Covid, early anakinra treatment reduces mortality by 55%

The anti Covid health train

An early and targeted administration of anakinra (anti-inflammatory already approved for some time in the EU and the United States for other indications), in association with the current therapeutic standard, has shown a relative reduction in 55% of mortality and an almost threefold benefit in preventing progression to severe respiratory failure (IRG) in hospitalized COVID-19 patients with poor prognosis, reducing the median time to ICU discharge by 4 days.

In addition, anakinra treatment increased the number of hospital discharges without evidence of infection with COVID-19, with a number of patients potentially in complete recovery 2.8 times higher than those treated with standard therapy and placebo.
These are some of the most important results, positive and definitive, at 28 days of SAVE-MORE, the first pivotal randomized and controlled study conducted on a large pool of hospitalized patients (about 600 between Italy and Greece) and specifically aimed at evaluating COVID-19 patients at risk of progression to severe respiratory failure (IRG) before admission to intensive care and demonstrating the benefit of prompt intervention to prevent disease aggravation and death.

The results – presented by Swedish Orphan Biovitrum (Sobi ™) (which supported the study) and the Hellenic Institute for the Study of Sepsis (which sponsored and conducted it) – have just been released on MedRxiv and proposed for publication in peer-reviewed journal.
The Italian centers included in the study are the Lazzaro Spallanzani National Institute of Infectious Diseases of Rome (Italian coordinating center of the study), the Agostino Gemelli IRCCS University Hospital in Rome, the IRCCS San Raffaele Hospital in Milan and the IRCCS Humanitas, the Territorial Social Health Authority of the Civil Hospitals of Brescia, the IRCCS Sacro Cuore Don Calabria Hospital in Negrar (VR), the Jesolo Hospital and the San Martino IRCCS Polyclinic Hospital of Genoa.

The trial evaluated the response in patients with moderate or severe pneumonia, identifying those at risk of developing an IRG by measuring the concentration of suPAR (soluble urokinase plasminogen activator receptor), a plasma biomarker that serves as a prognostic tool for early immune activation and which has already been associated with a poor prognosis in various conditions. Standard concomitant treatments were similar for the two arms and included dexamethasone, anticoagulants, and remdesivir.

“One of the decisive aspects in the treatment of hospitalized patients with COVID-19 is the exact positioning of the few drugs we have available” – explained the Prof. Massimo Fantoni, Infectious Disease and Covid 2 Primary at the Agostino Gemelli University Hospital in Rome. “The results of the SAVE-MORE study are very significant and make an important contribution in this regard. Patients with high levels of the suPAR biomarker treated with anakinra showed better survival, a reduction in progression to severe respiratory failure and a reduction in ICU hospitalization time ”.

“Anakinra is the first drug whose use is customized on the patient’s response to the virus” – said the Prof. Emanuele Nicastri, Infectious disease specialist and Director of the Infectious Diseases Division of the Spallanzani Institute in Rome. “For the first time, in fact, we have an extremely effective tool that allows a clear individualization of the therapy on a specific patient with those characteristics and a moderate or severe level of Covid-19”.

“The excessive inflammatory response to COVID-19 infection is one of the main causes of disease progression and mortality” – said the Lead Investigator Evangelos J. Giamarellos-Bourboulis, Professor of Internal Medicine and Infectious Diseases at the National Koper University of Athens, President of the European Shock Society and the European Sepsis Alliance – “therefore there is an urgent need for drugs capable of affecting hyperinflammation and preventing its evolution. The results of the SAVE-MORE study show that the risk of serious disease can be reduced by intervening early ”.

“COVID-19 infection can be serious and lead to death due to an excessive immune reaction, often referred to as “- specified the Prof. Lorenzo Dagna, Director of the Immunology, Rheumatology and Rare Diseases Unit of the San Raffaele Hospital in Milan. “Anakinra is an IL-1 α / β receptor antagonist, a substance that plays a central role in hyperinflammation in COVID-19: blocking IL-1 α / β early in the disease can significantly reduce the risk of evolution towards severe forms of disease. To date, no drugs have been approved for the treatment of the COVID-19 inflammatory response. Over a year ago, in the initial months of the pandemic, my group was the first to demonstrate the efficacy of this drug in a smaller group of patients. I am particularly pleased with the results of the current study which formally demonstrate the goodness of our intuition and the efficacy of anakinra in a larger group of patients with COVID-19. “.