Treatment of chronic migraine with Botox (onabotulinumtoxinA): Development, insights, and impact

Abstract

Chronic migraine (CM) is a neurological disease characterized by frequent migraine attacks that prevent affected individuals from performing daily activities of living, significantly diminish quality of life, and increase familial burden. Before onabotulinumtoxinA was approved for CM, there were few treatment options for these seriously disabled patients and none had regulatory approval. The terminology and recognition of CM evolved in parallel with the onabotulinumtoxinA clinical development program. Because there were no globally accepted classification criteria for CM when onabotulinumtoxinA was in development, the patient populations for the trials conducted by Allergan were determined by the Allergan migraine team in collaboration with headache scientists and clinicians. These trials and collaborations ultimately led to improvements in CM classifications. In 2010, onabotulinumtoxinA became the first medication and first biologic approved specifically to prevent headaches in patients with CM. Approval was based on 2 similarly designed phase 3, double-blind, randomized, placebo-controlled, multicenter clinical studies. Both studies showed significantly greater improvements in mean change from baseline in headache-day frequency in patients with CM receiving onabotulinumtoxinA compared with those receiving placebo. The safety and effectiveness of onabotulinumtoxinA have been established globally in >5000 patients with CM with or without medication overuse treated in clinical and observational studies. Benefits also include improvements in quality of life, fewer psychiatric comorbidities, and reduced healthcare resource utilization. Across studies, onabotulinumtoxinA was well tolerated; adverse events tended to be mild or moderate in severity and to decline over subsequent treatment cycles.

Figure 1.

Phase 2b studies of onabotulinumtoxinA conducted between 2001 and 2004. FSFD = fixed-site, fixed-dose, FTP = follow the pain.

Figure 2.

Mean (standard error) change from baseline in frequency of headache days in patients who completed 5 treatments of onabotulinumtoxinA versus placebo in the PREEMPT trial. Reprinted with permission from Aurora SK, et al.^[43] PREEMPT = Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy.

Figure 3.

Ongoing and completed Allergan-sponsored onabotulinumtoxinA trials. CaMEO = Chronic Migraine Epidemiology and Outcomes, CM PASS = Chronic Migraine Post-Authorization Safety Study, COMPEL = Chronic Migraine OnabotulinuMtoxinA Prolonged Efficacy open Label, PMS = Post-Marketing Surveillance, PREDICT = Patient Reported Outcomes in Patients With Chronic Migraine Treated With Botox, REPOSE = REal-life use of botulinum toxin for the symptomatic treatment of adults with chronic migraine, measuring healthcare resource utilization, and Patient-reported OutcomeS observed in practicE.

Figure 4.

Drs Mitchell Brin and Catherine Turkel at the 4th Galien Forum and the 2013 Prix Galien USA Awards ceremony in New York City in October 2013.