Isavuconazole Versus Voriconazole as the First-line Therapy for Solid Organ Transplant Recipients With Invasive Aspergillosis: Comparative Analysis of 2 Multicenter Cohort Studies

Transplantation. 2024 Nov 1;108(11):2260-2269. doi: 10.1097/TP.0000000000005082. Epub 2024 May 21.

Abstract

Background: Isavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients.

Methods: We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (n = 57) or VORI (n = 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation.

Results: Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027).

Conclusions: Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antifungal Agents* / adverse effects
  • Antifungal Agents* / therapeutic use
  • Aspergillosis* / diagnosis
  • Aspergillosis* / drug therapy
  • Aspergillosis* / mortality
  • Female
  • Humans
  • Invasive Fungal Infections / diagnosis
  • Invasive Fungal Infections / drug therapy
  • Invasive Fungal Infections / mortality
  • Male
  • Middle Aged
  • Nitriles* / adverse effects
  • Nitriles* / therapeutic use
  • Organ Transplantation* / adverse effects
  • Pyridines* / adverse effects
  • Pyridines* / therapeutic use
  • Retrospective Studies
  • Transplant Recipients
  • Treatment Outcome
  • Triazoles* / adverse effects
  • Triazoles* / therapeutic use
  • Voriconazole* / adverse effects
  • Voriconazole* / therapeutic use

Substances

  • isavuconazole
  • Antifungal Agents
  • Voriconazole
  • Nitriles
  • Pyridines
  • Triazoles