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

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.

Automated summary

This study aimed to estimate the incidence rate ratio of adverse events in chloroquine or hydroxychloroquine users. Through analysis of 46 eligible randomized controlled trials, it was found that the use of antimalarial drugs in patients increased the risk of developing general and gastrointestinal adverse events, while there was no significant increase in the risk of cardiovascular and ophthalmological adverse events.