Martins-Filho Paulo Ricardo, Ferreira Lis Campos, Heimfarth Luana, Araújo Adriano Antunes de Souza, Quintans-Júnior Lucindo José
Investigative Pathology Laboratory, Federal University of Sergipe, Aracaju, Sergipe, Brazil.
Health Sciences Graduate Program, Federal University of Sergipe, Aracaju, Sergipe, Brazil.
Lancet Reg Health Am. 2021 Oct;2:100062. doi: 10.1016/j.lana.2021.100062. Epub 2021 Aug 29.
Hydroxychloroquine (HCQ) is an anti-malarial and immunomodulatory drug considered a potential candidate for drug repurposing in COVID-19 due to their antiviral activity against SARS-CoV-2. Despite the potential antiviral effects and anti-inflammatory profile, the results based on clinical studies are contradictory. Therefore, the quality of the decision-making process from meta-analyses summarizing the available evidence selecting studies with different designs and unblinded trials is limited. The aim of this study was to synthesize the best evidence on the efficacy and safety of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19.
Searches were performed in PubMed, Web of Science, Embase, Lilacs, the website ClinicalTrials.gov and the preprint server medRxiv from January 1, 2020 to May 17, 2021. The following elements were used to define eligibility criteria: (1) Population: individuals at high-risk of exposure to SARS-CoV-2 (pre-exposure), individuals who had close contact with a positive or probable case of COVID-19 (post-exposure), non-hospitalized patients with COVID-19 and hospitalized patients with COVID-19; (2) Intervention: HCQ; (3) Comparison: placebo; (4) Outcomes: incidence of SARS-CoV-2 infection, need for hospitalization, length of hospital stay, need for invasive mechanical ventilation (MV), death, and adverse events; and (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Risk of bias was judged according to the Cochrane guidelines for RCTs. Treatment effects were reported as relative risk (RR) for dichotomous variables and mean difference (MD) for continuous variables with 95% confidence intervals (CI). We used either a fixed or random-effects model to pool the results of individual studies depending on the presence of heterogeneity. The GRADE system was used to evaluate the strength of evidence between use of HCQ and the outcomes of interest.
Fourteen blinded, placebo-controlled RCTs were included in this meta-analysis. Four trials (1942 patients: HCQ = 1271; placebo = 671) used HCQ as a prophylactic medication pre-exposure to COVID-19, two (1650 patients: HCQ = 821; placebo = 829) as a prophylactic medication post-exposure to COVID-19, three (1018 patients: HCQ = 497; placebo = 521) as treatment for non-hospitalized patients, and five (1138 patients: HCQ = 572; placebo = 566) as treatment for hospitalized patients with COVID-19. We found no decreased risk of SARS-CoV-2 infection among individuals receiving HCQ as pre-exposure (RR = 0.90; 95% CI 0.46 to 1.77) or post-exposure (RR = 0.96; 95% CI 0.72 to 1.29) prophylaxis to prevent COVID-19. There was no significant decreased risk of hospitalization for outpatients with SARS-CoV-2 infection (RR = 0.64; 95% CI 0.33 to 1.23) and no decreased risk of MV (RR = 0.81; 95% CI 0.49 to 1.34) and death (RR = 1.05; 95% CI 0.62 to 1.78) among hospitalized patients with COVID-19 receiving HCQ. The certainty of the results on the lack of clinical benefit for HCQ was rated as moderate. Moreover, our results demonstrated an increased risk for any adverse events and gastrointestinal symptoms among those using HCQ.
Available evidence based on the results of blinded, placebo-controlled RCTs showed no clinical benefits of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19.
There was no funding source.
羟氯喹啉（HCQ）是一种抗疟疾和免疫调节药物，因其对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）具有抗病毒活性，被认为是一种可能用于新型冠状病毒肺炎（COVID-19）药物重新利用的候选药物。尽管具有潜在的抗病毒作用和抗炎特性，但基于临床研究的结果相互矛盾。因此，通过荟萃分析总结现有证据来进行决策的过程质量有限，这些荟萃分析选择了设计不同且未设盲的试验。本研究的目的是综合关于HCQ作为暴露前和暴露后预防以及治疗非住院和住院COVID-19患者的疗效和安全性的最佳证据。
于2020年1月1日至2021年5月17日在PubMed、科学网、Embase、Lilacs、ClinicalTrials.gov网站和预印本服务器medRxiv上进行检索。使用以下要素来定义纳入标准：（1）人群：有接触SARS-CoV-2高风险的个体（暴露前）、与COVID-19确诊或疑似病例有密切接触的个体（暴露后）、非住院COVID-19患者和住院COVID-19患者；（2）干预措施：HCQ；（3）对照：安慰剂；（4）结局：SARS-CoV-2感染发生率、住院需求、住院时间、有创机械通气（MV）需求、死亡和不良事件；（5）研究类型：设盲、安慰剂对照、随机临床试验（RCT）。根据Cochrane随机对照试验指南判断偏倚风险。对于二分变量，治疗效果以相对风险（RR）报告，对于连续变量，以95%置信区间（CI）的平均差（MD）报告。根据异质性的存在，我们使用固定效应模型或随机效应模型汇总各个研究的结果。采用GRADE系统评估使用HCQ与感兴趣结局之间证据的强度。
本荟萃分析纳入了14项设盲、安慰剂对照的随机对照试验。四项试验（1942例患者：HCQ = 1271例；安慰剂 = 671例）将HCQ用作COVID-19暴露前的预防药物，两项试验（1650例患者：HCQ = 821例；安慰剂 = 829例）用作COVID-19暴露后的预防药物，三项试验（1018例患者：HCQ = 497例；安慰剂 = 521例）用于治疗非住院患者，五项试验（1138例患者：HCQ = 572例；安慰剂 = 566例）用于治疗住院COVID-19患者。我们发现，接受HCQ作为暴露前（RR = 0.90；95%CI 0.46至1.77）或暴露后（RR = 0.96；95%CI 0.72至1.29）预防以预防COVID-19的个体中，SARS-CoV-2感染风险没有降低。SARS-CoV-2感染门诊患者的住院风险没有显著降低（RR = 0.64；95%CI 0.33至1.23），接受HCQ的住院COVID-19患者的MV风险（RR = 0.81；95%CI 0.49至1.34）和死亡风险（RR = 1.05；95%CI 0.62至1.78）也没有降低。关于HCQ缺乏临床益处的结果的确定性被评为中等。此外，我们的结果表明，使用HCQ的人群中任何不良事件和胃肠道症状的风险增加。
基于设盲、安慰剂对照随机对照试验结果的现有证据表明，HCQ作为暴露前和暴露后预防以及治疗非住院和住院COVID-19患者没有临床益处。
无资金来源。
