The safety and efficacy of imatinib a tyrosine kinase inhibitor for the treatment of SARS-COV-2 induced pneumonia: a pilot study

Abstract

Introduction Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a wide spectrum of disease, approximately 15–20% of affected patients present with severe phenotype that require supplemental oxygen, including up to 5% who may develop critical illness. The main therapeutic strategies proposed for the management of COVID-19 pneumonia are direct antiviral and immunomodulatory treatments aiming to prevent disease progression. In this pilot study we are testing the hypothesis of using imatinib a tyrosine kinase inhibitor (TKI) as an immunomodulatory treatment to prevent disease progression, based on encouraging data from cellular, animal models and clinical trials, showing a beneficial role of TKI in the regulation of inflammation and endothelial barrier integrity, as well as their antiviral properties. Aim The primary end point is to assess the effect of the imatinib treatment, in terms of safety and efficacy, to prevent the progression of patients with moderate to severe COVID-19 pneumonia into critical illness and need for invasive mechanical ventilation. The secondary end point is a composite of change in clinical, laboratory and radiological parameters, including: clinical parameters − the percentage of patients reaching normal hypoxic index (HI) at time of hospital discharge, hospital length of stay and days on mechanical ventilation (MV) in patient intubated and mechanically ventilated, the changes in the levels of laboratory inflammatory markers: serum ferritin, serum C reactive protein (CRP), serum interleukin 6 (IL6), viral clearance presented by the delta time till negative SARS-CoV-2 PCR results, as well as the change in the chest radiological parameters (Computed tomography chest or radiography). Methods Thirty SARS-COV-2 positive patients with moderate to severe respiratory symptoms, were enrolled and randomized into three groups: group 1 Control, group 2 Low dose Imatinib (receiving 200 mg Imatinib/day) and group 3 Standard dose Imatinib (receiving 400 mg Imatinib/day). Results There was no significant difference between the three groups regarding the severity of the disease at baseline, as assessed by clinical, laboratory and radiological parameters. There was a nonstatistically significant difference in the primary end point of the study, regarding the number of patients in need for invasive mechanical ventilation, between the control group and the intervention groups receiving imatinib. Conclusion Despite the negative results regarding the efficacy of imatinib to flatten the curve of the illness and the prevention of more severe phenotype of the disease, our study showed positive findings regarding the medication’s safety and patients’ tolerability. These finding would pave the way for further studies to assess the concept of immunomodulation in the treatment of immunity derived disease, like sepsis and acute respiratory distress syndrome (ARDS).