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 48-year-old man and a 52-year-old woman were described, who developed anaphylaxis during off-label treatment with tocilizumab for COVID-19-induced cytokine storm.

The 48-year-old man (patient 1), who had asthma for ~20 years, presented with multiple complaints. He tested positive for SARS-CoV-2 PCR test and was found to have COVID-19 pneumonia. He was hospitalised, and he started receiving off-label treatment with oral hydroxychloroquine 2 × 200mg for 5 days and favipiravir at a loading dose of 2 × 800mg for the first day, followed by oral favipiravir 1 × 800mg for consecutive days (total 5 days) for COVID-19. Concomitantly, he received anticoagulant therapy with enoxaparin sodium [enoxaparin]. Additionally, for the treatment of asthma, he received formoterol, budesonide and ipratropium bromide. He was noted to have COVID-19-induced cytokine storm and macrophage activation syndrome (MAS), for which he started receiving off-label treatment with infusion of tocilizumab 8 mg/kg every 12 hours. He complained of itching without visible rash ~2 hours following the initiation of tocilizumab. Cardiac and respiratory system examinations were unremarkable. He started receiving pheniramine [pheniramine maleate] as he described to have pruritus. The second infusion of tocilizumab was scheduled to be given after 24 hours. On day 2, ~5 minutes following the initiation of tocilizumab, he developed shortness of breath, a drop in blood pressure and nausea, followed by respiratory and cardiac arrest. Hence, tocilizumab therapy was immediately discontinued. He was diagnosed to have tocilizumab-induced anaphylaxis, for which he was treated with epinephrine, pheniramine, ranitidine and methylprednisolone. He became conscious following treatment with epinephrine and cardiopulmonary resuscitation. The blood pressure stabilised, without requirement of an additional vasopressor. Since he continued to have MAS, he started receiving immune-globulin [immunoglobulin], after which no reaction was observed. Subsequently, he showed a significant improvement in clinical and laboratory findings. He was discharged and referred to the allergy clinic for confirmation of tocilizumab-induced reactions with skin tests. However, he refused to undergo skin tests.

The 52-year-old woman (patient 2), who presented with multiple symptoms, tested positive for SARS-CoV-2 PCR test and was noted to have COVID-19 pneumonia. She was hospitalised, and she started receiving off-label treatment with oral hydroxychloroquine 2 × 200mg for 5 days and favipiravir at a loading dose of 2 × 800mg for the first day, followed by oral favipiravir 1 x 800mg for consecutive days (total 5 days) for COVID-19. Concomitantly, she received anticoagulant therapy with enoxaparin sodium [enoxaparin]. She was noted to have COVID-19-induced cytokine storm and MAS, for which she started receiving off-label treatment with infusion of tocilizumab 8 mg/kg. Towards the end of the infusion, she developed diffuse rash, whole-body redness and worsening shortness of breath. Thus, she was suspected to have a drug-induced allergy, and the tocilizumab infusion was stopped. Blood pressure was noted to be 76/43, and she was treated with epinephrine, pheniramine [pheniramine maleate], ranitidine and methylprednisolone for anaphylaxis. Also, she received dopamine as an additional vasopressor therapy. Subsequently, the shortness of breath relieved, and she became normotensive. She was diagnosed to have developed tocilizumab-induced anaphylaxis. Further tocilizumab therapy was not planned. She improved and was discharged. She was referred to the allergy clinic for confirmation of tocilizumab-induced reactions with skin tests; however, she refused to undergo skin tests.