In this retrospective analysis of data from an active surveillance programme, we assessed safety of remdesivir by measuring the clinical outcomes (cure, improvement, no improvement, or death) in hospitalised patients with COVID-19 who were treated with remdesivir, and their subgroups. The cure/improvement rate was 84%, which is in accordance with the cure/improvement reported in historical cohorts [9,10,11,12,13,14,15,16]. Most patients were male, were in the age group of 40–60 years, required oxygen therapy, and received remdesivir for 5 days. Diabetes and hypertension were the most common comorbidities. Low cure rate and high mortality was seen in patients > 60 years old and in patients who required HFO, NIV or MV compared to patients on SLFO supplementation.
Remdesivir is a nucleotide prodrug effective against various RNA viruses such as Nipah virus, respiratory syncytial virus, Ebola virus, SARS-CoV-1, and the Middle East respiratory syndrome coronavirus (MERS-CoV) . Remdesivir is metabolised intracellularly to its ATP analogue, which inhibits viral RNA polymerase and thus halts viral replication . Remdesivir emerged as a candidate drug in the current COVID-19 pandemic and received full approval for use in COVID-19 by the USFDA [4, 18]. Remdesivir was well tolerated in clinical trials and in the compassionate-use programme. Common adverse events reported were nausea, elevated ALT levels, headache, hypokalaemia, worsening respiratory failure, and constipation [9,10,11, 13, 14]. In our analysis, 13% patients reported adverse events, with nausea and increased liver enzyme levels being the most common.
In the randomised, controlled ACTT-1 trials, patients in the remdesivir group were significantly more likely to have clinical improvements than those in the placebo group [9, 11]. In a robust pooled analysis that included patients enrolled in the SIMPLE-severe trial and a retrospective cohort of severe COVID-19 patients receiving standard-of-care, recovery rate was 74.4% at day 14 for patients in the remdesivir group . An improvement in the clinical status by at least 2 points on the ordinal scale (or being discharged alive) was seen in 71.9% of the patients and that by ≥ 1 points was seen in 76.2% of the patients on day 14 . The cure/improvement rate in our analysis was 83.99%.
In the SIMPLE-severe trial, patients randomised to a 5- or 10-day course of remdesivir did not show a significant difference . Results from a recent DISCOVERY trial also showed no clinical benefit of remdesivir in hospitalised COVID-19 patients who were symptomatic for more than 7 days and receiving oxygen support . Our analysis showed that most patients received a 5-day course of remdesivir therapy, which is in line with the DCGI-approved prescribing information.
The mortality rate following 5 days of treatment with remdesivir was 8% on day 14 in the SIMPLE-severe trial and 1% on day 28 in the SIMPLE-moderate study [9, 10]. Following 10 days of treatment with remdesivir, the mortality rate by day 15 was 6.7% in the ACTT-1 trial and 2% by day 14 in the SIMPLE-severe trial [10, 11]. The WHO Solidarity trial, which included 11,330 patients from 30 countries, showed no improvement in the mortality rate in patients randomised to remdesivir treatment compared with the local standard-of-control . In another pooled analysis, the mortality rate was 7.6% at day 14 in patients receiving remdesivir for 5–10 days . Two recent systematic review and meta-analysis have also supported the mortality benefits with the treatment of remdesivir [21, 22]. In our analysis, the mortality rate was 6.77% and multivariate analysis showed that remdesivir treatment for > 5 days was associated with lower odds of death compared to remdesivir treatment for < 5 days.
During the COVID-19 pandemic, several studies reported that older adults and those with comorbid hypertension, diabetes, obesity, and heart disease are at higher risk for developing life-threatening COVID-19 illness [14, 23]. In the current analysis, similar cure/improvement rate was observed irrespective of comorbid conditions. However, numerically higher mortality was observed in patients with cardiac disease (14.73%), followed by that in lung disease (10.75%), diabetes (9.93%), and hypertension (5.32%). Lower grade of respiratory support and age < 65 years were associated with a > 2 point improvement on the ordinal scale in patients treated with remdesivir . Our results showed higher patient clinical outcome when patients did not require oxygen support and were < 60 years of age. An Indian retrospective study, the SORT trial enrolled 350 patients treated with remdesivir and showed that patients who received remdesivir early (within 9 days of symptom onset) were more likely to have a lower incidence of mortality compared with those treated after ≥ 9 days of symptom onset, suggesting that initiating remdesivir earlier during the disease course in moderate-to-severe COVID-19 infection may show better clinical improvements/outcomes .
Our analysis had some limitations as well. This was a retrospective analysis of the data obtained from an active surveillance programme database; therefore, comparison of the results with the control group could not be performed. Moreover, this analysis could not detect the association using multivariate analysis. Cure/improvement rates were not defined in terms of the ordinal scale. The data collection instrument did not allow to collect information regarding the severity of disease and therefore it is most likely that majority of these patients were moderate or severe. Data was collected at a single time point. However, our analysis presents findings of a large cohort of COVID-19 patients treated with remdesivir in real-life clinical settings in India and adds to the clinical evidence on remdesivir use in COVID-19.
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