Gepants for headache prevention in children and adolescents: A multicenter chart review study

There is an unmet need for safe, evidence-based pharmacologic treatments for migraine prevention in children and adolescents. Rimegepant and atogepant, calcitonin gene-related peptide receptor antagonists (gepants), have been shown to be efficacious and well-tolerated preventive treatments in adults with migraine. While we await the results of randomized trials in children and adolescents, this study aimed to provide real-world evidence on the safety and effectiveness of rimegepant and atogepant as preventive headache treatments for youth.

This was a multisite retrospective chart review study. Sites included Children's Hospital of Philadelphia, Cincinnati Children's Hospital, and University of California San Francisco Benioff Children's Hospital. Inclusion criteria were patients under 18 years of age who were prescribed rimegepant and/or atogepant for preventive treatment. At University of California San Francisco Benioff Children's Hospital and Children's Hospital of Philadelphia, charts of all patients prescribed atogepant, as well as those prescribed rimegepant without a specified "as needed" indication, were reviewed. Data collection at Cincinnati Children's Hospital was a convenience sample based on providers' knowledge. Clinical and demographic data both before and after gepant treatment were abstracted into Research Electronic Data Capture. Descriptive statistics were used to summarize clinical observations.

Of 71 patients who met inclusion criteria, 26 used atogepant and 55 used rimegepant- including 10 who used both. The majority were adolescent females. Migraine was the most common diagnosis. Median number of previous preventive trials was six (interquartile range: 4-8) in the rimegepant group and seven (interquartile range: 5-8) in the atogepant group. Fifty-eight percent (32/55) of the rimegepant group and 43% (11/26) of the atogepant group saw at least some benefit. Four of 55 patients reported side effects with rimegepant-constipation, nausea, abdominal pain, fatigue, and transient worsening of headache (n = 1 for each; one patient reported abdominal pain and fatigue). Seven of 26 patients reported side effects with atogepant-nausea (2/26), fatigue (2/26), constipation (1/26), depressed mood (1/26), and feeling cold (1/26). No serious side effects were reported. An exploratory analysis for factors associated with response suggests that a longer headache history has a higher likelihood of benefit (odds ratio 1.41, 95% confidence interval: 1.07-1.85, p = 0.014), and in contrast, more severe limitations in functionality has lower likelihood of benefit (odds ratio 0.18, 95% confidence interval: 0.05-0.58, p = 0.004).

In this real-world evidence study, gepants for headache prevention in youth were generally well tolerated. Despite failure of multiple prior therapies, some patients benefited from these treatments. This small study was not designed to directly compare the effectiveness of the two medications. Both safety and efficacy in this population need further evaluation in randomized controlled trials.