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Evaluating dual calcitonin gene‐related peptide antagonists for chronic migraine prevention.

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Title: Evaluating dual calcitonin gene‐related peptide antagonists for chronic migraine prevention.
Authors: Graves, Kara S. (AUTHOR), To, Jason (AUTHOR), Paige, Hayley (AUTHOR), Kennedy, Amanda G. (AUTHOR), Sprouse‐Blum, Adam S. (AUTHOR), Devine, Derek (AUTHOR), MacDougall, Julie (AUTHOR)
Source: Headache: The Journal of Head & Face Pain. May2026, Vol. 66 Issue 5, p1099-1107. 9p.
Subjects: Migraine prevention, Therapeutic use of monoclonal antibodies, Combination drug therapy, Pearson correlation (Statistics), Chronic pain, Patient safety, Data analysis, Retrospective studies, Tertiary care, Descriptive statistics, Longitudinal method, Pre-tests & post-tests, Neuropeptides, Drug efficacy, Medical records, Acquisition of data, Statistics, Health outcome assessment, Data analysis software, Confidence intervals, Migraine, Evaluation, Chemical inhibitors
Geographic Terms: Vermont
Abstract: Objectives/Background: To explore the safety and effectiveness of using two preventive calcitonin gene‐related peptide (CGRP) antagonists in patients with chronic migraine. Although the literature supports concurrent use of CGRP antagonists for acute and preventive treatment of chronic migraine, it is unknown whether two concurrent preventive CGRP agents are safe and effective. Methods: Adults with chronic migraine who were prescribed two preventive CGRP antagonists, one monoclonal antibody (e.g., eptinezumab, erenumab, fremanezumab, galcanezumab) and one oral agent (gepant) (e.g., atogepant, rimegepant) were included in this retrospective cohort study. Patients served as their own controls in a pre–post analysis completed at the University of Vermont Health Network, including data from January 1, 2020 through December 31, 2024. Demographic, clinical, and medication data were recorded at baseline (immediately prior to the addition of a second CGRP antagonist) and after a minimum of 3 months of dual therapy. The primary outcome was the change in patient‐reported headache in days per month. Secondary outcomes included changes in severe headache or migraine in days per month, adverse events, and the rate and reasons for discontinuation of dual preventive therapy. Results: Of the 37 patients who were included, the average age was 54 years, and the population was primarily female (86%), White (94%), and commercially insured (57%). There was a significant decrease in headache days (median = 0; interquartile range = −5 to 0; p = 0.031) while on two CGRP antagonists, including 8 patients (22%) who achieved at least a 50% reduction in reported headache days. There was also a significant reduction in severe headache or migraine days (median = −2; interquartile range = −6 to 0; p < 0.001). There was no significant increase in adverse events with two CGRP antagonists (p = 0.219 sign test, p = 0.103 McNemar test). However, a single case of ischemic stroke was reported in a patient with multiple risk factors. Half of all patients (19, 51%) discontinued at least one CGRP antagonist by the end of the study period, primarily due to insurance restrictions or lack of perceived benefit. No patients discontinued due to reported side effects. Conclusion: Trialing two preventive CGRP antagonists may be an effective approach for some patients with chronic migraine who have exhausted other preventive treatment options, with some patients in this study experiencing a significant reduction in headache frequency and severity. Prospective studies with larger, more diverse populations should be completed to confirm these findings and investigate any potential stroke risks. Plain Language Summary: There is very little research on using two preventive calcitonin gene‐related peptide (CGRP) drugs together, especially among patients with chronic migraine who did not find sufficient benefit from treatment with a single anti‐CGRP medication. This study reviewed data for patients who were prescribed two concurrent preventive anti‐CGRP medications to examine their response to treatment and any reported adverse events. Findings suggest that dual CGRP antagonist therapy may be safe and lead to meaningful reductions in headache frequency and severity for some patients. [ABSTRACT FROM AUTHOR]
