A randomized clinical trial found that erenumab, a monoclonal antibody targeting the calcitonin gene–related peptide receptor, did not significantly reduce the frequency, severity, or duration of chronic cluster headache attacks compared with placebo.
Chronic cluster headache (CCH) is a rare and severely disabling headache disorder defined by attacks occurring for more than 1 year without remission or with remission periods shorter than 3 months. Limited treatment options have prompted investigation into calcitonin gene–related peptide (CGRP) pathway inhibitors, which have demonstrated efficacy in migraine and episodic cluster headache.
This double-blind, placebo-controlled trial enrolled 81 adults aged 18 to 65 years with CCH at 11 sites in Germany. Eligible participants had not responded to or could not tolerate prophylactic medications such as verapamil or lithium. Participants received a 280-mg subcutaneous loading dose of erenumab or placebo at baseline, followed by a 140-mg dose at week 4.
The primary end point—mean reduction in weekly attacks during weeks 5 and 6—was not met. The erenumab group had a mean (SD) reduction of 7.3 (8.6) attacks per week, compared with 5.9 (10.5) in the placebo group (difference, –1.5 attacks per week; 95% credible interval [CrI], –5.7 to 2.8). The posterior probability of a clinically meaningful effect—a reduction of more than 3 attacks per week—was 24%.
Secondary outcomes also did not differ significantly between groups. A reduction of 50% or more in weekly attacks was achieved in 31.7% of participants receiving erenumab compared with 45.0% receiving placebo. At week 6, 36.6% of the erenumab group and 35.0% of the placebo group reported improvement on the Patient Global Impression of Improvement (PGI-I) scale.
Exploratory outcomes, including changes in attack duration and pain severity, showed no significant differences. Use of acute medications slightly increased in both groups from baseline.
Adverse events were reported in 66% of the erenumab group and 43% of the placebo group. Most events were mild or moderate. One serious adverse event—atrial flutter with sigmoid diverticulitis—occurred in the erenumab group and resolved with treatment.
Although the trial planned to enroll 118 participants, it was terminated early due to difficulty recruiting patients who met the strict inclusion criteria. The findings align with previous negative trials of other CGRP-targeted agents in CCH, including galcanezumab and fremanezumab.
Authors note that CGRP-targeted therapies may be less effective in CCH than in other headache types and suggest further research into alternative pathophysiologic mechanisms.
Disclosures can be found in the study.
Source: JAMA Network
