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Safety evaluation of oral calcitonin-gene–related peptide receptor antagonists in patients with acute migraine: a systematic review and meta-analysis

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Abstract

Objective

Calcitonin gene-related peptide (CGRP) receptor antagonists have been suggested as novel treatments for acute migraine. This study aimed to use meta-analysis to compare the safety and tolerability of five existing oral CGRP receptor antagonists (BI44370TA, MK-3207, rimegepant, telcagepant, and ubrogepant) with that of a placebo or triptans against acute migraine.

Methods

Five prominent databases were searched to identify randomized controlled trials on this topic. The primary safety outcomes of interest were any adverse events (AEs) and treatment-related adverse events (TRAEs), and secondary outcomes were individual events, namely diarrhea, dizziness, dry mouth, fatigue, nausea, paresthesia, somnolence, upper abdominal pain, and vomiting.

Results

Fifteen studies met the eligibility criteria and were examined in detail. Although, compared to placebo, oral CGRP receptor antagonists significantly increased the incidence of any AEs (risk ratio [RR] = 1.15; 95% confidence interval [CI] = 1.07–1.23), there was no difference in the incidence of TRAEs (RR = 1.18; 95% CI = 1.00–1.38). Moreover, CGRP receptor antagonists were safer than triptans with respect to primary safety outcomes, such as any AEs (RR = 0.78; 95% CI = 0.63–0.98) and TRAEs (RR = 0.68; 95% CI = 0.58–0.79).

Conclusion

Despite oral CGRP receptor antagonists posing a significantly higher risk of AEs when compared to placebo, CGRP receptor antagonists have a favorable safety profile compared to triptans. Our findings inform strategies to enhance safety and tolerability in the treatment of acute migraine.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. NRF-2022R1F1A1063144). This research was supported by Kyungsung University Research Grants in 2021.

Author information

Author notes

  1. Nayoung Han and In-hwan Baek contributed equally to this study.

Authors and Affiliations

  1. College of Pharmacy, Kyungsung University, 309, Suyeong-ro, Nam-gu, Busan, 48434, Republic of Korea

    Seoyeon Lee & In-hwan Baek

  2. School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, 20 Cornwall St, Woolloongabba, QLD, 4102, Brisbane, Australia

    Christine E. Staatz

  3. College of Pharmacy, Jeju National University, 102 Jejudaehak-ro, Jeju, 63241, Republic of Korea

    Nayoung Han

  4. Department of Pharmacy, Seoul National University Bundang Hospital, 166 Gumi-ro, Bundang-Gu, Seongnam-Si, Gyeonggi-Do, 13620, Republic of Korea

    Seoyeon Lee

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  1. Seoyeon Lee
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  4. In-hwan Baek
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Contributions

NH and IB conceived and designed the work. SL, NH, and IB collected the data. SL and IB performed the analysis. NH, CES, NH, and IB gave substantial contributions to data acquisition and interpretation for the work. SL and NH drafted the work. CES and IH revised it critically for important intellectual content. All the authors gave the final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Nayoung Han or In-hwan Baek.

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The authors declare no competing interests.

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Statement of prior presentation

Results of this study have been partially presented at the 21st annual meeting of the Asian Conference on Clinical Pharmacy, Nagoya, Japan, 11–13 February, 2022.

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The authors declare no competing interests.

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Key points

• Oral CGRP receptor antagonists increase the risk of any adverse events compared to placebo, while no difference was found in the incidence of treatment-related adverse events between oral CGRP receptor antagonists and placebo.

• Oral CGRP receptor antagonists are safer than triptans in terms of any adverse events, treatment-related adverse events, dizziness, dry mouth, fatigue, paresthesia, and somnolence.

• Although the safety profile for ubrogepant is more favorable than that of triptans, more stringent safety monitoring is required in patients treated with 100 mg of ubrogepant.

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Lee, S., Staatz, C.E., Han, N. et al. Safety evaluation of oral calcitonin-gene–related peptide receptor antagonists in patients with acute migraine: a systematic review and meta-analysis. Eur J Clin Pharmacol 78, 1365–1376 (2022). https://doi.org/10.1007/s00228-022-03347-6

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