Effect of anakinra on mortality in COVID-19: a patient level meta-analysis

Kyriazopoulou, E.; Huet, T.; Cavalli, G.; Gori, A.; Kyprianou, M.; Pickkers, P.; Eugen-olsen, J.; Clerici, M.; Veas, F.; Chatellier, G.; Kaplanski, G.; Netea, M. G.; Pontali, E.; Gattorno, M.; Cauchois, R.; Kooistra, E.; Kox, M.; Bandera, A.; Beaussier, H.; Mangioni, D.; Dagna, L.; van der Meer, J.; Giamarellos-Bourboulis, E.; Hayem, G.; COVID-19, International collaborative group for Anakinra in

Background Anakinra may represent an important therapy to improve the prognosis of COVID-19 patients. This meta-analysis using individual patient data was designed to assess the efficacy and safety of anakinra treatment in patients with COVID-19. Methods Based on a pre-specified protocol (PROSPERO: CRD42020221491), a systematic literature search was performed in MEDLINE (PubMed), Cochrane, medRxiv.org, bioRxiv.org and clinicaltrials.gov databases for trials in COVID-19 comparing administration of anakinra with standard-of-care and/or placebo. Individual patient data from eligible trials were requested. The primary endpoint was the mortality rate and the secondary endpoint was safety. Findings Literature search yielded 209 articles, of which 178 articles fulfilled screening criteria and were full-text assessed. Aggregate data on 1185 patients from 9 studies were analyzed and individual patient data on 895 patients from 6 studies were collected. Most studies used historical controls. Mortality was significantly lower in anakinra-treated patients (38/342 [11.1%]) as compared with 137/553 (24.8%) observed in patients receiving standard-of-care and/or placebo on top of standard-of-care (137/553 [24.8%]); adjusted odds ratio (OR), 0.32; 95% CI, 0.20 to 0.51; p <0.001. The mortality benefit was similar across subgroups regardless of diabetes mellitus, ferritin concentrations, or baseline P/F ratio. The effect was more profound in patients exhibiting CRP levels >100 mg/L (OR 0.28,95%CI 0.27-1.47). Safety issues, such as increase of secondary infections, did not emerge. Interpretation Anakinra may be a safe anti-inflammatory treatment option in patients hospitalized with moderate-to-severe COVID-19 pneumonia to reduce mortality, especially in the presence of hyperinflammation signs such as CRP>100mg /L. Funding Sobi.