Galcanezumab effects on incidence of headache after occurrence of triggers, premonitory symptoms, and aura in responders, non-responders, super-responders, and super non-responders

Abstract

Background The goal of this observational, open-label, cohort study was to determine whether prophylactic migraine treatment with galcanezumab, a peripherally acting drug, alters the incidence of premonitory symptoms, and/or occurrence of headache after exposure to triggers or aura episodes in treatment-responders (≥ 50% reduction in monthly migraine days [MMD]), super-responders (≥ 70%), non-responders (< 50%) and super non-responders (< 30%). Methods Participants were administered electronic daily headache diaries to document migraine days and associated symptoms one month before and during the three months of treatment. Questionnaires were used to identify conscious prodromal and trigger events that were followed by headache prior to vs. after 3 months of treatment. Results After 3 months of galcanezumab treatment, (a) the incidence of premonitory symptoms that were followed by headache decreased by 48% in the 27 responders vs. 28% in the 19 non-responders, and by 50% in the 11 super-responders vs. 12% in the 8 super non-responders; (b) the incidence of visual and sensory aura that were followed by headache was reduced in responders, non-responders, and super-responders, but not in super non-responders; (c) the number of triggers followed by headache decreased by 38% in responders vs. 13% in non-responders, and by 31% in super-responders vs. 4% in super non-responders; and (d) some premonitory symptoms (e.g., cognitive impairment, irritability, fatigue) and triggers (e.g., stress, sleeping too little, bright light, aura) were followed by headache only in super non-responders. Conclusions Mechanistically, these findings suggest that even a mild decrease in migraine frequency is sufficient to partially reverse the excitability and responsivity of neurons involved in the generation of certain triggers and potentially premonitory symptoms of migraine. Trial registration ClinicalTrials.gov: NCT04271202. Registration date: February 10, 2020.

Pathophysiology of Migraine

“…Emerging results suggest the efficacy of treatment with ubrogepant when taken during the premonitory phase, 27 and a previous study suggested a positive effect of fremanezumab on nonheadache symptoms (such as cognition) and function on nonheadache days 88 . Galcanezumab has recently been shown to reduce premonitory symptom occurrence in migraine 28 …”

“…88 Galcanezumab has recently been shown to reduce premonitory symptom occurrence in migraine. 28 PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE. PACAP is another peptide found in perivascular trigeminal nerve fibers.…”

“…27 There is also emerging evidence that some of these therapies can actually reduce the occurrence of premonitory symptoms. 27,28 Historically, domperidone, 29,30 dihydroergotamine, 31,32 and naratriptan 33 had been tested in small studies during the premonitory phase, and results were encouraging but difficult to generalize to a wider population. For both patients and physicians, attack prediction with effective early treatment and pain prevention is a very attractive therapeutic strategy.…”

“…The ability to potentially treat a migraine attack before headache onset by patients reliably predicting their attacks using premonitory symptoms is a unique therapeutic option that is currently producing exciting outcomes in early studies of novel targeted migraine therapies 27 . There is also emerging evidence that some of these therapies can actually reduce the occurrence of premonitory symptoms 27,28 . Historically, domperidone, 29,30 dihydroergotamine, 31,32 and naratriptan 33 had been tested in small studies during the premonitory phase, and results were encouraging but difficult to generalize to a wider population.…”

Nine-Month Continuous Fremanezumab Prophylaxis on the Response to Triptans and Also on the Incidence of Triggers, Hypersensitivity and Prodromal Symptoms of Patients with High-Frequency Episodic Migraine

“…It has been recently demonstrated that anti-CGRP Mabs are able to evoke changes in the hyperexcited migraine brain, thoroughly offering adequate migraine prophylaxis but also improvements in the premonitory and accompanying symptoms of migraine [12,13]. We have previously demonstrated that fremanezumab was able to significantly reduce MHDs and also had other efficacies such as in disability and quality of life outcomes in HFEM patients [14], in agreement with the results of another real-life study in a large sample of patients treated with fremanezumab that likewise demonstrated an early and sustained efficacy in HFEM patients with multiple preventive treatment failures [15].…”