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Among patients with elevated soluble urokinase plasminogen receptor levels, standard care plus anakinra increased full recovery and lowered mortality compared with standard care alone.
Identifying patients at excess risk for severe COVID-19 is critical for devising treatment strategies (particularly those involving immune modulation) where early therapy is important. One predictor is plasma soluble urokinase plasminogen receptor (suPAR): Elevated suPAR has been associated with progression to severe respiratory failure. Accordingly, investigators in Greece and Italy designed a two-stage strategy to identify and treat patients with COVID-19 using anakinra, an interleukin (IL)-1 receptor antagonist that blocks the activity of both IL-1α and IL-1β.
In this confirmatory trial involving 594 patients with COVID-19 and suPAR levels ≥6 ng/mL, 189 were randomized to standard care plus placebo and 405 to standard care plus a 10-day course of anakinra. Among all participants, 91.6% had severe pneumonia and 85.9% received dexamethasone. On day 28, 50.4% of the anakinra group was fully recovered with no viral RNA detected compared with 26.5% of the standard-care group (P<0.0001). Twenty-eight–day mortality was 6.9% with standard care and 3.2% with anakinra (hazard ratio, 0.45; P=0.045). Treatment-emergent adverse events occurred in 16.0% of anakinra recipients and 21.7% of standard-care recipients.
By selecting subjects with elevated suPAR levels, only those at high risk were studied. This, coupled with early treatment using anakinra — a specific anticytokine agent — yielded impressive results (particularly given that nearly all subjects received dexamethasone). However, the laboratory assay for suPAR is not currently available in the U.S., and the NIH COVID-19 Guidelines, while acknowledging the possible role of IL-1 in pathogenesis, state that evidence for use of anakinra is currently insufficient. As editorialists note, finding the precise therapies effective against the cytokine storm elicited in COVID-19 remains elusive, with many possibilities yet to explore.
Créditos: Comité científico Covid