title: OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program.
abstract: 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.
  
  
  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.
authors: Swedish Neuroscience Institute, Seattle, WA, USA. sheena.aurora@swedish.org
authors: Sheena K
authors: SK
authors: Aurora
authors: Paul
authors: P
authors: Winner
authors: Marshall C
authors: MC
authors: Freeman
authors: Egilius L
authors: EL
authors: Spierings
authors: Jessica O
authors: JO
authors: Heiring
authors: Ronald E
authors: RE
authors: DeGryse
authors: Amanda M
authors: AM
authors: VanDenburgh
authors: Marissa E
authors: ME
authors: Nolan
authors: Catherine C
authors: CC
authors: Turkel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage* / Q000009:adverse effects; D002908:Chronic Disease; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000517:prevention & control*; D009465:Neuromuscular Agents / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D009465:Neuromuscular Agents; D019274:Botulinum Toxins, Type A