Tocilizumab & Sarilumab Have Limited Role in COVID-19 Treatment

The role of tocilizumab in COVID-19 treatment was not very clear. Tocilizumab is available in the market under the brand name of Actemra. Studies conducted in the first half of the year suggested the use of tocilizumab to reduce the risk of mechanical or non-mechanical ventilation in patients with COVID-19.

The current National Institutes of Health (NIH) guidelines released by the end of August 2020 suggest against the use of tocilizumab in patients with COVID-19.

Coronavirus
Coronaviruses infect animals, humans, and birds. Human coronaviruses, such as SARS, MERS, and 2019-nCoV cause respiratory distress and even death. The S protein is the infectious agent of the virus.

‘The current National Institutes of Health (NIH) guidelines released by the end of August 2020 suggest against the use of tocilizumab in patients with COVID-19. None of the IL-6 inhibitors is approved by the FDA for the treatment cytokine storm syndrome (CRS).’

Interleukin (IL)-6 is a pleiotropic, pro-inflammatory cytokine produced by a variety of cell types, including lymphocytes, monocytes, and fibroblasts. Infection by the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) induces the IL-6 production from the bronchial epithelial cells.

COVID-19 associated hypoxic (decreased levels of oxygen) respiratory failure & inflammation may be linked to the cytokine release – increased levels of IL-6 , C-reactive protein (CRP), D-Dimer & ferritin.

There are two classes of the FDA approved drugs capable of modulating the IL-6 responses. They are IL—6 Inhibitors (sarilumab & tocilizumab) or anti-IL-6 receptor monoclonal antibodies (siltuximab). The NIH panel recommends against the use of these agents in COVID-19 patients.

Tocilizumab Injection

This medication is an interleukin-6 (IL-6) receptor blocker, prescribed for rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis (SJIA) in 2 year old children either alone or with other medications.

There are randomized controlled trials that were carried out. These trials failed to establish the efficacy of sarilumab & tocilizumab in COVID-19 patients.

Sarilumab is a recombinant humanized IL-6 inhibitor monoclonal antibody approved by the FDA to treat rheumatoid arthritis. It is available as a sub cutaneous formulation. Currently intravenous sarilumab 400 mg & 200 mg are used as off label drugs for COVID-19 patients.

Siltuximab
Siltuximab injection is used to treat patients suffering from multicentric Castleman’s disease (MCD) in which the disease involves multiple lymph nodes or other distant tissues of the body.

Siltuximab must be prescribed only to patients who are having MCD, who are negative for Human Immunodeficiency Virus (HIV) and human herpesvirus-8 (HHV-8) negative.

The most important point to be noted is that this drug is not approved for the treatment of cytokine release syndrome (CRS). A clinical trial is in progress to study the effects of intravenous sarilumab in COVID-19 patients. The major adverse effects of sarilumab are reversible elevations in liver enzymes (Dose–Dependent), rare occurrences of neutropenia & thrombocytopenia.

Sarilumab
Sarilumab is prescribed for the treatment of moderate-to-severe rheumatoid arthritis in adult patients who have not shown adequate response either to one or more disease-modifying antirheumatic drugs (DMARDs).

Rheumatoid arthritis is an autoimmune disease in which the body’s immune system mistakenly attacks its own joints resulting in pain, swelling, and inflammation.

Sarilumab is used alone or in combination with methotrexate or other DMARDs.

It works by blocking the activity of interleukin-6, a cytokine substance that is responsible for causing inflammation.

Tocilizumab is a recombinant humanized IL-6 inhibitor monoclonal antibody approved by the FDA for treating patients with rheumatic disorders & CRS induced by chimeric antigen receptor cell therapy.

Earlier there were few studies which summarized the benefits of tocilizumab in Covid-19 patients. But the recent studies and NIH guidelines are strongly against treatment with tocilizumab in COVID-19 patients.

Siltuximab is a recombinant human – mouse chimeric monoclonal antibody that binds to IL-6. The FDA has approved its use to treat Castleman’s syndrome (rare disorder that involves an overgrowth of cells in the body's lymph nodes). It is dosed as an IV infusion. There are no studies which show the benefits of using siltuximab in COVID-19 patients.

Source-Medindia