Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2023 Mar 16;24(1):26.
doi: 10.1186/s10194-023-01560-x.

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

Sait Ashina  1   2   3   4 , Agustin Melo-Carrillo  1   2 , Ajayi Toluwanimi  5 , Nicolas Bolo  6 , Edina Szabo  1   2 , David Borsook #  7   8 , Rami Burstein #  9   10   11
Affiliations
Observational Study

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

Sait Ashina et al. J Headache Pain. .

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.

Keywords: CGRP monoclonal antibodies; Central sensitization; Hypothalamus; Migraine; Trigeminal.

PubMed Disclaimer

Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author).

S.A. received honoraria for consulting from Allergan/AbbVie, Amgen, Biohaven, Eli Lilly, Impel NeuroPharma, Novartis, Satsuma, Supernus, Theranica, Percept.

R.B. is the John Hedley-Whyte Professor of Anesthesia and Neuroscience at the Beth Israel Deaconess Medical Center and Harvard Medical School. He has received research support from the NIH: R01 NS094198-01A1, R37 NS079678, R01NS095655, R01 NS104296, R21 NS106345, Allergan, Teva, Dr. Reddy, Eli Lilly, Trigemina and the Migraine Research Foundation. He is a reviewer for NINDS, holds stock options in AllayLampand Percept; serves as consultant, advisory board member, or has received honoraria from: Alder, Allergan, Amgen, Autonomic Technologies, Avanir, Biohaven, CGRP Diagnostic, Dr. Reddy’s Laboratory, ElectroCore, Eli Lilly, GlaxoSmithKline, Merck, Pernix, Theranica, Teva, and Trigemina. CME fees from Healthlogix, Medlogix, WebMD/Medscape, and Patents 9061025, 11732265.1, 10806890, US2021-0015908, WO21007165, US2021-0128724, WO21005497.

DB has served as a consultant for Eli Lilly, Redpin Rx, and Luminous Mind.

