BackgroundRestraining maladaptive inflammation is considered a rationale strategy to treat severe coronavirus disease-19 (COVID-19) but available studies with selective inhibitors of pro-inflammatory cytokines have not provided unequivocal evidence of survival advantage. Late administration is commonly regarded as a major cause of treatment failure but the optimal timing for anti-cytokine therapy initiation in COVID-19 patients has never been clearly established.ObjectivesTo identify a window of therapeutic opportunity for maximizing the efficacy of interleukin (IL)-1 and IL-6 blockade in COVID-19.MethodsSurvival at the longest available follow-up was assessed in severe hyper-inflamed COVID-19 patients treated with anakinra, tocilizumab, sarilumab, or standard of care, stratified according to respiratory impairment at the time of treatment initiation.Results107 patients treated with biologics and 103 contemporary patients treated with standard of care were studied. After a median of 106 days of follow-up (range 3-186), treatment with biologics was associated with a significantly higher survival rate compared to standard therapy when initiated in patients with a PaO2/FiO(2) >= 100 mmHg (p < 0.001). Anakinra reduced mortality also in patients with PaO2/FiO(2) < 100 mmHg (p = 0.04).ConclusionsIL-1 and IL-6 blocking therapies are more likely to provide survival advantage in hyper-inflamed COVID-19 patients when initiated before the establishment of severe respiratory failure.

Respiratory Impairment Predicts Response to IL-1 and IL-6 Blockade in COVID-19 Patients With Severe Pneumonia and Hyper-Inflammation

Lanzillotta, Marco;Cavalli, Giulio;De Luca, Giacomo;Tomelleri, Alessandro;De Lorenzo, Rebecca;Rovere-Querini, Patrizia;Castagna, Antonella;Landoni, Giovanni;Ciceri, Fabio;Zangrillo, Alberto
Penultimo
;
Dagna, Lorenzo
Ultimo
2021-01-01

Abstract

BackgroundRestraining maladaptive inflammation is considered a rationale strategy to treat severe coronavirus disease-19 (COVID-19) but available studies with selective inhibitors of pro-inflammatory cytokines have not provided unequivocal evidence of survival advantage. Late administration is commonly regarded as a major cause of treatment failure but the optimal timing for anti-cytokine therapy initiation in COVID-19 patients has never been clearly established.ObjectivesTo identify a window of therapeutic opportunity for maximizing the efficacy of interleukin (IL)-1 and IL-6 blockade in COVID-19.MethodsSurvival at the longest available follow-up was assessed in severe hyper-inflamed COVID-19 patients treated with anakinra, tocilizumab, sarilumab, or standard of care, stratified according to respiratory impairment at the time of treatment initiation.Results107 patients treated with biologics and 103 contemporary patients treated with standard of care were studied. After a median of 106 days of follow-up (range 3-186), treatment with biologics was associated with a significantly higher survival rate compared to standard therapy when initiated in patients with a PaO2/FiO(2) >= 100 mmHg (p < 0.001). Anakinra reduced mortality also in patients with PaO2/FiO(2) < 100 mmHg (p = 0.04).ConclusionsIL-1 and IL-6 blocking therapies are more likely to provide survival advantage in hyper-inflamed COVID-19 patients when initiated before the establishment of severe respiratory failure.
2021
COVID-19
SARS-CoV-2
anakinra
interleukin-1
interleukin-6
sarilumab
tocilizumab
Aged
Antibodies, Monoclonal, Humanized
Disease-Free Survival
Female
Follow-Up Studies
Humans
Interleukin 1 Receptor Antagonist Protein
Interleukin-1
Interleukin-6
Male
Middle Aged
SARS-CoV-2
Severity of Illness Index
Survival Rate
COVID-19
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/116537
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 29
  • ???jsp.display-item.citation.isi??? 30
social impact