Remdesivir shortens time to improvement, but has no significant mortality effect
Patients hospitalized with COVID-19 had shorter times to clinical improvement when treated with remdesivir, but the drug had no significant effect in a time-to-death analysis, even when given with corticosteroids, according to researchers.
“Our study showed that outside of a clinical trial, remdesivir reduced the time to clinical improvement by 2 days,” Brian T. Garibaldi, MD, MEHP, associate professor of medicine and director of the Biocontainment Unit at Johns Hopkins, told Healio Primary Care. “Our study is important since we have not had many reports on the real-world effectiveness of COVID-19 treatments, particularly in a study population that has a high percentage of under-represented minorities, who have shouldered a disproportionate burden of COVID-19 illness.”
The FDA approved remdesivir in October 2020 for the treatment of hospitalized patients with COVID-19 based on the data from the Adaptive COVID-19 Treatment Trial. However, WHO recommends against remdesivir after data from the Solidarity Trial indicated that the drug appeared to have little or no effect on 28-day mortality.
To assess whether remdesivir, with or without corticosteroids, shortens time to clinical improvement, Garibaldi and colleagues conducted a multicenter, retrospective comparative effectiveness research study that included 2,483 patients with confirmed SARS-CoV-2 infection receiving care at a five-hospital health system. The researchers matched patients who received remdesivir with those who did not based on both time-invariant and time-dependent covariates.
Covariates included age, sex, race and ethnicity, Charlson Comorbidity Index, BMI, do not resuscitate or do not intubate orders, ratio of peripheral blood oxygen saturation to fraction of inspired oxygen, BP, pulse, temperature, respiratory rate, C-reactive protein level, complete white blood cell count, lymphocyte count, albumin level, alanine aminotransferase level, glomerular filtration rate, dimerized plasmin fragment D level and oxygen device.
The study’s primary outcome was the rate of clinical improvement, which was determined by either hospital discharge or a two-point decrease on the WHO severity score. The secondary outcome was 28-day mortality. An additional outcome of interest was clinical improvement and time to mortality associated with a combination of remdesivir and corticosteroid treatment.
“Corticosteroids is the key [therapy] that we need more data about in combination with remdesivir,” Garibaldi said. “The general idea is that remdesivir is an anti-viral drug that decreases viral replication, while dexamethasone is an anti-inflammatory drug that decreases inflammation caused by the immune system’s response to SARS-CoV-2, the virus that causes COVID-19.”
Among 342 patients (median age, 60 years; men, 55.3%; self-identified as not white race or ethnicity, 80.7%) who received remdesivir, 184 received corticosteroids and 158 received remdesivir alone. Patients who received remdesivir had a median 5 days to clinical improvement vs. 7 days in matched controls (adjusted HR [aHR] = 1.47; 95% CI, 1.22-1.79).
However, the researchers wrote that the difference in 28-day mortality rate among patients who received remdesivir (7.7%) vs. controls (14%) was not statistically significant in the time-to-death analysis (aHR = 0.7; 95% CI, .38-1.28). Among patients who received remdesivir, corticosteroids were not associated with a reduced risk for death (aHR = 1.94; 95% CI, .67-5.57).
“At this point in time, I think that any patient who is hospitalized with COVID-19 and requires supplemental oxygen (or has an oxygen saturation less than 94%) should receive remdesivir for 5 days (or less if they improve and are discharged prior to 5 days),” Garibaldi said.
He also said more research is needed on the combination of remdesivir with other therapies, including tocilizumab, a drug that targets the Il-6 pathway.
“By binding to the Il-6 receptor, this drug decreased inflammation and may improve outcomes in certain patients with COVID-19,” Garibaldi said. “It is not clear if using remdesivir in combination with tocilizumab will lead to better outcomes.”