Changing Treatment Landscape for Chronic Migraine Shows Promise Over 5 Years

New treatments for chronic migraine have been increasing, with robust evidence for eptinezumab, erenumab, fremanezumab, galcanezumab, and onabotulinumtoxin A.

Over the past 5 years, the growth of new treatment options, including calcitonin gene-related peptide (CGRP) antagonists and neuromodulatory devices, have been prominent in the chronic migraine space, according to a review published in The BMJ.1

Previous evidence in clinical studies have been focused on the prevention of episodic migraines, characterized as 0 to 14 headache days per month.2 As a result, there are limited data on the treatment of chronic migraine, characterized as 15 or more days per month of headache for 3 months, with at least 8 days of the month having the features of migraine.1

New treatments for chronic migraine have been increasing since 2018, with robust evidence for eptinezumab, erenumab, fremanezumab, galcanezumab, and onabotulinumtoxin A.1 There is also moderate evidence for topiramate and rimegepant, however, the latter is a newer drug, therefore guidelines are still in development.1

According to the review, botulinum toxins, including onabotulinumtoxin A, can reduce the number of headache days per month by 1.9. The treatment requires 31 standardized sites across the head and neck of 155 total units every 12 weeks and an optional 40 other units in other pain sites.1

After the third treatment, the patient’s pain should be assessed and if there is a benefit, the cycle should continue until the patient reverts back to episodic migraine.1

Furthermore, there have been several anti-CGRP monoclonal antibodies that have entered the market, delivered subcutaneously or intravenously, which target either CGRP ligands—including eptinezumab, fremanezumab, and galcanezumab—or receptor, including erenumab.1

Currently, rimegepant is the only CGRP receptor antagonist approved for the prevention of migraine, with 2 others approved for episodic migraine.1

The investigators of the review said that additional studies are needed to assess CGRP receptor antagonists for chronic migraine.1

Galcanezumab and erenumab have shown to have rapid onset of efficacy in some individuals. In the review, investigators said that 54% of those treated with galcanezumab had a 30% reduction in monthly migraine headache days compared with the placebo.1

For erenumab, investigators saw an adjusted odds ratio of achieving a 50% or greater reduction from baseline in migraine days was 1.8 for the 70 mg dosage and 1.9 for the 140 mg dosage. At week 4, the ratios were 2.2 and 2.4, respectively.1

The investigators also emphasized that CGRP agonists may also improve treatment outcomes if combined with onabotulinumtoxin A; however, this was based on a small case series of 17 individuals.

Additionally, the the study authors said that newer, noninvasive treatments, as well as non-drug therapies, including neuromodulation, require more research.1

They also believe that treatment decisions should remain patient-centered, focused on goals, preferences, reduction of disability, and improved quality of life, especially as the treatment space continues to evolve with new approaches and medications. The treatment expectations should consider comorbidities, risk factors, and the cost for patients, according to the study.1


1. Hovaguimian A, Roth J. Management of chronic migraine. BMJ. 2022;379:e067670 doi:10.1136/bmj-2021-067670

2. Katsarava Z, Buse DC, Manack AN, Lipton RB. Defining the differences between episodic migraine and chronic migraine. Curr Pain Headache Rep. 2012;16(1):86-92. doi:10.1007/s11916-011-0233-z