Objective: To evaluate safety and efficacy of onabotulinumtoxinA (BOTOX(®) ) as headache prophylaxis in adults with chronic migraine.
Background: Chronic migraine is a prevalent, disabling, and undertreated neurological disorder. OnabotulinumtoxinA is the only approved prophylactic therapy in this highly disabled patient population.
Design and methods: Two phase III, 24-week, double-blind, parallel-group, placebo-controlled studies, followed by a 32-week, open-label, single-treatment, onabotulinumtoxinA phase, were conducted (January 23, 2006 to August 11, 2008). Qualified subjects were randomized (1:1) to injections of onabotulinumtoxinA (155-195 U) or placebo every 12 weeks for 5 cycles (double-blind: 2, open-label: 3). The pooled primary variable was mean change from baseline in frequency of headache days. Secondary variables included proportion of patients with severe Headache Impact Test-6 score (≥ 60) and mean changes from baseline in frequencies of migraine days, moderate/severe headache days, and migraine episodes; cumulative hours of headache on headache days; and acute headache medication intakes. The primary time point was week 24. Assessments for the open-label phase (all patients treated with onabotulinumtoxinA) compared double-blind treatment groups (onabotulinumtoxinA/onabotulinumtoxinA vs placebo/onabotulinumtoxinA) and are summarized to give a descriptive view of consistent study results, with inferences regarding statistical significance only examined for week 56.
Results: A total of 1384 patients were randomized to onabotulinumtoxinA (n = 688) or placebo (n = 696) in the double-blind phase; 607 (88.2%) onabotulinumtoxinA/onabotulinumtoxinA and 629 (90.4%) placebo/onabotulinumtoxinA patients continued into the open-label phase. OnabotulinumtoxinA/onabotulinumtoxinA treatment statistically significantly reduced headache-day frequency vs placebo/onabotulinumtoxinA in patients with chronic migraine at week 56 (-11.7 onabotulinumtoxinA/onabotulinumtoxinA, -10.8 placebo/onabotulinumtoxinA; P = .019). Statistically significant reductions also favored onabotulinumtoxinA/onabotulinumtoxinA for several secondary efficacy variables at week 56, including frequencies of migraine days (-11.2 onabotulinumtoxinA/onabotulinumtoxinA, -10.3 placebo/onabotulinumtoxinA; P = .018) and moderate/severe headache days (-10.7 onabotulinumtoxinA/onabotulinumtoxinA, -9.9 placebo/onabotulinumtoxinA; P = .027) and cumulative headache hours on headache days (-169.1 onabotulinumtoxinA/onabotulinumtoxinA, -145.7 placebo/onabotulinumtoxinA; P = .018). After the open-label phase (all treated with onabotulinumtoxinA), statistically significant within-group changes from baseline were observed for all efficacy variables. Most patients (72.6%) completed the open-label phase; few discontinued because of adverse events. No new safety or tolerability issues emerged.
Conclusions: Repeated treatment with ≤ 5 cycles of onabotulinumtoxinA was effective, safe, and well tolerated in adults with chronic migraine.
© 2011 American Headache Society.