COVID-19 Evidence Alerts
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Current best evidence for clinical care (more info)

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Treatment Edington FLB, Gadellha SR, Santiago MB Safety of treatment with chloroquine and hydroxychloroquine: A ten-year systematic review and meta-analysis. Eur J Intern Med. 2021 Apr 5. pii: S0953-6205(21)00092-3. doi: 10.1016/j.ejim.2021.03.028.

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.

Discipline / Specialty Area Score
Public Health
Tropical and Travel Medicine
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Comments from MORE raters

Public Health rater

This is highly relevant as most practioners of other disciplines probably don't know this.

Rheumatology rater

Interesting review on 46 RCTs that included 23132 patients. CQ and HCQ use was not associated with serious adverse events. An increased risk ratio was 1.15 (95% CI 1.01-1.31) with mostly gastrointestinal events. Interestingly, ophthalmological and cardiovascular events were not frequent. As COVID19 is a new epidemic disease and treatments with CQ/HQC were short compared with LE or RA and currently substituted with other therapies, data for COVID-19 patients should be carefully regarded.

Tropical and Travel Medicine rater

The authors performed a systematic review of the adverse effects of treatment of a variety of conditions with Chloroquine or Hydroxychloroquine. They obtained their data by reviewing trials of the treatment of malaria, lupus, rheumatoid arthritis and COVID that used chloroquine/hydroxychloroquine and reported on adverse effects. They concluded that at usual doses adverse effects were minor, mostly GI or dermatologic. At higher the usual doses used for COVID-19, there were rare serious adverse effects but it was difficult to discern side effects from illness effects in some cases.