Efficacy and Safety of Galcanezumab as a Treatment of Refractory Episodic and Chronic Cluster Headache

Case Series and Narrative Review

Javier A. Membrilla MD; Marta Torres-Ferrus PhD, MD; Alicia Alpuente MD; Edoardo Caronna PhD, MD; Patricia Pozo-Rosich PhD, MD

Disclosures

Headache. 2022;62(10):1395-1405. 

In This Article

Abstract and Introduction

Abstract

Background: Galcanezumab, a monoclonal antibody targeting calcitonin gene–related peptide (CGRP), has demonstrated clinical benefit as a preventive treatment of episodic cluster headache (ECH) but not in chronic cluster headache (CCH) to this date. Our objective was to analyze our clinical experience of the compassionate use of galcanezumab in cluster headache and to conduct a narrative review of the published literature.

Methods: We present a case series of patients with refractory ECH and CCH treated with 240 mg galcanezumab monthly in an outpatient headache clinic. We recorded epidemiologic and clinical data and analyzed the disease evolution after 3 and 6 months. The review was performed following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results: We included three patients with ECH who were treated during a refractory cluster bout (mean duration of 83.7 days since the first attack, range 46.0–105.0 days) and six patients with CCH who had a high frequency of attacks (mean 35.8 attacks/week, range 7–56) and refractory to a mean of 5.2 preventive treatments (range, 3–9). In the CCH group, >50% frequency reduction was seen in 83% (5/6 patients) and the number of attacks per week showed a mean reduction of −24.2 at month 3 (range, −6 to −49) and −27.6 at month 6 (range, −7 to −49). In the ECH group, the bout ended a mean 17.3 days (range, 10–28) after galcanezumab administration. One third of patients reported mild adverse events, none of them leading to discontinuation.

Conclusion: In conclusion, our clinical experience supports the use of galcanezumab in patients with refractory cluster headache. These results might encourage the possibility of continuing clinical development with randomized controlled trials of anti-CGRP treatments in patients with cluster headache.

Introduction

Cluster headache (CH) is a primary headache disorder characterized by severe unilateral headache attacks that are localized in the orbital, supraorbital, or temporal regions; last from 15 to 180 min; are accompanied by at least one trigeminal-autonomic symptom ipsilateral to pain (e.g., conjunctival injection, lacrimation, nasal congestion and/or rhinorrhea, eyelid edema, forehead and facial sweating, and miosis and/or ptosis) or agitation; and occur between one attack every other day to eight attacks per day.[1] It affects 1 out of every 1000 people.[2] Headache aggregates in clusters or bouts (periods in which patients can have up to eight attacks in a day). Approximately 80% of patients with CH present at least 3-month headache-free periods between bouts (i.e., episodic CH [ECH]), and in the remaining 20%, the disorder is classified as chronic CH (CCH) because of the absence of the headache-free periods.[3] In ECH, preventive therapies are usually started during the bout and have the goal of shortening its duration and decreasing the number of attacks and intensity of pain, while in CCH the objective of preventive medication is to decrease attack frequency and to transition into an episodic phenotype. Current preventive therapies are nonspecific, have a low level of evidence, and can cause a high rate of adverse effects; so new, specific, and more effective strategies are needed in CH to reduce attack frequency and headache-related impact in this highly disabling disorder.

Calcitonin gene–related peptide (CGRP) is a neuropeptide that has been localized in both central and peripheral neurons, including sensory C and Aδ fibers arising from the trigeminal ganglion.[4] This neuropeptide has implications in CH pathophysiology, as it can promote activation of the trigeminal-autonomic reflex during a CH attack.[5] It is known that CGRP levels increase during CH attacks[6] and that exogenous CGRP infused to patients while in a bout can trigger CH-like attacks.[7] Therefore, monoclonal antibodies targeting CGRP and its receptor approved for migraine prevention could be a valid therapeutic strategy in patients with CH. A randomized placebo-controlled trial of galcanezumab in ECH[8] showed a statistically significant greater decrease in weekly frequency of CH attacks compared to placebo and led to the approval by the Food and Drug Administration for its use in ECH in the United States, using 300 mg at the onset of the cluster period and then monthly until the end of the bout.[9] In Europe, galcanezumab has not been approved by regulatory authorities owing to the absence of two trials in this disease, which are needed for approval.[10] However, as there is a lack of effective preventive treatments for a high proportion of patients with CH, the compassionate use of galcanezumab is an option to be considered for patients with refractory CH.

Our objective was to analyze our clinical experience of the compassionate use of galcanezumab in a cohort of patients with CH and to conduct a narrative review of the published literature.

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