Fostamatanib Therapy in Severe ARDS Requiring Extracorporeal Membrane Oxygenation (ECMO) Support

Abstract

Introduction: Neutrophil extracellular traps (NETs) are extrusions of intracellular DNA and granular material released by neutrophils as part of the host immune response. While intended as a defense mechanism, excessive production of NETs may play a role in the pathogenesis of ARDS. Fostamatinib appears to limit NET formation. A phase 2 study of fostamatinib for COVID-19 associated acute lung injury found fostamatinib to be associated with improved clinical outcomes. No patients in the clinical trial were on extracorporeal membrane oxygenator (ECMO) support. In this we report our experience with two critically ill patients on veno-venous (VV) ECMO treated with fostamatinib. Case 1: A 46-year-old male with no significant PMH was admitted with COVID-19 associated ARDS (CARDS). He required intubation on hospital day (HD) 10. Due to refractory hypoxemia, he was cannulated for VV ECMO that same day. By day 19, he had improved and was decannulated from ECMO. Following decannulation, he continued to struggle. He developed a pneumothorax which was addressed with a chest tube. Despite this he had refractory hypoxemia requiring neuromuscular blockade (NMB). Broad spectrum antibiotics were initiated. No superinfection was identified. He was again cannulated for VV ECMO on HD 30. On HD 36, fostamatinib was initiated at a dose of 150 mg bid for 14 days. The patient demonstrated fairly rapid improvement by HD 39, allowing for minimization of ECMO support. He was decannulated from VV ECMO on HD 46. He currently resides at home and has no need for oxygen. Case 2: A 53- year-old male with a PMH of psoriasis on etanercept was admitted with CARDS. He was intubated HD 1, but continued to require substantial support including prone positioning and NMB. On HD 5 he was cannulated for VV ECMO. He had early improvement and was decannulated on HD 10;however, he developed Staph aureus pneumonia resulting in marked clinical decline. On HD 12 he was placed back on VV ECMO support. He was also initiated on fostamatanib 150 mg twice daily for 14 days. He demonstrated fairly rapid improvement in oxygenation but required prolonged ECMO support for CO2 clearance. He was successfully decannulated from VV ECMO on HD 45. He is currently living at home. Conclusion: Fostamatinib appears safe to administer to COVID patients on ECMO. While it is speculative to make inferences with regards to efficacy, it is noteworthy that both critically ill COVID-19 patients treated with fostamatinib survived.