Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil; Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brazil.
Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brazil.
Eur J Intern Med. 2021 Jun;88:63-72. doi: 10.1016/j.ejim.2021.03.028. Epub 2021 Apr 5.
To estimate the incidence rate ratio (IRR) of adverse events (AE) in chloroquine or hydroxychloroquine users.
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 T and I. Subgroup analysis was performed, and publication bias was assessed by funnel-plot.
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.
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.
估计氯喹或羟氯喹使用者发生不良事件（AE）的发生率比值（IRR）。
我们系统地回顾了随机对照试验（RCT），使用 MEDLINE（2010-2020 年）和 EMBASE（2010-2020 年）数据库，报告了氯喹或羟氯喹使用者在治疗狼疮、类风湿关节炎、疟疾和 COVID-19 期间发生的 AE。本系统评价的方案在 PROSPERO 数据库（CRD42020197938）中注册。使用 Cochrane 偏倚风险工具评估纳入研究的质量，并通过定制的数据收集表独立地由两名作者提取相关数据。使用随机效应模型荟萃分析估计 AE 的 IRR，并通过 T 和 I 评估异质性。进行了亚组分析，并通过漏斗图评估发表偏倚。
46 项 RCT 符合我们的纳入标准，并纳入我们的分析（23132 名患者）。在纳入的 RCT 中，没有一例死亡归因于氯喹或羟氯喹的使用。抗疟药物使用期间发生一般 AE 的 IRR 为 1.15[CI95%1.01-1.31]。与对照组相比，接受抗疟治疗的 COVID-19 患者发生一般和胃肠道 AE 的风险分别增加了 83%和 165%。在疟疾研究中，抗疟药物使皮肤 AE 的风险增加了 92%，而在狼疮研究中降低了 65%。我们没有发现抗疟药物使用者发生心血管或眼科 AE 的风险显著增加。
我们的数据进一步证实，氯喹和羟氯喹具有良好的安全性，但在 COVID-19 住院患者中使用高于常规剂量时应谨慎。
