PMID- 35401219
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230413
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - Ontology-Based Classification and Analysis of Adverse Events Associated With the 
      Usage of Chloroquine and Hydroxychloroquine.
PG  - 812338
LID - 10.3389/fphar.2022.812338 [doi]
LID - 812338
AB  - Multiple methodologies have been developed to identify and predict adverse events 
      (AEs); however, many of these methods do not consider how patient population 
      characteristics, such as diseases, age, and gender, affect AEs seen. In this 
      study, we evaluated the utility of collecting and analyzing AE data related to 
      hydroxychloroquine (HCQ) and chloroquine (CQ) from US Prescribing Information 
      (USPIs, also called drug product labels or package inserts), the FDA Adverse 
      Event Reporting System (FAERS), and peer-reviewed literature from PubMed/EMBASE, 
      followed by AE classification and modeling using the Ontology of Adverse Events 
      (OAE). Our USPI analysis showed that CQ and HCQ AE profiles were similar, 
      although HCQ was reported to be associated with fewer types of cardiovascular, 
      nervous system, and musculoskeletal AEs. According to EMBASE literature mining, 
      CQ and HCQ were associated with QT prolongation (primarily when treating 
      COVID-19), heart arrhythmias, development of Torsade des Pointes, and retinopathy 
      (primarily when treating lupus). The FAERS data was analyzed by proportional 
      ratio reporting, Chi-square test, and minimal case number filtering, followed by 
      OAE classification. HCQ was associated with 63 significant AEs (including 21 
      cardiovascular AEs) for COVID-19 patients and 120 significant AEs (including 12 
      cardiovascular AEs) for lupus patients, supporting the hypothesis that the 
      disease being treated affects the type and number of certain CQ/HCQ AEs that are 
      manifested. Using an HCQ AE patient example reported in the literature, we also 
      ontologically modeled how an AE occurs and what factors (e.g., age, biological 
      sex, and medical history) are involved in the AE formation. The methodology 
      developed in this study can be used for other drugs and indications to better 
      identify patient populations that are particularly vulnerable to AEs.
CI  - Copyright (c) 2022 Ngai, Kalter, Byrd, Racz and He.
FAU - Ngai, Jamie
AU  - Ngai J
AD  - College of Pharmacy, University of Michigan, Ann Arbor, MI, United States.
FAU - Kalter, Madison
AU  - Kalter M
AD  - College of Literature, Science, and Arts, University of Michigan, Ann Arbor, MI, 
      United States.
FAU - Byrd, James Brian
AU  - Byrd JB
AD  - Department of Internal Medicine, Division of Cardiovascular Medicine, University 
      of Michigan Medical School, Ann Arbor, MI, United States.
FAU - Racz, Rebecca
AU  - Racz R
AD  - Division of Applied Regulatory Science, Center for Drug Evaluation and Research, 
      US Food and Drug Administration, Silver Spring, MD, United States.
FAU - He, Yongqun
AU  - He Y
AD  - Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann 
      Arbor, MI, United States.
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, MI, United States.
AD  - Center for Computational Medicine and Bioinformatics, University of Michigan 
      Medical School, Ann Arbor, MI, United States.
LA  - eng
PT  - Journal Article
DEP - 20220323
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8983871
OTO - NOTNLM
OT  - COVID-19
OT  - FAERS database
OT  - adverse event
OT  - chloroquine
OT  - drug
OT  - hydroxychloroquine
OT  - ontology
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- 2022/04/12 06:00
MHDA- 2022/04/12 06:01
PMCR- 2022/03/23
CRDT- 2022/04/11 05:27
PHST- 2021/11/10 00:00 [received]
PHST- 2022/03/07 00:00 [accepted]
PHST- 2022/04/11 05:27 [entrez]
PHST- 2022/04/12 06:00 [pubmed]
PHST- 2022/04/12 06:01 [medline]
PHST- 2022/03/23 00:00 [pmc-release]
AID - 812338 [pii]
AID - 10.3389/fphar.2022.812338 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Mar 23;13:812338. doi: 10.3389/fphar.2022.812338. 
      eCollection 2022.