High-dose anakinra is associated with clinical improvements in patients with coronavirus disease 2019 (COVID-19) and acute respiratory disease syndrome (ARDS) receiving noninvasive mechanical ventilation outside of the intensive care unit (ICU), according to study results published in The Lancet Rheumatology.
For this retrospective cohort study, the researchers aimed to assess clinical outcomes in patients with COVID-19, ARDS, and hyperinflammation receiving anakinra in addition to noninvasive ventilation and standard treatment outside of the ICU.
Researchers made COVID-19 diagnoses by quantitative reverse transcription polymerase chain reaction (RT-PCR) and chest radiography or a computed tomography (CT) scan. Patients were excluded from the study if they were already admitted to the ICU for mechanical ventilation, had evidence of bacterial infection, had concomitant administration of other anti-inflammatory agents or glucocorticoids, and were already enrolled in clinical trials.
A part of the COVID-19 biobank trial (ClinicalTrials.gov Identifier: NCT04318366), this study, conducted at the San Raffaele Hospital in Milan, Italy, included patients aged ≥18 years with COVID-19, moderate to severe ARDS, and hyperinflammation. Patients received respiratory support by continuous positive airway pressure (CPAP; positive end expiratory pressure, 10 cm H2O), 200 mg of hydroxychloroquine twice daily, and 400 mg of lopinavir with 100 mg ritonavir twice daily, according to standard treatment.
From March 17 to 27, 2020, 29 patients (median age, 62 years; 83% men) received off-label high-dose intravenous anakinra at a dose of 10 mg/kg per day (5 mg/kg twice daily, infused over 1 h) along with CPAP and standard treatment; the control group included 16 patients who were admitted to the hospital before initiation of the study and retrospectively fulfilled criteria for anakinra treatment and received noninvasive ventilation and standard treatment. Treatment duration lasted until sustained clinical benefit (defined as a 75% reduction in serum CRP and sustained respiratory improvement [PaO2:FiO2 >200 mm Hg] for at least 2 days, until death, bacteremia, or side effects emerge). Clinical outcomes were evaluated at 21 days, until discharge from hospital, ICU admission, or death.
Results showed that after 21 days of follow-up, 21 patients (72%) treated with high-dose anakinra had improved respiratory function and reduced CRP. Of the remaining 8 patients who did not have improved respiratory function, 5 (17%) were on mechanical ventilation and 3 (10%) died. In the control group, respiratory improvements were seen in 8 patients (50%); among those patients who did not show respiratory improvements, 1 (6%) was on mechanical ventilation and 7 (44%) died. Survival and mechanical ventilation-free survival were 90% and 72% in the high-dose anakinra group vs 56% and 50% in the control group, respectively (P =.009 and P =.15, respectively).
Overall, compared with participants in the control group who had persistent or recurrent increases in CRP and little improvement in PaO2:FiO2, patients in the anakinra group showed reductions in serum CRP and progressive improvements in PaO2:FiO2.
Limitations included retrospective nature of the study and small size of the cohorts that may limit findings.
“A more extended follow-up is also needed to assess long-term outcomes of treated patients,” the investigators noted. “Nevertheless, a sound rationale for use, objective improvements in respiratory and inflammatory variables, and comparisons with published studies assessing different treatments suggest that high-dose intravenous anakinra could have clinical benefit in COVID-19.”
Cavalli G, De Luca G, Campochiaro C, et al. Interlukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study [published online May 7, 2020]. Lancet Rheumatol. doi:10.1016 /S2665-9913(20)30127-2