From relative risk to lives lost: Meta-analysis–based projection of invasive fungal infection burden attributable to systemic corticosteroids.

Abstract

e18624 Background: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients with hematologic malignancies. Although meta-analyses identify systemic corticosteroid exposure as a strong relative risk factor for IFI, the absolute burden attributable to corticosteroids across heterogeneous baseline risk settings remains poorly defined. We applied meta-analysis-based projection modeling to translate relative risk estimates into absolute, population-level IFI outcomes. Methods: Using pooled odds ratios for IFI associated with systemic corticosteroid exposure from a published meta-analysis (OR 2.84; 95% CI 1.42–5.70), we projected IFI incidence under a proportional odds framework. The primary analysis assumed a baseline IFI incidence of 15% in patients not receiving corticosteroids, with sensitivity analyses conducted across baseline incidences ranging from 10% to 25%. IFI-related mortality was estimated using a case-fatality rate of 45%. Outcomes were expressed as projected IFI incidence, excess IFIs and IFI-attributable deaths per 1,000 patients, population attributable fractions, and one-way sensitivity analyses. Results: At a baseline IFI incidence of 15%, systemic corticosteroid exposure increased projected IFI incidence to approximately 34%, corresponding to an excess of ~190 IFIs per 1,000 patients. This translated into approximately 80 excess IFI-attributable deaths per 1,000 patients, with a plausible range of 25–160 based on uncertainty in the pooled effect estimate. Sensitivity analyses demonstrated a monotonic increase in projected IFI incidence with rising baseline risk, with corticosteroid-associated IFI incidence approaching 50% at higher baseline levels. Population-attributable fraction modeling indicated that when corticosteroid use prevalence exceeded 40%, nearly half of IFIs in the population were attributable to corticosteroid exposure. One-way sensitivity analyses identified the corticosteroid effect size as the dominant driver of excess IFI mortality, exceeding the influence of baseline incidence or IFI case-fatality assumptions. Conclusions: Projection modeling based on meta-analytic risk estimates demonstrates that systemic corticosteroid exposure is associated with a substantial and clinically meaningful absolute increase in IFIs and IFI-related mortality. Translating relative risk estimates into absolute population-level outcomes highlights the potential magnitude of preventable infectious harm associated with corticosteroid use and provides actionable insight to inform risk-mitigation strategies in high-risk hematologic populations.