A randomized controlled clinical trial on efficacy and safety of anakinra in patients with severe COVID‐19

Abstract

Introduction Hyperinflammatory state has a role in the pathogenesis of COVID‐19. Anakinra could reduce inflammation and help to combat the condition. In this study, we aimed to assess the safety and efficacy of anakinra (PerkinRA®) in severe COVID‐19. Method The study was an open‐label, randomized, controlled trial conducted in Imam Hossein Medical Center from May to July 2020. Patients with a confirmed diagnosis of COVID‐19 were included in this study. We administered anakinra 100 mg daily intravenously. All patients received COVID‐19 pharmacotherapy based on the represented national guideline. The need for invasive mechanical ventilation is considered the primary outcome. Results Thirty patients were included in this study, and 15 of them received Anakinra. Nineteen patients were male (63.3%), and 11 were female (36.7%). The mean age of patients was 55.77 ± 15.89 years. In the intervention group, the need for invasive mechanical ventilation was significantly reduced compared to the control group (20.0% vs. 66.7%, p = .010). Also, these patients had a significantly lower length of hospital stay ( p = .043). No significant higher rate of infection was recorded. Conclusion Anakinra as an immunomodulatory agent has been associated with the reduced need for mechanical ventilation in patients admitted to intensive care units because of severe COVID‐19. The medication reduced the hospital length of stay. Furthermore, no increased risk of infection was observed. Further randomized placebo‐controlled trials with a larger sample size are needed to confirm these findings.

The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases

“…With a half-life of 26 days, canakinumab is a preferred treatment option and has been approved for CAPS, juvenile idiopathic arthritis, rare periodic fever syndromes, and adult-onset Still's disease (AOSD) (Curran, 2012;Orrock and Ilowite, 2016;Malcova et al, 2020;Sfriso et al, 2020). In addition, a number of clinical trials have recently investigated anakinra and canakinumab as a therapeutic treatment for patients with COVID-19 (Kooistra et al, 2020;Landi et al, 2020;Kyriazopoulou et al, 2021;Kharazmi et al, 2022). These therapies have proven to be safe and effective in treating inflammation-driven diseases, however, some issues remain.…”

Anakinra treatment in multisystemic inflammatory syndrome in children (MIS-C) associated with COVID-19

“…According to adult studies, anakinra reduces the need for mechanical ventilation, length of stay in the hospital and intensive care unit, and mortality in patients with COVID-19 ( 19 , 20 ). But, unfortunately, despite intensive treatment, the mortality rate of MIS-C is reported to range between 1.2 and 1.7% ( 21 , 22 ).…”

“…The median resolution day of the fever was 3 (1-10) days after anakinra treatment. The lymphocyte counts, BNP, CRP, and D-dimer values of the patients became normal on the median day of 5 (1-18), 8.5 (5-53), 10 (1-33), and 11.5 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), respectively. The pattern of improvement in EF…”

Assessment of Admission COVID-19 Associated Hyperinflammation Syndrome Score in Critically-Ill COVID-19 Patients

“…Authors found that only patients with phenotype C (with a higher inflammatory status) benefit from corticosteroid therapy consistent with the study by Chen et al 7 It has also been shown that immunomodulatory drugs (tocilizumab, sarilumab (IL-6 inhibitors) and anakinra (interleukin-1 inhibitor)) are associated with the reduced need for IMV, improve survival in critically-ill COVID-19 patients; whereas in patients with mild COVID-19 pneumonia, immunomodulatory drugs do not improve outcomes. 51,52 Observational studies showed encouraging results on the use of IL-6 inhibitors in severe COVID-19 cases and a recent meta-analysis including 16 observational studies noted a decreased risk of death associated with the use of tocilizumab (OR 0.57 [95% CI 0.36-0.92]) compared to standard care. 53 In another prospective observational study from Italy, 56 severe COVID-19 cases with elevated inflammatory markers were analyzed for efficacy of sarilumab.…”