Internal and Emergency Medicine

, Volume 11, Issue 8, pp 1045–1057 | Cite as

Anti-CGRP monoclonal antibodies in migraine: current perspectives

  • Maria Adele Giamberardino
  • Giannapia Affaitati
  • Martina Curto
  • Andrea Negro
  • Raffaele Costantini
  • Paolo MartellettiEmail author


Migraine is a highly disabling neurological pain disorder in which management is frequently problematic. Most abortive and preventative treatments employed are classically non-specific, and their efficacy and safety and tolerability are often unsatisfactory. Mechanism-based therapies are, therefore, needed. Calcitonin gene-related peptide (CGRP) is recognized as crucial in the pathophysiology of migraine, and new compounds that target the peptide have been increasingly explored in recent years. First tested were CGRP receptor antagonists; they proved effective in acute migraine treatment in several trials, but were discontinued due to liver toxicity in long-term administration. Monoclonal antibodies against CGRP (LY2951742, ALD-403, and LBR-101/TEV-48125) or its receptor (AMG334) were subsequently developed. As reviewed in this study, numerous phase 1 and 2 trials and preliminary results of phase 3 trials have shown a good safety/tolerability profile and efficacy in migraine prevention, especially in high frequent episodic and chronic forms. Being macromolecules, these mAbs are not suitable for oral administration; however, their intravenous or subcutaneous delivery can be performed at relatively low frequency—every month or even quarterly—which enhances patients’ compliance. Although not all migraineurs respond to this treatment, and longer administration periods will be needed to assess long-term effects, the results so far obtained are extraordinarily promising. The future introduction of mAbs on the market will probably represent a turning point for prevention similar to that represented by triptans for abortive treatment in migraine.


Migraine CGRP Monoclonal antibodies against CGRP Migraine prophylaxis 


Compliance with ethical standards

Conflict of interest

In the past 3 years: Maria Adele Giamberardino received research funding from Epitech Group, honoraria for participation in Advisory Board Meeting from Bayer, and participation in conferences from IBSA Institute Biochimique and Helsinn Healthcare, and Royalties from IASP Press. Giannapia Affaitati received honoraria for participation in conferences from Helsinn Healthcare and IBSA Institute Biochimique. Raffaele Costantini declares no conflict of interest. Martina Curto declares no conflict of interest. Andrea Negro received travel grants and participated to the Advisory Boards of Allergan, Electrocore and Medtronic. Paolo Martelletti received travel grants, honoraria consultancy and participated to in the Advisory Boards of Allergan, Bayer, Medtronic, Mylan and Teva.

Statement of human and animal rights

There is no need to cite/report any Ethical Statement.

Informed consent

This is an Invited review and no patients have been involved in this research study.


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© SIMI 2016

Authors and Affiliations

  1. 1.Department of Medicine and Science of Aging, Headache Center and Geriatrics ClinicGabriele D’Annunzio UniversityChietiItaly
  2. 2.Department of Clinical and Molecular Medicine, Regional Referral Headache CenterSapienza UniversityRomeItaly
  3. 3.Regional Referral Headache CenterSant’Andrea HospitalRomeItaly
  4. 4.Department of PsychiatryHarvard Medical SchoolBostonUSA
  5. 5.Bipolar and Psychotic Disorders ProgramMcLean HospitalBelmontUSA
  6. 6.Institute of Surgical PathologyGabriele D’Annunzio UniversityChietiItaly

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