A France-based assessment of the IL-1 inhibitor was ended early on the recommendation of the safety monitoring board early this year.
Recombinant human interleukin 1 (IL-1) receptor antagonist anakinra is not associated with improved outcomes in patients with mild to moderate coronavirus 2019 (COVID-19) pneumonia, according to the first published findings of a randomized clinical trial assessing the promising agent in a particular patient group during the pandemic.
French investigators from the CORIMUNO-19 Collaborative group conducted the multi-center, open-label, Bayesian randomized controlled trial across 16 university hospitals. Their work was published in The Lancet Respiratory Medicine.
COVID-19 pneumonia has been linked to excessive patient inflammation and observed cytokine increases via IL-1—indicating the potential for benefitted outcomes via anakinra. As investigators noted, no definitive standard-of-care therapy has emerged for mild to moderate COVID-19 pneumonia.
“Anakinra has also been used at higher dose with an intravenous regimen in the management of critically ill patients with hamophagocytic lymphohystiocytosis and in patients with septic shock,” investigators wrote. “Severe COVID-19 pneumonia and haemophagocytic lymphohistiocytosis share biological and clinical features, and so the hypothesis that anakinra could be effective in COVID-19 has emerged.”
To assess the possibility, investigators recruited patients with mild to moderate COVID-19 pneumonia, severe SARS-CoV-2 infection confirmed by real-time RT-PCR, required 3 L/min of oxygen by mask or nasal cannula, a score of 5 on the World Health Organization (WHO) Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the ICU.
Patients were randomized 1:1 to either standard care plus anakinra (200 mg twice daily days 1-3, 100 mg twice daily day 4, 100 mg once day 5) or lone standard care.
Investigators sought co-primary outcomes of proportion of patients to die or need noninvasive mechanical ventilation by day 4, and survival without need for mechanical or noninvasive ventilation at day 14.
After screening 153 patients from April 8-26, investigators stopped the study early on the recommendation of the data and safety monitoring board. They had assigned 116 patients to either anakinra (n = 59) or usual care (n = 57).
Among the analyzed population, median age was 66 years old (IQR, 59 – 76), with 70% being men.
Among anakinra patients, 36% of patients reported a WHO-CPS score of >5 at day 4, versus 38% of usual care patients. At day 14, 28 (47%) of patients in the anakinra arm, versus 28 (51%) of patients in the usual care arm, needed ventilation or had died (median posterior hazard ratio [HR], 0.97; 95% CI, 0.62 – 1.52).
At 90 days, 27% of patients both in the anakinra arm and usual care arm had died. Investigators observed serious adverse events in nearly half of all patients administered the IL-1 inhibitor therapy (46%; P = .45).
Post-hoc analysis of the patients showed no benefit of anakinra on the primary outcomes in subgroups defined by C-reactive protein concentration >150 mg/L, and in patients with baseline corticosteroid use.
“This randomized clinical trial suggests that anakinra was not effective in reducing the need for non-invasive or mechanical ventilation or death in patients with COVID-19 and mild-to-moderate pneumonia,” investigators wrote. “These results are relevant for this patient population at the dose we used and cannot be extended to other populations with other doses.”
The team called for future assessment to observe the IL-1 inhibitor’s efficacy in other selected groups of patients with more severe COVID-19, and at other doses.