Development of onabotulinumtoxinA for chronic migraine

Discovery of the neuromuscular effects of botulinum toxin began in the early 19th century and has continued to evolve. Currently, onabotulinumtoxinA is approved by the U.S. Food and Drug Administration for two cosmetic and eight medical indications, including chronic migraine (CM). CM is a disabling form of migraine characterized by ≥15 headache days monthly and is believed to result from neuronal hypersensitivity to proinflammatory mediators, upregulation of sensory receptors, and consequent maladaptive pain responses with peripheral and central sensitization. OnabotulinumtoxinA achieves migraine prophylaxis in CM through regulation of vesicular trafficking and exocytosis, inhibition of peripheral release of neuropeptides and inflammatory peptides, and reduced cell surface expression of certain ion channels and receptors. Clinically, efficacy of onabotulinumtoxinA for CM has been shown in two phase III, placebo-controlled trials (PREEMPT 1 and PREEMPT 2). OnabotulinumtoxinA significantly reduced the number of headache days per 28-day cycle relative to placebo at week 24 (change from baseline: -8.4 days for onabotulinumtoxinA versus -6.6 days for placebo; P < 0.001, pooled data). OnabotulinumtoxinA improved health-related quality of life and had an acceptable safety profile. OnabotulinumtoxinA is the only approved treatment specifically for CM prevention and represents a safe and effective therapeutic for chronic migraineurs.