Reducing Episodic Cluster Headaches: Focus on Galcanezumab

Figures & data

Table 1 Diagnostic Criteria and Current Pharmacological Treatments for Cluster Headache

Panel A Diagnostic Criteria^a	Panel B Pharmacological Treatments Used for Cluster Headache^b
Cluster Headache (A) At least five attacks fulfilling criteria B-D (B) Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15–180 minutes (when untreated) (C) Either or both of the following: 1. At least one of the following symptoms or signs, ipsilateral to the headache: conjunctival injection and/or lacrimation; nasal congestion and/or rhinorrhoea; eyelid oedema; forehead and facial sweating; miosis and/or ptosis 1. A sense of restlessness or agitation (C) Occurring with a frequency between one every other day and 8 per day (D) Not better accounted for by another ICHD-III diagnosis	Acute Treatment Sumatriptan 6 mg (subcutaneous) Oxygen 100% at ≥6–12 L/min (until response, or for ≥15 min) Zolmitriptan 5 mg (nasal spray)
Episodic Cluster Headache (A) Attacks fulfilling criteria for “3.1 Cluster headache” and occurring in bouts (cluster periods) (B) At least two cluster periods lasting from 7 days to 1 year (when untreated) and separated by pain-free remission periods of ≥3 months.	Preventive Treatment Single injection or injection series with corticosteroids (suboccipital administration in the area of the greater occipital nerve) – Level A Lithium carbonate (900 mg per day) – Level C Verapamil (360 mg per day) – Level C Melatonin (10 mg per day) – Level C
Chronic Cluster Headache (A) Attacks fulfilling criteria for “3.1 Cluster headache”, and criterion B below. (B) Occurring without a remission period, or with remissions lasting <3 months, for at least 1 year.

Notes: ^aPanel A is data from Headache Classification Committee of the International Headache Society (IHS).¹ bPanel B is data from Robbins et al.¹⁶ We reported treatments with evidence of efficacy (Level A, B and C) in both episodic and chronic cluster headache.

Figure 1 Main sites of action for CGRP in cluster headache. Reproduced from Belin AC, Ran C, Edvinsson L. Calcitonin Gene-Related Peptide (CGRP) and cluster headache. Brain Sci. 2020;10(1):30. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.³⁶

Table 2 Galcanezumab Trials for eCH and cCH Prevention

	Study Population	Dose and Frequency	Main Endpoints	Primary Results	Key Secondary Results
Episodic cluster headache^Citation65	Galcanezumab: 49 Placebo: 57	Two administrations (baseline and month 1) of galcanezumab 300 mg s.c. or placebo s.c.	Primary Mean change from baseline in the weekly frequency of CH across week 1 through 3 Key secondary Percentage of patients with a reduction of at least 50% in the weekly frequency of CH at week 3	Galcanezumab: −8.7 ± 1.4 Placebo: −5.2 ± 1.3 (p = 0.040)	Galcanezumab: 71% Placebo: 53% (p = 0.046)
Chronic cluster headache^Citation66	Galcanezumab: 117 Placebo: 120	Three administrations (baseline, month 1 and month 2) of galcanezumab 300 mg s.c. or placebo s.c.	Primary Mean change from baseline in weekly frequency of CH across weeks 1–12 Key secondary Mean percentage of patients with at least 50% reduction from baseline in the weekly attack frequency across weeks 1–12	Galcanezumab: −5.4 Placebo: −4.6 (p = 0.334)	Galcanezumab: 32.6% Placebo: 27.1% (p = 0.170)

Note: Primary endpoints were reported as mean ± standard deviation, except for chronic cluster headache.⁶⁶

Abbreviations: eCH, episodic cluster headache; cCH, chronic cluster headache; s.c., subcutaneous; AEs, adverse events.

Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd Edition. Cephalalgia. 2018;38(1):1–211. doi:10.1177/0333102417738202

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