OnabotulinumtoxinA for Treatment of Chronic Migraine: Pooled Analyses of the 56‐Week PREEMPT Clinical Program
Authors: Aurora Sheena K. , Winner Paul , Freeman Marshall C. , Spierings Egilius L. , Heiring Jessica O. , DeGryse Ronald E. , VanDenburgh Amanda M. , Nolan Marissa E. , Turkel Catherine C. 
Published: September 2011

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.