PHILADELPHIA – Botulinum toxin type A was found to be an effective, well-tolerated prophylactic treatment for patients with transformed migraine, according to studies that were reported at the annual meeting of the American Headache Society.
The phase II botulinum toxin type A (Botox) trials were intended to identify a responsive patient population and the most appropriate dosing as well as to determine efficacy end points to guide phase III studies. Transformed migraine was defined as 16 or more headache days per month, 50% or more of which were migraines.
Dr. Benjamin Frishberg and Dr. David Dodick, who presented these studies at the meeting, said they found significant improvement with Botox compared with placebo in terms of number of headaches, number of headache days, and use of acute medications. The improvements were most notable in patients who were not on any other type of prophylactic treatment.
Dr. Frishberg is a neurologist in La Jolla, Calif., and Dr. Dodick is a neurologist at the Mayo Clinic in Scottsdale, Ariz. Their studies of Botox were supported by Allergan Inc., which is the drug's manufacturer.
Dr. Frishberg and Dr. Dodick reported on a randomized, double-blind, placebo-controlled study in which 1,200 patients were screened based on 30 days of self-reported headaches entered in an electronic diary.
Of these, 702 patients who reported chronic daily headache (CDH, defined as 16 or more headaches a month) were enrolled in a 30-day, single-blind placebo run-in period.
After this period, patients were classified as either placebo responders, or placebo nonresponders.
The mean age of patients was 43.4 years and 82.9% (582) of them were female. All of the patients had at least one migraine or probable migraine during the 30-day baseline period.
Of the 702 patients, 52% were receiving one or more prophylactic headache treatments, in addition to the treatment given in the trial.
The researchers then conducted a subanalysis that looked at 355 patients in the placebo nonresponse group, of whom 228 (64%) were not using prophylactic headache medications. This subset of 228 patients was aged 19–65 years (mean age of 42.4 years), and 86% female. All of these patients had CDH with 50% or more migraine days per month, which the researchers defined as transformed migraine.
The patients in the subset were randomized to receive injections of Botox (117) or placebo (111). Those in the Botox group received between 105 U and 260 U (average 190 U) over six to seven head and neck muscle areas using a modified follow-the-pain injection paradigm. the investigators said.
No significant differences were found between Botox and placebo in the predetermined primary efficacy end point, which was defined as mean change from baseline in the frequency of headache-free days at day 180 in placebo nonresponders, Dr. Frishberg and Dr. Dodick reported.
Several secondary end points were successfully met. The following statistically significant reductions from baseline were observed:
▸ Headache frequency in placebo nonresponders with 225 U and 150 U of Botox vs. placebo at day 240 (reductions in headache frequency of −8.4, −8.6 and −6.4, days respectively).
▸ Headache days in placebo nonresponders who received Botox vs. placebo at day 180 (40% vs. 20% reduction in headache days).
▸ Number of days of use of acute headache pain medications at day 90 in Botox users, compared with placebo (reduction from baseline of −5.7 vs. −3.3 days), as well as at day 180 (−7.8 vs. −4.1), day 210 (−8.5 vs. −4.0), and day 240 (−9.3 vs. −4.7).
Only 27 of the 702 placebo nonresponders (3.8%) discontinued the study due to adverse events. The most commonly reported adverse events in patients treated with Botox vs. placebo were muscular weakness (22% vs. 0%) and neck pain (13.3% vs. 0.5%).
Based on these results, Botox would seem to show the most promise in treating transformed migraine in patients who are not using other prophylactic medications, Dr. Frishberg said in an interview with this newspaper. Phase III trials were scheduled to begin late last year at 100 sites, he said.
