Arthritis drug might effectively treat life-threatening COVID-19 pneumonia

Tocilizumab (TCZ) might be the drug of hope to treat severe acute respiratory syndrome ’SARS’ caused by the novel coronravirus, ’SARS-CoV-2’. TCZ has been widely used in the treatment of rheumatoid arthritis (RA) for years, and now it seems that it might effectively treat critically ill COVID -19 pneumonia patients. TCZ is an interleukin-6 receptor (IL-6R) blocking biological agent, the generic name of the Roche/Genentech drug called RoActemra/Actemra.

The Italian Government Hospital and Cancer Institute of Naples, in direct cooperation with China, published their preliminary results on the success of TCZ in the treatment of coronavirus pneumonia. The Swiss based pharmaceutical giant Roche is awaiting the approval of the Italian Medical Agency to start clinical trials on RoActemra to evaluate its efficacy and safety profile on COVID-19 patients. Genentech, the American Roche subsidiary has initiated a comprehensive TCZ study across the US. The study plan is to evaluate intravenous Actemra/RoActemra on top of standard care in hospitalized adult patients with severe COVID-19 pneumonia. If successful, anti-IL 6R treatment might be approved for SARS-CoV-2 pneumonia in a couple of months.  Roche and Genentech have offered thousands of TCZ vials - free of charge - to the Italian and American Hospitals, concerning their extreme morbidity and mortality rate.

According to the present data on the coronavirus pandemic, 20% of the COVID-19 patients are admitted to hospital, 5-15% require intensive care, and 1-5% develop SARS, acute respiratory distress ’ARDS’, requiring artificial ventilation, oxygen and sometimes artificial maintenance of blood circulation alongside intensive supportive therapy.

The numbers of infected are likely to markedly increase during the coming weeks, greatly challenging the capacity of health systems worldwide. COVID-19 has become an emerging, rapidly evolving situation; there is an urgent need to find a drug that might efficiently treat the most serious complication of the coronavirus infection, the SARS-CoV-2 pneumonia.

Coronavirus disease 2019 ’COVID-19’ is caused by the newly discovered coronavirus ’SARS-CoV-2’. The median time from onset of symptoms of COVID-19 to development of ARDS has been reported as being as short as 7-9 days. No effective prophylactic or post-exposure therapy is currently available. 

Figure. Multiplication of light patchy areas in the grey parts indicates inflammatory fluid

Case report. Recently, chest computed tomography (CT) of a COVID patient has been published by the Radiological Society of North America. The Chinese man aged 44, who used to take goods to a Vuhan fishmarket, was admitted to hospital on December 25th, after he had had fever and cough for 13 days. Severe pneumonia and  acute respiratory distress was observed which was later related to COVID-19 disease. CT scans of his lung can be seen on the pictures during one week time, as the man died 7 days after being admitted to the hospital. 

In patients infected with SARS-CoV-2, it has been described that disease severity and prognosis are related to the characteristics of the immune response. Interleukin-6 (IL-6) and other components of the inflammatory cascade contribute to host defense against infections. However, exaggerated synthesis of IL-6 can lead to an acute severe systemic inflammatory response known as 'cytokine storm', or ’cytokine release syndrome’ (CRS). In the pathogenesis of SARS-CoV-2 pneumonia, a study found that a cytokine storm involving a considerable release of proinflammatory cytokines occurs, including IL-6, IL-12, and tumor necrosis factor α (TNF-α). It has been suggested that IL-6 blockade may constitute a novel therapeutic strategy for other types of cytokine storm, e.g. systemic inflammatory response associated with sepsis, macrophage activation syndrome, hemophagocytic lymphohistiocytosis and after T cell activating oncotherapy.

The remarkable beneficial effects of IL-6 blockade therapy using an IL-6R inhibitor has been described in patients with severe SARS-CoV-2 pneumonia in a retrospective case series from China. IL-6 might play a key role in the cytokine storm associated with serious adverse outcomes in patients with SARS-CoV-2 infection, thus theoretically, a blockade of IL-6 would be a suitable therapeutic target.

Currently, there are two available drugs based on human monoclonal antibodies against IL-6R: tocilizumab (RoActemra, Roche) and sarilumab (Kevzara, Sanofi). IL-6R inhibitors are currently licensed for RA, juvenile idiopathic arthritis (JIA) and giant cell arteritis (GCA) and are considered well tolerated and safe in general. The most common side effects reported are upper respiratory tract infections, headache, hypertension, and abnormal liver function tests. The most serious side effects are serious infections, complications of diverticulitis, and hypersensitivity reactions.

RoActemra has also been approved by the Hungarian Authorities for the treatment of RA, JIA and GCA.. If a patient fulfils the criteria of a severe disease, the costs of the treatment are covered by the National Health Insurance.

The TCZ dose in the treatment of RA is low (sc inj 162mg weekly or iv infusion 8mg/kg max. 800mg monthly), whereas in SARS-CoV-2 pneumonia the advised dose is sc inj 800mg or iv. infusion 8mg/kg max 800mg twice daily!