IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy?

• Published in: Pharmaceutical medicine Vol. 34; no. 4; pp. 223 - 231
• Main Authors: Atal, Shubham, Fatima, Zeenat
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2020; Springer Nature B.V
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - immunology; Betacoronavirus - immunology; Betacoronavirus - isolation & purification; Biomedical and Life Sciences; Biomedicine; Clinical trials; Clinical Trials as Topic; Coronavirus Infections - drug therapy; Coronavirus Infections - immunology; Coronavirus Infections - physiopathology; Coronaviruses; COVID-19; COVID-19 Drug Treatment; Current Opinion; Cytokines; Cytokines - immunology; Disease; Drugs; Gene expression; Hospitalization; Humans; Infections; Inflammation; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - immunology; Lungs; Mortality; Oxidative stress; Pandemics; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharmacotherapy; Pneumonia; Pneumonia, Viral - drug therapy; Pneumonia, Viral - immunology; Pneumonia, Viral - physiopathology; Proteins; Respiratory diseases; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Signal transduction; Viruses; Brazil; United States > US
• ISSN: 1178-2595; 1179-1993; 1179-1993
• DOI: 10.1007/s40290-020-00342-z

At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNFα), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be ‘life-saving’ as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies.