Future cytokine storm management may rely on biomarkers, predictors
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SCOTTSDALE, Ariz. — Future strategies for managing cytokine storm may rely on adequately predicting treatment response, according to a speaker at the Basic and Clinical Immunology for the Busy Clinician symposium.
“COVID, in its severe form, is an immune dysregulation state with elevated cytokines, acute systemic inflammatory symptoms and secondary organ dysfunction disproportionate to the initial trigger,” Puja Mehta, MBBS, of University College London, told attendees in a recorded presentation at the hybrid meeting. “In brief, the pathogenesis of cytokine storms has not been elucidated, but it is thought to occur in a genetically susceptible individual where a trigger results in a dysregulated immune activation.”
If rheumatologists intend to manage hyperinflammation in all its forms, beginning with COVID-19-associated hyperinflammation, it will be useful to develop multivariate models to identify at-risk patients, Mehta added.
“We talked about, ‘Look how far we have come,’ but here I am thinking that we haven’t really come that far in terms of predicting treatment response,” she said.
According to Mehta, the next step may involve figuring out how to use identified biomarkers for these patients, such as soluble urokinase plasminogen activator receptor (suPAR), to move from a prognostic to a predictive model of management.
“It would be nice to have something that we can actually use to predict response and help us select between tocilizumab [Actemra, Genentech] and baricitinib [Olumiant, Eli Lilly],” she said. “We still don’t know about genetics, interferon signatures and autoantibodies in the treatment space in terms of the therapeutic, predictive response.”
While research examines predictive management of patients with COVID-19, interleukin-6 inhibitors and Janus kinase inhibitors may provide aid.
Regarding baricitinib and tocilizumab, both therapies are welcome in cases of drug shortages, but there are still instances where one may be preferable to the other, Mehta said.
“Now, how do we pick between these two agents or even a combination?” she added.
Barcitinib is available in more locations and is cheaper in some countries, and has the benefit of being steroid-sparing in high-risk patients. Tocilizumab, meanwhile, may be preferable in patients who may be pregnant and in children due to convenient dosing options, Mehta said.
“Immunomodulation reduces mortality in a subgroup of patients with severe COVID-19,” she said. “The impact of genetics, interferon signatures and autoantibodies is as of yet unknown.”
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Mehta P. Sorting out cytokine storm and the role of immune based therapies. Presented at Basic and Clinical Immunology for the Busy Clinician, Feb. 25-26, 2023; Scottsdale, Arizona (hybrid meeting).
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