Support for biomarker studies to guide interleukin inhibitor use in COVID-19
medwireNews: Interleukin (IL)-1 inhibition is associated with a significant reduction in overall mortality risk among hospitalized patients with COVID-19 and hyperinflammation, while patients with markedly elevated C-reactive protein (CRP) or low lactate dehydrogenase may benefit from IL-6 inhibition, researchers report.
These findings are based on an observational study of 392 patients with COVID-19, respiratory insufficiency, and hyperinflammation (CRP ≥100 mg/L or ferritin ≥900 ng/mL) who were treated at the San Raffaele Hospital in Milan, Italy, between February and May 2020. A total of 16% received treatment with the IL-1 receptor inhibitor anakinra, while 14% were given an IL-6 receptor inhibitor (tocilizumab or sarilumab), and the remaining 70% did not receive IL inhibitors and formed the control group.
As reported in The Lancet Rheumatology, people treated with anakinra had a significantly lower 28-day mortality risk than those who did not receive IL inhibitors, at rates of 14% versus 32% and a significant hazard ratio (HR) of 0.45 on multivariable analysis. Mortality rates were not significantly different among patients treated with an IL-6 inhibitor compared with those in the control group, however, at 18% and 32%, respectively.
Lorenzo Dagna (San Raffaele University, Milan) and colleagues note that increasing serum CRP levels and decreasing serum lactate dehydrogenase levels were significantly and independently associated with an increased risk for mortality in the multivariable analysis, and they used interaction terms in a Cox regression analysis to evaluate whether these biomarkers were associated with response to IL inhibitor treatment.
In these analyses, there was a significant association between IL-6 inhibitor use and decreased mortality risk with increasing concentrations of CRP, and both IL-1 and IL-6 inhibition were significantly associated with reduced mortality risk with decreasing concentrations of lactate dehydrogenase.
“These hypothesis-generating findings suggest that the potential benefit of interleukin inhibition is highest in the early phases of disease, characterised by rampant inflammatory activation, but progressively fades in more advanced stages characterised by extensive disease burden and tissue damage,” say Dagna et al.
“[S]erum parameters such as C-reactive protein and lactate dehydrogenase might be useful to identify those patients who are more likely to respond better to cytokine inhibitors,” they add.
Writing in an accompanying comment, Randy Cron (University of Alabama at Birmingham, USA) says that “[u]ltimately, a personalised medicine approach to treating various cytokine storm syndromes, COVID-19 and others, should result in improved survival.”
He stresses that “[t]rial design will be crucial” for further investigation of such strategies, both in terms of identifying COVID-19 patients most likely to benefit from cytokine inhibitors and establishing the most appropriate regimen.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
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