covid-19: anakinra, a promising treatment

Antiviral monoclonal antibodies: big weak points

The arrival of the Omicron variant has rendered obsolete the use of the first monoclonal antibodies approved by the European Medicines Agency (EMA): Ronapreve, from the Roche (Switzerland) and Regeneron (United States) laboratories, and Regkirona, developed by Celltrion (South Korea). Two of them recently dubbed by the EMA still have some effectiveness: 1. Xevudy, from the GlaxoSmithKline laboratory, which can be used in the early treatment of infected patients at risk of developing a serious form. 2. Evusheld, from AstraZeneca, given in prevention to subjects who respond poorly to vaccines and carry comorbidities. As a reminder, monoclonal antibodies are proteins designed to bind to a target in order to neutralize it. Those developed against Sars-CoV-2 target a specific region of its spicule, with which it infects human cells. The trouble is that the variants have increased the number of their mutations, which ultimately has the effect of rendering all antiviral monoclonal antibodies ineffective. Good news, on December 16, the EMA approved anakinra (Kineret), capable, regardless of the variant, of blocking the terrible inflammatory (cytokine) storm implicated in the vast majority of pandemic-related deaths. Its strength is not to target the virus, but the main mechanism by which it kills!

Anakinra, a product known for twenty years

It is a drug that the Paris Match teams have already talked about. Dr. Gilles Hayem (Paris Saint-Joseph hospital group), rheumatologist, was one of the initiators of this treatment. “Rheumatologists have known about this product for twenty years,” he explains. Anakinra inhibits a pro-inflammatory protein called interleukin 1. Following certain stimuli (viruses, bacteria, etc.), a particular enzymatic complex of the human body called the inflammasome can be activated, giving rise to a hyperinflammatory phenomenon. During this process, interleukin 1 is the first cytokine to be produced in excess. Anakinra acting from the onset of the cytokine storm, it was logical to think that it had a serious chance of being effective in forms of Covid-19 with a severe evolutionary profile. In support of this postulate, a first series of studies was quickly launched in France and Italy. They could not be randomized (with blind draw to determine the distribution of anakinra or placebo to patients), because it was necessary to act quickly in hospitalized subjects, with severe respiratory impairment, on oxygen, and biological signs indicating a high risk of severe form in the short term. Of all these studies, the one conducted at Saint-Joseph Hospital and published in the “Lancet Rheumatology” was undoubtedly the most convincing: 52 patients treated with anakinra were compared to a control group that had not received it (44 subjects hospitalized at the same time and with a similar profile). Result: 25% of patients treated with anakinra died or were transferred to intensive care, against 73% of patients who did not receive the product! The other trials reported similar results.

Also read.Omicron wave: severe immunocompromised patients “in the eye of the storm”

Mortality reduced by up to 80%

“These more than encouraging results were not really taken into consideration by the members of the scientific council of the Elysée”, underlines Dr. Hayem. The reason ? “No randomization! Worse, a study by the University Hospital of Tours, evoking an alleged increased risk of mortality under anakinra, discredited the molecule before a statement of retraction was published by the National Medicines Safety Agency. It was finally a Greek study, randomized according to the rules, carried out in 594 patients at risk of serious forms that was able to convince the EMA: in addition to the standard treatment which included corticosteroids (dexamethasone), 189 subjects received a placebo and 405 the anakinra. After a twenty-eight-day follow-up, the number of patients having fully recovered was twice as high in the anakinra group as in the other, mortality half as low and even reduced by 80% in the most severely affected subjects. . Dr. Hayem adds: “Anakinra is a carbon copy of a natural interleukin-1 antagonist that the human body makes spontaneously. This biological treatment is much less expensive than monoclonal antibodies. The whole treatment costs about 500 euros, compared to the thousands of euros that cost the days in intensive care that it avoids. »

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