medwireNews: Early anakinra treatment may reduce the risk for poor outcomes in patients with COVID-19 who are at risk for progressing to respiratory failure on the basis of elevated soluble urokinase plasminogen activator receptor (suPAR) levels, SAVE-MORE trial data show.
“The clinical benefit with anakinra treatment was already apparent from day 14, and this is of clinical importance because the first 14 [days] is the period during which a patient is expected to worsen; anakinra benefit was maintained until day 28,” say Evangelos Giamarellos-Bourboulis (National and Kapodistrian University of Athens, Greece) and co-investigators.
The researchers report in Nature Medicine that the phase 3 SAVE-MORE trial included 594 hospitalized patients with COVID-19 and a suPAR level of 6 ng/mL or higher, indicating that they were at risk for progressing to respiratory failure. The majority (85.9%) of participants were receiving dexamethasone.
After 28 days of treatment, 50.4% of the 405 patients randomly assigned to receive the IL-1 receptor antagonist anakinra 100 mg/day had fully recovered, with no detectable viral RNA. By comparison, the recovery rate was 26.5% among the 189 patients given placebo.
After adjustment for disease severity, dexamethasone use, BMI, and country, Giamarellos-Bourboulis and team found that individuals who received anakinra were a significant 64% less likely to have a worse score on the 11-point World Health Organization Clinical Progression Scale (WHO-CPS) at day 28 than those who received placebo.
In confirmatory analyses, anakinra use, relative to placebo, was associated with a significant 42% lower odds for a worse 11-point WHO-CPS at day 14, 64% lower odds for persistent disease (WHO-CPS ≥1) at day 28, and 54% lower odds for severe disease or death (WHO-CPS ≥6) at day 28 after adjustment for confounding factors.
The risk for death at day 28 was a significant 55% lower in the anakinra versus the placebo arm, with mortality rates of 3.2% and 6.9%, respectively.
The researchers also report that, compared with placebo, anakinra use was associated with a significantly greater reduction in median Sequential Organ Failure Assessment score at day 7 from baseline (1 vs 0 points), and significantly shorter median stays in hospital (11 vs 12 days) or intensive care units (10 vs 14 days).
Furthermore, the rate of serious treatment-emergent adverse events was lower with anakinra than with placebo, at 16.0% versus 21.7%, but there was a trend for increased rates of neutropenia with anakinra (3.0 vs 0.5%).
“[T]he SAVE-MORE trial showed that early start of treatment with anakinra guided by suPAR levels in patients hospitalized with moderate and severe COVID-19 significantly reduced the risk of worse clinical outcome at day 28, ” conclude Giamarellos-Bourboulis et al.
However, they acknowledge that “[t]he introduction of suPAR to guide treatment could be problematic in settings where this tool is not available.”
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Nature Med 2021; doi:10.1038/s41591-021-01499-z