Interleukin-6 blocking agents for treating COVID-19: a living systematic review

Area of Science:

• Immunology
• Virology
• Clinical Medicine

Background:

• COVID-19 patients with autoantibodies against type I interferons may experience cytokine storms, leading to severe respiratory issues.
• Interleukin 6 (IL-6) is a key cytokine in this inflammatory process, prompting the use of IL-6 blocking agents for severe COVID-19.

Approach:

• A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate IL-6 blocking agents against standard care or placebo.
• Searches were performed on major clinical trial registries and databases up to June 7, 2022.
• Data extraction, risk of bias assessment, and certainty of evidence using the GRADE approach were performed independently by two researchers.

Key Points:

• Tocilizumab demonstrated a high-certainty benefit in reducing all-cause mortality at 28 days in hospitalized COVID-19 patients.
• Tocilizumab and sarilumab showed moderate-certainty evidence of little to no increase in clinical improvement at 28 days.
• Evidence regarding the efficacy and safety of sarilumab and other IL-6 blocking agents (clazakizumab, olokizumab, siltuximab, levilimab) is uncertain or very uncertain.

Conclusions:

• Tocilizumab offers a short-term survival benefit for hospitalized COVID-19 patients with likely no significant difference in adverse events.
• Clinical improvement and long-term outcomes for tocilizumab and sarilumab remain uncertain, as does the efficacy of other IL-6 blocking agents.
• The review concluded with no further updates planned due to the limited number of pending studies.