Voriconazole Provides Effective Prophylaxis for Invasive Fungal Infection in Patients Receiving Glucocorticoid Therapy for Graft-Versus-Host Disease

Patients on systemic glucocorticoids for graft-versus-host disease (GVHD) after hematopoietic cell transplant are susceptible to invasive fungal infections (IFI), which greatly contribute to morbidity and mortality. We evaluated the efficacy of prophylactic treatment options (voriconazole versus fluconazole or itraconazole) for IFI by performing a retrospective review of patients on glucocorticoids for GVHD given voriconazole (n = 97), fluconazole (n = 36), or itraconazole (n = 36). IFI developed in 7/72 (10%) patients on fluconazole/itraconazole versus 2/97 (2%) on voriconazole (P = 0.03) within the first 100 days of glucocorticoids. Five patients developed Aspergillus IFI on fluconazole/itraconazole (7%), compared to none on voriconazole (0%) (P = 0.008); Aspergillus IFI resulted in death in all 5 patients. We found that IFI occurred in patients who received an initial dose of at least 2 mg/kg/day of prednisone or equivalent; when the analysis was restricted to these patients, the hazard ratio (0.39; 95% confidence interval: 0.08–1.86) was consistent with a protective effect of voriconazole compared with fluconazole/itraconazole, although this subset analysis did not reach significance. Overall survival at 100 days after start of glucocorticoids was 77% in patients given fluconazole/itraconazole and 85% in those given voriconazole (P = 0.22). Our results suggest that voriconazole is more effective than fluconazole/itraconazole in preventing IFI, especially aspergillosis, in patients receiving glucocorticoids posttransplant.