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Same trials, different answers: reconciling four meta-analyses of anti-CGRP antibodies in cluster headache.

Created on 10 Oct 2026

Authors

Hiba Mustafa, Bayan Ayman Barawi, Carlo Baraldi, Lanfranco Pellesi

Published in

Pain management. Pages 1-7. Oct 09, 2026. Epub Oct 09, 2026.

Abstract

Monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway have been tested in cluster headache with mixed results, and four systematic reviews and meta-analyses reached different conclusions, leaving clinicians without a clear answer on whether, and in whom, to use these drugs.
PubMed and Google Scholar were searched up to June 2026. We re-express the placebo-controlled evidence as the number needed to treat (NNT) for a ≥ 50% reduction in attacks, separately by subtype and by agent, summarize the pooled safety data, and translate the findings into a concrete framework for everyday practice.
Only galcanezumab in episodic disease met its primary endpoint (the reduction in weekly attacks). Its ≥50% responder rate translates into an NNT of 5, though this estimate derives from a single trial and should be interpreted cautiously. Eptinezumab missed both its primary and key secondary endpoints and was stopped for futility. A concordant ≥50% responder signal emerged only in exploratory, non-multiplicity-controlled analyses (nominal NNT = 6). No agent shows a measurable benefit in the chronic form. These antibodies are best regarded as a second-line option in selected patients with episodic cluster headache, after standard prevention has been optimized.

PMID:
42855968
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.

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