Fremanezumab Aids Reversion from Chronic Migraine to Episodic Migraine

December 1, 2020
Victoria Johnson
Victoria Johnson

Victoria Johnson, Assistant Editor for NeurologyLive, joined the MJH Life Sciences team in October 2020. Follow her on Twitter @_vic_j or email her at

SAP Partner | <b>Montefiore Health System</b>

A new post hoc analysis following the HALO CM study that showed a reduction in headache days with use of fremanezumab.

A new post hoc analysis suggests that fremanezumab may help increase reversion of chronic migraine (CM) to episodic migraine (EM) for patients with the headache disorder.

Rates of reversion from CM to EM (CM-EM), measured in 2 ways, were higher in fremanezumab-treated patients with CM than placebo. Under a less-strict definition, 50.5% of patients treated quarterly (1 dose; n =185; P = .108) and 53.7% of patients treated monthly (n = 196; P = .012) reverted to EM versus placebo (44.6%; n = 159). Under another more stringent definition, 31.2% of patients treated quarterly (n = 114; P = .008) and 33.7% of patients treated monthly (n = 123; P = .001) reverted to EM versus placebo (22.4%; n = 80).1

Richard B. Lipton, MD, Edwin S. Lowe Professor and vice chair of neurology, professor of epidemiology and population health, and professor of psychiatry and behavioral sciences, Albert Einstein College of Medicine, and director, Montefiore Headache Center, and colleagues state in their paper that “fremanezumab is efficacious as a preventive therapy for CM, based on significantly reduced frequency of headache and migraine days compared with placebo.” They note that their analysis shows “the potential [of fremanezumab] for reversion from a CM to an EM classification, a clinically relevant goal of preventive therapy.”

Reversion from CM to EM was defined 2 ways: 1, a less strict definition, as a reduction in the monthly average number of headache days over the 3 months of treatment; and 2, in a more stringent way, requiring a reduction in headache days from baseline for each month of treatment.

READ MORE: Fremanezumab Efficacy Shows Consistency Across Monthly, Quarterly Dosing Regimens

Lipton and colleagues analyzed the randomized, double-blind, placebo-controlled, parallel group HALO CM (NCT02621931) trial of fremanezumab which included data from 1088 patients with CM. These patients were randomized to receive placebo (n = 357), quarterly treatment (n = 366), or monthly treatment (n = 365) over the course of 3 months. Following ICHD-3 criteria, patients had to have migraine for at least 12 months, at least 15 headache days and 8 migraine days per month.2 A reduction of migraine required patients to experience less than 15 headache days per month.

The primary analysis of HALO CM previously showed significant reductions in monthly average headache days from baseline, with quarterly patients experiencing a mean reduction of 4.3 days (standard deviation [SD], 0.3) and monthly patients experiencing a mean reduction of 4.6 days (SD, 0.3). Placebo patients experienced a reduction of 2.5 days (SD, 0.3; P <.001 for both comparisons).

Lipton and colleagues found some negative predictors of (CM-EM) that need to be further studied. In patients who did not revert to EM (CM-CM), rates of onabotulinumtoxinA use (CM-CM, 20% [n = 108]; CM-EM, 10% [n = 55]), topiramate use (CM-CM, 33% [n = 182]; CM-EM, 27% [n = 248]), and concomitant preventive medication use (CM-CM, 24% [n = 132]; CM-EM, 18% [n = 98]) were higher than those of CM-EM patients. In CM-CM patients, 57% (n = 314) also had medication overuse as compared to 50% (n = 268) of CM-EM patients. Medication overuse was defined as the use of acute headache medication on at least 15 days of the month, use of migraine-specific medication on at least 10 days, or use of combination medications on at least 10 days.2 These data show medication use may likely be associated with baseline migraine severity.

CM-EM patients experienced fewer monthly average headache days at baseline (mean, 18.4 days; SD, 2.9) than those who did not (mean, 22.6 days; SD, 3.9), which may also support the need to consider initial migraine severity as an additional variable.

“Future studies with fremanezumab should evaluate whether certain acute medications are more likely to predict failure to revert than others, though this may represent a treatment-resistant population. Further work would be needed to elucidate the relationship between medication overuse and reversion from CM to EM,” Lipton and colleagues wrote.

1. Lipton RB, Cohen JM, Bibeau K, et al. Reversion from chronic migraine to episodic migraine in patients treated with fremanezumab: Post hoc analysis from HALO CM study. Headache. Published online November 11, 2020. doi:10.1111/head.13997
2. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211. doi: 10.1177/0333102417738202