Study Points to Combined Efficacy of Erenumab, OnabotulinumtoxinA for Chronic Migraine

November 8, 2020
Gianna Melillo

Gianna is an associate editor of The American Journal of Managed Care® (AJMC®). She has been working on AJMC® since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey.

Patients with chronic migraine who received a combination therapy of erenumab and onabotulinumtoxinA exhibited significant reductions in monthly headache days and monthly migraine days.

Patients with chronic migraine (CM) who received a combination therapy of erenumab and onabotulinumtoxinA exhibited significant reductions in monthly headache days (MHDs) and monthly migraine days (MMDs), according to results of a retrospective chart review published in Journal of Pain & Palliative Care Pharmacotherapy.

It is estimated that just under 1% of the US population suffers from CM, defined as a headache occurring on 15 or more days per month for at least 3 months with features of migraine on at least 8 days each month.

“Migraines are thought to be mediated through peripheral activation of nociceptive neurons that leads to neurogenic inflammation and central sensitization through the trigeminal vascular pathway,” the researchers wrote, although the exact underlying cause of migraine is unclear.

Erenumab, a calcitonin gene-related peptide (CGRP) inhibitor, was first approved by the FDA in 2018 for the prevention of migraine in adults. The treatment is administered via self-injection once a month and works to block the CGRP receptor.

Similarly, onabotulinumtoxinA was approved by the FDA in 2010 to treat CM. However, the treatment prevents acetylcholine release by cleaving the 25 kDa synaptosomal-associated protein (SNAP-25), which inhibits vesicle fusion and release.

“Current theories suggest that onabotulinumtoxinA…modifies the local release of pro-inflammatory mediators involved in the transduction of pain, such as CGRP and substance P, resulting in decreased neurogenic inflammation in sensory neurons at nerve terminals,” the researchers explained.

Patients between the ages 18 and 70 who presented to a headache clinic between May 2018 and October 2018 were included in the study. All participants (n = 78) received a diagnosis of CM and had a baseline treatment of onabotulinumtoxinA for at least 9 months prior to the addition of erenumab.

The researchers analyzed MHDs and MMDs at baseline and after 30, 60, and 90 days. The majority of participants were female (85.9%), and the mean (SD) age was 48.5 (12.3) years. “At baseline, while on onabotulinumtoxinA, mean MHDs were 22.5 (8.7) and mean MMDs were 15.8 (8.3),” the authors wrote. Sixty-five patients (83.3%) had previously failed at least 3 preventative therapies.

After 30 days, patients exhibited a mean reduction of 6.8 MHDs (P <. 001) and 7.0 MMDs (P <.001), a reduction of 7.2 MHDs (P < .001) and 6.7 MMDs (P < .001) at 60 days, and a reduction of 8.1 MHDs (P < .001) and 7.4 MMDs (P < .001) at 90 days.

The observational nature of the study, the lack of a control group, anda relatively small number of participants all mark limitations to the study. The researchers were also unable to control for comorbid conditions like obesity, psychiatric conditions, or other chronic pain.

Results suggest patients still suffering from CM while taking onabotulinumtoxinA may benefit from a combination therapy with erenumab.

“Further investigation is needed to determine if erenumab in combination with onabotulinumtoxinA has an enhanced effect on the modulation of CGRP release from peripheral unmyelinated C fibers while also blocking CGRP receptors in the myelinated A-delta fibers,” the authors concluded. “Additional randomized control trials are needed to further guide clinical practice.”


Armanious M, Khalil N, Lu Y, Jimenez-Sanders R. Erenumab and onabotulinumtoxinA combination therapy for the prevention of intractable chronic migraine without aura: a retrospective analysis. J Pain Palliat Care Pharmacother. Published online October 30, 2020. doi:10.1080/15360288.2020.1829249