Serious adverse events with tocilizumab: Pharmacovigilance as an aid to prioritize monitoring in COVID‐19

Gatti, Milo; Fusaroli, Michele; Caraceni, Paolo; Poluzzi, Elisabetta; Ponti, Fabrizio De; Raschi, Emanuel

doi:10.1111/bcp.14459

Cited by 48 publications

(47 citation statements)

References 23 publications

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“…10 In the absence of a proven effective antiviral therapy, and because of its approval in cytokine release syndrome, tocilizumab has been considered a promising drug for the treatment of severe COVID-19 infections. 17 Clinical studies have shown very good effects of tocilizumab on clinical and biochemical parameters in patients with COVID-19. For this reason, tocilizumab, a humanized monoclonal antibody against the IL-6 receptor (IL-6R), has been recommended in severe COVID-19 disease by the National Health Commission of China.…”

Section: Discussionmentioning

confidence: 99%

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Tocilizumab and liver injury in patients with COVID-19

Serviddio

Villani

Stallone

et al. 2020

Therap Adv Gastroenterol

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Current mortality rate in patients with COVID-19 disease is about 2%, whereas 5% of patients require admission to the intensive care unit. It is assumed that interleukin (IL)-6 may be involved in the pathogenesis of severe COVID-19 infections; therefore, in the absence of a specific antiviral therapy, some authors have suggested that tocilizumab – a drug used to block the signal transduction pathway of IL-6 – could have beneficial effects in the management of severe COVID-19 disease. However, mild-to-moderate elevation in transaminases and drug-induced liver injury have been observed in patients treated with tocilizumab. We present seven cases of patients with elevated liver enzymes [up to five times the upper limit of normal (ULN)] at baseline who received tocilizumab for life-threatening COVID-19 disease. All patients had no history of liver or pulmonary disease and were admitted for acute hypoxemic respiratory failure, dyspnea and fever due to COVID-19 bilateral pneumonia. IL-6 was available in six patients, and was significantly increased particularly in those with severe impairment of lung function. All patients received tocilizumab (8 mg/kg/day) for two consecutive days because of lack of improvement after hydroxychloroquine, azithromycin and lopinavir/ritonavir treatment. After tocilizumab administration, clinical condition rapidly improved and liver function test normalized within 3 weeks of treatment. Tocilizumab may be effective for the treatment of severe COVID-19 disease, even in patients with elevated liver function tests. Further studies are needed to evaluate the impact of tocilizumab use on liver function tests in patients with pre-existing chronic liver disease.

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Section: Discussionmentioning

confidence: 99%

“…In the absence of a proven effective antiviral therapy, and because of its approval in cytokine release syndrome, tocilizumab has been considered a promising drug for the treatment of severe COVID-19 infections. 17 …”

Section: Discussionmentioning

confidence: 99%

Tocilizumab and liver injury in patients with COVID-19

Serviddio

Villani

Stallone

et al. 2020

Therap Adv Gastroenterol

View full text Add to dashboard Cite

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“… 22 Tocilizumab, a humanized monoclonal antibody against the interleukin-6 receptor, is also known to cause severe liver injury. 23 A retrospective, observational cohort study reported a decreased need for invasive mechanical ventilation and a lower risk of death in patients with severe pneumonia. In this study, when compared with the standard care group, the tocilizumab group had a significantly higher elevation of ALT.…”

Section: Mechanism Of Hepatic Injury From Sars-cov-2 Virusmentioning

confidence: 99%

COVID-19 in Chronic Liver Disease and Liver Transplantation

Mohammed

Paranji

Chen

et al. 2020

Journal of Clinical Gastroenterology

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The coronavirus disease 2019 (COVID-19) pandemic has brought challenges to clinicians caring for patients with chronic liver disease. In the past 6 months, COVID-19 has led to over 150,000 deaths in the United States and over 660,000 deaths around the world. Mounting evidence suggests that chronic liver diseases can have an adverse effect on the clinical outcomes of patients with COVID-19. We present a comprehensive review of the latest literature on preexisting liver diseases and its interrelationship with COVID-19 infection in cirrhosis, hepatocellular carcinoma, nonalcoholic fatty liver disease, autoimmune hepatitis, and viral hepatitis B. As social distancing and telemedicine gain new footing, we synthesize recommendations from 3 major hepatology societies [American Association for the Study of Liver Disease (AASLD), the European Association for the Study of Liver (EASL), and the Asian Pacific Association for the Study of Liver (APASL)] to present the best approaches for caring for patients with liver diseases as well as those requiring liver transplantation.

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“…Besides, unlike TCs, tocilizumab is an expensive drug that also needs close monitoring during its parenteral administration since it may cause serious anaphylactic reactions, liver injury, and secondary bacterial infections (Stone et al, 2020). On the other hand, TCs are cheap, safe, and effective orally, not needing close monitoring and neither increasing the risk of bacterial coinfection; therefore, TCs are more effective than tocilizumab in the management of COVID-19 (Gatti et al, 2020).…”

Section: Anti-inflammatory Effects Of Tetracyclines In Covid-19mentioning

confidence: 99%

Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives

et al. 2021

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Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 15% of severe cases require an intensive care unit (ICU) admission and mechanical ventilation due to development of acute respiratory distress syndrome (ARDS). Tetracyclines (TCs) are a group of bacteriostatic antibiotics, like tetracycline, minocycline, and doxycycline, effective against aerobic and anaerobic bacteria as well as Gram-positive and Gram-negative bacteria. Based on available evidences, TCs may be effective against coronaviruses and thus useful to treat COVID-19. Thus, this review aims to provide a brief overview on the uses of TCs for COVID-19 management. SARS-CoV-2 and other coronaviruses depend mainly on the matrix metalloproteinases (MMPs) for their proliferation, cell adhesion, and infiltration. The anti-inflammatory mechanisms of TCs are linked to different pathways. Briefly, TCs inhibit mitochondrial cytochrome c and caspase pathway with improvement of lymphopenia in early COVID-19. Specifically, minocycline is effective in reducing COVID-19–related complications, through attenuation of cytokine storm as apparent by reduction of interleukin (IL)-6, IL-1, and tumor necrosis factor (TNF)-α. Different clinical trials recommend the replacement of azithromycin by minocycline in the management of COVID-19 patients at high risk due to two main reasons: 1) minocycline does not prolong the QT interval and even inhibits ischemia-induced arrhythmia; 2) minocycline displays synergistic effect with chloroquine against SARS-CoV-2. Taken together, the data presented here show that TCs, mainly doxycycline or minocycline, may be potential partners in COVID-19 management, derived pneumonia, and related complications, such as acute lung injury (ALI) and ARDS.

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Serious adverse events with tocilizumab: Pharmacovigilance as an aid to prioritize monitoring in COVID‐19

Cited by 48 publications

References 23 publications

Tocilizumab and liver injury in patients with COVID-19

Tocilizumab and liver injury in patients with COVID-19

COVID-19 in Chronic Liver Disease and Liver Transplantation

Pleiotropic Effects of Tetracyclines in the Management of COVID-19: Emerging Perspectives

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