Anakinra, a recombinant interleukin (IL)-1 receptor antagonist, may have a beneficial effect in patients with severe COVID-19 with a significant inflammatory response; however, additional trials are needed to better understand the role of IL-1 receptor antagonism in COVID-19, according to a commentary published in Lancet Rheumatology.
Reports during the early COVID-19 pandemic indicated a hyperinflammatory state among patients with severe COVID-19, but the clinical characteristics, pathophysiology, and phenotype still remain unclear.
Increased levels of cytokines and ferritin in patients with severe COVID-19 have been described as modest compared with the levels observed in patients with the prototype cytokine storm syndromes, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome.
With regard to the hyperinflammatory state in severe COVID-19, researchers explored multiple therapeutic options, including corticosteroids, tocilizumab, and IL-1 pathway antagonism. Treatment with canakinumab, a selective IL-1β inhibitor, had disappointing results for COVID-19; however, according to experts, these results cannot be extrapolated to anakinra, which induces both IL-1α and IL-1β blockade.
In a systematic review and meta-analysis, Kyriazopoulou and colleagues evaluated studies aimed at determining the safety and efficacy of anakinra in hospitalized patients with COVID-19.
The meta-analysis included aggregate data from 1185 patients in 9 studies and patient-level data from 895 patients from 6 studies. Treatment with anakinra compared with standard of care or placebo was associated with lower mortality risk (25% vs 11%, respectively; adjusted odds ratio, 0.32, P <.0001). There was no safety signal associated with anakinra.
Study findings suggested that anakinra was not beneficial compared with dexamethasone; however, these findings are in contrast to previous studies that showed the added value of combining IL-6 blockade with corticosteroids compared with using corticosteroids alone.
Although there is no consensus on the definition of a hyperinflammatory response, simple, widely available clinical measures, including C-reactive protein (CRP), were used in previous research. The beneficial effect of anakinra was more pronounced in patients with a significant inflammatory response, defined as a CRP concentration of greater than 100 mg/L.
“The COVID-19 pandemic has shown the importance of multispecialty collaboration. Further prospective trials of IL-1 pathway antagonism are needed, and rheumatologists should be central to the design of such trials to ensure thoughtful stratification of patients to maximize benefit and minimize harm,” the authors of the commentary concluded.
Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Tattersall RS, McGonagle D, Manson JJ. A role for interleukin-1 receptor antagonism in severe COVID-19? Lancet Rheumatol. Published online August 9, 2021. doi:10.1016/S2665-9913(21)00249-6