麻豆传媒

Survival rates were significantly higher, though mechanical ventilation-free survival did not differ between hospitalized COVID-19 patients treated with high-dose anakinra (Kineret), an interleukin-1 receptor antagonist, and patients receiving only standard treatment, a small retrospective study in Italy found.

While versus historical controls receiving only standard care (90% vs 56%, respectively, P=0.009), the difference in mechanical ventilation-free survival was non-significant between groups (72% vs 50%, P=0.15), reported Giulio Cavalli, MD, of Vita-Salute San Raffaele University in Milan, and colleagues, writing in The Lancet Rheumatology. The study may have been underpowered for the latter outcome, with 29 patients receiving anakinra and 16 controls.

The authors emphasized that treatment with high-dose anakinra, which is used to treat autoinflammatory disorders such as rheumatoid arthritis, was "safe and associated with clinical improvement in 72% of patients," including improvements in respiratory function and reductions in C-reactive protein, a marker of inflammation.

"Our study is the first to suggest that a high dose of the arthritis drug anakinra may be able to block the overreaction of the immune system caused by COVID-19," Cavalli said in a statement.

Indeed, the authors cited a previous phase III trial that found anakinra in sepsis "showed significant survival benefit in patients with hyperinflammation." They added that compared with other cytokine-blocking agents, "anakinra has a remarkable record of safety and a short half-life, which allows prompt discontinuation."

An accompanying editorial by Kate Kernan, MD, and Scott Canna, MD, both of Children's Hospital of Pittsburgh, noted prior research indicating associations between .

"These and other emerging data rightly focus more attention on the host inflammatory response and might herald a shift in how we approach the host-virus relationship," Kernan and Canna wrote.

They also noted that the higher 21-day survival rate was "accompanied by a more rapid and complete improvement in C-reactive protein" in the anakinra group, characterized as "remarkable in a condition with 30-50% mortality in patients who develop clinical ARDS."

And while the editorialists noted that both ferritin and C-reactive protein values were higher in this cohort than in other hospitalized adults with COVID, they "correlated better with the risk of mortality, and, thus, might help identify a subset of patients who are most likely to benefit from anti-inflammatory treatments."

Cavalli and colleagues examined consecutive adult patients with COVID-19, moderate-to-severe acute respiratory distress syndrome (ARDS), and hyperinflammation managed with non-invasive ventilation outside of the intensive care unit. Standard treatment was 200 mg hydroxychloroquine twice daily and 400 mg lopinavir and 100 mg ritonavir twice daily. Patients in the anakinra group received high-dose anakinra 5 mg/kg twice daily.

From March 17 to March 27, high-dose anakinra was given to 29 patients on top of standard treatment. Median patient age was 62, over 80% were men, and over 85% had severe ARDS. They were compared with a historical cohort of 16 patients who did not receive anakinra. Seven other patients received low-dose subcutaneous anakinra, but their treatment was stopped after 7 days due to lack of improvement.

After 21 days, 21 patients in the high-dose anakinra group had improvements in respiratory function compared with 10 of 16 historical controls. Five patients versus one patient required mechanical ventilation, respectively, and three patients in the anakinra group versus seven in the comparison group died.

Notably, in the anakinra group, 13 were discharged from the hospital, while three no longer needed supplemental oxygen, three were receiving low-flow supplemental oxygen, and two no longer had ARDS. In the comparison group, seven were discharged from the hospital and one was still receiving low-flow supplemental oxygen.

Treatment was continued for adverse events in seven patients after a median of 9 days, with four having bacteremia, specifically Staphylococcus epidermidis, while three had increases in serum liver enzymes. Two patients in the comparison group had bacteremia and five had increases in liver enzymes, as well.

Three patients in the anakinra group and two in the comparison group had thromboembolism attributed to COVID-19 pathogenic events.

Noting the many limitations to the study, including its small size, its retrospective nature, use of historical controls, and restriction to a single center, Kernan and Canna said the findings should be interpreted as "exploratory" but still merit further research.

"In view of the biological plausibility of anakinra, the pharmacokinetic and safety profile of the drug, and a growing body of positive experience in autoinflammation and cytokine storm, these data are promising and support [prioritizing] this approach in the planning and [enrollment] of [randomized] controlled trials," the editorialists wrote.

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