Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomised trials.

Summary

Across eight RCTs (n=3224), adjunct corticosteroids reduced 30-day mortality in hospitalized CAP (OR 0.72). A pre-registered effect model identified baseline CRP as the key effect modifier: patients with CRP >204 mg/L had substantial mortality reduction (OR ~0.43), while those with CRP ≤204 mg/L derived no benefit.

Key Findings

• Eight RCTs (n=3224) showed lower 30-day mortality with adjunct corticosteroids versus placebo (OR 0.72, 95% CI 0.56–0.94).
• Effect-model external validation identified CRP as the sole predictor of benefit; CRP >204 mg/L had marked mortality reduction (OR ~0.43), CRP ≤204 mg/L showed no benefit (OR ~0.98).
• Findings were pre-registered and validated on two recent trials, supporting reproducibility and generalizability.

Clinical Implications

For hospitalized CAP, consider adjunct corticosteroids when baseline CRP >204 mg/L; avoid routine use at lower CRP. Incorporate CRP-based algorithms, while monitoring hyperglycemia and secondary infection risks.

Limitations

• Heterogeneity in corticosteroid regimens and dosing across trials
• Adverse events and long-term outcomes were not the primary focus

Future Directions

Prospective trials implementing CRP-guided corticosteroid strategies, including optimal dosing/duration and safety profiling in high-CRP CAP.