CGRP Medication Did Not Prevent Cluster Headache Attacks
Investigators find that erenumab, a calcitonin gene-related peptide receptor (CGRP) monoclonal antibody, is not a preventative treatment for chronic cluster headache.
Investigators found that erenumab, a calcitonin gene-related peptide receptor (CGRP) monoclonal antibody, did not prevent attacks of chronic cluster headache. CGRP plays a role in the pathophysiology of cluster headache, but treatment for this chronic condition is limited.1
Investigators find that erenumab, a calcitonin gene-related peptide receptor (CGRP) monoclonal antibody, is not a preventative treatment for chronic cluster headache. | Image Credit: goodluz - stock.adobe.com
Cluster headache is rare, causing very painful headaches in or around one eye and side of the head. Cluster periods can last from weeks to months, then usually stop for a period of time, lasting for months or years. Treatment can be used to shorten cluster headache attacks and lessen pain, but there is some medication used to reduce the number of cluster headaches.
Currently, there is no cure for cluster headaches, but fast-acting treatments can include oxygen, triptans, octreotide as an injection, local anesthetics, and dihydroergotamine. Preventative treatments can include calcium channel blockers, corticosteroids, galcanezumab (Emgality), lithium, noninvasive vagus nerve stimulation, and nerve blocks.2
The investigators of the study (NCT04970355) aimed to determine the efficacy of erenumab, with a loading dose of 280 mg followed by 140 mg after 4 weeks, compared with a placebo as preventative treatment of chronic cluster headache. The study lasted for 10 weeks and had a randomized, double-blind, placebo-controlled design. Patients included were 18 to 64 years of age with a documented history of chronic cluster headaches for 12 or more months prior to screening. Individuals included also needed to be able to determine if the headaches were from cluster attacks or another type of headache.3
The primary outcome included the reduction of weekly cluster headache attack frequency, averaging for 7 days, from baseline over the last 2 weeks of the double-blind study, and secondary outcomes included the percentage of patients who had a 50% or greater reduction from baseline, averaging for 7 days, of weekly cluster headache attacks and patient global impression improvement (PGI-I) at week 6. Other outcomes included reduction from baseline in the weekly number of cluster headache attacks in each of the last 2 weeks, reduction from baseline in the number of weekly cluster headache attacks over the entire trial period, the discontinuation rates due to attack frequency or severity, safety and tolerability of the drug, and discontinuation of treatment due to all causes during the trial.3
There were 81 patients included in the study from December 2, 2021, and September 27, 2023, with 74.1% being male and having a mean age of 48.9 years, according to the study investigators. There was a mean of 21.5 attacks per week at baseline. The study was concluded prematurely due to an insufficient number of patients meeting the inclusion criteria.1
The study authors reported that the primary end point was not met, with the mean weekly cluster headache attacks reducing by –7.3 attacks per week with erenumab and –5.9 attacks per week with the placebo. Only 31.7% of patients had a 50% greater reduction in weekly attacks with the study drug compared with 45% in the placebo group. Furthermore, only 36.6% and 35%, respectively, had a PGI-I score improvement.1
As for adverse events (AEs), there were more patients in the erenumab group who experienced AEs compared with the placebo group, and most AEs were mild or moderate. The most frequent AE was upper respiratory tract infection, and only 2 patients experienced serious AEs in the study drug group.1
READ MORE: Headache and Migraine Resource Center
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REFERENCES
1. Mecklenburg J, Gaul C, Fitzek M, et al. Erenumab for Chronic Cluster Headache: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(6):e2516318. doi:10.1001/jamanetworkopen.2025.16318
2. Mayo Clinic. Cluster headache. August 26, 2023. Accessed July 8, 2025. https://www.mayoclinic.org/diseases-conditions/cluster-headache/symptoms-causes/syc-20352080
3. Efficacy of Erenumab in Chronic Cluster Headache (CHERUB01). ClinicalTrials.gov identification: NCT04970355. January 23, 2025. Accessed July 8, 2025. https://clinicaltrials.gov/study/NCT04970355
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