ALLEVIATE
Trial question
What is the effect of eptinezumab in patients with episodic cluster headache?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
22.0% female
78.0% male
N = 229
229 patients (51 female, 178 male).
Inclusion criteria: adult patients with episodic cluster headache.
Key exclusion criteria: confounding and clinically significant pain syndromes; lifetime history of psychosis, bipolar mania, or dementia; risk of suicide; clinically significant CVD; failure on a previous treatment targeting the calcitonin gene-related peptide pathway.
Interventions
N=112 eptinezumab (intravenous infusion of a dose of 400 mg over 45-60 minutes).
N=117 placebo (matching intravenous placebo over 45-60 minutes).
Primary outcome
Least-squares mean reduction in number of weekly cluster headache attacks over weeks 1-2
4 events
4.6 events
4.6 events
3.4 events
2.3 events
1.1 events
0.0 events
Eptinezumab
Placebo
No significant
difference ↔
No significant difference in least-squares mean reduction in the number of weekly cluster headache attacks over weeks 1-2 (4 events vs. 4.6 events; AD -0.7 events, 95% CI -2.6 to 1.3).
Secondary outcomes
Significant increase in the percentage of patients achieving ≥ 50% response at week 2 (50.9% vs. 37.3%; OR 1.77, 95% CI 1.03 to 3.07).
No significant difference in mean reduction in the number of daily attacks over days 1-3 (0.2 events vs. 0.4 events; MD -0.1, 95% CI -0.4 to 0.2).
No significant difference in mean number of attacks ≤ 24 hours after trial medication (2.1 events vs. 2 events; MD 0.1, 95% CI -0.3 to 0.5).
Safety outcomes
No significant difference in treatment-emergent adverse events.
Conclusion
In adult patients with episodic cluster headache, eptinezumab was not superior to placebo with respect to a least-squares mean reduction in the number of weekly cluster headache attacks over weeks 1-2.
Reference
Rigmor H Jensen, Cristina Tassorelli, Stewart J Tepper et al. Efficacy and Safety of Eptinezumab in Episodic Cluster Headache: A Randomized Clinical Trial. JAMA Neurol. 2025 May 19:e251317. Online ahead of print.
Open reference URL