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

Abstract

Background:Recently, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have emerged as potential antiviral and immunomodulatory options for the treatment of 2019 coronavirus disease . 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 PubMed, MEDLINE, Cochrane, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, and the ClinicalTrials.gov for all the RCTs comparing CQ or HCQ with placebo or other active agents, published before March 31, 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 17 studies for CQ and HCQ, respectively, that satisfied our inclusion criteria. Of these studies, we performed meta-analysis on the ones that were placebo-controlled, which included 6 studies for CQ and 14 studies for HCQ. We did not limit our analysis to published reports 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 1,096 participants (n=558 HCQ and n=538 placebo). The overall mild or total AEs were statistically higher comparing CQ or HCQ to placebo. The AEs were further categorized into four groups and analyses revealed that neurologic, gastrointestinal, dermatologic, and ophthalmic AEs were higher in participants taking CQ compared to placebo. Although this was not evident in HCQ treated groups, further analyses suggested that there were more AEs attributed to other organ system that were not included in the categorized meta-analyses. Additionally, meta-regression analyses revealed that total AEs was affected by dosage for the CQ group. Conclusions: Taken together, we found that participants taking either CQ or HCQ have more AEs than participants taking placebo. Precautionary measures should be taken when using these drugs to treat COVID-19. : medRxiv preprint Data Collection and Outcome MeasuresBibliographic details and abstracts of all citations retrieved by the literature search were downloaded to Endnotes X9. All studies were screened and evaluated by two independent reviewers (LR, PNT), which were then checked by a third reviewer (SY). Discrepancies were resolved by discussion in group conferences. Completed data were then thoroughly checked by two additional reviewers (WX, JLO). Data including first author, year of publication, trial design, All rights reserved. No reuse allowed without permission.was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. : medRxiv preprint country where studies took place, purpose of treatment, trial duration, dosage regimen, outcomes and AEs were extracted using a standardized...

Efficacy of various treatment modalities for nCOV‐2019: A systematic review and meta‐analysis

“…Two recent meta-analyses conducted by Ren et al and Wang et al found that patients taking chloroquine or hydroxychloroquine had more adverse events compared to patients assigned to placebo group. 64,65 Another meta-analysis published a couple of months ago by Sarma et al 66 found no association of hydroxychloroquine with virological cure, death or clinical worsening and safety in nCOV-2019 patients. Similar findings on hydroxychloroquine with or without azithromycin were observed from another meta-analysis of five trials which although did observe a trend but the results were not found to be statistically significant in terms of negative conversion of nCOV-2019 (odds ratio [OR] 1.95; 95%CI 0.19 to 19.73) and reduction in progression rate (OR 0.89 95%CI 0.58 to 1.37).…”

Systematic Review and Meta-analysis of the Safety of Chloroquine and Hydroxychloroquine From Randomized Controlled Trials on Malarial and Non-malarial Conditions

“…respectively [114]. Eljaaly et al searched PubMed and EMBASE databases for RCTs of adults comparing AE of HCQ with placebo for any indication.…”

Antiviral mechanisms of candidate chemical medicines and traditional Chinese medicines for SARS-CoV-2 infection

“…Taken together, the CQ and its derivatives can shorten the course of SARS-CoV-2, reduce the inflammatory responses to infection, inhibit the deterioration of pneumonia, improve lung imaging performance, and promote the negative conversion of the virus (Kearney, 2020;Li and Liu, 2020). However, recent reports show that treatment with HCQ is associated with numerous adverse effects in patients with COVID-19, such as frequent QTc prolongation, erythema multiforme, acute generalized exanthematous pustulosis (Bessiere et al, 2020;Delaleu et al, 2020;Mercuro et al, 2020;Monte Serrano et al, 2020;Ren et al, 2020b;Torjesen, 2020). On Jun 16, 2020, the US Food and Drug Administration revoked the emergency use authorization for chloroquine and hydroxychloroquine due to their lack of efficacy and safety concerns (http://www.…”