In this episode, I’ll discuss the optimal timing of remdesivir initiation in hospitalized COVID-19 patients administered with dexamethasone.
Research on remdesivir and dexamethasone for COVID-19 patients began in parallel, and information on the timing of starting these therapies has not been available.
However, researchers recently published in Clinical Infectious Diseases a cohort study of over 1500 patients that examined outcomes when remdesivir was initiated prior to/simultaneously with dexamethasone, or after dexamethasone.
93 patients had initiated remdesivir prior to dexamethasone and 373 co-initiated the two drugs simultaneously. Together this formed the ‘exposure group’. 149 patients were given remdesivir after dexamethasone and 929 did not receive remdesivir at all. Together this formed the ‘non-exposure group’.
The hazard ratio for time to clinical improvement was 1.23 in favor of the exposure group and the hazard ratio for time to positive IgG antibody was 1.22 also in favor of the exposure group.
Among those patients that survived, the exposure group had:
- Shorter hospital length of stay by 2.65 days
- Lower WHO clinical progression scale scores from five days of follow-up onwards
- Lower risks of in-hospital death with a hazard ratio of 0.59
- No increase in the risk of ARDS
The authors concluded:
Initiation of remdesivir prior to or simultaneously with dexamethasone was associated with significantly shorter time to clinical improvement and positive IgG antibody, lower risk of in-hospital death, in addition to shorter length of hospital stay in patients with moderate COVID-19.
Keep in mind when interpreting these results that the patients were not very sick; the majority of the cohort did not require supplemental oxygen or mechanical ventilation. The authors suggest that the benefit may come from remdesivir preventing cytokine storm and then dexamethasone preventing any hyper-inflammation that develops later in the course of the virus. While this may be true, the definition of simultaneous administration was fairly loose, meaning only that the administration of the two medications happened on the same day, not within a specific number of minutes from each other.
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