Treatment with anakinra may reduce mortality risk in patients hospitalized with moderate to severe COVID-19 pneumonia, according to findings from a systematic review published in Lancet Rheumatology.
Interleukin (IL)-1 receptor anakinra has been used as an off-label agent for treatment of COVID-19 during the COVID-19 pandemic; however, its exact benefits for patients with moderate to severe COVID-19 remain unclear.
To evaluate the effect of anakinra treatment in patients with COVID-19 in a hospital setting, the study authors conducted a systematic review of the Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases of studies describing the use of anakinra for inpatients with COVID-19. Eligible studies included comparisons of anakinra with standard of care treatment, placebo, or both.
The primary endpoint was mortality within 28 days of hospital admission. Meta-analysis of mortality data was performed using the Mantel-Haenszel method. Pooled odds ratios (ORs) were used to compare endpoints across treatment methods. Analyses were adjusted for age, medical comorbidities, baseline ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2), C-reactive protein (CRP) levels, and lymphopenia.
A total of 178 fulltext articles were screened for eligibility, of which 9 were selected for analysis. One study had a randomized controlled design; the remaining 8 were observational studies. Three studies were conducted in France, 3 in Italy, 1 in the Netherlands, 1 in Greece, and 1 in Oman.
Six studies provided patient-level data for a total of 895 patients, among whom 103 (12%) were receiving mechanical ventilation at baseline. A total of 342 patients received anakinra during hospitalization, among whom 38 (11%) died during follow-up. In the pooled standard-of-care cohort, 137 of 553 (25%) patients died.
In adjusted models, the pooled odds ratio (OR) for mortality was significantly lower with anakinra compared with standard of care (OR, 0.32; 95% CI, 0.20-0.51). The mortality benefit was similar across subgroups, defined by diabetes status, ferritin concentration, and baseline PaO2/FiO2 ratio. The effect of anakinra on survival was more significant in patients with CRP levels greater than 100 mg/L (OR, 0.28; 95% CI, 0.17-0.47). Among patients with CRP levels of 100 mg/L or lower, no difference was observed between anakinra and standard of care.
When administered in the absence of dexamethasone, anakinra offered a significant survival benefit (OR, 0.23; 95% CI, 0.12-0.43). However, when co-administered with dexamethasone, anakinra did not appear to increase survival rates compared with standard of care (OR, 0.72; 95% CI, 0.37-1.41). No new safety signals were observed, and anakinra was not associated with significantly increased risk for secondary infections (OR, 1.35; 95% CI, 0.59-3.10).
These data provide insight into the potential survival benefits associated with anakinra treatment for COVID-19. However, larger randomized trials are needed to clarify the most effective means of reducing COVID-19-related mortality.
“Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L,” the study authors wrote.
Disclosure: This research was supported by Sobi. Please see the original reference for a full list of authors’ disclosures.
Kyriazopoulou E, Huet T, Cavalli G, et al. Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis. Lancet Rheumatol. Published online August 9, 2021. doi:10.1016/S2665-9913(21)00216-2