Early treatment of COVID-19 with anakinra guided by soluble urokinase
plasminogen receptor plasma levels: a double-blind, randomized
controlled phase 3 trial
Early increase of soluble urokinase plasminogen activator receptor
(suPAR) serum levels is indicative of increased risk of progression of
coronavirus disease 2019 (COVID-19) to respiratory failure. The
SAVE-MORE double-blind, randomized controlled trial evaluated the
efficacy and safety of anakinra, an IL-1 alpha/beta inhibitor, in 594
patients with COVID-19 at risk of progressing to respiratory failure as
identified by plasma suPAR >= 6 ng ml(-1), 85.9% (n = 510) of whom were
receiving dexamethasone. At day 28, the adjusted proportional odds of
having a worse clinical status (assessed by the 11-point World Health
Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as
compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The
median WHO-CPS decrease on day 28 from baseline in the placebo and
anakinra groups was 3 and 4 points, respectively (odds ratio (OR) =
0.40, P < 0.0001); the respective median decrease of Sequential Organ
Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1
points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased
(hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.
The SAVE-MORE phase 3 study demonstrates the efficacy of anakinra, an
IL-1 alpha/beta inhibitor, in patients with COVID-19 and high serum
levels of soluble plasminogen activator receptor
