The effect of erenumab on brain network function in episodic migraine patients: a randomized, placebo-controlled clinical trial (RESET BRAIN).
Headache
Neuroimaging
Prevention
Therapy
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
08
06
2023
accepted:
12
07
2023
revised:
12
07
2023
medline:
23
10
2023
pubmed:
8
8
2023
entrez:
7
8
2023
Statut:
ppublish
Résumé
We aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide receptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect following treatment discontinuation. This was a randomized, double-blind, placebo-controlled, multicenter trial with a crossover design performed in adult episodic migraine patients with previous treatment failure. Patients were randomized (1:1) to 12 weeks of erenumab 140 mg or placebo, followed by a 12-week crossover. Resting state (RS) functional connectivity (FC) changes of brain networks involved in migraine were investigated using a seed-based correlation approach. Sixty-one patients were randomized to treatment. In each treatment sequence, 27 patients completed the visit at week 12. Forty-four enrolled patients, 22 in each treatment sequence, completed the study procedures with no major protocol violations. We observed a carry-over effect of erenumab during the placebo treatment and therefore data analysis was performed as a parallel comparison of erenumab vs placebo of the first 12 weeks of treatment. From baseline to week 12, compared to placebo, patients receiving erenumab showed RS FC changes within the cerebellar, thalamic and periaqueductal gray matter networks, significantly associated with clinical improvement. Compared to non-responders, patients achieving a 50% reduction in migraine days had distinct patterns of thalamic and visual network RS FC. Brain RS FC changes reversed when erenumab was stopped. A lower baseline RS FC of the pontine network identified patients responding to erenumab. Erenumab modulates RS FC of networks involved in migraine pathophysiology. In line with clinical response, erenumab-induced brain RS FC changes tend to reverse when treatment is stopped.
Sections du résumé
BACKGROUND
BACKGROUND
We aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide receptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect following treatment discontinuation.
METHODS
METHODS
This was a randomized, double-blind, placebo-controlled, multicenter trial with a crossover design performed in adult episodic migraine patients with previous treatment failure. Patients were randomized (1:1) to 12 weeks of erenumab 140 mg or placebo, followed by a 12-week crossover. Resting state (RS) functional connectivity (FC) changes of brain networks involved in migraine were investigated using a seed-based correlation approach.
RESULTS
RESULTS
Sixty-one patients were randomized to treatment. In each treatment sequence, 27 patients completed the visit at week 12. Forty-four enrolled patients, 22 in each treatment sequence, completed the study procedures with no major protocol violations. We observed a carry-over effect of erenumab during the placebo treatment and therefore data analysis was performed as a parallel comparison of erenumab vs placebo of the first 12 weeks of treatment. From baseline to week 12, compared to placebo, patients receiving erenumab showed RS FC changes within the cerebellar, thalamic and periaqueductal gray matter networks, significantly associated with clinical improvement. Compared to non-responders, patients achieving a 50% reduction in migraine days had distinct patterns of thalamic and visual network RS FC. Brain RS FC changes reversed when erenumab was stopped. A lower baseline RS FC of the pontine network identified patients responding to erenumab.
CONCLUSION
CONCLUSIONS
Erenumab modulates RS FC of networks involved in migraine pathophysiology. In line with clinical response, erenumab-induced brain RS FC changes tend to reverse when treatment is stopped.
Identifiants
pubmed: 37550498
doi: 10.1007/s00415-023-11879-9
pii: 10.1007/s00415-023-11879-9
pmc: PMC10576673
doi:
Substances chimiques
erenumab
I5I8VB78VT
Calcitonin Gene-Related Peptide Receptor Antagonists
0
Antibodies, Monoclonal, Humanized
0
Antibodies, Monoclonal
0
Types de publication
Randomized Controlled Trial
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5600-5612Investigateurs
Federico Bruno
(F)
Angela Campanella
(A)
Valeria Caponnetto
(V)
Luca Dall'Occhio
(L)
Marcello Silvestro
(M)
Roberto Vuotto
(R)
Informations de copyright
© 2023. The Author(s).
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