Anakinra: Timely Targeted Anticytokine Therapy for Severe COVID-19

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.

COMMENT

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.

https://www.jwatch.org/na54236/2021/11/03/anakinra-timely-targeted-anticytokine-therapy-severe-covid?fbclid=IwAR2Gewz71iUNrLkrjHCCctYRNw533mwgxmqt8XdyOYEryoRrtelhasE9CUU

Créditos: Comité científico Covid