Copyright of Headache: The Journal of Head & Face Pain is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Objectives/Background: To explore the safety and effectiveness of using two preventive calcitonin gene‐related peptide (CGRP) antagonists in patients with chronic migraine. Although the literature supports concurrent use of CGRP antagonists for acute and preventive treatment of chronic migraine, it is unknown whether two concurrent preventive CGRP agents are safe and effective. Methods: Adults with chronic migraine who were prescribed two preventive CGRP antagonists, one monoclonal antibody (e.g., eptinezumab, erenumab, fremanezumab, galcanezumab) and one oral agent (gepant) (e.g., atogepant, rimegepant) were included in this retrospective cohort study. Patients served as their own controls in a pre–post analysis completed at the University of Vermont Health Network, including data from January 1, 2020 through December 31, 2024. Demographic, clinical, and medication data were recorded at baseline (immediately prior to the addition of a second CGRP antagonist) and after a minimum of 3 months of dual therapy. The primary outcome was the change in patient‐reported headache in days per month. Secondary outcomes included changes in severe headache or migraine in days per month, adverse events, and the rate and reasons for discontinuation of dual preventive therapy. Results: Of the 37 patients who were included, the average age was 54 years, and the population was primarily female (86%), White (94%), and commercially insured (57%). There was a significant decrease in headache days (median = 0; interquartile range = −5 to 0; p = 0.031) while on two CGRP antagonists, including 8 patients (22%) who achieved at least a 50% reduction in reported headache days. There was also a significant reduction in severe headache or migraine days (median = −2; interquartile range = −6 to 0; p &lt; 0.001). There was no significant increase in adverse events with two CGRP antagonists (p = 0.219 sign test, p = 0.103 McNemar test). However, a single case of ischemic stroke was reported in a patient with multiple risk factors. Half of all patients (19, 51%) discontinued at least one CGRP antagonist by the end of the study period, primarily due to insurance restrictions or lack of perceived benefit. No patients discontinued due to reported side effects. Conclusion: Trialing two preventive CGRP antagonists may be an effective approach for some patients with chronic migraine who have exhausted other preventive treatment options, with some patients in this study experiencing a significant reduction in headache frequency and severity. Prospective studies with larger, more diverse populations should be completed to confirm these findings and investigate any potential stroke risks. Plain Language Summary: There is very little research on using two preventive calcitonin gene‐related peptide (CGRP) drugs together, especially among patients with chronic migraine who did not find sufficient benefit from treatment with a single anti‐CGRP medication. This study reviewed data for patients who were prescribed two concurrent preventive anti‐CGRP medications to examine their response to treatment and any reported adverse events. Findings suggest that dual CGRP antagonist therapy may be safe and lead to meaningful reductions in headache frequency and severity for some patients. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Headache: The Journal of Head &amp; Face Pain is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=193490640
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  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1111/head.70057
    Languages:
      – Code: eng
        Text: English
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      Pagination:
        PageCount: 9
        StartPage: 1099
    Subjects:
      – SubjectFull: Migraine prevention
        Type: general
      – SubjectFull: Therapeutic use of monoclonal antibodies
        Type: general
      – SubjectFull: Combination drug therapy
        Type: general
      – SubjectFull: Pearson correlation (Statistics)
        Type: general
      – SubjectFull: Chronic pain
        Type: general
      – SubjectFull: Patient safety
        Type: general
      – SubjectFull: Data analysis
        Type: general
      – SubjectFull: Retrospective studies
        Type: general
      – SubjectFull: Tertiary care
        Type: general
      – SubjectFull: Descriptive statistics
        Type: general
      – SubjectFull: Longitudinal method
        Type: general
      – SubjectFull: Pre-tests & post-tests
        Type: general
      – SubjectFull: Neuropeptides
        Type: general
      – SubjectFull: Drug efficacy
        Type: general
      – SubjectFull: Medical records
        Type: general
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      – SubjectFull: Statistics
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      – SubjectFull: Data analysis software
        Type: general
      – SubjectFull: Confidence intervals
        Type: general
      – SubjectFull: Migraine
        Type: general
      – SubjectFull: Evaluation
        Type: general
      – SubjectFull: Chemical inhibitors
        Type: general
      – SubjectFull: Vermont
        Type: general
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      – TitleFull: Evaluating dual calcitonin gene‐related peptide antagonists for chronic migraine prevention.
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            – D: 01
              M: 05
              Text: May2026
              Type: published
              Y: 2026
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