Heiko Pohl1, Dagny Holle-Lee2, Sarah D Broicher3, Inka Schwerdtner3, Andreas R Gantenbein4, Charly Gaul5. 1. Klinik für Neurologie, Universitätsspital Zürich, Zürich, Schweiz. 2. Klinik für Neurologie, Universitätsklinikum Essen, Essen, Deutschland. 3. Lilly Deutschland GmbH, Bad Homburg, Deutschland. 4. RehaClinic Bad Zurzach, Bad Zurzach, Schweiz. 5. Kopfschmerzzentrum Frankfurt, Dalbergstraße 2a, 65929, Frankfurt am Main, Deutschland. c.gaul@kopfschmerz-frankfurt.de.
Abstract
BACKGROUND: Cluster headache (CH) is a highly debilitating headache disorder characterized by frequent attacks of excruciating unilateral pain accompanied by cranial autonomic symptoms. Calcitonin gene-related peptide (CGRP) is implicated in the pathophysiology of CH. OBJECTIVES: Preventive efficacy and tolerability of the anti-CGRP antibody galcanezumab in patients with episodic (eCH) and chronic CH (cCH). Review of the study results and the challenges in developing drugs for the preventive treatment of CH. MATERIALS AND METHODS: In two international multicenter phase III trials galcanezumab 300 mg given subcutaneously every 4 weeks was compared with placebo. The double-blind study period (8 weeks in eCH, 12 weeks in cCK) was preceded by a baseline period in both trials. The primary endpoint was the reduction in weekly attack frequency. RESULTS: In the eCH trial, 106 patients were randomized to either galcanezumab (n = 49) or placebo (n = 57). The mean weekly attack frequency during the first 3 weeks decreased by 52% in the galcanezumab group compared with 27% in the placebo group (p = 0.036). In the cCH trial, 237 patients were randomized to galcanezumab (n = 117) or placebo (n = 120). The primary endpoint was not met in this study. The reduction in mean weekly attack rate was 5.4 with galcanezumab versus 4.6 with placebo (p = 0.334). Galcanezumab was well tolerated in both studies. CONCLUSIONS: Galcanezumab had a significant effect in the prevention of eCH attacks but not in cCH. Possible reasons for this discrepancy are discussed.
BACKGROUND: Cluster headache (CH) is a highly debilitating headache disorder characterized by frequent attacks of excruciating unilateral pain accompanied by cranial autonomic symptoms. Calcitonin gene-related peptide (CGRP) is implicated in the pathophysiology of CH. OBJECTIVES: Preventive efficacy and tolerability of the anti-CGRP antibody galcanezumab in patients with episodic (eCH) and chronic CH (cCH). Review of the study results and the challenges in developing drugs for the preventive treatment of CH. MATERIALS AND METHODS: In two international multicenter phase III trials galcanezumab 300 mg given subcutaneously every 4 weeks was compared with placebo. The double-blind study period (8 weeks in eCH, 12 weeks in cCK) was preceded by a baseline period in both trials. The primary endpoint was the reduction in weekly attack frequency. RESULTS: In the eCH trial, 106 patients were randomized to either galcanezumab (n = 49) or placebo (n = 57). The mean weekly attack frequency during the first 3 weeks decreased by 52% in the galcanezumab group compared with 27% in the placebo group (p = 0.036). In the cCH trial, 237 patients were randomized to galcanezumab (n = 117) or placebo (n = 120). The primary endpoint was not met in this study. The reduction in mean weekly attack rate was 5.4 with galcanezumab versus 4.6 with placebo (p = 0.334). Galcanezumab was well tolerated in both studies. CONCLUSIONS: Galcanezumab had a significant effect in the prevention of eCH attacks but not in cCH. Possible reasons for this discrepancy are discussed.
Authors: Miguel J A Láinez; Jean Schoenen; Chad Stroud; Jennifer Bardos; Mark Bangs; Phebe Kemmer; Richard Wenzel; Dulanji K Kuruppu; James Michael Martinez; Tina M Oakes Journal: Headache Date: 2021-11-22 Impact factor: 5.311