Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care

Abstract

Background: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care.

Methods: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality.

Results: After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001).

Conclusions: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19.

Clinical trials registration: NCT04292899 and EUPAS34303.

Keywords: SARS-CoV-2; antiviral treatment; remdesivir; severe COVID-19.

Figure 1.

Study population. *Based on IPTW, the number of patients in the remdesivir and non-remdesivir cohorts were modestly different from the original sample size (some patients weighted more, and some patients weighted less based on the patients’ propensity scores). Abbreviations: IPTW, stabilized inverse probability of treatment weighting method; OSA, ordinal scale assessment.

Figure 2.

Proportion (95% confidence interval) of patients at day 14 in the remdesivir-cohort and non-remdesivir-cohort with: (A) recovery, based on the 7-point ordinal scale* and (B) mortality** (after stabilized inverse probability of treatment weighting). *Recovery was defined as baseline score of 2–4 improved to 5–7, or baseline score of 5 improved to 6–7, or baseline score of 6 improved to 7. P-values, odds ratios between treatment groups, and its 95% confidence interval were from the weighted logistic regression model with all baseline factors included in the model as covariates. After stepwise model selection, insignificant baseline factors were removed from the final model. The final model for day 14 included age, sex, baseline ordinal scale, hypertension, and COVID-19 antiviral medications within the biologic and hydroxychloroquine groups. **P-values, odds ratios between treatment groups, and its 95% confidence interval were from the weighted logistic regression model with all baseline factors included in the model as covariates. After stepwise model selection insignificant baseline factors removed from the final model. The final model for day 14 included age, race, baseline ordinal scale, cardiovascular, and chronic obstructive pulmonary disease. Abbreviation: COVID-19, coronavirus disease 2019.