PMID- 30674039
OWN - NLM
STAT- MEDLINE
DCOM- 20190408
LR  - 20200225
IS  - 1179-1918 (Electronic)
IS  - 1173-2563 (Linking)
VI  - 39
IP  - 3
DP  - 2019 Mar
TI  - Adverse Event Profiles of Anti-CTLA-4 and Anti-PD-1 Monoclonal Antibodies Alone 
      or in Combination: Analysis of Spontaneous Reports Submitted to FAERS.
PG  - 319-330
LID - 10.1007/s40261-018-0735-0 [doi]
AB  - BACKGROUND AND OBJECTIVE: Immune checkpoint inhibitors (ICIs)-cytotoxic 
      T-lymphocyte antigen-4 (CTLA-4) and programmed death receptor-1 (PD-1) monoclonal 
      antibodies (mAbs)-either as single agents or in combination have become the 
      standard of care for an increasing number of indications. Understanding both the 
      ICI-associated adverse events (AEs) and the possible rank-order of these drugs in 
      terms of susceptibility is essential if we are to improve the curative effect and 
      reduce toxicity. METHODS: We detected signals of the AEs of ICIs by data mining 
      using the US Food and Drug Administration (FDA) AEs Reporting System (FAERS) 
      database. The definition relied on the preferred terms (PTs) and the standardized 
      MedDRA Queries (SMQs) provided by the Medical Dictionary for Regulatory 
      Activities (MedDRA). Disproportionality analysis was performed by calculating the 
      reporting odds ratios (ROR) with 95% confidence intervals (CIs). RESULTS: Adverse 
      effects of CTLA-4 and PD-1 mAbs were most commonly observed in the skin, 
      gastrointestinal tract, endocrine systems, liver, and lung, and they included 
      rash, diarrhea, colitis, and thyroid dysfunction. Thyroid dysfunction, type 1 
      diabetes mellitus, and pneumonitis were more closely associated with the use of 
      anti-PD-1, whereas colitis, diarrhea, hypophysitis, and adrenal insufficiency 
      were more closely associated with anti-CTLA-4; rash and hepatitis occurred 
      similarly in both. Disproportionality signals for less common AEs in other organ 
      systems, including the renal, neurological, cardiac, ocular, musculoskeletal, and 
      hematologic systems, were also detected. Nivolumab and pembrolizumab have very 
      similar safety profiles, but the signal strength of AEs increased when combined 
      with ipilimumab. CONCLUSIONS: The results of this study are in agreement with 
      clinical observations, suggesting the usefulness of pharmacovigilance in 
      "real-world" safety monitoring.
FAU - Ji, Huan-Huan
AU  - Ji HH
AD  - Department of Pharmacy, Children's Hospital of Chongqing Medical University, 
      Ministry of Education Key Laboratory of Child Development and Disorders, China 
      International Science and Technology Cooperation Base of Child Development and 
      Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, 400014, 
      China.
FAU - Tang, Xue-Wen
AU  - Tang XW
AD  - Department of Pharmacy, Children's Hospital of Chongqing Medical University, 
      Ministry of Education Key Laboratory of Child Development and Disorders, China 
      International Science and Technology Cooperation Base of Child Development and 
      Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, 400014, 
      China.
AD  - School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
FAU - Dong, Zhi
AU  - Dong Z
AD  - Department of Pharmacy, Children's Hospital of Chongqing Medical University, 
      Ministry of Education Key Laboratory of Child Development and Disorders, China 
      International Science and Technology Cooperation Base of Child Development and 
      Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, 400014, 
      China.
FAU - Song, Lin
AU  - Song L
AD  - Department of Pharmacy, Children's Hospital of Chongqing Medical University, 
      Ministry of Education Key Laboratory of Child Development and Disorders, China 
      International Science and Technology Cooperation Base of Child Development and 
      Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, 400014, 
      China. songlin0409@sina.com.
FAU - Jia, Yun-Tao
AU  - Jia YT
AUID- ORCID: 0000-0001-8294-1012
AD  - Department of Pharmacy, Children's Hospital of Chongqing Medical University, 
      Ministry of Education Key Laboratory of Child Development and Disorders, China 
      International Science and Technology Cooperation Base of Child Development and 
      Critical Disorders, Chongqing Key Laboratory of Pediatric, Chongqing, 400014, 
      China. jiayuntaomail@tom.com.
LA  - eng
GR  - cstc2016shmszx130048/Chongqing Science and Technology Commission/
GR  - 2016ZDXM017/the Health and Family Planning Commission of Chongqing grants/
PT  - Journal Article
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 31YO63LBSN (Nivolumab)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal/administration & dosage/*adverse effects
MH  - Antibodies, Monoclonal, Humanized/adverse effects
MH  - CTLA-4 Antigen/immunology
MH  - Child
MH  - Child, Preschool
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology
MH  - Female
MH  - Humans
MH  - Infant
MH  - Male
MH  - Middle Aged
MH  - Nivolumab/adverse effects
MH  - *Pharmacovigilance
MH  - Programmed Cell Death 1 Receptor/immunology
MH  - United States
MH  - United States Food and Drug Administration
MH  - Young Adult
EDAT- 2019/01/24 06:00
MHDA- 2019/04/09 06:00
CRDT- 2019/01/24 06:00
PHST- 2019/01/24 06:00 [pubmed]
PHST- 2019/04/09 06:00 [medline]
PHST- 2019/01/24 06:00 [entrez]
AID - 10.1007/s40261-018-0735-0 [pii]
AID - 10.1007/s40261-018-0735-0 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2019 Mar;39(3):319-330. doi: 10.1007/s40261-018-0735-0.