Efficacy of anakinra in reducing progression to organ dysfunction in patients with pneumonia (INSPIRE): a randomised, double-blind, placebo-controlled, phase IIa trial.

Summary

In a double-blind phase IIa RCT of 60 hospitalized pneumonia patients enriched by presepsin (>350 pg/mL) and qSOFA=1, anakinra 100 mg daily for 10 days reduced progression to organ dysfunction (20% vs 50%; p=0.011) and 90-day mortality (20.0% vs 43.3%; p=0.029) versus placebo. Serious TEAEs were fewer with anakinra and none were treatment-related.

Key Findings

• Primary endpoint (SOFA +2 by day 7 and/or 90-day death) reduced from 50.0% (placebo) to 20.0% (anakinra); p=0.011
• 90-day mortality reduced from 43.3% to 20.0%; p=0.029
• Serious TEAEs occurred less frequently with anakinra (33.3% vs 50%) and none were treatment-related
• Cytokine production (TNFα, IFNγ) by blood mononuclear cells was attenuated with anakinra

Clinical Implications

Supports presepsin-guided IL-1 blockade as a precision therapy to prevent deterioration in pneumonia. If replicated in larger RCTs, this could inform sepsis bundle updates and personalized immunomodulation.

Limitations

• Small, single phase IIa sample size (n=60) limits generalizability
• Conducted in pneumonia with qSOFA=1; applicability to broader sepsis phenotypes requires study

Future Directions

Larger, multicenter phase III trials to confirm efficacy, refine presepsin thresholds, and assess timing/duration; head-to-head comparisons with other immunomodulators.