Overview on the use of IL-6 agents in the treatment of patients with cytokine release syndrome (CRS) and pneumonitis related to COVID-19 disease

ABSTRACT

Introduction

A novel coronavirus pneumonia (COVID-19) has caused significant life loss and healthcare burden globally. COVID-19 is known to cause a cytokine release syndrome (CRS) like response, and interleukin-6 (IL-6) is one of the cytokines involved. Clinicians are using IL-6 inhibitors to CRS, and researchers are investigating the use of IL-6 inhibitors, namely tocilizumab, sarilumab, siltuximab, in COVID-19 management.

Areas covered

In this article, we will discuss the pharmacology of these three inhibitors and summarize available clinical data via literature search on PubMed with keywords of tocilizumab, sarilumab, siltuximab, and COVID-19. While awaiting more data from randomized clinical trials on these drugs, observational studies and clinical reports have demonstrated IL-6 inhibitors showed some benefits in improving clinical outcome and a well-tolerated safety profile.

Expert opinion

There is a role for suppressing the immune response with IL-6 inhibitors that will continue to require investigation. These agents are available and have demonstrated a mild safety profile. There may be advantages to a targeted approach to suppressing the hyperinflammatory state of the disease. Timing, the long-term effects, and what cocktail of medications demonstrates the strongest outcomes are all important considerations as IL-6 inhibitors continue to be evaluated in this global pandemic.

KEYWORDS:

• COVID-19
• interleukin-6 inhibitors
• cytokine release syndrome
• tocilizumab
• sarilumab
• siltuximab. Pneumonitis
• cytokine storm

Article highlights

• Patients with COVID-19 pneumonitis may experience an excessive amount of circulating proinflammatory cytokines that can cause cytokine release syndrome (CRS). Interleukin (IL)-6 is a type of proinflammatory cytokine, and strategies to reduce the amount of IL-6 have been considered as a method to manage patients with COVID-19.

• Three IL-6 inhibitors, tocilizumab, sarilumab, siltuximab, are being researched to investigate their roles in managing COVID-19. Sarilumab and tocilizumab are indicated for rheumatoid arthritis, while tocilizumab has additional indications for other immunological diseases. Siltuximab is indicated for multicentric Castleman’s disease. The ability of these agents to reduce immune reactions prompts their trials in COVID-19.

• Observational studies of sarilumab also indicated some benefits of this drug in COVID-19 management. However, the only randomized controlled trial based in the United States has been terminated after a failure of meeting the primary endpoint of the trial. The drug manufacturer continues its trial outside of the United States. We currently do have not adequate report for siltuximab. Only observational studies are currently available, and data are not adequate enough to draw conclusions regarding the efficacy and safety of siltuximab.

• To manage COVID-19, further data are necessary to guide clinicians to determine the benefits of monotherapy vs. combination therapy in the most appropriate subset of patients. Additionally, more studies are needed to determine the timing of administration, the route of administration, as well as short-term and long-term adverse drug reactions.This box summarizes the key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One peer reviewer has received a travel grant from Kiniksa Pharmaceuticals Ltd. to attend the 2019 AHA Scientific Sessions. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.