Treatment with anakinra, an interleukin-1 receptor antagonist, was found to decrease mortality and reduce the need for invasive mechanical ventilation compared with standard of care (SOC) in hospitalized patients with COVID-19, according to the results of a meta-analysis published in Infection and Chemotherapy.
In this systematic review and meta-analysis, researchers aimed to determine the safety and efficacy of anakinra therapy vs SOC in patients with severe COVID-19. They identified 15 studies with a total of 3530 adult patients (mean age, 55.25 years). Of the 15 studies, 5 were observational studies, 5 were case series, 4 were case reports, and 1 was a randomized clinical trial (RCT). With the exception of the RCT, all were single-center studies. Of the 3530 patients, 757 received anakinra either alone or in combination with other drugs, and 1685 received SOC.
Treatment efficacy outcomes were assessed by comparing the rate of mortality and the need for mechanical ventilation between the 2 groups. All-cause mortality, assessed in 6 studies, showed that patients receiving anakinra therapy had a significantly lower mortality rate than those receiving SOC (14.0% [33/235] vs 33.9% [62/183]; odds ratio [OR], 0.34; 95% CI, 0.21-0.54; I2=48%). Similarly, the need for mechanical ventilation, assessed in 7 studies, was much higher in the patients receiving SOC (adjusted OR, 0.68; 95% CI, 0.49-0.95; I2=50%).
Safety outcomes were evaluated by comparing risk for thromboembolism and elevated liver transaminase levels from 3 studies (2 cohort studies and 1 RCT). Of 262 patients, 147 received anakinra therapy and 115 received SOC. There were no statistically significant associations between the 2 groups for either risk of thromboembolism (adjusted OR, 1.59; 95% CI, 0.65-3.91; I2=0%) or elevated liver transaminase levels (adjusted OR, 1.35; 95% CI, 0.61-3.03; I2=76%). Researchers noted that the lack of differences in the safety profile “may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra’s safety profile.”
Subgroup analyses accounting for gender, diabetes, and cardiovascular comorbidities showed no differences between the 2 groups.
Limitations of this study included the small number of studies, the low certainty of evidence, and varied heterogeneity. Treatment protocols were different in various studies, including “differences in dosage, mode, and timing of anakinra administration.” Moreover, SOC was not established because corticosteroids were not as widely used.
“More extensive studies (RCTs) with long term follow-up of patients are required to provide conclusive evidence on the most effective dosing strategies and adverse effects” regarding the use of anakinra therapy in patients with severe COVID-19, concluded the researchers.
Somagutta MKR, Lourses Pormento MK, Hamid P, et al. The safety and efficacy of anakinra, an interleukin-1 antagonist in severe cases of COVID-19: a systematic review and meta-analysis. Infect Chemother. 2021;53(2):221-237. doi:10.3947/ic.2021.0016