Scientific Evidence on the efficacy of botox for Chronic Migraine
BOTULINUM TOXIN A
Systematic reviews on the efficacy of botulinum toxin A are based mainly on two large multicentre RCTs, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) 1 and PREEMPT 2. Both trials were conducted in patients with chronic migraine over 24 weeks. Patients received two sets of injections at 12 week intervals, followed by an open label phase.46,66,67
In PREEMPT 1 the primary endpoint of reduction in headache episodes from baseline compared to placebo was negative. However, there was significant reduction in secondary endpoints of headache days with
botulinum toxin A versus placebo (-7.8 v -6.4; p=0.006) and migraine days (-7.6 v -6.1; p=0.002).68
In PREEMPT 2 the primary endpoint was changed (prior to completion of the trial and before analysis) to reduction in headache days. It was stated that this was a better measure than headache episodes in patients
with chronic migraine due to the prolonged, continuous nature of their headaches. There was a significant reduction in both headache days for botulinum toxin A versus placebo (-9.0 v -6.7; p<0.001) and migraine days (-8.7 v -6.3; p<0.001) compared with baseline. There was also a significant reduction in headache episodes in PREEMPT 2 for botulinum toxin A versus placebo (-5.3 v -4.6; p=0.003).69
Post hoc analysis of pooled data from both trials of those patients who had previously used three or more migraine preventatives reported a bigger difference, compared to placebo, in headache days and migraine
days for botulinum toxin A (-7.4 v -4.7; p<0.001) and migraine days (-7.1 v -4.3; p<0.001) compared with baseline.70
In both PREEMPT trials about two thirds of the patients overused abortive treatments. In such patients MOH should be addressed first (see section 5). However, in patients where treatment of MOH has been unsuccessful, botulinum toxin A should still be considered.
A meta-analysis of trials of patients with episodic migraine or tension-type headache found no difference in efficacy compared to placebo.66
Five individual RCTs provided low-strength evidence about the comparative effectiveness of botulinum toxin A versus other drugs for chronic migraine prevention in 350 adults ages 18–65 with 12–24 migraine days per month. No significant differences in likelihood of migraine prevention or improvement in migraine disability assessment were found for botulinum toxin A compared to topiramate. Absolute scores of the Headache Impact Test were significantly better with topiramate than botulinum toxin A, however, the need for acute
drugs did not differ between the two. A single RCT examined the comparative effectiveness of botulinum
toxin A versus divalproex sodium and found no differences between the two drugs for migraine prevention,
migraine-related disability, or quality of life.46
Adverse events were slightly more common in patients injected with botulinum toxin A compared to placebo
(RR 1.25, 95% CI, 1.14 to1.36), although they were not more likely to withdraw from the study as a result.
Adverse events included ptosis, muscle weakness, neck pain and stiffness, paraesthesia and skin tightness.46,66
Botulinum toxin A (BotoxR) has been accepted with restricted use in NHSScotland for adults with chronic
migraine (headaches on at least 15 days per month of which at least eight days are with migraine) whose
condition has failed to respond to ≥3 prior oral prophylactic treatments, where medication overuse has
been appropriately managed.70 This was based on clinical effectiveness and a cost-utility analysis (Markov
model) which compared botulinum toxin A to best supportive care, over a three-year time horizon. The
analysis reported that botulinum toxin A resulted in an incremental cost-effectiveness ratio (ICER) of ￡10,816
and quality-adjusted life year (QALY) gain of 0.12.70 Botulinum toxin A is required to be administered by
appropriately trained personnel in hospital specialist centres, which may have implications for service delivery.
R Botulinum toxin A is not recommended for the prophylactic treatment of patients with episodic
migraine.
R Botulinum toxin A is recommended for the prophylactic treatment of patients with chronic migraine
where medication overuse has been addressed and patients have been appropriately treated with
three or more oral migraine prophylactic treatments.
