当抗病毒药物适得其反时：一项评价 COVID-19 重症患者使用法匹拉韦的临床结局的多中心队列研究。
When antivirals backfire: An evaluation of favipiravir's clinical outcomes in critically ill patients with COVID-19: A multicenter cohort study.
机构信息
Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia; College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; King Abdullah International Medical Research Center-King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia; Saudi Critical Care Pharmacy Research (SCAPE) Platform, Riyadh, Saudi Arabia; Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
出版信息
J Infect Public Health. 2023 Sep;16(9):1492-1499. doi: 10.1016/j.jiph.2023.06.011. Epub 2023 Jun 14.
BACKGROUND
Favipiravir is an oral antiviral, that might treat COVID-19 by enhancing viral eradication, particularly in patients with mild-to-moderate disease. Yet, the findings on the use of favipiravir in critically ill patients with COVID-19 are inconsistent. Therefore, this study aimed to assess the effectiveness and safety of favipiravir in critically ill patients with COVID-19.
METHOD
A multicenter retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care units (ICUs) was conducted from March 2020 to July 2021. Patients were categorized based on favipiravir use (control vs. favipiravir). The primary outcome was in-hospital mortality. Secondary outcomes included mechanical ventilation (MV) duration, 30-day mortality, ICU length of stay (LOS), hospital LOS, and complications during the stay.
RESULTS
After propensity score (PS) matching (1:1 ratio), 146 patients were included in the final analysis. A higher in-hospital and 30-day mortality were observed in patients receiving favipiravir compared to the control group at crude analysis (65.3% vs. 43.8%; P-value=0.009 and 56.3% vs. 40.3; P-value=0.06, respectively); however, no differences were observed using multivariable Cox proportional hazards regression analysis (HR 1.17; 95% CI 0.73, 1.87; P-value =0.51 and HR 0.86; 95% CI 0.53, 1.39; P-value=0.53, respectively). Conversely, the MV duration and ICU LOS were longer in patients who received favipiravir than the control group (β coefficient 0.51; CI 0.09, 0.92; P-value = 0.02, β coefficient 0.41; CI 0.17, 0.64; P-value = 0.0006, respectively). Complications during the stay were comparable between the two groups.
CONCLUSION
The use of favipiravir in critically ill patients with COVID-19 did not demonstrate a reduction in mortality; instead, it was linked with longer MV duration and ICU stay. This finding suggests limiting favipiravir use to infections where it is more effective, other than COVID-19. Further randomized clinical trials are needed to confirm these findings.
背景
法匹拉韦是一种口服抗病毒药物，通过增强病毒清除，可能对 COVID-19 有治疗作用，尤其是在轻症至中度疾病患者中。然而，关于法匹拉韦在 COVID-19 重症患者中的应用的研究结果并不一致。因此，本研究旨在评估法匹拉韦在 COVID-19 重症患者中的疗效和安全性。
方法
一项多中心回顾性队列研究纳入了 2020 年 3 月至 2021 年 7 月期间入住重症监护病房（ICU）的 COVID-19 重症成年患者。根据法匹拉韦的使用情况（对照组与法匹拉韦组）对患者进行分类。主要结局是住院死亡率。次要结局包括机械通气（MV）时间、30 天死亡率、ICU 住院时间（LOS）、住院 LOS 和住院期间的并发症。
结果
在倾向评分（PS）匹配（1:1 比例）后，共有 146 名患者纳入最终分析。与对照组相比，接受法匹拉韦治疗的患者在住院期间和 30 天死亡率更高（粗分析分别为 65.3% vs. 43.8%；P 值=0.009 和 56.3% vs. 40.3%；P 值=0.06）；然而，多变量 Cox 比例风险回归分析并未显示差异（HR 1.17；95%CI 0.73, 1.87；P 值=0.51 和 HR 0.86；95%CI 0.53, 1.39；P 值=0.53）。相反，接受法匹拉韦治疗的患者 MV 时间和 ICU LOS 长于对照组（β系数 0.51；CI 0.09, 0.92；P 值=0.02，β系数 0.41；CI 0.17, 0.64；P 值=0.0006）。两组患者在住院期间的并发症发生率相当。
结论
法匹拉韦在 COVID-19 重症患者中的应用并未降低死亡率，反而与 MV 时间延长和 ICU 住院时间延长有关。这一发现表明，除 COVID-19 外，应将法匹拉韦的使用限制在更有效的感染中。需要进一步的随机临床试验来证实这些发现。
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