Isavuconazole for treatment of invasive fungal diseases caused by more than one fungal species

Abstract

The optimal approach to treat invasive fungal disease (IFD) caused by more than one fungal species is unknown. We documented the efficacy and safety of isavuconazole for treatment of IFDs caused by more than one fungal species. VITAL was a single-arm, international, open-label study evaluating the efficacy and safety of isavuconazole (200 mg orally or intravenously every 8 hours for 48 hours, then once daily) for treatment of rare IFDs. The primary outcome was the overall response at Day 42; key secondary outcomes were overall responses at Day 84 and end of treatment (EOT), mortality at Days 42 and 84, and safety. This analysis includes patients with IFD caused by multiple fungal species. Fifteen patients were included in this analysis (including Aspergillus spp., n = 11; without Aspergillus spp., n = 4); median treatment duration was 97 days [range, 6-544] days). Overall treatment success was observed in 2/15 patients (13.3%) at Days 42 and 84, and 2/14 (14.3%) at EOT. All-cause mortality was 2/15 (13.3%) at Day 42 and 4/15 (26.7%) at Day 84. All patients had ≥1 treatment-emergent adverse event (TEAE); 12 patients (80.0%) had serious TEAEs; TEAEs led to discontinuation of isavuconazole in two patients (13.3%). Isavuconazole may be useful to treat some IFDs caused by multiple fungal species.

Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis in patients with renal impairment: Challenges and lessons of the VITAL trial

“…Among patients with other emerging fungal infections, more than half of evaluable patients responded by EOT . The overall success rate at EOT was considerably less for patients with mixed fungal infections; still, two‐thirds of patients in this group were confirmed alive at the end of the study . In patients with IA, the rate of treatment success overall at EOT (8/24 [33.3%]) was similar to that observed with isavuconazole in patients with proven and probable IFD in the SECURE trial (35%), and was highest in the subgroup of patients without renal impairment (66.7%).…”

“…or dimorphic fungi, 26 patients with IFD caused by other rare moulds or yeasts, 15 patients with IFD caused by multiple (mixed) fungal species and 24 patients with IA and renal impairment at enrolment. Patients with IFD caused by multiple fungal species were not specifically targeted for enrolment but were allowed to participate at the discretion of the investigator(s) (see accompanying article). After the protocol amendment redefining renal impairment on the basis of eGFR instead of CrCl (see previous section), 4 of the 24 patients initially categorised as having renal impairment were omitted from that analysis population (Table ).…”

“…The most common underlying condition in these patients was diabetes mellitus (5 of 38 patients) and no underlying condition was identified in half of this patient group. Data regarding risk factors for infections with other fungal species reported in the accompanying articles are also comparatively limited. A recent analysis of data from the literature found that the most common underlying risk factor for fusariosis was haematological malignancy, which was consistent with the most common underlying risk factors observed in the VITAL trial in patients with fusariosis alone .…”

“…The VITAL trial was designed and conducted to determine the efficacy and safety of isavuconazole (active moiety of the prodrug isavuconazonium sulphate) for the treatment of IA in patients with renal impairment, or in patients with IFDs caused by rare moulds, including Mucorales spp., yeasts or dimorphic fungi. This article provides an overview of the planning, performance, challenges and lessons of the VITAL trial, which has previously reported the efficacy and safety of isavuconazole for the treatment of mucormycosis, cryptococcosis and other endemic mycoses, other rare moulds and yeasts and mixed fungal infections …”

EQUAL Aspergillosis Score 2018: An ECMM score derived from current guidelines to measure QUALity of the clinical management of invasive pulmonary aspergillosis

“…For targeted first line treatment of invasive pulmonary aspergillosis isavuconazole or voriconazole with therapeutic drug monitoring (TDM) is recommended (five points) . Voriconazole target plasma trough range is 1‐5.5 mg/L .…”