Dysautonomia associated with immune checkpoint inhibitors.
Autoimmune autonomic ganglionopathy
Dysautonomia
Immune-related adverse events
Pharmacovigilance
Review of literature
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
25
01
2023
accepted:
14
03
2023
revised:
15
02
2023
medline:
16
6
2023
pubmed:
21
3
2023
entrez:
20
3
2023
Statut:
ppublish
Résumé
The purpose of this study is to report the clinical characteristics of dysautonomia associated with immune checkpoint inhibitors (ICIs). We reported two patients with autoimmune autonomic ganglionopathy (AAG) occurring as immune-related adverse events (irAEs). We also performed a review of previous case reports presenting dysautonomia during ICI therapy. Moreover, we conducted pharmacovigilance analyses using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to investigate dysautonomia associated with ICI. Two patients in our care developed both AAG and autoimmune encephalitis following ICI therapy for lung cancers. We comprehensively reviewed 13 published cases (M:F = 11:2, mean onset age of 53 years) with ICI-associated dysautonomia including AAG (n = 3) and autonomic neuropathy (n = 10). Of these, ICI monotherapy was performed in seven and combination ICI use in six. In 6 of 13 patients, dysautonomia appeared within one month after the start of ICIs. Orthostatic hypotension was observed in 7 and urinary incontinence or retention in five. All patients except three showed gastrointestinal symptoms. Anti-ganglionic acetylcholine receptor antibodies were undetectable. All but two patients received immune-modulating therapy. Immuno-modulating therapy was effective in three patients with AAG and two patients with autonomic neuropathy, but ineffective in the others. Five patients died, of either the neurological irAE (n = 3) or cancer (n = 2). The pharmacovigilance analyses using FAERS showed that ipilimumab monotherapy and the combination of nivolumab and ipilimumab constituted significant risks for developing dysautonomia, consistent with the review of literature. ICIs can cause dysautonomia including AAG, and autonomic neuropathy is a neurological irAE.
Identifiants
pubmed: 36939931
doi: 10.1007/s00415-023-11667-5
pii: 10.1007/s00415-023-11667-5
doi:
Substances chimiques
Ipilimumab
0
Immune Checkpoint Inhibitors
0
Nivolumab
31YO63LBSN
Autoantibodies
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3413-3423Subventions
Organisme : Japan Society for the Promotion of Science
ID : JP20H03592
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
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