Commentary
VALENCIA, SPAIN – OnabotulinumtoxinA injections for the treatment of refractory chronic migraine halved the number of days of work per month missed because of migraine while quadrupling the number of crystal-clear, headache-free days in a large, prospective, real-world study.
“OnabotulinumtoxinA [Botox] is a valuable addition to current treatment options in patients with chronic migraine,” Dr. Modar Khalil concluded in summarizing his study findings at the International Headache Congress.
Bruce Jancin/Frontline Medical News
Dr. Modar Khalil
He presented a prospective study of 465 patients with chronic migraine treated with onabotulinumtoxinA in Hull, England.
The results paralleled the findings of the earlier PREEMPT (Phase-3 Research Evaluating Migraine Prophylaxis Therapy) study program which led to marketing approval of onabotulinumtoxinA for chronic migraine in the United Kingdom as well as the United States. However, the Hull patients were more representative of the sort of chronic migraine patients typically seen in tertiary headache clinics. Their chronic migraine was more severe than in the PREEMPT population: 97% of the Hull group had failed three or more preventive therapies at baseline, compared with only one-third of PREEMPT participants, noted Dr. Khalil of the Hull Royal Infirmary.
The Hull patients had a median 4-year history of chronic migraine. Prior to undergoing their first cycle of onabotulinumtoxinA therapy they averaged 27 total headache days and 15 migraine days per month.
The three coprimary study endpoints were at least a 50% reduction in headache days in the first month after onabotulinumtoxinA therapy, compared with the month before, at least a 50% reduction in migraine days, or a doubling of the number of crystal-clear days.
Fifty-nine percent of patients achieved at least one of those targets, 39% reached two, and 21% attained all three. The goal most frequently met was the 50% or greater reduction in monthly migraine days, achieved by 47% of patients. Forty-six percent met the target for an increase in crystal-clear days, while 27% of patients experienced at least a 50% reduction in headache days, Dr. Khalil said at the meeting sponsored by the International Headache Society and the American Headache Society.
The highest response rate was seen in patients with what he termed moderate-frequency chronic migraine as defined by 21-25 days of headache per month. Seventy-four percent of those patients met at least one of the three coprimary endpoints. In contrast, patients with a baseline headache frequency of 26-30 days per month had a 50% response rate, while those with 16-20 headache days had a 59% response rate.
A tougher standard – a 75% or greater reduction in either migraine days or headache days or at least a threefold increase in crystal-clear days – was achieved in one-third of patients. Fourteen percent met any two of the goals, and 6% met all three goals at the higher bar.
The median number of work days missed per month due to headache fell from 4 to 2 in the study population.
The most common adverse event was neck stiffness, reported by 16% of treated patients. In addition, 15% reported injection site pain lasting at least 24 hours, 9% experienced drooping of the upper eyelid, and 1.5% had difficulty swallowing.
Dr. Khalil noted that while a real-world, prospective, observational study such as this offers advantages over a controlled clinical trial, which often enrolls a select patient population, it has the disadvantage of not having an active comparator arm. That’s important because it’s well known that migraine studies tend to have a high placebo response rate.
In other Botox-related news at the IHC Congress, Rami Burstein, Ph.D., received the 2015 International Headache Society Cephalalgia Award given by the editorial board of the journal Cephalalgia for the most important paper in the field of headache medicine published in that journal in the past year. Dr. Burstein, professor of anesthesiology at Harvard Medical School, Boston, earned the honor, which comes with a 10,000 euro award, for his work in elucidating the mechanism of benefit for Botox in migraine (Cephalalgia 2014;34:853-69).
Dr. Khalil’s study was supported by Allergan. He reported having no financial conflicts.
