Headache Medicine 2020, 11(3):77 ISSN 2178-7468, e-ISSN 2763-6178
77
ASAA
DOI: 10.48208/HeadacheMed.2020.21
Headache Medicine
© Copyright 2020
Commentary
Anti-CGRP monoclonal antibodies in chronic cluster headache
Aline Turbino Neves Martins da Costa
Federal University of São Paulo, São Paulo, Brazil.
Cluster headache is known by excruciatingly painful side-locked headache attacks with ipsilateral cranial
autonomic symptoms and restlessness, often usual several times a day. It has a prevalence of 0.1%,
with male preponderance. Calcitonin gene-related peptide (CGRP) plays an important role in cluster
headache pathophysiology as we know.
Anti-CGRP monoclonal antibody galcanezumab was approved for the prophylactic treatment of cluster
headache. Two randomized, placebo-controlled clinical studies showed positive results. In episodic
cluster headache, a signicant reduction of attack frequency was noticed, leading to approval by the
US Federal Drug Administration (FDA) in June 2019, but the effect was not signicant in chronic cluster
headache (CCH).
Chronic cluster headache is refractory to other preventive therapies and severely affected by high fre-
quencies of attacks happening for months, an individual treatment attempt with an anti-CGRP antibody
appears to be a therapeutic option with a conclusive pathophysiological reason. It is a difcult condition
to be treated with limited therapeutic options.
Galcanezumab trial was negative in chronic cluster headache, the results may be explained due to
methodological limitations. It must be considered that the placebo effect may be larger during open-la-
bel treatment than in placebo-controlled studies. In this case, patients know they may receive placebo.
Another consideration are the patients in randomized controlled trial (RCT) series showing patients who
highly refractory to other preventive treatments, with a documented use of 2–11 preventive treatments
previous to the anti-CGRP agent.
Real life data published in a recent article from Cephalalgia1 may revert the idea that galcanezumab
is ineffective for CCH. A signicant reduction of attack frequency was noticed in a study, showing a
50% responder rate, moreover, 36% presented 75% reduction in headaches. Signicant reduction of
attack frequency started in one week. In the rst month, a signicant decrease during the use of acute
headache medication and pain intensity during attacks, according to the numerical rating scale (NRS),
was observed. Treatment attempts with anti-CGRP antibodies are successful in an important number of
CCH patients with insufcient response to other treatments, providing reason to make these treatments
accessible for highly disabled CCH patients on an individual basis.
The war is not over, further studies are necessary to test this hypothesis. Although evidence from RTC
is lacking, galcanezumab may be worth in CCH considering severe pain and patients extremely re-
fractory to previous treatments. Other MAbs should also be analyzed in CCH treatment, until patients
responded to anti-CGRP treatment, experiencing a rapid and signicant reduction of attack frequency
and pain intensity.
Aline Turbino Neves Martins da Costa
https://orcid.org/0000-0002-7947-8490
Reference
Ruscheweyh R, et al. Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache:
Results from a retrospective case series support individual treatment attempts.
Cephalalgia
. 2020;40(14):1574-84
alineturbino@gmail.com
Received: September 15, 2020
Accepted: September 19, 2020
Edited by
Marcelo Moraes Valença
