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Anti-CGRP monoclonal antibodies in migraine: current perspectives

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Abstract

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.

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Authors and Affiliations

  1. Department of Medicine and Science of Aging, Headache Center and Geriatrics Clinic, Gabriele D’Annunzio University, Chieti, Italy

    Maria Adele Giamberardino & Giannapia Affaitati

  2. Department of Clinical and Molecular Medicine, Regional Referral Headache Center, Sapienza University, Via di Grottarossa, 1035, 00189, Rome, Italy

    Martina Curto, Andrea Negro & Paolo Martelletti

  3. Regional Referral Headache Center, Sant’Andrea Hospital, Rome, Italy

    Martina Curto, Andrea Negro & Paolo Martelletti

  4. Department of Psychiatry, Harvard Medical School, Boston, USA

    Martina Curto

  5. Bipolar and Psychotic Disorders Program, McLean Hospital, Belmont, MA, USA

    Martina Curto

  6. Institute of Surgical Pathology, Gabriele D’Annunzio University, Chieti, Italy

    Raffaele Costantini

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  1. Maria Adele Giamberardino
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Correspondence to Paolo Martelletti.

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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.

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Giamberardino, M.A., Affaitati, G., Curto, M. et al. Anti-CGRP monoclonal antibodies in migraine: current perspectives. Intern Emerg Med 11, 1045–1057 (2016). https://doi.org/10.1007/s11739-016-1489-4

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