Onabotulinum toxin A in the treatment of chronic migraine: patient selection and special considerations

Discovered by serendipity, onabotulinum toxin A (BoNT-A) is the only US Food and Drug Administration-approved treatment for the prevention of chronic migraine (CM), one of the most disabling and burdensome human conditions. Its efficacy, safety and tolerability, proved by the largest and longest migraine therapeutic trial (the Phase III Research Evaluating Migraine Prophylaxis Therapy program [PREEMPT]), have been replicated by various real-life studies also in the presence of medication overuse. The benefit of BoNT-A prophylaxis is likely due to its ability to counteract peripheral and central nociceptive sensitization through reversible chemical denervation of pericranial sensitive afferents. Its efficacy increases considerably over time during long-term treatments, significantly varying among patients. The present review focuses on the state-of-the art of current knowledge on putative instrumental, biochemical and clinical predictors of BoNT-A responsiveness, outlining the need for a thorough characterization of the full phenotypic migraine picture when trying to predict good responders. Available evidence suggests that disentangling the BoNT-A responsiveness puzzle requires 1) a reappraisal of easy-obtainable clinical details (eg, site and quality of pain, presence of cranial autonomic symptoms), 2) a proper stratification of patients with CM according to their headache frequency, 3) the evaluation of potential synergistic effects of concomitant prophylaxis/treatment and 4) a detailed assessment of modifiable risk factors evolution during treatment.