PMID- 33423151
OWN - NLM
STAT- MEDLINE
DCOM- 20211101
LR  - 20211101
IS  - 1573-7373 (Electronic)
IS  - 0167-594X (Linking)
VI  - 152
IP  - 1
DP  - 2021 Mar
TI  - Neuroimmunological adverse events associated with immune checkpoint inhibitor: a 
      retrospective, pharmacovigilance study using FAERS database.
PG  - 135-144
LID - 10.1007/s11060-020-03687-2 [doi]
AB  - PURPOSE: To investigate the characteristics and risk factors for neurologic 
      adverse events (AEs) induced by immune checkpoint inhibitors (ICIs). METHODS: An 
      observational, retrospective, and pharmacovigilance study based on the FAERS 
      database collected between January 2014 and December 2019 was conducted. 
      ICI-related AEs were defined as adverse reactions in patients using anti-PD-1 
      (nivolumab and pembrolizumab), anti-PD-L1 (atezolizumab, avelumab, and 
      durvalumab), and anti-CTLA-4 (ipilimumab and tremelimumab). Neurologic AEs 
      previously reported to be associated with ICI were evaluated in the 
      disproportionality analysis using the reporting odds ratio (ROR). RESULTS: Among 
      50,406 ICI-related reports, 3619 (7.2%) neurological case was found: 1985 with 
      anti-PD-1, 372 with anti-PD-L1, 366 with anti-CTLA-4, and 896 with the 
      combination of ICIs. In comparison to non-ICI drug use, ICI use demonstrated 
      higher risk for neurologic complication, including hypophysitis/hypopituitarism, 
      myasthenia gravis, encephalitis/myelitis, meningitis, Guillain-Barre syndrome, 
      vasculitis, and neuropathy. The risk of neurologic AEs associated with ICI 
      combination therapy was as high as or even higher than ICI monotherapy, most 
      significantly in hypophysitis/hypopituitarism. The proportion of serious 
      neurological events and death related to combination therapy has been decreasing 
      in recent years. Older age, male and female sex, and metastasis were not 
      significant risk factors for the incidence of neurologic ICI-related AEs. 
      Patients at older age, with melanoma or non-small cell lung cancer, or on dual 
      ICI therapy may be at higher risk of fatal neurologic AEs. CONCLUSION: ICI use is 
      associated with a higher risk of neurological complications, with dual ICI 
      therapy posing a higher risk, while older age, sex, or metastasis were not. 
      Patients at older age, with certain cancer types, or on dual ICI therapy may be 
      at higher risk of fatal neurologic AEs.
FAU - Mikami, Takahisa
AU  - Mikami T
AUID- ORCID: 0000-0003-1851-5259
AD  - Department of Neurology, Tufts Medical Center, Boston, MA, USA. 
      taka.mikami.tmd@gmail.com.
AD  - Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount 
      Sinai, Mount Sinai Beth Israel, New York, NY, USA. taka.mikami.tmd@gmail.com.
FAU - Liaw, Bobby
AU  - Liaw B
AD  - Department of Hematology and Medical Oncology, Icahn School of Medicine at Mount 
      Sinai, Mount Sinai Beth Israel, New York, NY, USA.
FAU - Asada, Mizuho
AU  - Asada M
AD  - Department of Pharmacy, Medical Hospital, Tokyo Medical and Dental University, 
      Tokyo, Japan.
FAU - Niimura, Takahiro
AU  - Niimura T
AD  - Department of Clinical Pharmacology and Therapeutics, Tokushima University 
      Graduate School of Biomedical Sciences, Tokushima, Japan.
FAU - Zamami, Yoshito
AU  - Zamami Y
AD  - Department of Clinical Pharmacology and Therapeutics, Tokushima University 
      Graduate School of Biomedical Sciences, Tokushima, Japan.
AD  - Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan.
FAU - Green-LaRoche, Deborah
AU  - Green-LaRoche D
AD  - Department of Neurology, Tufts Medical Center, Boston, MA, USA.
FAU - Pai, Lori
AU  - Pai L
AD  - Department of Hematology and Oncology, Tufts Medical Center, Boston, MA, USA.
FAU - Levy, Michael
AU  - Levy M
AD  - Department of Neurology, Massachusetts General Hospital and Harvard Medical 
      School, Boston, MA, USA.
FAU - Jeyapalan, Suriya
AU  - Jeyapalan S
AD  - Department of Neurology, Tufts Medical Center, Boston, MA, USA.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20210109
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents, Immunological/*adverse effects
MH  - Databases, Factual
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology
MH  - Female
MH  - Humans
MH  - Immune Checkpoint Inhibitors/*adverse effects
MH  - Immune System Diseases/chemically induced/epidemiology
MH  - Immunotherapy/adverse effects
MH  - Incidence
MH  - Male
MH  - Middle Aged
MH  - Nervous System Diseases/*chemically induced/epidemiology
MH  - Pharmacovigilance
MH  - Retrospective Studies
OTO - NOTNLM
OT  - FAERS database
OT  - Immune checkpoint inhibitors
OT  - Neurologic adverse events
EDAT- 2021/01/11 06:00
MHDA- 2021/11/03 06:00
CRDT- 2021/01/10 20:50
PHST- 2020/10/25 00:00 [received]
PHST- 2020/12/23 00:00 [accepted]
PHST- 2021/01/11 06:00 [pubmed]
PHST- 2021/11/03 06:00 [medline]
PHST- 2021/01/10 20:50 [entrez]
AID - 10.1007/s11060-020-03687-2 [pii]
AID - 10.1007/s11060-020-03687-2 [doi]
PST - ppublish
SO  - J Neurooncol. 2021 Mar;152(1):135-144. doi: 10.1007/s11060-020-03687-2. Epub 2021 
      Jan 9.