PHILADELPHIA — OnabotulinumtoxinA appears to be a safe, effective, and well-tolerated headache prophylactic for patients with chronic migraine.
Two large randomized controlled trials showed that the toxin significantly reduced migraine frequency and improved headache-related disability over 24 weeks, Dr. David W. Dodick reported at the International Headache Congress.
The studies—PREEMPT 1 and 2—were conducted at 22 centers in North America and Europe, and included 1,384 patients (average age 41 years). Each trial consisted of a 4-week baseline period, during which patients kept a daily headache diary, followed by 24 weeks of treatment during which patients received two injection cycles of either placebo or onabotulinumtoxinA (Botox), which has not been approved by the Food and Drug Administration for migraine prophylaxis. From 24-56 weeks, there was an open-label trial consisting of three injection cycles of the study drug, said Dr. Dodick of the Mayo Clinic Arizona, Phoenix.
At baseline, patients reported a mean of 20 headache days per month, 19 of which were considered migraine days, with a mean of 290 cumulative headache hours. The mean score on the Headache Impact Test–6 (HIT-6) survey was 65, indicating severe impact. Most of the patients (93%) also reported severe headache-related disability, and 65% were overusing acute pain medications.
During the double-blind phase, patients randomized to the treatment group received two injection cycles (one every 12 weeks) of onabotulinumtoxinA 155 U. The medication was injected at 31 sites across seven muscle areas in the head and neck. At the physicians' discretion, an additional 40 units could be injected among three additional muscle groups; the maximum dose was 195 U.
The study's main end point was frequency of headache days; secondary end points were frequency of migraine days, moderate/severe headache days, monthly headache hours, and proportion of patients with a severe HIT-6 score.
At 24 weeks, patients in the active group had a significantly greater reduction in headache days and migraine days than those taking placebo (−8 vs. −6, respectively). The HIT-6 score also declined significantly more among the active group (−5 points vs. −2 points). Patients receiving the study drug experienced a greater decrease in cumulative headache hours per month (−120 vs. −80 hours), and a lower proportion had a severe score on the HIT-6 survey (68% vs. 78%).
“The only outcome that was not statistically significantly better among the active group than the placebo group was the percentage overusing acute pain medications. However, the use of triptans did decrease significantly in the active group compared to the placebo group,” Dr. Dodick said at the congress, which was sponsored by the International Headache Society and the American Headache Society.
Adverse events occurred in 62% of those taking the study drug and 52% of those taking placebo—a significant difference. There were also significantly more treatment-related adverse events in the onabotulinumtoxinA group (29% vs. 13%). One serious treatment-related adverse event did occur in the active group—a severe post-injection migraine that required hospitalization. Adverse events occurring in more than 5% of the entire study group were neck pain (9%) and upper respiratory infection (5%). Four patients in the active group and one in the placebo group discontinued active injections because of an adverse event.
The study was sponsored by Allergan Inc., manufacturer of the study drug. Dr. Dodick reported having received honoraria from the company.
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