Tocilizumab for severe COVID‐19 pneumonia: Case series of 5 Australian patients

Abstract

Aim: To describe the first Australian cases of severe acute respiratory syndromecoronavirus 2 (SARS-CoV2) disease (COVID-19) pneumonia treated with the interleukin-6 receptor antagonist tocilizumab. Methods: Retrospective, open-label, real-world, uncontrolled, single-arm case series conducted in 2 tertiary hospitals in NSW, Australia and 1 tertiary hospital in Victoria, Australia. Five adult male patients aged between 46 and 74 years with type 1 respiratory failure due to COVID-19 pneumonia requiring intensive care unit (ICU) admission and biochemical evidence of systemic hyperinflammation (C-reactive protein greater than 100 mg/L; ferritin greater than 700 μg/L) were administered variabledose tocilizumab. Results: At between 13 and 26 days follow-up, all patients are alive and have been discharged from ICU. Two patients have been discharged home. Two patients avoided endotracheal intubation. Oxygen therapy has been ceased in three patients. Four adverse events potentially associated with tocilizumab therapy occurred in three patients: ventilator-associated pneumonia, bacteremia associated with central venous catheterization, myositis and hepatitis. All patients received broad-spectrum antibiotics, 4 received corticosteroids and 2 received both lopinavir/ritonavir and hydroxychloroquine. The time from first tocilizumab administration to improvement in ventilation, defined as a 25% reduction in fraction of inspired oxygen required to maintain peripheral oxygen saturation greater than 92%, ranged from 7 hours to 4.6 days. Conclusions: Tocilizumab use was associated with favorable clinical outcome in our patients. We recommend tocilizumab be included in randomized controlled trials of treatment for patients with severe COVID-19 pneumonia, and be considered for compassionate use in such patients pending the results of these trials. | 1031 WEST ET al.

Clinical Management of COVID-19: A Review of Pharmacological Treatment Options

“…Similarly to anakinra and corticosteroids, TCZ has been employed as supportive therapy in COVID-19 to manage symptoms of hyper-inflammation and other immune responses. Several published case series and reports observed remarkable clinical responses following the use of TCZ in COVID-19 patients, including the clinical resolution of septic shock, reduction in the markers of inflammation, enhanced negative conversion, and reduced need for invasive mechanical ventilation [128][129][130][131][132][133][134][135][136][137][138][139].…”

Pharmacology and Adverse Events of Emergency-Use Authorized Medication in Moderate to Severe COVID-19

“…Only about 0% to 6% of patients receiving tocilizumab were considered to have causal AEs [ 69 , 71 , 74 , 75 ]. The most common AE was alteration in liver-function studies (i.e., elevated ALT and AST and hyperbilirubinemia) [ 68 , 70 , 71 , 72 , 73 , 75 , 76 , 77 , 78 ], but whether AE was more likely to occur in patients receiving tocilizumab remains controversial [ 77 , 79 ]. Other common AEs include neutropenia [ 70 , 71 , 73 , 74 , 77 ], which appeared to occur more frequently in patients receiving tocilizumab [ 74 , 77 ] and might be managed with granulocyte colony-stimulating factor if necessary, and secondary bacterial infections [ 18 , 21 , 22 , 23 , 74 , 77 , 78 , 80 ].…”

“…The most common AE was alteration in liver-function studies (i.e., elevated ALT and AST and hyperbilirubinemia) [ 68 , 70 , 71 , 72 , 73 , 75 , 76 , 77 , 78 ], but whether AE was more likely to occur in patients receiving tocilizumab remains controversial [ 77 , 79 ]. Other common AEs include neutropenia [ 70 , 71 , 73 , 74 , 77 ], which appeared to occur more frequently in patients receiving tocilizumab [ 74 , 77 ] and might be managed with granulocyte colony-stimulating factor if necessary, and secondary bacterial infections [ 18 , 21 , 22 , 23 , 74 , 77 , 78 , 80 ]. There were also reports of allergic reactions [ 72 , 81 ], sudden cardiorespiratory collapse [ 68 , 69 ], acute respiratory distress syndrome [ 70 ], pulmonary embolism [ 77 ], anemia [ 68 ], thrombocytopenia [ 68 ], increased serum levels of creatinine [ 75 ], and neurological adverse effects [ 82 ].…”

A bond between rheumatic diseases and cancer in the elderly: The interleukin‐6 pathway

“…8 Targeting the IL-6 pathway might lead to innovative therapeutic approaches not only for rheumatic diseases 9,10 and cancer 11 but also for COVID-19. 7 In this context, the COVID-19 pandemic has drastically affected the management and treatment strategies of rheumatic diseases as well as cancer. [12][13][14] Therefore, given the enhanced relevance during the present pandemic, we sought to recall the common pro-inflammatory bond between these age-related conditions, rheumatic diseases, and cancer, focusing on the IL-6 role and its targeting with potential implications for future therapeutic approaches.…”

“…The current coronavirus disease 19 (COVID-19) pandemic has placed under the spotlight the role of the cytokine release syndrome and IL-6, with the advent of targeted therapies in this setting. 7 Indeed, a hyperinflammation state, dependent on cytokine release syndrome (CRS) and IL-6, has been linked with the COVID-19 fatality rate. 8 Targeting the IL-6 pathway might lead to innovative therapeutic approaches not only for rheumatic diseases 9,10 and cancer 11 but also for COVID-19.…”