JAMA Neurol

Is eptinezumab effective as a preventive treatment for episodic cluster headache?

June 2, 2025

Eptinezumab didn’t meet the primary endpoint of reducing weekly attack frequency in episodic cluster headache, though higher responder rates and patient-reported improvements were observed. These findings suggest limited efficacy for eptinezumab in this indication, and current preventive management should continue to prioritize established therapies.

Study details: The double-blind, randomized, placebo-controlled ALLEVIATE trial (NCT04688775) evaluated IV eptinezumab 400 mg vs. placebo for the preventive treatment of episodic cluster headache in adults (n=231) across 64 international sites. The primary endpoint was change from baseline in weekly attack frequency during weeks 1–2. Safety was assessed by monitoring treatment-emergent adverse events over a 4-week randomized phase.

Results: Eptinezumab didn’t significantly reduce the number of weekly attacks compared with placebo (least-squares mean change: -4.0 vs. -4.6; between-group difference, 0.7; 95% confidence interval [CI], -1.3 to 2.6; P=0.50). However, a greater proportion of eptinezumab-treated patients achieved a ≥50% reduction in attack frequency at weeks 2, 3, and 4 (week 4: 66.7% vs. 50.5%; OR, 2.14; 95% CI, 1.21-3.83; P=0.009). Improvements in average daily pain and patient-reported outcomes were numerically greater with eptinezumab. Adverse event rates were similar between groups (25.0% vs. 26.5%).

Source:

Jensen RH, et al. (2025, May 19). JAMA Neurol. Efficacy and Safety of Eptinezumab in Episodic Cluster Headache: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40388178/