Vollesen ALH, et al. - Researchers assessed if calcitonin gene-related peptide (CGRP) induces cluster headache attacks in episodic cluster headache in the active phase, episodic cluster headache in remission phase, and chronic cluster headache. The findings showed that calcitonin gene-related peptide provokes cluster headache attacks in active-phase episodic cluster headache and chronic cluster headache; however, not in remission-phase episodic cluster headache. Results of this study suggested that anti-CGRP drugs could be useful in cluster headache management.

Methods

• It was a randomized, double-blind, placebo-controlled, 2-way crossover study set at the Danish Headache Center, Rigshospitalet Glostrup, in Denmark.
• Analyses were intent to treat.
• From December 2015 to April 2017, inclusion took place.
• Diagnosis of episodic/chronic cluster headache, patients aged 18 to 65 years, and safe contraception in women were the inclusion criteria.
• A history of other primary headache (except episodic tension-type headache < 5 days/month), individuals who were pregnant or nursing; cardiovascular, cerebrovascular, or psychiatric disease; and drug misuse were the exclusion criteria.
• For this analysis, 37 subjects with cluster headaches received intravenous infusion of 1.5 μg/minute of CGRP or placebo over 20 minutes on 2 study days.
• Difference in incidence of cluster headache-like attacks, difference in area under the curve (AUC) for headache intensity scores (0 to 90 minutes), and difference in time to peak headache between CGRP and placebo in the three groups were the main outcomes and measures.

Results

• Out 91 patients evaluated for eligibility, 32 patients (35.2%) were involved in the study.
• The study results showed that the mean (SD) age was 36 (10.7) years (range, 19-60 years), and the mean weight was 78 kg (range, 53-100 kg).
• It was observed that 27 men (84.4%) finished the examination.
• Compared with 1 of 9 in the placebo group (mean, 11%; 95% CI, 0-37) (P=.05), calcitonin gene-related peptide induced cluster headache attacks in 8 of 9 subjects in the active phase (mean, 89%; 95% CI, 63-100).
• No patients with episodic cluster headaches reported attacks after CGRP or placebo in the remission phase.
• Compared with none after placebo (P=.02), calcitonin gene-related peptide-induced attacks occurred in 7 of 14 patients with chronic cluster headaches (mean, 50%; 95% CI, 20-80).
• It was observed that the mean AUC from 0 to 90 minutes for CGRP was 1.903 (95% CI, 0.842-2.965), and the mean AUC from 0 to 90 minutes for the placebo group was 0.343 (95% CI, 0-0.867) (P=.04) in patients with episodic active phase.
• It was noted that the mean AUC from 0 to 90 minutes for CGRP was 1.214 (95% CI, 0.395-2.033), and the mean AUC from 0 to 90 minutes for the placebo group was 0.036 (95% CI, 0-0.114) (P=.01) in patients with chronic cluster headache.
• Findings revealed that the mean AUC from 0 to 90 minutes for CGRP was 0.187 (95% CI, 0-0.571), and the mean AUC from 0 to 90 minutes for placebo was 0.019 (95% CI, 0-0.062) (P > .99) in the remission phase.