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. 2025 Jul;15(7):425-439.
doi: 10.1080/17581869.2025.2509474. Epub 2025 May 30.

Repurposed versus disease-specific medicinals for the prophylaxis of migraine: an updated systematic review

Savvas-Ilias Christofilos  1   2 , Theodoros Mavridis  1   3 , Viktor Gkotzamanis  1 , Sofia Vasilopoulou  1 , Christina I Deligianni  1   4 , Dimos-Dimitrios Mitsikostas  1
Affiliations

Repurposed versus disease-specific medicinals for the prophylaxis of migraine: an updated systematic review

Savvas-Ilias Christofilos et al. Pain Manag. 2025 Jul.

Abstract

Background: Gepants, selective antagonists of the calcitonin gene-related peptide (CGRP) receptor, and monoclonal antibodies targeting CGRP or its receptor (anti-CGRP mAbs) are promising migraine treatments, demonstrating superior tolerability than traditional preventives. While their efficacy over placebo is established, their comparative benefit-risk profiles remain to be fully elucidated.

Objective: To indirectly compare the benefit-risk ratios of gepants with anti-CGRP mAbs and repurposed preventives.

Methods: A comprehensive search of PubMed/MEDLINE and ClinicalTrials.gov was conducted to identify phase-3, placebo-controlled trials of gepants (atogepant, rimegepant), anti-CGRP mAbs (eptinezumab, erenumab, fremanezumab, galcanezumab), and traditional treatments (propranolol, topiramate, onabotulinumtoxinA). The number needed to treat (NNT) for achieving ≥50% reduction in migraine days and the number needed to harm (NNH) for adverse effects were calculated to determine the likelihood to help versus harm (LHH) values.

Results: Twenty-seven studies were included: 15 of mAbs, 4 of gepants, 2 of onabotulinumtoxin A, and 6 of standard treatments. Atogepant and fremanezumab exhibited the highest LHH in episodic migraine, and galcanezumab and eptinezumab performed favorably in chronic migraine concerning treatment discontinuation and treatment-related adverse effects.

Conclusions: Anti-CGRP/R medications present a more favorable benefit/risk ratio than traditional treatments. These findings, combined with individual patient histories and preferences, can inform clinical decision-making.

Keywords: CGRP; atogepant; eptinezumab; erenumab; fremanezumab; rimegepant.

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Conflict of interest statement

Savvas-Ilias Christofilos has nothing to disclose. Theodoros Mavridis has nothing to disclose related to the submitted work. Christina I. Deligianni has nothing to disclose related to the submitted work. Dimos-Dimitrios D. Mitsikostas has received honoraria, research, and travel grants from Allergan/AbbVie, Amgen, Biogen, Cefaly, Genesis Pharma, Eli Lilly, Electrocore, Lundbeck, Mertz, Merck-Serono, Novartis, Pfizer, Roche, Sanofi, Specifar, and Teva. He participated in clinical trials for Amgen, Novartis, Cefaly, Eli Lilly, Electrocore, Genesis Pharma, Lundbeck, Merz, Specifar, and Teva as principal investigator. He is President of the board of the Hellenic Headache Society and Co-chairman of the management group of the Headache Panel at the European Academy of Neurology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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