CGRP infusion has been shown to provoke cluster headache attacks in active-phase episodic cluster headache and in chronic cluster headache, but not in remission-phase episodic headache.
Results of a double-blind, placebo-controlled, 2-way crossover study published online in JAMA Neurology showed that, in the active phase, CGRP induced cluster headache attacks in 8/9 patients (mean, 89%; 95% CI, 63-100). This compared to 1/9 following a placebo infusion (mean, 11%; 95% CI, 0-37) (p=0.05). In the remission phase, no patients with episodic cluster headaches reported attacks after CGRP or placebo. However, in chronic cluster headache, CGRP induced attacks in 7/14 patients (mean, 50%; 95% CI, 20-80) compared with none after placebo (p=0.02).
Area under the curve (AUC) data for headache intensity are summarised in Table 1.
Recently reported Phase 3 data have questioned the potential of CGRP inhibition in chronic cluster headache, though there is continued support for their potential in the treatment of episodic cluster headache.
Table 1. AUC for headache intensity scores (0 to 90 minutes)
|CGRP infusion||Placebo||p value|
|Episodic active phase||1.903 (95% CI 0.842-2.965)||0.343 (95% CI 0-0.867)||p=0.04|
|Chronic cluster headache||1.214 (95% CI 0.395-2.033)||0.036 (95% CI 0-0.114)||P=0.01|
|Remission phase||0.187 (95% CI 0-0.571)||0.019 (95% CI 0-0.062)||p>0.99|
Vollesen ALH, Snoer A, Beske RP et al. Effect of infusion of calcitonin gene-related peptide on cluster headache attacks: A randomized clinical trial. JAMA Neurol. 2018 Jul 9. doi: 10.1001/jamaneurol.2018.1675. [Epub ahead of print]