New disease-specific treatments for migraine prevention

Preventive migraine treatment has been fundamentally changed by the development of treatments targeting calcitonin gene-related peptide or its receptor in the trigeminal nerve, said Professor Rashmi Halker Singh, Mayo Clinic, Scottsdale, AZ, at the closing AAN 2021 Plenary Neurology Year in Review. They offer hope for patients when other medications fail, when they have medical comorbidities, and when there is a risk of medication overuse.

Need for new migraine treatments

Traditional therapies do not meet the needs of people who have migraine

Migraine is the second leading cause of years lived with disability worldwide,1 said Professor Halker Singh, and its prevalence among adult Americans is 15.9%.2

However, traditional therapies have not met the needs of people who have migraine, she said:

  • Over 80% of patients discontinue oral preventive medications at 12 months3
  • Over 20% of patients have a cardiovascular contraindication to triptans4
  • An additional 25% of patients have at least two cardiovascular risk factors identified as precautions for triptans4


Calcitonin gene-related peptide is a new target for treatment

Four decades of research have led to the identification of calcitonin gene-related peptide (CGRP) as a target for treatment, said Professor Halker Singh.

The resulting development of monoclonal antibodies (mAbs) that target CGRP or its receptor and are administered monthly or quarterly subcutaneously or intravenously has now changed views on preventive treatment for migraine.5

Their mechanism of action has been clarified by recent studies, explained Professor Halker Singh, which show:

  • CGRP receptors are located on Aδ-fibers in the trigeminal nerve and are concentrated within the nodes of Ranvier, which play an important role in conducting pain signals6
  • CGRP released from C fibers binds to the CGRP receptors on Aδ-fibers6

Monoclonal Abs to the CGRP ligand or to its receptors on Aδ-fibers can therefore stop pain signal propagation, said Professor Halker Singh.

There has also been a suggestion that the mechanism of action might involve reduced hypothalamic activation as a direct or indirect effect.7


Efficacy and tolerability of CGRP-targeting treatments

Approximately 50% of patients with episodic migraine experience a 50% reduction in monthly migraine days

Two large meta-analyses have demonstrated that CGRP mAbs are an effective and safe preventive treatment for episodic migraine.8,9 Efficacy and tolerability have also been demonstrated for chronic migraine.10

Approximately 50% of patients with episodic migraine experience a 50% reduction in monthly migraine days (MMD),9 said Professor Halker Singh.

Furthermore, preclinical data suggest that CGRP mAbs and botulinum toxin type A, which blocks CGRP release from C fibers, act synergistically within the trigeminovascular system to reduce migraine frequency.11

Similar tolerability for CGRP monoclonal antibodies and placebo

In terms of tolerability, there is no real difference between CGRP mAbs and placebo in the clinical trials, added Professor Halker Singh, and very few people withdrew from the trials because of adverse events. However, all CGRP mAbs carry cautions for hypersensitivity and injection site reactions.9

CGRP mAbs offer hope to many patients when other medications fail, when they have medical comorbidities, or when they are at risk of medication overuse, concluded Professor Halker Singh.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.


  1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211–59.
  2. Burch R, et al. The prevalence and impact of migraine and severe headache in the United States: Updated age, sex, and socioeconomic-specific estimates from government health surveys. Headache. 2021;61:60–8.
  3. Hepp Z, et al. Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: A retrospective claims analysis. Cephalalgia 2017;37:470–85.
  4. Dodick DW, et al. Migraine patients with cardiovascular disease and contraindications: an analysis of real-world claims data. J Primary Care Comm Health 2020;11:1–10.
  5. Dodick DW, et al. CGRP ligand and receptor monoclonal antibodies for migraine prevention: Evidence review and clinical implications. Cephalalgia 2019;39:445–58.
  6. Edvinsson JCA, et al. C-fibers may modulate adjacent Aδ-fibers through axon-axon CGRP signaling at nodes of Ranvier in the trigeminal system. J Headache Pain 2019;20:105.
  7. Ziegeler C, et al. Central effects of erenumab in migraine patients: An event-related functional imaging study. Neurology 2020;95:e2794–e2802.
  8. Deng H, et al. Efficacy and safety of calcitonin-gene related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine – an updated systematic review and meta-analysis. BMC Neurology 2020;20:57.