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Assessment of Chloroquine and Hydroxychloroquine Safety Profiles: A Systematic Review and Meta-Analysis

BACKGROUND: Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have recently emerged as potential antiviral and immunomodulatory options for the treatment of 2019 coronavirus disease (COVID-19). To examine the safety profiles of these medications, we systematically evaluated the adverse ev...

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Autores principales: Ren, Lu, Xu, Wilson, Overton, James L., Yu, Shandong, Chiamvimonvat, Nipavan, Thai, Phung N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591721/
https://www.ncbi.nlm.nih.gov/pubmed/33154723
http://dx.doi.org/10.3389/fphar.2020.562777
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author Ren, Lu
Xu, Wilson
Overton, James L.
Yu, Shandong
Chiamvimonvat, Nipavan
Thai, Phung N.
author_facet Ren, Lu
Xu, Wilson
Overton, James L.
Yu, Shandong
Chiamvimonvat, Nipavan
Thai, Phung N.
author_sort Ren, Lu
collection PubMed
description BACKGROUND: Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have recently emerged as potential antiviral and immunomodulatory options for the treatment of 2019 coronavirus disease (COVID-19). To examine the safety profiles of these medications, we systematically evaluated the adverse events (AEs) of these medications from published randomized controlled trials (RCTs). METHODS: We systematically searched MEDLINE, the Cochrane library, the Cochrane Central Register of Controlled Trials (CENTRAL), and the ClinicalTrials.gov for all the RCTs comparing CQ or HCQ with placebo or other active agents, published before June 20, 2020. The random-effects or fixed-effects models were used to pool the risk estimates relative ratio (RR) with 95% confidence interval (CI) for the outcomes. RESULTS: The literature search yielded 23 and 19 studies for CQ and HCQ, respectively, that satisfied our inclusion criteria. Of these studies, we performed meta-analysis on 6 studies for CQ and 18 studies for HCQ. We did not limit our analysis to published records involving viral treatment alone; data also included the usage of either CQ or HCQ for the treatment of other diseases. The trials for the CQ consisted of a total of 2,137 participants (n = 1,077 CQ, n = 1,060 placebo), while the trials for HCQ involved 2,675 participants (n = 1,345 HCQ and n = 1,330 control). The overall mild and total AEs were significantly higher in CQ-treated non–COVID-19 patients, HCQ-treated non–COVID-19 patients, and HCQ-treated COVID-19 patients. The AEs were further categorized into four groups and analyses revealed that neurologic, gastrointestinal (GI), dermatologic, and sensory AEs were higher in participants taking CQ compared to placebo, while GI, dermatologic, sensory, and cardiovascular AEs were higher in HCQ-treated COVID-19 patients compared to control patients. Moreover, subgroup analysis suggested higher AEs with respect to dosage and duration in HCQ group. Data were acquired from studies with perceived low risk of bias, so plausible bias is unlikely to seriously affect the main findings of the current study. CONCLUSIONS: Taken together, we found that participants taking either CQ or HCQ exhibited more AEs than participants taking placebo or control. Precautionary measures should be taken when using these drugs to treat COVID-19. The meta-analysis was registered on OSF (https://osf.io/jm3d9). REGISTRATION: The meta-analysis was registered on OSF (https://osf.io/jm3d9).
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spelling pubmed-75917212020-11-04 Assessment of Chloroquine and Hydroxychloroquine Safety Profiles: A Systematic Review and Meta-Analysis Ren, Lu Xu, Wilson Overton, James L. Yu, Shandong Chiamvimonvat, Nipavan Thai, Phung N. Front Pharmacol Pharmacology BACKGROUND: Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have recently emerged as potential antiviral and immunomodulatory options for the treatment of 2019 coronavirus disease (COVID-19). To examine the safety profiles of these medications, we systematically evaluated the adverse events (AEs) of these medications from published randomized controlled trials (RCTs). METHODS: We systematically searched MEDLINE, the Cochrane library, the Cochrane Central Register of Controlled Trials (CENTRAL), and the ClinicalTrials.gov for all the RCTs comparing CQ or HCQ with placebo or other active agents, published before June 20, 2020. The random-effects or fixed-effects models were used to pool the risk estimates relative ratio (RR) with 95% confidence interval (CI) for the outcomes. RESULTS: The literature search yielded 23 and 19 studies for CQ and HCQ, respectively, that satisfied our inclusion criteria. Of these studies, we performed meta-analysis on 6 studies for CQ and 18 studies for HCQ. We did not limit our analysis to published records involving viral treatment alone; data also included the usage of either CQ or HCQ for the treatment of other diseases. The trials for the CQ consisted of a total of 2,137 participants (n = 1,077 CQ, n = 1,060 placebo), while the trials for HCQ involved 2,675 participants (n = 1,345 HCQ and n = 1,330 control). The overall mild and total AEs were significantly higher in CQ-treated non–COVID-19 patients, HCQ-treated non–COVID-19 patients, and HCQ-treated COVID-19 patients. The AEs were further categorized into four groups and analyses revealed that neurologic, gastrointestinal (GI), dermatologic, and sensory AEs were higher in participants taking CQ compared to placebo, while GI, dermatologic, sensory, and cardiovascular AEs were higher in HCQ-treated COVID-19 patients compared to control patients. Moreover, subgroup analysis suggested higher AEs with respect to dosage and duration in HCQ group. Data were acquired from studies with perceived low risk of bias, so plausible bias is unlikely to seriously affect the main findings of the current study. CONCLUSIONS: Taken together, we found that participants taking either CQ or HCQ exhibited more AEs than participants taking placebo or control. Precautionary measures should be taken when using these drugs to treat COVID-19. The meta-analysis was registered on OSF (https://osf.io/jm3d9). REGISTRATION: The meta-analysis was registered on OSF (https://osf.io/jm3d9). Frontiers Media S.A. 2020-10-14 /pmc/articles/PMC7591721/ /pubmed/33154723 http://dx.doi.org/10.3389/fphar.2020.562777 Text en Copyright © 2020 Ren, Xu, Overton, Yu, Chiamvimonvat and Thai http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Ren, Lu
Xu, Wilson
Overton, James L.
Yu, Shandong
Chiamvimonvat, Nipavan
Thai, Phung N.
Assessment of Chloroquine and Hydroxychloroquine Safety Profiles: A Systematic Review and Meta-Analysis
title Assessment of Chloroquine and Hydroxychloroquine Safety Profiles: A Systematic Review and Meta-Analysis
title_full Assessment of Chloroquine and Hydroxychloroquine Safety Profiles: A Systematic Review and Meta-Analysis
title_fullStr Assessment of Chloroquine and Hydroxychloroquine Safety Profiles: A Systematic Review and Meta-Analysis
title_full_unstemmed Assessment of Chloroquine and Hydroxychloroquine Safety Profiles: A Systematic Review and Meta-Analysis
title_short Assessment of Chloroquine and Hydroxychloroquine Safety Profiles: A Systematic Review and Meta-Analysis
title_sort assessment of chloroquine and hydroxychloroquine safety profiles: a systematic review and meta-analysis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591721/
https://www.ncbi.nlm.nih.gov/pubmed/33154723
http://dx.doi.org/10.3389/fphar.2020.562777
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