Anakinra Deemed Safe, Anti-inflammatory Drug for Patients With COVID-19

Anakinra treatment may reduce mortality risk in patients with moderate-to-severe COVID-19, according to a study published in The Lancet.¹ The safe, anti-inflammatory treatment is especially useful when patients present symptoms of hyperinflammation.

“This study is, to our knowledge, the first patient-level meta-analysis to analyses the effects of anakinra treatment in patients admitted to hospital with moderate to severe COVID-19,” investigators stated. “Most importantly, this study identifies a subgroup of patients who might benefit most from treatment with anakinra: those with C-reactive protein (CRP) concentrations higher than 100 mg/L.”

Investigators conducted 2 systematic literature searches on December 28, 2020, and January 22, 2021, including studies from Medline (PubMed), Cochrane, medRxiv, bioRxiv, and ClinicalTrials.gov . Search criteria of randomized trials, comparative studies, and observational studies involved the keywords “COVID-19,” “SARS-CoV-2,” “interleukin-1,” “Interleukin blockade,” and “anakinra.”

The primary endpoint was mortality after 28 days and the secondary endpoint assessed the safety and risk of adverse events, such as secondary infections, for patients receiving anakinra.

Eligible studies were those that followed PICO statements: patients admitted to the hospital with COVID-19 infection, anakinra treatment, a standard of care or placebo comparator group, and mortality rate or rate of adverse events. Only those available in full text and written in English were included.

Investigators collected data such as study design, publication date, number of patients, age and comorbidities, CRP concentrations at baseline, onset of respiratory failure, country of origin, and patient-level data.

A total of 178 full-text articles fulfilled eligibility criteria, ultimately resulting in the analysis of 9 studies and 1185 patients (509 in the anakinra cohort and 676 in the control cohort). Individual patient-level data was available for 895 patients in 6 of the studies. Eight of the studies were observational in nature and 1 utilized a randomized control study design. Approximately 12% (n = 103/895) of patients were reported as being on mechanical ventilation at baseline.

After adjusting for factors such as age, comorbidities, and lymphopenia, mortality was significantly lower in the anakinra-treated cohort (n = 38/342, 11%) when compared with patients in the placebo or standard of care groups (n = 137/553, 25%). Regardless of comorbidities and other factors, mortality benefit was similar for all subgroups. However, anakinra was significantly more effective in lowering mortality for patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17–0·47]). Efficacy was not related to baseline ferritin concentrations.

Seven studies were performed before dexamethasone treatment was administered, 1 analyzed anakinra-treated patients receiving dexamethasone, and 1 included both anakinra-treated and control patients after dexamethasone treatment. A significant survival benefit was seen in patients who received anakinra without dexamethasone (559 patients; OR 0·23 [95% CI 0·12–0·43]), but not for those who received dexamethasone in addition to anakinra (239 patients; 0·72 [0·37–1·41]; pBreslow =0·012). The drug was not associated with an increased risk of adverse events or secondary infections when compared with the standard of care cohort (OR 1·35 [95% CI 0·59–3·10]).

The retrospective, observational design of the study potentially increased the risk of bias and confounder. Additionally, most data was recorded before dexamethasone was incorporated as standard-of-care treatment for patients with COVID-19.

“Larger randomized trials are urgently needed to clarify the place of anakinra in the anti-COVID19 armamentarium; ongoing trials include the REMAP-CAP trial (an international, multifactorial, adaptive platform randomly assigning patients to tocilizumab or sarilumab or anakinra or standard of care and comparing in-hospital mortality and days free of organ support to day 21 among the groups), and the placebo-controlled randomized controlled trial SAVE-MORE (NCT04680949) in Greece and Italy,” investigators concluded.

Reference:

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 [published online ahead of print, 2021 Aug 9]. Lancet Rheumatol. 2021;10.1016/S2665-9913(21)00216-2. doi:10.1016/S2665-9913(21)00216-2