Clinical improvement seen in a small study of patients with severe COVID-19 treated with the arthritis drug Anakinra

The first study to report the use of the rheumatoid arthritis drug anakinra to treat patients with COVID-19 showed that high-dose anakinra was safe, improved breathing and reduced signs of cytokine storm in 72% (21/29) of patients. It was found to be associated with, and was reported in the results of patients studied in a hospital in Milan for 21 days (registered March 17-27, 2020). Lancet rheumatism journal.

All 29 patients received standard care (non-invasive ventilation (CPAP), hydroxychloroquine, and lopinavir / ritonavir) and Drug treatment (Daily high dose intravenous infusion of anakinra at 10 mg / kg body weight). They were compared to 16 patients who received only standard treatment. However, this study is not a randomized controlled trial, but a gold standard for establishing treatment efficacy.

“Iran’s Hospital of San Raffaele and the University of Vita Salute San Raffaele, Department of Immunology, Rheumatology, Allergies and Rare Diseases, said Professor Lorenzo Dagna,” said: To survive the most severe symptoms of COVID-19 and do so without overwhelming the hospital’s intensive care capabilities, it has already met rigorous safety trials and used in sufficient quantities to meet the needs of the current pandemic. The treatment that can be done is ideal. “

Dr. Giulio Cavalli, Department of Immunology, Rheumatology, Allergy and Rare Diseases at San Raffaele Hospital and Vita Salute San Raffaele University in Italy, said: It may be able to block the immune system overreaction caused by COVID-19. The results are interesting and the drug deserves controlled trials in large randomized trials. “

Most people with COVID-19 experience only mild symptoms, but in severely affected patients the immune system overreacts, causing a storm of immune proteins called cytokines. Cytokines cause hyperinflammation, Acute respiratory distress syndrome (ARDS) and reduce blood oxygen levels. ARDS is the leading cause of death from coronavirus disease. Estimated mortality rates for patients admitted to the intensive care unit with COVID-19 and ARDS range from 28% to 78%. The patient’s breathing is maintained until the inflammation subsides, but the number of patients requiring ventilation can exceed the number of intensive care units equipped with ventilators. Treatment is urgently needed to improve the prognosis of critically ill patients treated outside of ICU.

The drug anakinra is already approved by the US Food and Drug Administration and the European Medicines Agency to treat rheumatoid arthritis, Still’s disease, and recurrent fever. It works by blocking the inflammatory cytokine IL-1. Viewpoint work. Lancet rheumatism Earlier this week, I will explain why intravenous anakinra is effective and safe for the treatment of cytokine storm syndrome. The authors of the current study say that anakinra is more safe and has a shorter half-life than other cytokine blockers, making it suitable for critically ill patients.

In this study, treatment with high-dose anakinra at 21 days was associated with decreased serum C-reactive protein and progressive improvement in respiratory function in 21 (72%) of 29 patients. It was. The survival rate was 90% (26 out of 29). Five of the 29 patients (17%) needed mechanical ventilation.

The authors compare these observations with those seen in a group of 16 patients who received standard treatment before the start of the current study (between March 10 and 17). Most of the 16 patients experienced a persistent or recurrent increase in C-reactive protein. Half of the patients (8 patients, 50%) had improved respiratory function and 56% (9 of 16) survived. One patient received mechanical ventilation (6%).

The authors report that high-dose anakinra was generally safe. Of the side effects, 4 patients (14%) in the high-dose anakinra group had bacteremia (blood bacteria), but 2 patients in the standard-treatment group (13%). There were no inflammatory recurrences following discontinuation of Anakinra. The causes of death for patients receiving high doses of anakinra intravenously were pulmonary thromboembolism, respiratory failure, and multiple organ failure (one patient per cause of death). The causes of death in the comparison group were respiratory failure (3 cases), multiple organ failure (3 cases), and pulmonary thromboembolism (1 case).

The authors warn that the retrospective nature of the study and the small number of patients in the group make it impossible to draw definitive conclusions. The findings should be validated in controlled trials carried out over a long period to check the long-term results. Ah Randomized controlled trial The use of intravenous anakinra to treat COVID-19 is ongoing, but is evaluating lower doses and does not include patients with ARDS.

“Patients in our study were severely ill, had an average age of 62 years, and had an underlying illness, which increased the risk of death from COVID-19. Administration of a dose of intravenous anakinra ICU in the context of COVID-19 pandemic overload and lack of ICU resources appears to suppress systemic inflammation and is associated with a progressive improvement in respiratory function. It was also equally important in the treatment of COVID-19, which seemed to be able to postpone or avoid intubation in most patients. Based on promising results, this approach is related to resource availability. Again, the results were confirmed in controlled trials, ”said Chiara Tassandin, co-author of this study at the Department of Infectious Diseases at San Raffaele Hospital in Italy. Well .

Writing a linked comment, lead author Dr. Scott Kanna of the University of Pittsburgh Medical Center (who was not involved in the study) said: Anakinra, The pharmacokinetic and safety profile of the drug, and the body of increasing positive experience in auto-inflammatory and cytokine storms, these data are promising and prioritize this approach in the design and enrollment of randomized controlled trials. We support this. ”