Remdesivir treatment for patients with severe COVID-19 is linked to lower mortality and faster clinical improvements, according to systematic review and meta-analysis findings published in BMC Infectious Diseases.
Conflicting evidence exists for the therapeutic effects of remdesivir in COVID-19.
Investigators therefore sought to assess the efficacy of remdesivir treatment for COVID-19 — both alone and combined with other drugs — as well as associated risks.
The investigators conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs), comparing remdesivir monotherapy and combination therapy with control drugs for risk and/or efficacy. The reviewers searched the Cochrane Library, Embase, SCIE, PubMed, and American Clinical Trial Center databases from inception through March 2022, without language restriction. All study participants had confirmed diagnosis of COVID-19 and were assigned to intervention groups of remdesivir alone, remdesivir in combination with other drugs, or a control group. The meta-analysis included 32 observational studies and 10 RCTs.
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Remdesivir is not indicated for use in combination with other drugs.
Severity of COVID-19 disease was associated with use of remdesivir in meta-regression. The investigators found mortality in the subgroup of patients with severe COVID-19 was reduced with remdesivir (risk ratio [RR], 0.57; 95% CI, 0.48-0.68) but had no effect in the subgroup of patients with moderate COVID-19 infection.
The analysis also indicated that remdesivir shortened the time to clinical improvement (mean difference [MD], -2.51; 95% CI, -2.75 to -2.28; 3 RCTs) and was associated with upgraded clinical status (RR, 1.08; 95% CI, 1.01-1.17; 2 RCTs).
Investigators noted neither liver damage (RR, 0.87; 95% CI, 0.68-1.11) nor kidney damage (RR, 0.88; 95% CI, 0.70-1.10) was caused by use of remdesivir.
Notably, the overall meta-analysis of the RCTs showed that use of remdesivir did not improve mortality in COVID-19 (RR, 0.94; 95% CI, 0.83-1.07; P =.366), and did not reduce duration of hospital stay (MD, 0.26; P =.850). Recovery rate was increased fractionally (RR, 1.09; P =.002). Incidence of adverse events or serious adverse events was not affected by remdesivir.
However, meta-analysis of the observational studies indicated remdesivir use helped to reduce mortality (RR, 0.73; P =.003) and helped patients recover (RR, 1.18; P =.004), but did not reduce duration of hospital stay (RR, -1.23; P =.314).
Remdesivir combined with steroids, favipiravir, or convalescent plasma had no effect on mortality, compared with remdesivir alone, the investigators found. Remdesivir combined with tocilizumab significantly increased mortality (RR, 2.03; P =.011; 3 studies).
Combined with steroids, remdesivir had no positive or passive significance in mortality, duration of hospital stay, new admission to ICU at baseline, or liver injury in patients with COVID-19, the investigators reported. Remdesivir combined with favipiravir did not have a significantly different effect compared with favipiravir alone, and remdesivir combined with convalescent plasma did not have a significantly different effect compared with remdesivir alone.
Heterogeneity existed in the observational studies in terms of mortality, duration of hospital stay, recovery, and clinical improvement. Heterogeneity existed in the RCTs in terms of hospital stay, adverse events, serious adverse events, and use of mechanical ventilation. Quality of evidence was reported as low in the observational studies and high in the RCTs.
Systematic review and meta-analysis limitations include underpowered sample sizes in many of the included studies.
“The use of remdesivir can help to reduce the mortality of patients with severe COVID-19 and shorten the time to clinical improvement,” review authors concluded, adding that “There was no benefit of remdesivir combination therapy for other clinical outcomes,” and that “Remdesivir is not indicated for use in combination with other drugs.”
