title: Anti-CGRP monoclonal antibodies in migraine: current perspectives.
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.
authors.affiliation: Department of Medicine and Science of Aging, Headache Center and Geriatrics Clinic, Gabriele D'Annunzio University, Chieti, Italy.
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Giamberardino
authors.affiliation: Department of Medicine and Science of Aging, Headache Center and Geriatrics Clinic, Gabriele D'Annunzio University, Chieti, Italy.
authors.forename: Giannapia
authors.initials: G
authors.lastname: Affaitati
authors.affiliation: Department of Clinical and Molecular Medicine, Regional Referral Headache Center, Sapienza University, Via di Grottarossa, 1035, 00189, Rome, Italy.|Regional Referral Headache Center, Sant'Andrea Hospital, Rome, Italy.|Department of Psychiatry, Harvard Medical School, Boston, USA.|Bipolar and Psychotic Disorders Program, McLean Hospital, Belmont, MA, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Curto
authors.affiliation: Department of Clinical and Molecular Medicine, Regional Referral Headache Center, Sapienza University, Via di Grottarossa, 1035, 00189, Rome, Italy.|Regional Referral Headache Center, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Negro
authors.affiliation: Institute of Surgical Pathology, Gabriele D'Annunzio University, Chieti, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Costantini
authors.affiliation: Department of Clinical and Molecular Medicine, Regional Referral Headache Center, Sapienza University, Via di Grottarossa, 1035, 00189, Rome, Italy. paolo.martelletti@uniroma1.it.|Regional Referral Headache Center, Sant'Andrea Hospital, Rome, Italy. paolo.martelletti@uniroma1.it.
authors.forename: Paolo
authors.identifier: http://orcid.org/0000-0002-6556-4128
authors.initials: P
authors.lastname: Martelletti
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008881:Migraine Disorders / Q000188:drug therapy*; D059408:Pain Management / Q000379:methods*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D018015:Receptors, Calcitonin Gene-Related Peptide; C000604315:fremanezumab
keywords: CGRP; Migraine; Migraine prophylaxis; Monoclonal antibodies against CGRP