Most Covid-19 patients either presented asymptomatically or with mild symptoms. However, around 5% presented or progressed to critically ill and around 2.3% succumbed to the illness. (1) The overwhelming host inflammatory response is the culprit leading to those severe and death events.
To date, glucocorticoids such as dexamethasone and methylprednisolone have been the standard of care for critically ill patients and are known to improve survival.
Two anti-inflammatory agents indicated for autoimmune diseases, tocilizumab and baricitinib have also been explored extensively for their role in Covid-19 patients. Their role as adjunctive treatment to the standard care has been suggested as below:
Tocilizumab
Tocilizumab is a monoclonal antibody that inhibits Interleukin-6 (IL-6) receptors and the IL-6 mediated acute-phase inflammatory response.
REMAP-CAP study concluded that treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival in Covid-19 patients treated in ICU. (2)
It is recommended to add tocilizumab to the standard of care for critically ill hospitalised Covid-19 patients within 24-48 hours of mechanical ventilation initiation. (Grade 2B) (3)
The recommended dose of Tocilizumab is 8mg/kg, up to a maximum of 800mg, administered as an intravenous infusion over 1 hour as a single dose. An additional dose can be given 12 to 24 hours later at the clinician’s discretion.
Baricitinib
Baricitinib is an anti-inflammatory agent used in autoimmune diseases by selectively inhibit of Janus-Kinase (JAK-1 and JAK-2) receptors.
COV-BARRIER phase 3 trial recruited participants who initially requiring baseline oxygen support. Patients on Baricitinib and standard of care (SOC) was compared to those on placebo plus SOC.
The primary endpoint was the proportion of those who progressed to high-flow oxygen or non-invasive ventilation, invasive mechanical ventilation or extracorporeal membrane oxygenation, or death by day 28.
COV-BARRIER unpublished results suggested that the reduction in the composite primary endpoint in the baricitinib group did not achieve a statistical significance. (4)
However, the secondary endpoint of all-cause mortality at day 28 was significantly lower in the baricitinib group. (4)
It’s recommended that baricitinib or tocilizumab be added to usual care for hospitalized adults with COVID-19 who have initiated high-flow supplemental oxygen or non-invasive ventilation within the prior 24 to 48 hours (Grade 2B). (3)
For hospitalized adults with COVID-19 who are receiving low-flow supplemental oxygen and have progressively increased oxygen requirements despite dexamethasone plus with significantly elevated inflammatory markers, baricitinib or tocilizumab is suggested to be added to usual care. (Grade 2C). (3)
The recommended dose of baricitinib is 4mg daily, administered orally or crushed for nasogastric tube delivery for up to 14 days or until discharged. For renal impairment patients with eGFR 30 to 60ml/min/1.73m2, 2mg OD is recommended. (4)
References
Mcintosh K. COVID-19: Clinical features. UpToDate. https://www.uptodate.com/contents/covid-19-clinical-features. Accessed August 12, 2021.
REMAP-CAP Investigators, Gordon AC, Mouncey PR, et al. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med. 2021;384(16):1491-1502. doi:10.1056/NEJMoa2100433
Eichler AF, Vora SR. Practice Changing UpDates. UpToDate. https://www.uptodate.com/contents/practice-changing-updates#H24_130713. Accessed August 12, 2021.
Marconi VC, Ramanan AV, de Bono S, et al. Efficacy and safety of BARICITINIB in patients With covid-19 infection: Results from The randomised, double-blind, placebo-controlled, parallel-group COV-BARRIER Phase 3 trial. 2021. doi:10.1101/2021.04.30.21255934
Wang J, Jiang M, Chen X, Montaner LJ. Cytokine storm and Leukocyte changes in MILD Versus Severe SARS‐CoV‐2 infection: Review OF 3939 Covid‐19 patients in China and EMERGING pathogenesis and therapy concepts. Journal of Leukocyte Biology. 2020;108(1):17-41. doi:10.1002/jlb.3covr0520-272r
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