Anakinra authorized to treat severe coronavirus disease 2019; Sepsis breakthrough or time to reflect?

Area of Science:

• Immunology
• Critical Care Medicine
• Pharmacology

Background:

• The European Medicines Agency (EMA) and FDA approved recombinant human interleukin-1 receptor antagonist (rhIL-1ra) for hospitalized COVID-19 patients at risk of progression.
• This decision followed positive results from the SAVE-MORE phase 3 clinical trial, guiding Anakinra treatment based on suPAR levels.

Purpose of the Study:

• To conduct a literature review and theoretical analysis of IL-1 blockade for COVID-19 treatment.
• To assess the clinical applicability of SAVE-MORE trial results and evaluate the rationale for interleukin-1 suppression in COVID-19.
• To examine this therapeutic approach as a model for inflammation-suppressing sepsis treatments.

Main Methods:

• Literature review and theoretical analysis of IL-1 blockade in COVID-19.
• Stepwise analysis of the SAVE-MORE clinical trial data and its implications.
• Evaluation of interleukin-1 suppression as a COVID-19 treatment strategy.

Main Results:

• Anakinra's proposed mechanism for COVID-19 may misinterpret disease pathogenesis, as COVID-19 shares characteristics with sepsis.
• The history of anti-inflammatory therapies for sepsis shows limited success, contradicting potential benefits in COVID-19.
• While the SAVE-MORE trial showed positive results, this success may represent a pattern of initial positive findings followed by failure to replicate in subsequent studies for inflammation-suppressing sepsis treatments.

Conclusions:

• Further research into rhIL-1ra for COVID-19 and similar inflammatory conditions may not yield significant breakthroughs.
• The current approach to developing inflammation-suppressing sepsis therapies, including for COVID-19, might be insufficient.
• A novel approach is likely necessary to discover effective treatments for sepsis and related critical illnesses.