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.