Other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study flowchart
Fig. 2
Fig. 2
Identification of a galcanezumab responder. Patient’s e-diary entry data were used to compute percentage of monthly migraine and headache days during the 1-month pre-treatment period and the 3-month treatment period. Daily documentation of headache intensity, laterality, throbbing, photophobia, phonophobia, and nausea were used to distinguish between headache and migraine days. Note that the percentage of monthly migraine days (MMD) decreased by > 50% during the treatment period (from 47% before treatment to 18.6% during the 3 months of treatment)
Fig. 3
Fig. 3
Identification of galcanezumab non-responder. Note that the percentage of monthly migraine days (MMD) decreased by < 50% during the treatment period (from 80% before treatment to 54.6% during the 3 months of treatment)
Fig. 4
Fig. 4
Galcanezumab effects on migraine days per month in (A) all 46 patients, (B) 24 responders only, and (C) 19 non-responders. Differences in percentages of migraine days per month at baseline (before treatment) and in each of the 3 treatment months are shown in box-and-whisker plots (median [IQR]) combined with scatterplots of individual values. Note that the percentage of migraine days per month decreased significantly, although to a different extent, in all 3 groups
Fig. 5
Fig. 5
Headache intensity (A) and incidences of photophobia (B), phonophobia (C), and nausea (D) during migraine attacks. Box-and-whisker plots (median [IQR]) combined with scatterplots of individual values are illustrated for each of the 4 periods (baseline and during the 3 months treatment). Note that in spite of the decrease in migraine days per month (Fig. 4), the remaining post-treatment attacks were mostly migraineous as indicated by the headache intensity and continuous presence of photophobia, phonophobia and nausea. Abbreviations: Bl - baseline, 1M - 1 month, 2M - 2 month, 3M - 3 month
Fig. 6
Fig. 6
Galcanezumab effects on incidence of headache after occurrence of premonitory symptoms in responders and non-responders. A Incidence of all premonitory symptoms that were followed by headache decrease by the galcanezumab treatment in both, responders and non-responders. Note that after occurrence of premonitory symptoms, responders experienced significantly less headaches than non-responders (p = 0.004, DF = 1, Fisher exact). B Incidences of headache following occurrence of each of the 9 most common premonitory symptoms (i.e., premonitory symptoms that prior to treatment were followed by headache in > 20% of all patients) during the 3-month treatment period. The 100% (in A and B) represents incidences of all (A) and individual (B) premonitory symptoms that were followed by headache prior to treatment initiation
Fig. 7
Fig. 7
Galcanezumab effects on incidence of headache after occurrence of premonitory symptoms in super-responders and super non-responders. A Incidence of all premonitory symptoms that were followed by headache decrease nearly fourfold more in the super-responders than the super non-responders. Note that after occurrence of premonitory symptoms, super-responders experienced significantly less headaches than super non-responders (p = 0.001, DF = 1, Fisher exact). B Incidences of headache following occurrence of each of the 9 most common premonitory symptoms during the 3-month treatment period. Note that in the super non-responder group galcanezumab treatment did not reduce incidence of headache after occurrence of 7/9 premonitory symptoms
Fig. 8
Fig. 8
Galcanezumab effects on incidence of headache after occurrence of aura in responders vs. non-responders (A), and super-responders vs. super non-responders (B). Complete absence of effect in the super non-responders suggest the galcanezumab ability to reduce incidence of headache after aura is secondary to the reduction in migraine days per month
Fig. 9
Fig. 9
Galcanezumab effects on incidence of triggers that were followed by headache in responders and non-responders. A Incidence of all triggers that were followed by headache after galcanezumab treatment decreased in both, responders and non-responders. Note that after occurrence of, or exposure to triggers, responders experienced significantly less headaches than non-responders (p = 0.0001, DF = 1, Fisher exact). B Incidences of headache following occurrence of, or exposure to each trigger during the 3-month treatment period. The 100% (in A and B) represents incidences of all (A) and individual (B) premonitory symptoms that were followed by headache prior to treatment initiation
Fig. 10
Fig. 10
Galcanezumab effects on incidence of triggers that were followed by headache in super-responders and super non-responders. A Incidence of all triggers that were followed by headache after galcanezumab treatment in super-responders and super non-responders. Note that after occurrence of, or exposure to triggers, super-responders experienced significantly less headaches than super non-responders (p = 0.0001, DF = 1, Fisher exact). B Incidences of headache following occurrence of, or exposure to each trigger during the 3-month treatment period. Note that in the super non-responders, galcanezumab treatment had no effect on 9/11 triggers, and in the super-responders, it had no effect 3/11 triggers
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Blau JN. Migraine prodromes separated from the aura: complete migraine. Br Med J. 1980;281(6241):658–660. doi: 10.1136/bmj.281.6241.658. - DOI - PMC - PubMed
    1. Wober C, Brannath W, Schmidt K, Kapitan M, Rudel E, Wessely P, et al. Prospective analysis of factors related to migraine attacks: the PAMINA study. Cephalalgia. 2007;27(4):304–314. doi: 10.1111/j.1468-2982.2007.01279.x. - DOI - PubMed
    1. Giffin NJ, Ruggiero L, Lipton RB, Silberstein SD, Tvedskov JF, Olesen J, et al. Premonitory symptoms in migraine: an electronic diary study. Neurology. 2003;60(6):935–940. doi: 10.1212/01.wnl.0000052998.58526.a9. - DOI - PubMed
    1. Cuvellier JC, Mars A, Vallee L. The prevalence of premonitory symptoms in paediatric migraine: a questionnaire study in 103 children and adolescents. Cephalalgia. 2009;29(11):1197–1201. doi: 10.1111/j.1468-2982.2009.01854.x. - DOI - PubMed
    1. Pascual J, Quintela E, Cuvellier JC, Mars A, Vallee L. Premonitory symptoms in migraine patients. Cephalalgia. 2010;30(5):639. doi: 10.1177/0333102409357479. - DOI - PubMed

Publication types

Associated data