Measures of Functioning in Patients With Episodic Migraine: Findings From a Double‐Blind,Randomized, Placebo‐Controlled Phase 2b Trial With Galcanezumab

Objective – To evaluate 12‐week changes from baseline of 2 disease‐specific patient‐reported outcome (PRO) measures in adults with migraine treated with galcanezumab, an investigational humanized antibody binding calcitonin gene‐related peptide (CGRP), or placebo. Background – Preventing headache‐related functional impairment is an important goal of migraine preventive treatment and a measurement target for PROs. Understanding which drugs have the potential to improve patient functioning in addition to preventing migraine headaches is vital to lessening patient burden. Design/Methods – This Phase 2b double‐blind, randomized, placebo‐controlled study enrolled adults with episodic migraine. Galcanezumab (120 mg subcutaneous injection; n = 60) or placebo (n = 127) was administered every 28 days for 12 weeks. Post hoc secondary analyses were conducted for those who completed 12 weeks of treatment on 2 PROs: The Migraine‐Specific Quality of Life Questionnaire (MSQ) v2.1 and the Headache Impact Test? (HIT‐6). Results – Analysis of covariance revealed significant differences in least square mean changes from baseline between galcanezumab and placebo for all MSQ domains including total mean change placebo of 18.63, galcanezumab of 27.36 (95% CI 2.449, 15.008; P‐value of .0067); Role Function‐Restrictive mean change placebo of 22.40, galcanezumab of 31.92 (95% CI 2.636, 16.518; P‐value of .0071); Role Function‐Preventive mean change placebo of 13.43, galcanezumab of 19.76 (95% CI 0.476, 12.185; P‐value of .0342); and Emotional Function mean change placebo of 16.88, galcanezumab of 26.61 (95% CI 2.789, 16.674; P‐value of .0063). At baseline, mean number of migraine headache days (MHDs) did not correlate with MSQ total scores or HIT‐6. At 12 weeks post‐treatment, MHD correlated with MSQ and HIT‐6 scores (all P < .0001). Change in MHD was associated with change in MSQ domains and change in HIT‐6 scores (all P < .0001). Conclusions – In comparison with placebo, treatment with galcanezumab was associated with significant functional improvements as reflected by changes in MSQ scores. Change in MHD was associated with improvements in MSQ and reductions in HIT‐6 scores, indicating the clinical importance of these changes in relation to PROs that measure function.     

Central effects of galcanezumab in migraine: a pilot study on Steady State Visual Evoked Potentials and occipital hemodynamic response in migraine patients

BackgroundThe discovery of the prominent action of Calcitonin Gene Related Peptide –CGRP- on trigeminal afferents and meningeal vessels, opened a new era in migraine treatment. However, how the block of nociceptive afferents could act on central mechanisms of migraine is still not clear. In this pilot study we aimed to test the effect of 3 months Galcanezumab (CGA) therapy on occipital visual reactivity in migraine patients, using the Steady State Visual Evoked Potentials-SSVEPs and Functional Near Infrared Spectroscopy –fNIRS.MethodThirteen migraine patients underwent clinical and neurophysiological examination in basal condition (T0), 1 h after GCA injection (T1) and after 3 months of GCA treatment (T2). Ten healthy volunteers were also evaluated.ResultsAt T2, there was a reduction of headache frequency and disability. At T2, the EEG power significantly diminished as compared to T0 and T1 at occipital sites, and the topographical analysis confirmed a restoration of SSVEPs within normal values. The Oxyhemoglobin levels in occipital cortex, which were basically increased during visual stimulation in migraine patients, reverted to normal values at T2.ConclusionsThe present pilot study indicates that Galcanezumab could act on cortical targets located beyond the pain network, restoring the abnormal occipital reactivity. This effect could indicate the possible disease modifying properties of CGRP related monoclonal antibodies.     

Safety and efficacy of galcanezumab in Taiwanese patients: a post-hoc analysis of phase 3 studies in episodic and chronic migraine

Abstract

Objective

Migraine is a chronic, disabling neurological disease affecting >1 billion people worldwide. Migraine remains undertreated in Asia, including Taiwan. Galcanezumab is a humanized monoclonal antibody that selectively binds calcitonin gene-related peptide, a peptide firmly established in the pathophysiology of migraine, with demonstrated efficacy and safety in patients with episodic or chronic migraine. Our objective was to evaluate the efficacy and safety of galcanezumab in Taiwanese patients with episodic or chronic migraine.     

Raynaud's Phenomenon Associated With Calcitonin Gene-Related Peptide Monoclonal Antibody Antagonists

Two cases are reported of migraineurs who reported Raynaud's phenomenon (RP) exacerbated while taking monoclonal antibodies to the calcitonin gene-related peptide (CGRP) ligand (fremanezumab and galcanezumab) and 1 case of new onset RP while taking the CGRP receptor antagonist (erenumab). The prevalence of primary and secondary RP, causes of secondary RP, co-morbidity with migraine, and medications which might induce or exacerbate RP are reviewed. The pathophysiology of how CGRP monoclonal antagonists might exacerbate or induce RP is discussed. The cases suggest but do not prove causation.     

Galcanezumab for the prevention of cluster headache

ABSTRACT

Introduction

Cluster headache (CH) is among the worst painful conditions. The available therapies are scarce and not specific, leaving many patients unsatisfied because of poor efficacy and/or tolerability. Patients not responding to common treatments are offered semi-invasive and invasive procedures with uncertain results. Based on the current understanding of CH pathophysiology, new possible therapeutic approaches come from drugs interfering with Calcitonin Gene Related Peptide (CGRP).