single-center recently published retrospective study, off-label use of rimegepant (Nurtec ODT; Pfizer), an oral calcitonin gene–related peptide (CGRP) receptor antagonist, was associated with patient-reported improvement in most adolescents treated for acute migraine.¹

Published in Headache, the findings were drawn from a chart review of 12 patients younger than 18 years treated at a tertiary pediatric headache center between 2020 and 2023. These results added limited real-world data to a therapeutic area in which randomized pediatric evidence remains sparse. Although rimegepant is approved by the FDA for acute and preventive treatment of episodic migraine in adults, it does not currently carry a pediatric indication.

Study Overview and Key Findings

Investigators, including lead study author Konstantinos Tourlas, MD, a headache medicine specialist at the Cleveland Clinic in Ohio, conducted a retrospective review of adolescents who received at least 1 dose of rimegepant for acute migraine and had follow-up data available. All patients met International Classification of Headache Disorders, 3rd edition criteria for migraine. The mean age at first dose was 15.3 years, and 75% of the cohort were female.

Migraine phenotypes included episodic migraine without aura (33%), episodic migraine with aura (8%), chronic migraine without aura (33%), and hemiplegic migraine (25%). Patients had tried a mean of 3.9 prior acute medications, including triptans, nonsteroidal anti-inflammatory drugs, dihydroergotamine, and antiemetics. At follow-up, 10 of 12 patients (83%) reported either complete pain freedom or reduction in headache intensity within 2 hours of taking rimegepant. Three patients (25%) reported pain freedom; 7 (58%) reported partial improvement, and no patients reported worsening of symptoms.

No statistically significant differences were observed in height, weight, systolic or diastolic blood pressure, or available liver function tests before and after rimegepant use. Laboratory data were available for 5 patients; 1 had a mild, transient elevation in alkaline phosphatase that normalized on repeat testing. Notably, no documented adverse events or clinically meaningful changes in growth parameters, blood pressure, or liver function tests were observed during the trial.¹

Limitations and Next Steps

The study’s limitations included its retrospective, single-center design; small sample size; heterogeneity in migraine subtype; reliance on patient-reported outcomes; and absence of standardized attack-level data. The study authors noted that placebo response rates in pediatric migraine trials are known to be high, which complicates interpretation in uncontrolled settings.²

Tourlas et al also continued that prospective, randomized controlled trials will be necessary to establish efficacy, optimal dosing, and longer-term safety of rimegepant in adolescents. At present, rimegepant use in adolescents remains off-label, and access may be limited by insurance coverage policies. Given the retrospective design, absence of a control group, and small sample size, investigators concluded that the findings should be interpreted cautiously.

Clinical Context: Pediatric Migraine and Treatment Gaps

Migraine affects approximately 7% to 10% of children and adolescents annually and is a leading cause of disability in this population. Acute treatment guidelines from the American Academy of Neurology and American Headache Society recommend ibuprofen as first-line therapy, with triptans as second-line agents in adolescents.²

Four triptan formulations are FDA-approved for pediatric use (rizatriptan, almotriptan, zolmitriptan nasal spray, and sumatriptan/naproxen).³ However, triptan nonresponse and recurrence rates remain clinically relevant, and use is contraindicated in certain cardiovascular conditions.² In addition, their role in hemiplegic migraine remains controversial.

Read more: Published SPACE Study Reinforces Efficacy of Fremanezumab for Pediatric Episodic Migraine

CGRP plays a central role in migraine pathophysiology. Elevated CGRP levels have been documented during acute migraine attacks, with normalization following pain resolution.⁴ Rimegepant and other gepants selectively antagonize the CGRP receptor without vasoconstrictive effects, differentiating them mechanistically from triptans.¹

In adults, rimegepant demonstrated superiority to placebo for 2-hour pain freedom in phase 3 randomized trials (21% vs 11%; P <.001), with low rates of adverse events.⁵ It later received FDA approval for both acute and preventive treatment of episodic migraine.¹

However, pediatric data remain limited. Expert consensus has highlighted theoretical concerns regarding CGRP inhibition during development, given CGRP’s roles in vascular regulation and bone physiology.⁶ To date, pediatric evidence has largely focused on monoclonal anti-CGRP therapies for prevention rather than gepants for acute treatment.⁷

REFERENCES
1. FDA approves new treatment for migraine. FDA. February 27, 2020. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-treatment-migraine
2. Oskoui M, Pringsheim T, Holler-Managan Y, et al. Practice guideline update summary: acute treatment of migraine in children and adolescents. Neurology. 2019;93(11):487-499. doi:10.1212/WNL.0000000000008095
3. Drug approval information: triptans. FDA. https://www.accessdata.fda.gov
4. Goadsby PJ, Edvinsson L, Ekman R. Release of vasoactive peptides in migraine. Ann Neurol. 1990;28(2):183-187. doi:10.1002/ana.410280213
5. Croop R, Lipton RB, Kudrow D, et al. Oral rimegepant for acute treatment of migraine. N Engl J Med. 2019;381:142-149. doi:10.1056/NEJMoa1811090
6. Szperka CL, VanderPluym JH, Oakley CB, et al. Recommendations on the use of anti-CGRP monoclonal antibodies in children and adolescents. Headache. 2018;58(10):1658-1669. doi:10.1111/head.13407
7. Greene KA, Irwin SL, Gelfand AA. CGRP monoclonal antibodies for preventive treatment of refractory pediatric headache disorders. Pediatr Neurol. 2021;121:40-46. doi:10.1016/j.pediatrneurol.2021.04.005