French doctors administered anakinra, an anti-inflammatory drug normally used to treat rheumatoid arthritis, to 52 COVID-19 patients at the Saint-Joseph Public Hospital in Paris between 24 March and 6 April and compared their progress with that of 44 historical coronavirus patients at the hospital who were not treated with the drug.
According to The Daily Telegraph, 13 (25%) of the patients injected subcutaneously with anakinra either died or had to be placed on ventilators, compared with 32 patients (73%) in the historical group. "Anakinra reduced both (the) need for invasive mechanical ventilation in the ICU and mortality among patients with severe forms of COVID-19, without serious side effects," the 17 doctors who carried out the study said.
However, perhaps mindful of ongoing international controversies over whether the anti-malarial hydroxychloroquine and other drugs are effective against coronavirus, the doctors said further research was needed, adding: "Confirmation of efficacy will require controlled trials."
Up to 30% of patients admitted to hospital with COVID-19 need to be placed on ventilators because they develop potentially fatal breathing difficulties, a condition known as acute respiratory distress syndrome associated with inflammation of the lungs or respiratory tract.
Doctors at Saint-Joseph said that administering anakinra appeared to reduce inflammation. Jean-Jacques Mourad, one of the authors of the study, said: "We saw that many patients we had been having difficulty treating were getting better."
Scientists are now awaiting the results of other ongoing anakinra trials.
The report says another French doctor, Didier Raoult, championed the unproven benefits of hydroxychloroquine as a treatment for COVID-19. He has become internationally famous since Donald Trump backed the drug and said he was taking it himself.
The US president's claims were called into question by an influential study published last week, which concluded that hydroxychloroquine did not help treat COVID-19 and could be dangerous, increasing the risk of abnormal heart rhythms and death. However, more than 100 scientists and clinicians have since raised doubts about the data used for that study and called for it to be independently validated.
Abstract
Background: Mortality of patients with coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), and systemic inflammation is high. In areas of pandemic outbreak, the number of patients can exceed maximum capacity of intensive care units (ICUs), and, thus, these individuals often receive non-invasive ventilation outside of the ICU. Effective treatments for this population are needed urgently. Anakinra is a recombinant interleukin-1 receptor antagonist that might be beneficial in this patient population.
Methods: We conducted a retrospective cohort study at the San Raffaele Hospital in Milan, Italy. We included consecutive patients (aged ≥18 years) with COVID-19, moderate-to-severe ARDS, and hyperinflammation (defined as serum C-reactive protein ≥100 mg/L, ferritin ≥900 ng/mL, or both) who were managed with non-invasive ventilation outside of the ICU and who received standard treatment of 200 mg hydroxychloroquine twice a day orally and 400 mg lopinavir with 100 mg ritonavir twice a day orally. We compared survival, mechanical ventilation-free survival, changes in C-reactive protein, respiratory function, and clinical status in a cohort of patients who received additional treatment with anakinra (either 5 mg/kg twice a day intravenously [high dose] or 100 mg twice a day subcutaneously [low dose]) with a retrospective cohort of patients who did not receive anakinra (referred to as the standard treatment group). All outcomes were assessed at 21 days. This study is part of the COVID-19 Biobank study, which is registered with ClinicalTrials.gov, NCT04318366.
Findings: Between March 17 and March 27, 2020, 29 patients received high-dose intravenous anakinra, non-invasive ventilation, and standard treatment. Between March 10 and March 17, 2020, 16 patients received non-invasive ventilation and standard treatment only and comprised the comparison group for this study. A further seven patients received low-dose subcutaneous anakinra in addition to non-invasive ventilation and standard treatment; however, anakinra treatment was interrupted after 7 days because of a paucity of effects on serum C-reactive protein and clinical status. At 21 days, treatment with high-dose anakinra was associated with reductions in serum C-reactive protein and progressive improvements in respiratory function in 21 (72%) of 29 patients; five (17%) patients were on mechanical ventilation and three (10%) died. In the standard treatment group, eight (50%) of 16 patients showed respiratory improvement at 21 days; one (6%) patient was on mechanical ventilation and seven (44%) died. At 21 days, survival was 90% in the high-dose anakinra group and 56% in the standard treatment group (p=0·009). Mechanical ventilation-free survival was 72% in the anakinra group versus 50% in the standard treatment group (p=0·15). Bacteraemia occurred in four (14%) of 29 patients receiving high-dose anakinra and two (13%) of 16 patients receiving standard treatment. Discontinuation of anakinra was not followed by inflammatory relapses.
Interpretation: In this retrospective cohort study of patients with COVID-19 and ARDS managed with non-invasive ventilation outside of the ICU, treatment with high-dose anakinra was safe and associated with clinical improvement in 72% of patients. Confirmation of efficacy will require controlled trials.
Authors
Giulio Cavalli, Giacomo De Luca, Corrado Campochiaro, Emanuel Della-Torre, Marco Ripa, Diana Canetti, Chiara Oltolini, Barbara Castiglioni, Chiara Tassan Din, Nicola Boffini, Alessandro Tomelleri, Nicola Farina, Annalisa Ruggeri, Patrizia Rovere-Querini,
Giuseppe Di Lucca, Sabina Martinenghi, Raffaella Scotti, Moreno Tresoldi, Fabio Ciceri, Alberto Zangrillo, Paolo Scarpellini, Lorenzo Dagna
[link url="https://www.telegraph.co.uk/news/2020/06/01/arthritis-drug-may-aid-virus-fight-french-doctors-say/?WT.mc_id=e_DM1251908&WT.tsrc=email&etype=Edi_FPM_New_ES&utmsource=email&utm_medium=Edi_FPM_New_ES20200601&utm_campaign=DM1251908"]Full report in The Daily Telegraph[/link]
[link url="https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30127-2/fulltext"]The Lancet abstract[/link]