April 29, 2020
(Editors note: This article was updated at 11:00 PM, April 29, 2020, to reflect new remdesivir data)
By Douglas L. Jennings, PharmD, FACC, FAHA, FCCP, FHFSA, BCPS
The COVID-19 pandemic rages onward, largely held in check only by extreme social distancing. In my last blogs1, I explored the evidence supporting the various drug therapies that have been advocated to combat this relentless scourge. Since then, new evidence has emerged for several of these therapies, prompting me to publish this update.
Hydroxychloroquine: Shifting away from hopeful fact?
No drug has been more controversial in treating the COVID-19 pandemic, as hydroxychloroquine garnered strong acclaim from media pundits and politicians alike, despite the initial shaky evidence. This once hopeful agent has come under scrutiny, as a small randomized study from China showed no difference in rates of viral clearance between it and the standard of care. These results must be viewed cautiously however, as this study mostly included patients with mild-to-moderate disease who were receiving concomitant antiviral agents, and significant differences in the baseline characteristics of the population suggest imperfections in the randomization scheme.
Adding to this, a retrospective analysis of over 350 VA patients also showed no benefit of hydroxychloroquine. In fact, compared with the standard therapy group, the risk of death from any cause was higher in the hydroxychloroquine group; this difference was not seen group who received hydroxychloroquine with azithromycin.
It’s important to recognize that neither of these studies has been peer-reviewed, so these results must be viewed as preliminary. Nonetheless, in light of these recent publications, the FDA has issued a warning against the use of hydroxychloroquine for treating COVID-19 outside of the hospital or clinical trial setting.
Remdesivir: hopeful fact now fading
Preliminary data from China suggest that in a 237 patient randomized trial of severe COVID-19 disease showed that remdesivir was not associated with any change in to clinical improvement, 28-day mortality, or clearance of SARS-CoV-2 viremia. Similar to the hydroxychloroquine data, these have not been formally peer-reviewed. Furthermore, there are similar trials running in the United States that will shed more light on the utility of this agent. Still, these results from China are disappointing.
Update: This just in! Results from a NIH sponsored clinical trial found that patients who received remdesivir took an average of 11 days to recover as compared with 15 days for those who received a placebo. The rates of mortality were also numerically lower (8- versus 11%), although this was not statistically significant. These findings led Dr Anthony Fauci to declare remdesivir as 'the new standard of care' for treating COVID-19 on April 28th, 2020.
Sarilumab: remaining mostly fiction
Sarilumab is an immunomodulating agent that works by antagonizing IL-6. This class of medications is believed to be helpful for managing the adverse immunologic sequelae of COVID-19 infection, which can manifest as cytokine storm and severe respiratory and circulatory compromise. Unfortunately, Sanofi and Regeneron announced that their phase 3 study of Sarilumab will only continue for the sickest patients and only at the highest doses after preliminary results suggest little effect of the therapy.
Tocilizumab: Last bastion of hope?
Tocilizumab is another IL-6 immunomodulatory agent that has anecdotal success in managing patients with more severe manifestations of COVID-19. On April 27th, preliminary results from a small study in France showed that the 65 patients randomized to tocilizumab had a lower chance of dying or requiring mechanical ventilation than the 63 patients randomized to standard of care therapies. These data, like all that I have presented, have not been peer-reviewed, so they must be viewed cautiously. However, it’s uplifting at least to end this blog on a positive note, and hope that once these studies are published we will gain a deeper insight into which agents may help save lives and palliate the physical misery of COVID-19 infection.
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.