PREEMPT 1 Versus PREEMPT 2
Although pooled analyses from the two studies showed overall positive results, the findings differed regarding primary end points between PREEMPT 1 and PREEMPT 2.
In PREEMPT 1, onabotulinumtoxin A was not more effective than placebo regarding change from baseline frequency of headache episodes to headache frequency at week 24. There was a significant imbalance at baseline in the frequency of headache episodes between the onabotulinumtoxin A and placebo groups. In a post-hoc analysis of headache episode frequency during the first 14 days of baseline, no significant between-group differences were shown. When this baseline was used, significant between-group differences favoring onabotulinumtoxin A were observed at weeks four, eight, 20, and 24. At week 24, statistically significant mean improvements were also observed for frequencies of headache days (-7.8, onabotulinumtoxin A; -6.4, placebo) and migraine days (-7.6, onabotulinumtoxin A; -6.1, placebo).
PREEMPT 1 included 341 patients randomized to onabotulinumtoxin A, and 338 to placebo. A total of 18 (5.3%) of patients receiving onabotulinumtoxin A reported serious adverse events, compared with eight (2.4%) receiving placebo. Neck pain (8.2%) and muscular weakness (5.9%) were reported by patients receiving onabotulinumtoxin A, while upper respiratory tract infection and sinusitis were experienced by 6.0% and 5.1%, respectively, of the placebo group.
For PREEMPT 2, however, Dr. Dodick and colleagues found that onabotulinumtoxin A was significantly more effective than placebo (n = 358) in achieving its primary end point—reduction in frequency of headache days. Patients who received onabotulinumtoxin A (n = 347) also had significant improvement compared with those who received placebo regarding all secondary end points, including frequency of migraine days, frequency of moderate/severe headache days, monthly cumulative headache hours on headache days, proportion of patients with severe HIT-6 score, and frequency of headache episodes.
Overall, 15 (4.3%) of onabotulinumtoxin A patients in PREEMPT 2 reported serious adverse events, compared with eight (2.2%) placebo patients. Neck pain and muscular weakness were reported by 9.8% and 5.2%, respectively, of patients using onabotulinumtoxin A.
The Future of Migraine Treatment?
“Onabotulinumtoxin A is shown to be an effective, safe, and well-tolerated treatment for the prophylaxis of chronic migraine,” Dr. Dodick said. In addition, multiple IM treatments of onabotulinumtoxin A, from 155 U to 195 U per treatment cycle, were safe and well tolerated. “Pooled analyses from the PREEMPT 1 and 2 trials demonstrate that treatment with onabotulinumtoxin A resulted in highly significant improvements in onabotulinumtoxin A–treated patients versus placebo-treated patients in frequency of headache days in patients suffering from chronic migraine,” Dr. Dodick’s group reported.”
—Laura Sassano
Suggested Reading
Lima MM, Padula NA. Santos LC, et al. Critical analysis of the international classification of headache disorders diagnostic criteria (ICHD I-1988) and (ICHD II-2004), for migraine in children and adolescents. Cephalalgia. 2005;25(11): 1042-1047.
Petri S, Tölle T, Straube A, et al. Botulinum toxin as preventive treatment for migraine: a randomized double-blind study. Eur Neurol. 2009;62(4):204-211.
Sidebar: Patients Treated With Botox Have Reduced MIDAS Scores
PHILADELPHIA—Sustained reduction in migraine-related disability, headache days, and acute medication use were observed in patients treated with onabotulinumtoxin A, according to data presented at the 14th Congress of the International Headache Society.
Ira M. Turner, MD, of the Center for Headache Care and Research at Island Neurological Associates, PC, in Plainview, New York, and colleagues, retrospectively reviewed 40 patients treated with onabotulinumtoxin A for chronic migraine (15 or more headache days per month) or high frequency migraine (eight to 14 headache days per month) in three consecutive monthly treatment cycles. The primary end point was a reduction in Migraine Disability Assessment (MIDAS) scores. Reduced headache days and acute medication use were secondary end points.
“The average MIDAS score at baseline was 62.8,” Dr. Turner and investigators stated. “Over the next three cycles, these scores were reduced to 29.2, 31.1, and 24.8.” A reduction in headache days was also seen. “These were reduced from a baseline of 20.7 headache days to 11.6, 9.8, and 9.6 days over successive cycles.” A similar sustained decrease for acute medication intake was also noted, from a baseline average of 51.5 doses per month to 27.9, 24.4, and 21.4 monthly doses.
“This retrospective data review of our community-based experience with chronic migraine and high frequency migraine suggests a sustained response to regular onabotulinumtoxin A treatments at roughly three-month intervals in regard to migraine-related disability,” Dr. Turner’s group concluded. A concomitant persisting decrease in headache days and acute medication usage was also shown. “In combination, these have resulted in much less time lost from work and social and family activities, as well as pharmaco-economic savings in terms of reduced acute medication, primarily triptan, usage.”