Analysis Reveals Improved Functional Outcomes Among Migraineurs Taking Erenumab

Among patients with episodic migraine (EM) in whom 2 to 4 preventives were not useful, erenumab was efficacious in improving functional outcomes after 12 weeks of treatment. Results from the multicenter placebo-controlled LIBERTY study were published in the Journal of Neurology, Neurosurgery & Psychiatry.

Erenumab, a monoclonal antibody, was approved by the FDA in 2018 and is administered monthly via self-injection of a 70- or 140-mg dose. The treatment blocks the calcitonin gene-related peptide receptor, which is believed to play a crucial role in migraine.

LIBERTY was a phase 3b trial that randomized 246 patients 1:1 to erenumab 140 mg or placebo every 4 weeks for 12 weeks between March and October 2017. The trial was conducted in 16 countries across Europe and Australia and included a screening phase (0-2 weeks), a baseline phase (4 weeks), a double-blind treatment phase (12 weeks), and an ongoing open-label treatment phase and safety follow-up phase.

“An important component of migraine management is to evaluate headache-related functional impairment reported by patients and measured by patient-reported outcomes (PROs),” the authors wrote.

To better understand the treatment’s effects on functional outcomes, such as migraine’s impact on everyday activities and work productivity, the researchers evaluated Migraine Physical Function Impact Diary (MPFID), Headache Impact Test (HIT-6), and Work Productivity and Activity Impairment (WPAI) scores at week 12. Questionnaires were administered to participants either at home or during clinic visits throughout the double-blind treatment phase.

All participants were between the ages 18 and 65, had EM—defined as 4 to 14 migraine days per month—and had no meaningful reduction in migraine frequency when taking 2 to 4 prior treatments including propranolol/metoprolol, topiramate, or flunarizine, among others.

Of the patients randomized in LIBERTY, 240 (97.6%) completed the double-blind treatment phase;the control and study groups were well balanced in terms of baseline demographic and disease characteristics.

Analyses at week 12 revealed:

• Erenumab significantly improved MPFID-Physical Impairment (PI) and -Everyday Activities (EA) scores vs placebo (treatment difference [TD], −3.5; 95% CI, −5.7 to –1.2; P = .003; TD, −3.9; 95% CI, −6.1 to –1.7; P <.001, respectively)
• Patients on erenumab were more likely to have a ≥ 5-point reduction in MPFID score (odds ratio [OR] vs placebo: MPFID-EA, 2.1; 95% CI, 1.2-3.6; MPFID-PI, 2.5; 95% CI, 1.4-4.5)
• 55 of 119 (46.2%) patients in the erenumab group­ had ­a­ ≥5­-point­ reduction­ in ­HIT-6 total­ score­ from ­baseline, which was nearly 2 times higher compared with 26.6% of patients in the placebo group (OR, 2.4; 95% CI, 1.4-4.1; P = .002)
• In 3 of 4 WPAI domains, erenumab showed improvement vs placebo (P <.05)
• 36­ (30%)­ patients­ in­ the­ erenumab­ group­ had­ a­ ≥50%­ reduction from baseline in mean monthly migraine days (MMD) compared with 17 (14%) in the placebo group (OR, 2.7; 95% CI, 1.4-5.2; P = .002)

“These findings confirm that the efficacy observed in traditional parameters such as MMD, migraine-specific medication treatment days, and response rates translate into functional improvement,” the authors wrote. Observed benefits were sustained throughout the 12-week phase.

Because the study was conducted on patients with EM, the researchers caution against generalizing findings to those with chronic migraine. In addition, the short duration of the study marks a limitation, as long-term correlation of treatment with erenumab and patient functioning remain unknown. But an ongoing, 3-year open-label extension is being conducted. Because some patients did not work, the WPAI sample size was smaller, which may account for statistically significant differences in only some WPAI subscores.

“In these analyses of the phase 3b LIBERTY study, patients receiving erenumab 140 mg showed significantly higher levels of improvement of migraine-related functional and physical impairment, improved work productivity, improvement in everyday activities and patients’ lives, compared with those taking placebo,” the researchers concluded. “The findings of these analyses add to previous erenumab efficacy and safety data obtained from the LIBERTY study.”

Reference

Lanteri-Minet M, Goadsby PJ, Reuter U, et al. Effect of erenumab on functional outcomes in patients with episodic migraine in whom 2-4 preventives were not useful: results from the LIBERTY study. J Neurol Neurosurg Psychiatry. Published online January 5, 2021. doi:10.1136/jnnp-2020-324396