Effect of remdesivir on patients with COVID-19: A network meta-analysis of randomized control trials.

Several randomized controlled trials (RCTs) were conducted to investigate the effect of remdesivir for patients with COVID-19, but their results were conflicting. Thus, we conducted a network meta-analysis comparing the rate of clinical improvement among patients with COVID-19 who received 5-day course of remdesivir versus 10-day course of remdesivir versus standard care. Our network meta-analysis of 4 randomized controlled trials demonstrated that the rate of clinical improvement was significantly higher in the 5-day remdesivir group and 10-day remdesivir group compared to standard care group (OR [95% confidence interval [CI]] =1.89 [1.40-2.56], P <0.001, OR [95% CI] =1.38 [1.15-1.66], P <0.001, respectively). In addition, the rate of clinical improvement was significantly higher in the 5-day remdesivir group compared to the 10-day remdesivir group (OR [95% confidence interval [CI]] =1.37 [1.01-1.85], P =0.041). Our analysis demonstrated that the use of remdesivir for patients with COVID-19 was associated with the significantly higher clinical improvement rate compared with standard care alone.

Summary

Remdesivir is a monophosphoramidate prodrug that has a broad antiviral spectrum including coronaviruses and inhibits all human and animal coronaviruses in vitro. Several randomized controlled trials (RCTs) were conducted to investigate the effect of remdesivir for patients with COVID-19, but their results were conflicting. Thus, we conducted a network meta-analysis comparing the rate of clinical improvement among patients with COVID-19 who received 5-day course of remdesivir versus 10-day course of remdesivir versus standard care.

Our network meta-analysis of 4 randomized controlled trials demonstrated that the rate of clinical improvement was significantly higher in the 5-day remdesivir group and 10-day remdesivir group compared to standard care group (OR [95 % confidence interval [CI]] = 1.89 [1.40–2.56], P < 0.001, OR [95 % CI] = 1.38 [1.15–1.66], P < 0.001, respectively). In addition, the rate of clinical improvement was significantly higher in the 5-day remdesivir group compared to the 10-day remdesivir group (OR [95 % confidence interval [CI]] = 1.37 [1.01–1.85], P = 0.041).

Several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), but none have yet been shown to be effective.

Short communication

Remdesivir is a monophosphoramidate prodrug that has a broad antiviral spectrum including coronaviruses and inhibits all human and animal coronaviruses in vitro (Sheahan et al., 2017). Several randomized controlled trials (RCTs) were conducted to investigate the effect of remdesivir for patients with COVID-19, but their results were conflicting (Wang et al., 2020; Beigel et al., 2020; Goldman et al., 2020; ANON, 2020). Thus, we conducted a network meta-analysis comparing the rate of clinical improvement among patients with COVID-19 who received 5-day course of remdesivir versus 10-day course of remdesivir versus standard care. All RCTs which investigated the efficacy of remdesivir for patients with COVID-19 were identified including preliminary reports. The outcome of interest was the clinical improvement within 14 days after randomization. The definition of clinical improvement was applied according to each study protocol. Odds ratios (ORs) of the rate of clinical improvement were extracted from each trial. Then, we performed network meta-analysis using “netmeta” 3.6.2 package (R Foundation for Statistical Computing, Vienna, Austria) (Neupane et al., 2014). Our analysis included 4 RCTs which enrolled a total of 2290 patients with COVID-19 assigned to the 5-day remdesivir group (N = 400), 10-day remdesivir group (N = 1090), and standard care group (N = 800) (Wang et al., 2020; Beigel et al., 2020; Goldman et al., 2020; ANON, 2020). The definitions of clinical improvement were a two-point reduction in patients’ admission status on a six-point ordinal scale (1=discharged or having reached discharge criteria; 2=hospital admission but not requiring oxygen therapy; 3=hospital admission for oxygen therapy; 4=hospital admission for noninvasive ventilation or high-flow oxygen therapy; 5=hospital admission for extracorporeal membrane oxygenation (ECMO) or mechanical ventilation; 6=death), or live discharge from the hospital, whichever came first in one trial (Wang et al., 2020), satisfied categories 1, 2, or 3 on the eight-category ordinal scale (1 = not hospitalized, no limitations of activities; 2 = not hospitalized, limitation of activities, home oxygen requirement, or both; 3=hospitalized, not requiring supplemental oxygen and no longer requiring ongoing medical care; 4=hospitalized, not requiring supplemental oxygen but requiring ongoing medical care; 5=hospitalized, requiring any supplemental oxygen; 6=hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices; 7=hospitalized, receiving invasive mechanical ventilation or ECMO; 8=death) in one (Beigel et al., 2020), an improvement of at least 2 points from baseline on the 7-point ordinal scale (1=death; 2=hospitalized, receiving invasive mechanical ventilation or ECMO; 3=hospitalized, receiving noninvasive ventilation or high-flow oxygen devices; 4=hospitalized, requiring low-flow supplemental oxygen; 5=hospitalized, not requiring supplemental oxygen but receiving ongoing medical care; 6=hospitalized, requiring neither supplemental oxygen nor ongoing medical care; and 7 = not hospitalized) in two (Goldman et al., 2020; ANON, 2020). A Pooled analysis demonstrated that the rate of clinical improvement was significantly higher in the 5-day remdesivir group and 10-day remdesivir group compared to standard care group (OR [95 % confidence interval [CI]] = 1.89 [1.40–2.56], P < 0.001, OR [95 % CI] = 1.38 [1.15–1.66], P < 0.001, respectively) (Fig. 1 A). In addition, the rate of clinical improvement was significantly higher in the 5-day remdesivir group compared to the 10-day remdesivir group (OR [95 % confidence interval [CI]] = 1.37 [1.01–1.85], P = 0.041) (Fig. 1B). Our analysis demonstrated that the use of remdesivir for patients with COVID-19 was associated with the significantly higher clinical improvement rate compared with standard care alone. In addition, the rate of clinical improvement was significantly higher in the 5-day group compared with the 10-day group. We could not analyze other outcomes including mortality and safety outcomes since these were not reported in the press release of the second SIMPLE trial (ANON, 2020). The full data of the trial in a peer-reviewed journal is expected for better understanding of the effect of remdesivir on patients with COVID-19.

Fig. 1

Forest plots among treatment strategies for clinical improvement (random-effects model); A: versus Standard care; B: versus 10-day remdesivir CI = confidence interval; OR = odds ratio.

Disclosure

None.

Funding

None.