Remdesivir benefit greatest when given early in COVID-19

Treatment with remdesivir is associated with reduced risk of hospitalization and death in non-hospitalized and hospitalized COVID-19 patients, respectively, especially when given early during the disease course, according to studies presented at ECCMID 2022.

“We’ve long understood that antivirals work optimally for respiratory viruses when they are given as early as possible, without delay. This data confirms that antiviral treatment is now initiated sooner in hospitalizations and that throughout the pandemic, remdesivir has remained the foundation for hospitalized patients with COVID-19,” said PINETREE co-author Dr Robert Gottlieb from Baylor University Medical Center and Baylor Scott & White Research Institute in Dallas, Texas, US.

The double-blind, placebo-controlled, phase III PINETREE trial enrolled non-hospitalized patients with COVID-19 who were at high risk for severe disease were randomized to receive intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2 and 3) or placebo within 7 days of symptom onset. [ECCMID 2022, abstract L0447]

In the primary analysis, remdesivir significantly reduced the risk of COVID-19-related hospitalization compared with placebo at day 28 (0.7 percent vs 5.3 percent; p=0.008), with no deaths in either group. 

The current post hoc analysis stratified the patients by time of symptom onset as well as the number of risk factors present at baseline.

While reductions in hospitalization risk were seen with remdesivir vs placebo regardless of time of symptom onset, patients who received remdesivir within 5 days of symptom onset derived a greater benefit (0.5 percent vs 4.6 percent; hazard ratio [HR], 0.11; p=0.03) than those who were given remdesivir at >5 days of symptoms onset (1.3 percent vs 6.7 percent; HR, 0.18; p=0.12).

In addition, the risk of hospitalization was also lower with remdesivir vs placebo particularly in patients with ≤2 risk factors for severe disease (0 percent vs 2.4 percent; HR, unestimable) compared with those with >2 risk factors (1.7 percent vs 9.2 percent; HR, 0.17; p=0.02).

Benefit in hospitalized patients

In another retrospective study on 557,164 patients hospitalized with COVID-19 across the US, the use of combination therapy including remdesivir has increased from <1 percent in May 2020 to approximately 41 percent in Jun 2021. There have also been more patients who were initiated on these therapies within 2 days of hospitalization — from 41 percent to 92 percent between May 2020 to June 2021. [ECCMID 2022, abstract 04472]

During this period, survival improved substantially, with death rates declining from 16 percent to 9 percent over time. Furthermore, the length of hospitalization also decreased from a median of 6 to 5 days while that for ICU dropped from 5 to 4 days.

“As healthcare providers’ experience and confidence in COVID-19 therapeutic options has increased, so too has the use of therapeutic combinations, reflecting the incremental incorporation of evidence-based therapies,” said Gottlieb.

A separate real-world study on 1,080 hospitalized patients with COVID-19 in two Italian University Hospitals further validated the survival benefit with remdesivir therapy. [ECCMID 2022, abstract P2013]

At 28 days, hospitalized patients treated with remdesivir had a 74 percent lower risk of death than those who did not receive remdesivir (HR, 0.26; p<0.0001).

The researchers also found several risk factors that were associated with death risk, including chronic kidney disease, age, and non-invasive or invasive ventilation.  

“Further studies are needed to assess the correct timing of administration, to evaluate its use in those who do not require oxygen administration, and to clarify its efficacy against the current variants of concerns, and understand the impact of drug resistance,” suggested the researchers.