, according to a large retrospective analysis. The results lend hope that the combination may be synergistic, according to Andrew Blumenfeld, MD, director of the Headache Center of Southern California in Carlsbad. Dr. Blumenfeld presented at the American Headache Society’s 2021 annual meeting. The study was published online April 21 in Pain Therapy.
Dr. Andrew Blumenfeld
The retrospective analysis showed a 4-day reduction in headache days per month. In contrast, in the pivotal study for erenumab, the most commonly used anti-CGRP antibody among subjects in the study, showed a 2-day benefit in a subanalysis of patients who had failed at least two oral preventives.
There is mechanistic evidence to suggest the two therapies could be synergistic. OnabotulinumtoxinA is believed to inhibit the release of CGRP, and antibodies reduce CGRP levels. OnabotulinumtoxinA prevents activation of C-fibers in the trigeminal sensory afferents, but does not affect A-delta fibers.
On the other hand, most data indicate that the anti-CGRP antibody fremanezumab prevents activation of A-delta but not C-fibers, and a recent review argues that CGRP antibody nonresponders may have migraines driven by C-fibers or other pathways. “Thus, concomitant use of medications blocking the activation of meningeal C-fibers may provide a synergistic effect on the trigeminal nociceptive pathway,” the authors wrote.
Study finding match clinical practice
The results of the new study strengthen the case that the combination is effective, though proof would require prospective, randomized trials. “I think that it really gives credibility to what we are seeing in practice, which is that combined therapy often is much better than therapy with onabotulinumtoxinA alone, said Deborah Friedman, MD, MPH, who was asked to comment on the findings. Dr. Friedman is professor of neurology and ophthalmology at the University of Texas, Dallas.
Dr. Deborah Friedman
The extra 4 migraine-free days per month is a significant benefit, said Stewart Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “It’s an extra month and a half of no disability per year, and that’s on top of what onabotulinumtoxinA does. So it’s really a very important clinical finding,” Dr. Tepper said in an interview.
Dr. Stewart Tepper
Many insurance companies refuse to pay for the combination therapy, despite the fact that relatively few migraine patients would likely seek it out, according to Dr. Friedman. “It’s just kind of a shame,” she said.
Insurance companies often object that the combination therapy is experimental, despite the widespread use of combination therapies in migraine. “It’s no more experimental in my opinion than any other combination of medications that we use. For people that have severe migraine, we use combination therapy all the time,” said Dr. Friedman.