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2020 ; 2
(6
): e325-e331
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gab.com Text
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Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute
respiratory distress syndrome, and hyperinflammation: a retrospective cohort
study
#MMPMID32501454
Cavalli G
; De Luca G
; Campochiaro C
; Della-Torre E
; Ripa M
; Canetti D
; Oltolini C
; Castiglioni B
; Tassan Din C
; Boffini N
; Tomelleri A
; Farina N
; Ruggeri A
; Rovere-Querini P
; Di Lucca G
; Martinenghi S
; Scotti R
; Tresoldi M
; Ciceri F
; Landoni G
; Zangrillo A
; Scarpellini P
; Dagna L
Lancet Rheumatol
2020[Jun]; 2
(6
): e325-e331
PMID32501454
show ga
BACKGROUND: Mortality of patients with coronavirus disease 2019 (COVID-19), acute
respiratory distress syndrome (ARDS), and systemic inflammation is high. In areas
of pandemic outbreak, the number of patients can exceed maximum capacity of
intensive care units (ICUs), and, thus, these individuals often receive
non-invasive ventilation outside of the ICU. Effective treatments for this
population are needed urgently. Anakinra is a recombinant interleukin-1 receptor
antagonist that might be beneficial in this patient population. METHODS: We
conducted a retrospective cohort study at the San Raffaele Hospital in Milan,
Italy. We included consecutive patients (aged ?18 years) with COVID-19,
moderate-to-severe ARDS, and hyperinflammation (defined as serum C-reactive
protein ?100 mg/L, ferritin ?900 ng/mL, or both) who were managed with
non-invasive ventilation outside of the ICU and who received standard treatment
of 200 mg hydroxychloroquine twice a day orally and 400 mg lopinavir with 100 mg
ritonavir twice a day orally. We compared survival, mechanical ventilation-free
survival, changes in C-reactive protein, respiratory function, and clinical
status in a cohort of patients who received additional treatment with anakinra
(either 5 mg/kg twice a day intravenously [high dose] or 100 mg twice a day
subcutaneously [low dose]) with a retrospective cohort of patients who did not
receive anakinra (referred to as the standard treatment group). All outcomes were
assessed at 21 days. This study is part of the COVID-19 Biobank study, which is
registered with ClinicalTrials.gov, NCT04318366. FINDINGS: Between March 17 and
March 27, 2020, 29 patients received high-dose intravenous anakinra, non-invasive
ventilation, and standard treatment. Between March 10 and March 17, 2020, 16
patients received non-invasive ventilation and standard treatment only and
comprised the comparison group for this study. A further seven patients received
low-dose subcutaneous anakinra in addition to non-invasive ventilation and
standard treatment; however, anakinra treatment was interrupted after 7 days
because of a paucity of effects on serum C-reactive protein and clinical status.
At 21 days, treatment with high-dose anakinra was associated with reductions in
serum C-reactive protein and progressive improvements in respiratory function in
21 (72%) of 29 patients; five (17%) patients were on mechanical ventilation and
three (10%) died. In the standard treatment group, eight (50%) of 16 patients
showed respiratory improvement at 21 days; one (6%) patient was on mechanical
ventilation and seven (44%) died. At 21 days, survival was 90% in the high-dose
anakinra group and 56% in the standard treatment group (p=0·009). Mechanical
ventilation-free survival was 72% in the anakinra group versus 50% in the
standard treatment group (p=0·15). Bacteraemia occurred in four (14%) of 29
patients receiving high-dose anakinra and two (13%) of 16 patients receiving
standard treatment. Discontinuation of anakinra was not followed by inflammatory
relapses. INTERPRETATION: In this retrospective cohort study of patients with
COVID-19 and ARDS managed with non-invasive ventilation outside of the ICU,
treatment with high-dose anakinra was safe and associated with clinical
improvement in 72% of patients. Confirmation of efficacy will require controlled
trials. FUNDING: None.