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Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis

Published:April 05, 2021DOI:https://doi.org/10.1016/j.ejim.2021.03.028

      Highlights

      • Our data reinforces the notion that chloroquine and hydroxychloroquine have a good safety profile.
      • Users of both antimalarial presented a higher risk of mild and self-limited adverse events.
      • A ten-year meta-analysis did not reveal a statistically significant higher risk of cardiovascular events in chloroquine and hydroxychloroquine users.
      • Ventricular arrhythmias and myocardial infarction were reported in hospitalized COVID-19 patients using higher than usual doses of chloroquine or hydroxychloroquine.

      Abstract

      Objective

      To estimate the incidence rate ratio (IRR) of adverse events (AE) in chloroquine or hydroxychloroquine users.

      Methods

      We systematically reviewed randomized controlled trials (RCTs), using MEDLINE (2010-2020) and EMBASE (2010-2020) databases, reporting AE in chloroquine or hydroxychloroquine users during treatment for lupus, rheumatoid arthritis, malaria and COVID-19. The protocol for this systematic review is registered at the PROSPERO database (CRD42020197938). The quality of the included studies was assessed using the Cochrane risk-of-Bias tool and relevant data were extracted though a customized data collection form, independently, by two authors. The IRR of AE was estimated using a random-effect model meta-analysis and heterogeneity was evaluated by T2 and I2. Subgroup analysis was performed, and publication bias was assessed by funnel-plot.

      Results

      Forty-six RCTs met our eligibility criteria and were included in our analysis (23132 patients). There was not a single death attributed to chloroquine or hydroxychloroquine use in the included RCTs. The IRR of general AE during antimalarial use was 1.15 [CI 95% 1.01-1.31]. COVID-19 patients treated with either antimalarial presented an 83% and 165% higher risk of developing general and gastrointestinal AE, respectively, in comparison with controls. The use of antimalarial increased the risk of developing dermatological AE by 92% in malarial studies and reduced by 65% in lupus studies. We did not find a significatively higher risk of cardiovascular nor ophthalmological AE in antimalarial users.

      Conclusions

      Our data reinforces that chloroquine and hydroxychloroquine have a good safety profile though caution is advised when using higher than usual doses in hospitalized COVID-19 patients.

      Keywords

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