Tocilizumab

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a report, a 40-year-old man developed viral myocarditis and worsening of COVID-19 during off-label use of tocilizumab for COVID-19 and a 69-year-old woman developed increased viral replication and worsening of COVID-19 during off-label use of tocilizumab for COVID-19 [time to reactions onset not stated].

Case 1: The man, who was diagnosed with COVID-19, started receiving off label treatment with hydroxychloroquine and azithromycin. He continued to develop bilateral chest infiltrates, worsening hypoxemia, and accessory muscle fatigue over next two days. He required intubation and was transferred to the medical ICU. Subsequently, he was diagnosed with acute respiratory distress syndrome (ARDS) and started receiving treatment with prone positioning, low tidal volume ventilation and a bumetanide. On day 4 of admission, he developed septic shock and was initiated on norepinephrine drip. He was started on a dose of IV tocilizumab 400mg due to decompensation and increasing inflammatory markers suggestive of cytokine release syndrome (CRS). The next day, an ECG revealed ST segment depression in leads V4 to V6 and increased troponin levels were noted. ECG also showed mild global hypokinesis and the findings were consistent with viral myocarditis. Swan-Ganz catheter measurements showed a reduced cardiac index. He developed a fever of 42.8°C and indexes of septic shock. Repeat laboratory investigations suggested the development of secondary haemophagocytic lymphohistiocytosis (sHLH). Despite a reduced CRP following the tocilizumab administration, the decompensation had occurred. He received treatment with four unspecified vasopressor agents for shock, but were refractory. Afterwards, he died [immediate cause of death not stated].

Case 2: The woman, who had a history of rheumatoid arthritis, type 2 diabetes mellitus and aplastic anaemia, was diagnosed with COVID-19. She was started on off label treatment with azithromycin and hydroxychloroquine. On day 2 of admission, she progressed to septic shock and acute hypoxaemic respiratory failure. She required intubation and was started on norepinephrine. She also received an off label dose of IV tocilizumab 560mg for CRS associated with COVID-19. On day 3, her shock worsened. She required maximum dose of three unspecified vasopressor agents along with stress dose steroids. She developed acute kidney injury and required continuous venovenous haemodialysis. On day 4 of admission, her inflammatory markers continued to increase, and she received a second dose of IV tocilizumab 700mg. Despite the second dose, her clinical status had worsened and she developed sHLH and died [immediate cause of death not stated]. Despite a reduced CRP following the tocilizumab administration, the decompensation had occurred.