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

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.