By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
SYNOPSIS: An analysis of two retrospective cohort studies of solid organ transplant recipients with invasive aspergillosis found that isavuconazole and voriconazole had similar efficacy, but isavuconazole was better tolerated.
SOURCE: Fernández-Ruiz M, Gioia F, Bodro M, et al; SOTIS and DiasperSOT Study Groups. 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; May 21. doi: 10.1097/TP.0000000000005082. [Online ahead of print].
Fernández-Ruiz and colleagues performed a post hoc analysis of two large Spanish retrospective cohort studies (SOTIS and DiasperSOT) that included solid organ transplant (SOT) recipients with invasive aspergillosis (IA) treated with either isavuconazole or voriconazole. Patients received the antifungal as first-line therapy for at least 48 hours, either alone or in combination with other agents.
The entire cohort included a total of 134 patients with posttransplant IA, with 57 (42.5%) patients who received isavuconazole and 77 (57.5%) patients who received voriconazole. The groups were relatively comparable at baseline. Approximately one-half (50.9% and 50.6%, respectively) of each group received combination therapy, mostly an echinocandon or nebulized liposomal amphotericin B.
The primary outcome of clinical response at 12 weeks was almost identical in each treatment group: 59.6% and 59.7% in isavuconazole and voriconazole recipients, respectively. The relative results were similar after adjustment with propensity scoring and after matching. The all-cause mortality was 28.1% in isavuconazole recipients and 29.9% in voriconazole recipients, while attributable mortality (death within four weeks and no other cause identified) was 15.8% and 22.1% (P = 0.363), respectively. In contrast, isavuconazole was better tolerated, with 17.5% developing a treatment emergent adverse effect (TEAE) compared to 37.7% of voriconazole recipients (P = 0.011), and resultant treatment discontinuation occurred less frequently with isavuconazole as well. The excess TEAEs in the voriconazole group primarily was the result of a greater incidence of neurological and visual events.
COMMENTARY
These results are consistent with earlier studies not limited to transplant recipients. The most recent (albeit aging) Infectious Diseases Society of America (IDSA) guideline recommends voriconazole treatment, with isavuconazole being an alternative, along with liposomal amphotericin B.1 The guideline also states that combination therapy (with voriconazole and an echinocandin) “may be considered in select patients.”
One-half the patients in each group may have affected outcomes, but this likely would have had a similar effect in each. The similar outcomes with each triazole therapy are consistent with previous studies, as is the greater tolerability of isavuconazole. Voriconazole not infrequently may cause delirium and visual disturbance and, with long-term use, may cause cutaneous malignancies as well as fluorosis. It also is a strong inhibitor of CYP3A4, CYP2C19, and CYP2C9, leading to a wide variety of drug-drug interactions, while isavuconazole is a weaker inhibitor of CYP3A4 and CYP3A5 and is neither a substrate nor inhibitor of CYP2C19 and CYP2C9ematic. Thus, both drugs interact with many drugs, but isavuconazole often is considered less problematic in this regard. In addition, its pharmacokinetics are more reliable to the extent that, in contrast to voriconazole, therapeutic drug monitoring usually is considered unnecessary. In this regard, it must be noted that voriconazole levels were not performed in the DiasperSOT study.
The study reviewed here suggests, because of comparable efficacy, greater tolerability, and ease of use, that isavuconazole is preferred over voriconazole in the treatment of IA. Of note is that a recent study, although performed in Brazil with potential lack of applicability in the United States, found that use of isavuconazole was cost-saving relative to use of voriconazole.2
References
- Patterson TF, Thompson GR 3rd, Denning DW, et al. Executive summary: Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2016;63:433-42.
- Araujo GLV, Murta Amaral L, Ponzio V, Rocha JL. Economic and budgetary impact evaluation of isavuconazole (Cresemba®) versus voriconazole (Vfend®) for the treatment of patients with possible invasive aspergillosis from the perspective of the Brazilian supplementary health system. PLoS One 2024;19:e0299056.
