By Trushil Shah, MD, MS
Assistant Professor of Medicine, University of Texas Southwestern, Dallas
SYNOPSIS: This systematic review and meta-analysis of 16 randomized controlled trials (RCTs) studied the use of adjunctive corticosteroid therapy in community-acquired pneumonia. All-cause mortality, intensive care unit admission, and incidence of adverse events were similar in patients who received corticosteroids compared to standard care. However, the corticosteroid therapy group had a lower incidence of progression to mechanical ventilation.
SOURCE: Saleem N, Kulkarni A, Snow TAC, et al. Effect of corticosteroids on mortality and clinical cure in community-acquired pneumonia: A systematic review, meta-analysis, and meta-regression of randomized control trials. Chest 2023;163:484-497.
Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide. Corticosteroids have been considered in the management of severe CAP, given their anti-inflammatory and immunomodulatory effects that potentially can mitigate progression of disease. There is evidence of benefit in the use of corticosteroid therapy in patients with COVID-19 pneumonia and in some studies focused on acute respiratory distress syndrome (ARDS). However, the role of corticosteroids in the treatment of CAP remains controversial, with conflicting evidence reported in the literature.
This systematic review and meta-analysis included studies from 1956 to February 2022, including the more recent IMPROVE-GAP trial (2019), Santeon-CAP trial (2021), and ESCAPe study (2022).1-4 The primary outcome was all-cause mortality. Secondary outcomes included intensive care unit (ICU) admission, mechanical ventilation, and clinical cure, defined as the resolution of fever and clinical signs of pneumonia within seven days, in addition to adverse events.
Sixteen trials met the eligibility criteria. All-cause mortality (risk ratio [RR], 0.85; 95% confidence interval [CI], 0.67-1.07; P = 0.17), need for ICU admission (RR, 0.66; trial sequential analysis (TSA)-adjusted 95% CI, 0.37-1.12), treatment failure (RR, 0.78; 95% CI, 0.37-1.67; P = 0.52), and the incidence of adverse events (RR, 1.10; 95% CI, 0.97-1.25; P = 0.14) were similar between patients receiving corticosteroids and patients assigned to the control group. Need for mechanical ventilation (RR, 0.51; 95% CI, 0.33-0.77; P = 0.001) was lower among patients receiving corticosteroids compared with those receiving standard care. However, corticosteroid use may be associated with higher rates of hospital readmission (RR, 1.20; 95% CI, 1.05-1.38; P = 0.008).
COMMENTARY
Considerable interest exists in the use of adjunctive corticosteroids in CAP, and multiple randomized controlled trials (RCTs) have been performed to investigate this question. A 2015 meta-analysis of RCTs by Siemieniuk et al concluded that systemic corticosteroid therapy may reduce mortality by ~3%, mechanical ventilation by ~5%, and hospital stay by ~1 day.5 This meta-analysis sparked a renewed interest in using corticosteroids in CAP, but was limited by low-quality, smaller studies. As such, most society guidelines did not recommend corticosteroids in CAP due to the limitations in this previous meta-analysis and the lack of high-quality data.
More recently, interest in exploring steroids in CAP resumed, especially after evidence from COVID-19-associated pneumonia and ARDS suggested a significant benefit of dexamethasone and other steroids.6 Better-powered trials of corticosteroids in CAP, including the IMPROVE-GAP trial (816 patients), Santeon-CAP trial (401 patients), and ESCAPe study (586 patients), however, showed mixed results.2-4 The IMPROVE-GAP study was negative for steroids decreasing length of stay or mortality, in addition to reporting a higher incidence of gastrointestinal bleeding (2.2%) in the steroid group vs. the control group (0.7%). The authors concluded that the use of corticosteroids in a bundled intervention in CAP is not effective and may result in net harm. In contrast, the Santeon-CAP study showed that oral dexamethasone reduced the length of stay and ICU admission rate in adults hospitalized with CAP. The ESCAPe trial did not meet its primary endpoint of 60-day mortality and was not positive for any secondary outcomes except for reduced duration of mechanical ventilation in patients needing mechanical ventilation.
Given these conflicting data, the meta-analysis by Saleem et al provides important insights into the risks and benefits of adjunctive corticosteroid use in hospitalized CAP patients. While this meta-analysis did not show any significant reduction in all-cause mortality, it did show a reduced need for mechanical ventilation as a benefit of using corticosteroids in hospitalized CAP patients. The corticosteroid group had a higher incidence of hyperglycemia and a higher readmission rate as compared to the standard therapy group. However, the rates of infections and gastrointestinal bleeding were not significantly different. This suggests that there seems to be a benefit to the use of corticosteroids in patients with severe CAP, although it needs to be weighed against the increased risk of readmission.
Based on this meta-analysis, I think there is a subpopulation of CAP patients who would benefit from adjunctive corticosteroids. Data in current trials are limited by the use of different corticosteroids with varying duration of therapy and varying severity of patients included. Future RCTs are needed to answer this question, and until then, use of corticosteroids in CAP patients remains a clinical judgment call.
REFERENCES
- Saleem N, Kulkarni A, Snow TAC, et al. Effect of corticosteroids on mortality and clinical cure in community-acquired pneumonia: A systematic review, meta-analysis, and meta-regression of randomized control trials. Chest 2023;163:484-497.
- Lloyd M, Karahalios A, Janus E, et al. Effectiveness of a bundled intervention including adjunctive corticosteroids on outcomes of hospitalized patients with community-acquired pneumonia: A stepped-wedge randomized clinical trial. JAMA Intern Med 2019;179:1052-1060.
- Wittermans E, Vestjens SM, Spoorenberg SMC, et al. Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: A randomised clinical trial. Eur Respir J 2021;58:2002535.
- Meduri GU, Shih M-C, Bridges L, et al. Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia. Intensive Care Med 2022;48:1009-1023.
- Siemieniuk RAC, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med 2015;163:519-528.
- Chaudhuri D, Sasaki K, Karkar A, et al. Corticosteroids in COVID-19 and non-COVID-19 ARDS: A systematic review and meta-analysis. Intensive Care Med 2021;47:521-537.
