BACKGROUND: Despite several randomised controlled trials (RCTs) on the use of adjuvant treatment with corticosteroids in patients with community-acquired pneumonia (CAP), the effect of this intervention on mortality remains controversial. We aimed to evaluate heterogeneity of treatment effect (HTE) of adjuvant treatment with corticosteroids on 30-day mortality in patients with CAP.
METHODS: In this individual patient data meta-analysis, we included RCTs published before July 1, 2024, comparing adjuvant treatment with corticosteroids versus placebo in patients hospitalised with CAP. The primary endpoint was 30-day all-cause mortality, collected across all trials, and analyses followed the intention-to-treat principle. We analysed HTE 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), comparing PSI class I-III versus class IV-V. For effect modelling, we trained a corticosteroid-effect model on six trials and externally validated it using data from two trials, received after model preregistration. This model classified patients into two groups: no predicted benefit and predicted benefit from adjuvant treatment with corticosteroids. The literature search was registered on PROSPERO, CRD42022380746.
FINDINGS: We included eight RCTs with 3224 patients. Across all eight trials, 246 (7·6%) patients died within 30 days (106 [6·6%] of 1618 in the corticosteroid group vs 140 [8·7%] of 1606 in the placebo group; odds ratio [OR] 0·72 [95% CI 0·56-0·94], p=0·017). The corticosteroid-effect model, which selected C-reactive protein (CRP), showed significant HTE during external validation in the two most recent trials. In these trials, 154 (11·4%) of 1355 patients died within 30 days (88 [13·1%] of 671 in the placebo group vs 66 [9·6%] of 684 in the corticosteroid group; OR 0·71 [95% CI 0·50-0·99], p=0·044). Among patients predicted to have no benefit (CRP =204 mg/L, n=725), no significant effect was observed (OR 0·98 [95% CI 0·63-1·50]), whereas for those with predicted benefit (CRP >204 mg/L, n=630), 39 (13·0%) of 301 patients died in the placebo group compared with 20 (6·1%) of 329 in the corticosteroid group (0·43 [0·25-0·76], pinteraction=0·026). No significant HTE was found between less severe CAP (PSI class I-III, n=229) and severe CAP (PSI class IV-V, n=1126). Corticosteroid therapy significantly increased hyperglycaemia risk (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 risk (30 [3·7%] of 814 in the placebo group vs 57 [7·0%] of 819 in the corticosteroid group; 1·95 [1·24-3·07], p=0·0038).
INTERPRETATION: Overall, adjuvant therapy with corticosteroids significantly reduces 30-day mortality in patients hospitalised with CAP. The treatment effect varied significantly among subgroups based on CRP concentrations, with a substantial mortality reduction observed only in patients with high baseline CRP.
FUNDING: None.
| Specialty Area | Score |
|---|---|
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Respirology/Pulmonology | |
| Intensivist/Critical Care |
I am a trauma-intensivist so CAP is not really something I deal with - we do use steroids locally in treating CAP.
This meta-analysis of RCTs involves patients with community-acquired pneumonia receiving steroids vs without steroids. The authors also acquire patient-level data from the trials and use those data in their analyses. The study has strong methodology for both the meta-analyses part and the patient level part. The study demonstrated that there was a mortality benefits for high-risk patients (whose CRP > 204). The data from this study may allow clinicians to consider their treatment options for patients with CAP.
For hospitalists, pneumonia season is upon us. Finding ways to treat it better is always of interest. We use steroids to treat reactive airways and infection all the time. We just survived COVID and in sick pneumonias, steroids were helpful. Figuring out who they are helpful for in patients with CAP would be very beneficial. In this study, they did a meta-analysis using elevated CRP as a cut off and found that sicker patients hospitalized with pneumonia did better with steroids. It is worthwhile considering a trial expressly aimed at this population to confirm, but in the meantime I will be more likely to use steroids in my patients with pneumonia.
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