Results of a landmark study showed that onabotulinumtoxinA (BoNTA) effectively reduced headache symptoms, episodes, disability, and health-related quality of life (HRQOL) in patients with chronic migraine (CM). These findings from the Phase III Research Evaluating Migraine Prophylaxis Clinical Program (PREEMPT) were presented at the 14th annual International Headache Congress in Philadelphia.1 "Across a wide range of outcome measures, BoNTA was shown to help patients with chronic migraine," said David Dodick, MD, associate professor of neurology at the Mayo Clinic in Scottsdale, Arizona, and an author of the study.
PREEMPT is a multicenter, randomized, placebo-controlled trial involving more than 1300 patients with chronic migraine. Dr Dodick reported on the effects of BoNTA used for treatment and prophylaxis in patients with CM from 66 sites in North America and Europe during the double-blind phase of the PREEMPT 2 trial. Those with CM were identified using the International Classification of Headache Disorders, 2nd edition, criteria and experienced 15 or more days of headache per month. The mean age was 41 years, and 85.4% were women.
The mean Headache Impact Test (HIT)-6 score at baseline was 65.5 for the BoNTA group and 65.4 for those treated with placebo. After 24 weeks of treatment, frequency of headache days was reduced by an average of 9 days in the BoNTA group and 6.7 days in the placebo group. Frequency of headache episodes was reduced by an average of 5.3 episodes in those treated with BoNTA and 4.6 episodes in those treated with placebo. Patients treated with BoNTA also experienced an average of 8.7 fewer migraine/probable migraine days while those treated with placebo experienced 5.8 fewer days. "In patients with a history of migraine who came in with chronic daily headache, even those overusing medications responded effectively," said Dr Dodick.
Overall, patients with CM receiving BoNTA reduced their use of triptans, but they did not reduce their consumption of pain medications, said Dr Dodick. Total adverse events were reported in 62.4% of patients treated with BoNTA and 51.7% of patients treated with placebo.However, 1 treatment-related serious adverse event was reported among those who received BoNTA, and none was reported in the placebo group.
Richard Lipton, MD, director of the Montefiore Headache Center in New York also presented results of PREEMPT.2 Using the Migraine-Specific Quality of Life Questionnaire version 2.1, his team found that most patients had very poor HRQOL at baseline. When patients were assessed at weeks 12 and 24, HRQOL was shown to increase significantly in those treated with BoNTA compared with those treated with placebo. “The relief that BoNTA brings and the enormous improvement in functioning and vitality is striking,” said Lipton.
BoNTA is not approved for the treatment of migraine, but it has been used as an off-label treatment by neurologists and headache specialists for years. In 2008, a Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) stated that BoNTA is probably ineffective for the treatment of episodic migraine and chronic tension-type headache (level B). It also stated that there is no strong evidence showing the efficacy of BoNTA in patients with chronic daily headache.3 Dr Dodick said the results of PREEMPT are consistent with the AAN report, because PREEMPT only focuses on patients with CM.
PREEMPT is the largest placebo-controlled trial in patients with CM, said Dr Dodick. "The only other drug studied to this extent was topiramate," he said. It is possible that the results of this study could contribute to FDA approval of BoNTA for the treatment of CM. "Only time will tell," he said.
1. Dodick DW, Smith TR, Becker WJ, et al. Botulinum neurotoxin type A for treatment of chronic migraine: PREEMPT 2 trial double-blind phase. Presented at: the International Headache Conference; September 9-13, 2009; Philadelphia.
2. Lipton RB, Varon S, Grosberg B, et a. Botulinum neurotoxin type A treatment improves health-related quality of life and reduces the impact of chronic migraine: results from the double-blind phase of the PREEMPT clinical program. Presented at: the International Headache Conference; September 9-13, 2009; Philadelphia.
3. Naumann M, So Y, Argoff CE, et al; Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Assessment: botulinum neurotoxin in the treatment of autonomic disorders and pain (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2008;70:1707-1714.