PMID- 35431928
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Pancreatic Adverse Events Associated With Immune Checkpoint Inhibitors: A 
      Large-Scale Pharmacovigilance Analysis.
PG  - 817662
LID - 10.3389/fphar.2022.817662 [doi]
LID - 817662
AB  - Backgrounds: Immune checkpoint inhibitors (ICIs) are considered cornerstones of 
      oncology treatment with durable anti-tumor efficacy, but the increasing use of 
      ICIs is associated with the risk of developing immune-related adverse events 
      (irAEs). Although ICI-associated pancreatic adverse events (AEs) have been 
      reported in patients treated with ICIs, the clinical features and spectrum of 
      pancreatic AEs are still not well-defined. Therefore, this study aimed to 
      identify the association between pancreatic AEs and ICIs treatments and to 
      characterize the main features of ICI-related pancreatic injury (ICIPI) based on 
      the Food and Drug Administration Adverse Event Reporting System (FAERS) database. 
      METHODS: Data from the first quarter of 2015 to the first quarter of 2021 in the 
      database were extracted to conduct a disproportionality analysis. The selection 
      of AEs related to the pancreas relied on previous studies and preferred terms 
      from the Medical Dictionary for Regulatory Activities. Two main 
      disproportionality analyses-the reporting odds ratio (ROR) and information 
      component (IC)-were used to evaluate potential associations between ICIs and 
      pancreatic AEs. RESULTS: In total, 2,364 cases of pancreatic AEs in response to 
      ICIs were extracted from the FAERS database, of which, 647 were identified as 
      ICI-associated pancreatitis and 1,293 were identified as ICI-associated diabetes 
      mellitus. Generally, significant signals can be detected between pancreatic AEs 
      and all ICIs treatments (ROR(025) = 3.30, IC(025) = 1.71). For monotherapy, the 
      strongest signal associated with pancreatitis was reported for anti-PD-L1 
      (ROR(025) = 1.75, IC(025) = 0.76), whereas that with diabetes mellitus was 
      reported for anti-PD-1 (ROR(025) = 6.39, IC(025) = 2.66). Compared with 
      monotherapy, combination therapy showed stronger associations with both 
      ICI-associated pancreatitis (ROR(025) = 2.35, IC(025) = 1.20 vs. ROR(025) = 1.52, 
      IC(025) = 0.59) and ICI-associated diabetes mellitus (ROR(025) = 9.53, IC(025) = 
      3.23 vs. ROR(025) = 5.63, IC(025) = 2.48), but lower fatality proportion. 
      CONCLUSIONS: ICIs were significantly associated with the over-reporting frequency 
      of pancreatic AEs, in which combination therapy posed a higher reporting 
      frequency. Therefore, patients should be informed of these potential toxicities 
      before ICIs medications are administered.
CI  - Copyright (c) 2022 Zhang, Fang, Wu, Huang, Bin, Liao, Shi, Liao and Huang.
FAU - Zhang, Yue
AU  - Zhang Y
AD  - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Fang, Yisheng
AU  - Fang Y
AD  - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Wu, Jianhua
AU  - Wu J
AD  - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Huang, Genjie
AU  - Huang G
AD  - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Bin, Jianping
AU  - Bin J
AD  - Department of Cardiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Liao, Yulin
AU  - Liao Y
AD  - Department of Cardiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Shi, Min
AU  - Shi M
AD  - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Liao, Wangjun
AU  - Liao W
AD  - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
FAU - Huang, Na
AU  - Huang N
AD  - Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20220401
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9012537
OTO - NOTNLM
OT  - CTLA-4
OT  - FAERS
OT  - PD-1/PD-L1
OT  - combination therapy
OT  - diabetes mellitus
OT  - immune checkpoint inhibitors
OT  - pancreatic adverse events
OT  - pancreatitis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/19 06:00
MHDA- 2022/04/19 06:01
PMCR- 2022/04/01
CRDT- 2022/04/18 06:32
PHST- 2021/11/18 00:00 [received]
PHST- 2022/03/11 00:00 [accepted]
PHST- 2022/04/18 06:32 [entrez]
PHST- 2022/04/19 06:00 [pubmed]
PHST- 2022/04/19 06:01 [medline]
PHST- 2022/04/01 00:00 [pmc-release]
AID - 817662 [pii]
AID - 10.3389/fphar.2022.817662 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Apr 1;13:817662. doi: 10.3389/fphar.2022.817662. 
      eCollection 2022.