Efficacy of Adjuvant Corticosteroid Therapy for CAP Varied Significantly Based on C-Reactive Protein Concentrations
Clinical question: Can baseline C-reactive protein concentrations help identify which patients with community-acquired pneumonia (CAP) are most likely to benefit from adjuvant treatment with corticosteroids?
Background: CAP is a heterogeneous disease and a leading cause of morbidity and mortality. The use of corticosteroids to treat patients hospitalized with CAP is evolving, and factors such as the causative pathogen may impact treatment effects. There is a widespread hypothesis that corticosteroids may provide the most benefit for patients with severe CAP. However, severe CAP does not have a universal definition, and the population that would most benefit has not been precisely identified.
Study design: Individual patient meta-analysis using heterogeneity of treatment effect (HTE) analysis
Setting: Hospitals in Italy, the Netherlands, Switzerland, Spain, the U.S., and France
Synopsis: The authors included eight randomized controlled trials (RCTs) comparing adjuvant therapy with corticosteroids versus placebo in patients hospitalized with CAP. The RCTs were published between 2005 and 2023 and represented 3,224 patients. Across all trials, the corticosteroid therapy group had significantly reduced 30-day mortality (6.6% versus 8.7%, P=0.017). An HTE analysis was performed on the first six studies, and C-reactive protein (CRP) was identified as an important treatment modifier with a concentration of 204 mg/L as a cutoff for predicted benefit. The resulting HTE model was then validated on data from the two most recent RCTs. Among patients with a CRP over 204 mg/L, adjuvant corticosteroid therapy was associated with significantly reduced mortality (13.0% versus 6.1%; number needed to treat, 14; Pinteraction=0.026). No significant difference was observed in patients with a CRP up to 204 mg/L. There was a significant increase in hospital re-admissions and hyperglycemia associated with corticosteroid treatment. Point estimates also showed harmful effects of corticosteroids in patients with influenza, consistent with other studies. Limitations include pooling studies with significant methodological differences spanning nearly 20 years.
Bottom line: A markedly elevated CRP concentration (over 200 mg/L) may help identify patients with CAP who are most likely to benefit from adjuvant corticosteroid treatment, however, causative pathogens and risk of side effects should be considered.
Citation: Smit JM, et al. Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomised trials. Lancet Respir Med. 2025;13(3):221-233. doi:10.1016/S2213-2600(24)00405-3.
Dr. Klein is an attending physician and associate medical director for quality in the division of hospital medicine at Maine Medical Center in Portland, Maine, and an assistant professor of medicine at Tufts University School of Medicine in Boston.