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24-09-2021 | Rheumatology | News | Article

suPAR-guided anakinra cuts odds of poor outcomes with COVID-19

Author:
Laura Cowen

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.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

24 September 2021: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

Nature Med 2021; doi:10.1038/s41591-021-01499-z

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