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The clinical benefits of anakinra

The health of COVID-19 patients can quickly degenerate. It is therefore crucial to be able to identify risks and treat them according to the clinical situation. When a case progresses towards the severe state, levels of suPAR (soluble urokinase plasminogen activator receptor) rise more rapidly and sooner than other known biomarkers of severity (CRP, IL-6, ferritin, D-dimer). This denotes an abnormal presence of calprotectin and of IL-1⍺/β, pro-inflammatory cytokines that induce deregulated and pathogenic inflammation.

Researchers at the University of Athens, who discovered that suPAR is a biomarker in severe cases, had previously shown the clinical benefits of anakinra (phase 2 SAVE trials). This is a molecule that blocks the activity of IL-1⍺/β in patients with elevated levels of suPAR. The same team then led the SAVE-MORE phase 3 clinical trial, on a representative sample and in double-blind conditions, in order to confirm the first results and to evaluate the safety of their approach.

Between December 2020 and March 2021, 1 060 COVID-19 patients were classified according to their levels of suPAR and to other clinical criteria of severity as defined by the World Health Organisation. 594 patients with a level higher than 6 ng/ml were selected. Considered to be high-risk, 91,6% of them had developed severe pneumonia. 85,9% received a standard treatment using dexamethasone, while 405 were treated with sub-cutaneous anakinra and 189 with a placebo.

After 28 days, 50,4% of the patients treated with anakinra were completely cured (no viral RNA detected), against 26,5% who had received the placebo. Mortality rates were 3,2% and 6,9% respectively. In addition, anakinra reduced the risk of COVID-19 persisting, reduced severity by day 28, and shortened by 4 days the time spent in the emergency services. After only 7 days of treatment, patients had higher levels of lymphocytes while levels of IL-6 and CRP were lower. It is clear that this molecule limits hyper-inflammation. Some serious side-effects were observed following treatment, mainly involving infections, but here again they were fewer in patients having received anakinra (16% vs 21,7%). Other less serious side-effects also followed this pattern (hyperglycemia, liver problems).

So this study validated the SAVE trials and demonstrated that classifying COVID-19 patients according to their levels of suPAR and treating those most at risk (>6 ng/ml) very promptly with anakinra has real clinical benefits, from the 14th day of treatment. In addition, the low mortality rates amongst all these severe cases also reflects the improvement of standard treatments since the beginning of the pandemic. The authors note that patients with high levels of suPAR who need respiratory assistance at the moment of testing should be treated with tocilizumab, a blocker of IL-6 which is more appropriate in this instance.

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