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letter
. 2021 Feb 1;44(1):7. doi: 10.18773/austprescr.2020.086

Evolving evidence for immunosuppressants in COVID-19

PMCID: PMC7900274  PMID: 33664542
letter Aust Prescr. 2021 Feb 1;44(1):7.

Letter to the Editor

Ajay K Shukla 1

I read with great interest the informative article on the role of immunosuppression in the treatment of COVID-19.1 While appreciating their efforts, I wish to make a few observations.

In the section where the authors have stated the role of systemic corticosteroids, there are two more findings that are worth mentioning. First, a study found that SARS patients treated with high-dose pulse therapy of methylprednisolone had systemic damage along with metabolic alterations at 12-years follow-up.2 Second, in the RECOVERY trial, treatment with a daily dose of dexamethasone for up to 10 days was associated with reduced 28-day mortality in COVID-19 patients with respiratory support.3

REFERENCES

  • 1.Shivakumar S, Smibert OC, Trubiano JA, Frauman AG, Liew DF. Immunosuppression for COVID-19: repurposing medicines in a pandemic. Aust Prescr 2020;43:106-7. 10.18773/austprescr.2020.037 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Wu Q, Zhou L, Sun X, Yan Z, Hu C, Wu J, et al. Altered lipid metabolism in recovered SARS patients twelve years after infection. Sci Rep 2017;7:9110. 10.1038/s41598-017-09536-z [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al.; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 - preliminary report. N Engl J Med 2020 [Epub 2020 Jul 17]. https://doi.org/ 10.1056/nejmoa2021436 [DOI]
letter Aust Prescr. 2021 Feb 1;44(1):7.

Authors’ response

Senthuran Shivakumar 1, Olivia C Smibert 2, Jason A Trubiano 3, Albert G Frauman 4, David FL Liew 5

The authors of the article, comment:

Evidence in COVID-19 continues to evolve at a rapid pace. While the promise of certain therapeutic options has not materialised, other medicines have emerged from clinical trials with proven clinical efficacy.

While early observational data were promising, tocilizumab failed to improve clinical status and reduce mortality in the COVACTA trial1a or prevent intubation in the BACC Bay trial.2a Dexamethasone, in contrast, has demonstrated some clinical and mortality benefit in advanced disease in the RECOVERY trial.3a As Ajay Shukla points out, the adverse effects of corticosteroids are broad and potentially long-term and should be closely monitored.4,5 Despite dexamethasone, mortality rates remain high. Successful strategies potentially hinge on strategic selection of the mode and timing of immunomodulation in appropriate clinical settings. Refining this treatment paradigm may only be achieved through rigorous clinical trial evaluation.

Trials evaluating the efficacy and safety of multiple immunosuppressive therapies, including tumour necrosis factor inhibitors6 and tyrosine kinase inhibitors,7 continue as we still grapple with this evolving global health crisis. Resources such as the Australian National COVID-19 Clinical Evidence Taskforce’s Living Guidelines8 provide a useful reference point, with important clinical information and summation of emerging evidence for healthcare workers.

While evidence evolves, therapies will either be discounted as unsafe or ineffective or be validated and approved as standard of care. As therapeutic validation occurs, it is important to remember that prescribing outside of clinical trials remains off label and should be conducted in an ethical and considered manner.9

REFERENCES

  • 1a.Furlow B. COVACTA trial raises questions about tocilizumab’s benefit in COVID-19. Lancet Rheumatol 2020;2:e592. 10.1016/S2665-9913(20)30313-1 [DOI] [PMC free article] [PubMed] [Google Scholar]
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  • 3a.Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al.; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19 - preliminary report. N Engl J Med 2020 [Epub 2020 Jul 17]. https://doi.org/ 10.1056/nejmoa2021436 [DOI]
  • 4.Arabi YM, Mandourah Y, Al-Hameed F, Sindi AA, Almekhlafi GA, Hussein MA, et al. Saudi Critical Care Trial Group . Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome. Am J Respir Crit Care Med 2018;197:757-67. 10.1164/rccm.201706-1172OC [DOI] [PubMed] [Google Scholar]
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  • 8.National COVID-19 Clinical Evidence Taskforce. Caring for people with COVID-19. Living guidelines. 2020 Dec 3. https://covid19evidence.net.au [cited 2021 Jan 4]
  • 9.Day R. Off-label prescribing. Aust Prescr 2013;36:182-3. 10.18773/austprescr.2013.075 [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Australian Prescriber are provided here courtesy of Therapeutic Guidelines Ltd

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