4% of onabotulinumtoxinA patients and 51.7% of placebo patients. Most patients reported adverse events that were mild to moderate in severity and few discontinued (onabotulinumtoxinA, 3.8%; placebo, 1.2%) due to adverse events. No unexpected treatment-related adverse Wnt pathway events were identified. Conclusions.— The pooled PREEMPT results demonstrate that onabotulinumtoxinA is an effective prophylactic treatment for chronic migraine. OnabotulinumtoxinA resulted in significant

improvements compared with placebo in multiple headache symptom measures, and significantly reduced headache-related disability and improved functioning, vitality, and overall health-related quality of life. Repeat treatments with onabotulinumtoxinA were safe and well tolerated. Chronic migraine (CM) is a complex, progressive headache disorder affecting approximately 1.3-2.4% of the general adult population.1-3 According to the second edition of the International Classification of Headache Disorders (ICHD-II) learn more and subsequent revised ICHD criteria, CM is recognized as a complication of migraine that is distinguished from episodic migraine (EM) by the frequency of headache.4,5 CM is characterized by

headache on ≥15 days per month, of which at least 8 headache days per month meet criteria for migraine without aura or respond to migraine-specific treatment.5 CM is associated with significant disability, reduced health-related quality of life (HRQoL), and considerable

healthcare cost.6,7 Patients with CM are less Thymidylate synthase likely to attend social functions and perform household work compared with those with EM, and 1 in 5 CM sufferers is occupationally disabled, thereby affecting their ability to lead productive lives.8,9 Few preventative treatments for CM have been investigated, and none is currently approved for CM prophylaxis.10-13 The effectiveness of both acute migraine treatments and prophylactic medications may be further complicated by frequent overuse of acute headache pain medication (eg, simple analgesics, triptans, opioids, ergots) by this patient population.14-16 OnabotulinumtoxinA (BOTOX®; Allergan, Inc., Irvine, CA, USA) has shown efficacy in relieving pain associated with a variety of conditions, including migraine headache.10,11,17-27 Previous exploratory trials evaluating the efficacy and safety of onabotulinumtoxinA in headache prophylaxis have yielded mixed results.10,11,28-30 In 2 large, randomized, placebo-controlled exploratory studies of EM, no significant between-group difference was observed in frequency of headache episodes.28,29 The baseline mean number of headache days in these studies was approximately 8-10 per month. A study of chronic tension-type headache (CTTH) did not observe a significant difference favoring onabotulinumtoxinA in the number of headache-free days per month.30 These trials have not established the efficacy of onabotulinumtoxinA in either EM or CTTH.