Efficacy of early anti-inflammatory treatment with high doses IV Anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia

Pontali, Emanuele; Volpi, Stefano; Signori, Alessio; Antonucci, Giancarlo; Castellaneta, Marco; Buzzi, Davide; Montale, Amedeo; Bustaffa, Marta; Angelelli, Alessia; Caorsi, Roberta; Giambruno, Elisa; Bobbio, Nicoletta; Feasi, Marcello; Gueli, Ilaria; Tricerri, Francesca; Calautti, Francesca; Castagnola, Elio; Moscatelli, Andrea; Rollandi, Gian Andrea; Ravelli, Angelo; Cassola, Giovanni; Sormani, Maria Pia; Gattorno, Marco

Background Interleukin-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes. Objective To analyse the efficacy and safety of early anti-inflammatory treatment (AIT) with i.v anakinra with or without glucocorticoids (GC) in COVID19 pneumonia. Methods We performed a retrospective single-centre cohort study on patients admitted for COVID19 pneumonia from February 26th to April 29th, 2020 to assess the efficacy of early AIT with i.v. Anakinra (100mg every 8 hours for 3 days, with tapering) alone or in combination with GC (i.v. methylprednisolone, 1-2 mg/kg daily, with tapering). Standard of care (SOC) treatment was: hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on Overall Survival (OS) was assessed by a Propensity Score adjusted Cox model. Results 128 patients were analyzed; 63 received early AIT (30 anakinra, 33 anakinra and CG) at admission; 65 patients (44 with SOC, 21 SOC plus late rescue AIT) did not and were used as controls. After adjusting for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted HR=0.26, p<0.001). The effect was similar in patients receiving anakinra alone (adjusted HR=0.28, p=0.04) and anakinra plus GC (adjusted HR=0.33, p=0.07). Late rescue treatment did not show a significant advantage over SOC alone (adjusted HR=0.82, p=0.70). Conclusions This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of i.v. anakinra with or without GC.