TOPLINE:
Preventive treatment with the calcitonin gene-related peptide (CGRP) receptor monoclonal antibody erenumab for 6 weeks was not associated with significant reductions in weekly headache attacks, pain severity, or attack duration in adults with chronic cluster headache (CCH), a new phase 2 placebo-controlled trial showed.
METHODOLOGY:
- The CHERUB01 phase 2 12-week, double-blind, placebo-controlled randomized clinical trial was conducted at 11 sites in Germany between 2021 and 2023.
- About 81 adults with CCH (mean age, 49 years; 74% men) who failed to respond to standard prophylactic therapies were randomly assigned to receive either subcutaneous erenumab (280 mg at baseline, followed by 140 mg at week 4) or a matching placebo.
- The primary endpoint was change in the mean number of weekly CH attacks from baseline to weeks 5 and 6.
- Secondary endpoints included the proportion of patients achieving a ≥ 50% reduction in attacks and the number of participants with Patient Global Impression of Improvement (PGI-I) scores of 1 or 2 at week 6. Exploratory endpoints included reduction in CH attack duration and change in mean pain severity on the numeric pain rating scale.
TAKEAWAY:
- The primary endpoint was not met. Although there was a greater reduction in the mean number of weekly attacks for the erenumab group compared to the placebo group, the difference was not statistically significant (-7.3 vs -5.9 attacks per week; 95% credible interval, -5.7 to 2.8).
- There was no significant difference between groups in the proportion of participants achieving a ≥ 50% reduction in weekly attacks, the number of patients with improved PGI-I scores, changes in attack duration, or change in pain severity.
- Adverse events were more common in the erenumab group compared to the placebo group (66% vs 43%), with most considered to be mild or moderate.
IN PRACTICE:
“Erenumab failed to show a benefit over placebo in patients with CCH, indicating that blockade of peripheral CGRP receptors has no beneficial role in the prophylaxis of CCH,” the investigators wrote.
“To date, all double-blind controlled trials in CCH using an mAb affecting the CGRP pathway were negative, leading to the conclusion that future research should revisit the role of CGRP in CCH,” they added.
SOURCE:
This study was led by Jasper Mecklenburg, MD, Charité – UniversitätsmedizinBerlin, Berlin, Germany. It was published online on June 17 in JAMA Network Open.
LIMITATIONS:
Data on patients who progressed from episodic headache to CCH were missing. Additionally, the onset timing of current CCH episodes was unclear, with no detailed records of past steroid responses or reasons for prior treatment failures with verapamil or lithium, which relied on patient recall.
DISCLOSURES:
This trial was funded by a grant from Novartis Pharma GmbH to Charité – UniversitätsmedizininBerlin. Several investigators reported having financial ties with various sources including the funding company. Full details are listed in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
