“Rem-Yes-ivir” or “Remdesi-Don’t”: What Does the Latest Evidence Say?

^{By Douglas L. Jennings, PharmD, FACC, FAHA, FCCP, FHFSA, BCPS}

As we head into the Christmas season, the battle against the COVID-19 pandemic rages onward. Weary health care providers slog onward against a resilient foe, and the virus continues to infect and kill record numbers of Americans on a daily basis. Remdesivir, an antiviral medication with activity against several viruses including SARS-CoV-2, was the first FDA approved treatment for this most odious scourge. Unfortunately, recent evidence has cast doubt on the efficacy of this once hopeful treatment modality.

The World Health Organization, or WHO, recently updated their guidelines to recommend against the use of remdesivir for SARS-CoV-2 infection, no matter the severity of the patient’s disease. This recommendation is rooted in the fact that the available evidence found that remdesivir does not affect the risk of dying from COVID-19 or needing mechanical ventilation, among other important outcomes.

In preparing this recommendation, the WHO convened an international panel of 24 experts and four survivors of COVID-19 to review data and make recommendations. The recommendation against remdesivir was based on data from four randomized trials including 7,333 people hospitalized with COVID-19.  The panel concluded that most patients would not prefer intravenous treatment with remdesivir given the low certainty evidence.

Adding to this uncertainty, the National Institute of Health (NIH) also recently updated their recommendations, which suggest that remdesivir can be used in hospitalized patients who require supplemental oxygen. However, they recommend against use for patients who require mechanical ventilation due to the lack of data showing benefit at this advanced stage of the disease.

Finally, the Infectious Disease Society of America (IDSA) has also weighed in. These experts suggest against the routine use of remdesivir in patients with COVID-19 admitted to the hospital without the need for supplemental oxygen and with oxygen saturation >94% on room air. However, in hospitalized patients with severe COVID-19, the IDSA panel suggests remdesivir over no antiviral treatment. Severe illness is defined as patients with SpO₂ ≤94% on room air, and those who require supplemental oxygen, mechanical ventilation, or ECMO.

In reading these conflicting recommendations, it’s easy to become disorientated. One group suggests remdesivir for none, another says only for those with moderate disease but not for those most ill, while yet another grants preference for those with the most severe disease.

It’s important to reiterate that all of these recommendations are based on the same body of evidence, and that each expert panel concedes that the strength of this evidence is weak.

For what it’s worth, I’ll offer my humble opinion. I’m by no means an expert in infectious diseases, but I am an expert in evidence-based medicine, and I have acquired a fair amount of common clinical sense in my 15 year career as an acute care pharmacist. I agree with the WHO that the body of evidence does not support a mortality benefit for remdesivir, but I stop short in agreeing that means that it should not be offered to any patients with COVID-19 infection. I agree with the NIH that the best patient to offer therapy to is a hospitalized patient with moderate hypoxemia. I think that if the patient is able, they should participate in the decision to use remdesivir after they have been apprised of the risks and possible benefit of said therapy. I agree with the NIH (and disagree with the IDSA) that patients with severe disease should not be considered for remdesivir. I believe that in these patients—who are presumably further along in their disease course—viral replication is less important, and the focus of the clinician should be on supportive measures aimed at curtailing the collateral damage from infection (ie corticosteroids to suppress excessive immune activation and inflammation).

Ultimately, the bottom line from this latest round of recommendations is that the available evidence for remdesivir is very shaky, and additional studies are sorely needed in order to reconcile these various opinions.

Dr Jennings is currently an Associate Professor of Pharmacy at Long Island University and the clinical pharmacist for the Heart Transplant and LVAD teams at NewYork- Presbyterian Hospital Columbia University Irving Medical Center.  He is an active researcher in his field, and he has published over 120 peer-reviewed abstracts and manuscripts, primarily focusing on the pharmacotherapy of patients under mechanical circulatory support. As a recognized expert in this area, he has been invited to speak at numerous national and international venues, including meetings in France, Saudia Arabia, India. Finally, Dr. Jennings has been active in professional organizations throughout his career. He is a fellow of the American College of Clinical Pharmacy, the American College of Cardiology, the Heart Failure Society of America, and the American Heart Association. 

References:

1. NIH. Therapeutic Management of Patients with COVID-19. https://www.covid19treatmentguidelines.nih.gov/therapeutic-management/. December 3, 2020.
2. World Health Organization (WHO). WHO recommends against the use of remdesivir in COVID-19 patients. https://www.who.int/news-room/feature-stories/detail/who-recommends-against-the-use-of-remdesivir-in-covid-19-patients. November 20, 2020.
3. Infectious Disease Society of America. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-9. December 2, 2020.