OnabotulinumtoxinA (Botox, Allergan Inc) continues to relieve migraine headache when given over the long term, according to a retrospective analysis of patients with chronic migraine treated for 9 treatment cycles, 12 weeks apart.
“Doctors can now tell their patients that Botox is a safe and effective treatment for chronic migraine, with data now reported over 9 treatment cycles, almost double the duration of the previous data set from earlier studies,” Andrew Blumenfeld, MD, from the Headache Center of Southern California, Encinitas, California said.
Until now, there have been limited data on the durability of benefit for onabotulinumtoxinA treatment for chronic migraine beyond 5 cycles, Dr. Blumenfeld said.
The results of the study were presented here at the American Pain Society (APS) 33rd Annual Scientific Meeting. It was funded by Allergan Inc.
Botox first won US Food and Drug Administration (FDA) approval in 2010 for headache prophylaxis in adults with chronic migraine who experience headaches on 15 or more days per month, with each headache lasting more than 4 hours.
Subsequently, 2 large phase 3 trials and a smaller, uncontrolled study found that onabotulinumtoxinA produced statistically and clinically meaningful improvements in multiple headache symptoms compared with placebo. The studies treated patients for 5 cycles, or 56 weeks.
In the current study, Dr. Blumenfeld and his group extended their treatment to comprise 9 cycles given 12 weeks apart, for a total of 108 weeks. They reviewed the medical records for 33 patients who were treated for chronic migraine at their center. All patients had 15 or more headache days per month, each lasting 4 hours or more.
The patients received at least 7 to 9 onabotulinumtoxinA injection cycles with an interval of 12 ± 2 weeks between injections, and the dose of onabotulinumtoxinA ranged from 155 to 195 units, using the PREEMPT (Phase 3 Research Evaluating Migraine Prophylaxis Therapy) injection protocol.
Of the 33 patients in this review, 17 received 8 cycles of onabotulinumtoxinA treatment and 10 received 9 cycles.
Results of the review showed excellent tolerability, with very few adverse events, Dr. Blumenfeld said. Response over all treatment cycles was maintained, and there was progressive improvement over multiple treatment cycles, he added.
Table. Treatment Response After 7 and 9 Cycles of OnabotulinumtoxinA
EndpointBaseline7 Cycles9 Cycles
Mean headache days19.086.256.57
Mean headache-free days10.9223.7523.43
greater than 50% reduction in headache days (%)–8590
The proportions of patients who were deemed to be incapacitated according to Migraine Disability Assessment scores were 53% at baseline and 7% at cycle 7. In addition, 50% of patients had a 5-point or greater reduction in Headache Impact Test-6 score by cycle 7 compared with their score at baseline.
No serious adverse events occurred, Dr. Blumenfeld said.
“BotulinumtoxinA probably blocks sensory afferents to the trigeminal nucleus caudalis by blocking the release of sensory peptides such as CGRP [calcitonin gene-related peptide], substance P, and glutamate for trigeminal, occipital, cervical unmyelinated C fibers,” Dr. Blumenfeld explained.
“My hope is that our experience will increase awareness of an effective treatment to help these very disabled chronic migraine patients,” he added.
“This pilot investigation is important in that it shows that the botulinum agent is effective over a long period,” said Forest Tennant, MD, DrPH, from the Veract Intractable Pain Clinic in West Covina, California. “This is excellent news for the patient who suffers migraines. It is clearly a call for pain practitioners to incorporate botulinum agents into their practice. As of now it is still underused.”
This study is also a call to begin discussion on why botulin derivatives work, Dr. Tennant added.
“It is apparently a form of homeopathy in that the injections are given around the pain site and create a self-healing, autoimmune, anti-inflammatory reaction. All homeopathic agents are, quote, ‘toxic’ at high dosages, so the word ‘toxin’ when attached to botulinum is unfortunate.”