The following is a summary of “Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomised trials,” published in the March 2025 issue of Lancet Respiratory Medicine by Smit et al. 

The impact of adjuvant corticosteroid therapy on 30-day mortality in patients hospitalized with community-acquired pneumonia (CAP) remains a topic of debate despite multiple randomized controlled trials (RCTs). This individual patient data meta-analysis aimed to assess the heterogeneity of treatment effect (HTE) of corticosteroid use on 30-day all-cause mortality in patients with CAP. Researchers included RCTs published before July 1, 2024, that compared corticosteroid treatment with placebo. The primary endpoint was 30-day mortality, analyzed according to the intention-to-treat principle. HTE was evaluated using both risk modeling—categorizing CAP severity based on the pneumonia severity index (PSI)—and effect modeling, which classified patients into predicted benefit or no benefit groups using a corticosteroid-effect model trained on six trials and externally validated on two additional trials. 

A total of eight RCTs comprising 3,224 patients were included, with 246 (7.6%) deaths within 30 days (106 [6.6%] in the corticosteroid group vs. 140 [8.7%] in the placebo group; [OR] 0.72 [95% CI 0.56–0.94], p=0.017). The corticosteroid-effect model, incorporating C-reactive protein (CRP) as a key predictor, demonstrated significant HTE during external validation. In the two most recent trials, which included 1,355 patients, 154 (11.4%) died within 30 days (88 [13.1%] in the placebo group vs. 66 [9.6%] in the corticosteroid group; OR 0.71 [95% CI 0.50–0.99], p=0.044). Patients with CRP ≤204 mg/L (n=725) showed no significant benefit (OR 0.98 [95% CI 0.63–1.50]), whereas those with CRP >204 mg/L (n=630) experienced a significant mortality reduction (39 [13.0%] deaths in the placebo group vs. 20 [6.1%] in the corticosteroid group; OR 0.43 [95% CI 0.25–0.76], pinteraction=0.026). 

No significant HTE was found when comparing less severe CAP (PSI class I–III, n=229) and severe CAP (PSI class IV–V, n=1,126). However, corticosteroid therapy significantly increased the risks of hyperglycemia (44 [12.8%] of 344 in the placebo group vs. 84 [24.8%] of 339 in the corticosteroid group; OR 2.50 [95% CI 1.63–3.83], p<0.0001) and hospital re-admission (30 [3.7%] of 814 in the placebo group vs. 57 [7.0%] of 819 in the corticosteroid group; OR 1.95 [95% CI 1.24–3.07], p=0.0038). In conclusion, adjuvant corticosteroid therapy significantly reduces 30-day mortality in hospitalized patients with CAP; however, its benefits are primarily confined to those with elevated baseline CRP levels. These findings suggest that CRP concentrations may serve as a key biomarker to guide corticosteroid use in CAP, optimizing treatment efficacy while minimizing associated risks.

Source: thelancet.com/journals/lanres/article/PIIS2213-2600(24)00405-3/abstract