Community-acquired pneumonia (CAP) is a leading cause of hospitalisation with high mortality. It can be caused by various pathogens, including viruses, bacteria, and fungi, complicating treatment. Adjuvant corticosteroid treatment may help reduce excessive inflammation, which is linked to higher mortality.
While RCTs and a meta-analysis suggest survival benefits, the routine use of corticosteroids remains debated, with conflicting guidelines. The concept of heterogeneity of treatment effect (HTE) examines how treatment effects vary across patients, particularly in severe pneumonia. However, defining severe CAP is difficult, and HTE cannot be confirmed via aggregate data meta-analysis. Individual patient data meta-analysis can explore HTE more effectively, and a data-driven predictive analysis can provide individualised treatment predictions, addressing the limitations of conventional methods.
An individual patient data meta-analysis included RCTs published before July 1, 2024, comparing corticosteroids with placebo in hospitalised CAP patients. The primary endpoint was 30-day all-cause mortality, analysed using the intention-to-treat principle. HTE was analysed using risk and effect modelling. For risk modelling, patients were classified as having less severe or severe CAP based on the pneumonia severity index (PSI). For effect modelling, a corticosteroid-effect model was trained on six trials and externally validated with data from two additional trials. This model categorised patients into two groups: those with no predicted benefit and those with predicted benefit from corticosteroids.
The analysis included eight RCTs with 3224 patients. Within 30 days, 246 (7.6%) patients died, with a significantly lower mortality in the corticosteroid group (6.6%) compared to the placebo group (8.7%). The corticosteroid-effect model, which used C-reactive protein (CRP) levels, showed significant HTE during external validation. In the two most recent trials, corticosteroids reduced 30-day mortality in patients with high CRP (>204 mg/L), but no significant effect was seen in those with low CRP (≤204 mg/L). No significant HTE was found based on the severity of CAP (PSI class I–III vs. IV–V).
Corticosteroids did not significantly increase the risk of hospital-acquired infections or bleeding, but they did raise the risks of hyperglycemia and hospital readmissions. Patients with more severe CAP (PSI class IV–V) showed greater absolute benefits from corticosteroids, likely due to higher baseline mortality risk.
The study suggests that baseline CRP is a key predictor for determining who benefits most from corticosteroids, rather than the severity of CAP alone. The findings support the 2024 SCCM guideline's recommendation for corticosteroids in severe CAP but emphasise the importance of defining subgroups based on CRP levels.
The study also highlighted potential harms when corticosteroids were used for viral infections, and suggested caution, particularly without bacterial co-infection. Treatment regimens based on patient response and early initiation of corticosteroids (within 24–48 hours) showed greater benefits, although these findings should be interpreted cautiously. The study provides new evidence that CRP levels can guide corticosteroid treatment in CAP, marking the first data-driven confirmation of CRP as a predictor for treatment benefit.
Overall, adjuvant corticosteroid therapy significantly reduces 30-day mortality in hospitalised CAP patients. The treatment effect varied by subgroup, with a notable mortality reduction seen only in patients with high baseline CRP concentrations.
Source: The Lancet
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