Comprehensive assessment of erenumab efficacy in participants with high-frequency episodic migraine with at least one previously failed preventive treatment: The EMBRACE study.

Objective: To evaluate the effect of erenumab treatment beyond monthly migraine days in patients with high-frequency episodic migraine who did not respond to at least one previous migraine preventive treatment.

Background: Reduction in monthly migraine days has been the efficacy standard for migraine preventive treatments; however, it does not fully capture the holistic benefit of the therapy. Erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide pathway, has demonstrated reduction in monthly migraine days and improvement in function in patients with episodic and chronic migraine.

Methods: In this phase 4, interventional, double-blind, randomized, placebo-controlled, multicenter, global study, treatment with erenumab was assessed over 4 months in adults with high-frequency episodic migraine. The study was conducted at 61 sites located across North America and Europe between September 2020 and October 2023. Patients with ≥1 qualifying oral triptan-treated migraine attack at baseline were randomized to receive erenumab 140 mg or placebo subcutaneously once monthly. The primary endpoint was change from baseline in mean monthly hours of at least moderate headache pain intensity over months 1, 2, and 3; secondary endpoints included change from baseline in mean monthly function, mean monthly duration of at least moderate pain intensity in migraine attacks, and mean monthly peak migraine pain intensity. Safety outcomes were also assessed.

Results: Of 512 randomized patients, 510 received erenumab 140 mg (n = 254) or placebo (n = 256) once monthly. Demographics and baseline characteristics were balanced between the two treatment arms. Erenumab 140 mg was superior to placebo in reducing duration of moderate or severe headache pain intensity over months 1, 2, and 3 (least squares mean [95% confidence interval {CI}] difference, -7.95 [-11.45, -4.46]; p < 0.001). Compared with placebo, erenumab significantly reduced migraine functional impact as assessed by the four domains of the Migraine Functional Impact Questionnaire, with a least squares mean (95% CI) difference of -7.36 (-10.80, -3.92) for physical functioning, -7.10 (-10.34, -3.87) for usual activities, -6.82 (-10.37, -3.27) for social functioning, and - 7.05 (-10.76, -3.34) for emotional functioning (p < 0.001 for all domains). Significant reductions with erenumab compared with placebo were also observed in duration of at least moderate pain intensity in residual or break-through migraine attacks (least squares mean [95% CI] difference, -1.07 [-1.92, -0.22]; p = 0.013) and peak migraine pain intensity (-0.48 [-0.85, -0.11]; p = 0.011). Incidence of grade 3 adverse events was 1.6% with erenumab and 1.2% with placebo; no grade 4 or fatal adverse events were reported in either treatment arm.

Conclusion: Findings from the EMBRACE study demonstrated that treatment with erenumab in patients with high-frequency episodic migraine can provide positive therapeutic effects on ictal burden and pain, with residual migraine attacks tending to be shorter and less painful, with less overall impact.