Systematic review and network meta-analysis of clinical outcomes associated with isavuconazole versus relevant comparators for patients with invasive aspergillosis

Herbrecht, Raoul; Kuessner, Daniel; Pooley, N; Posthumus, Jan; Escrig, C.

doi:10.1080/03007995.2018.1502659

Cited by 12 publications

(16 citation statements)

References 26 publications

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“…Higher survival rates were identified at 12 weeks for possible versus probable/proven cases in the 3 mg/kg group (82% vs 58%; P = 0.06) compared with the 10 mg/kg group (65% vs 50%; P = 0.15) 172 . Notably, while response rates to voriconazole and liposomal amphotericin are comparable across these trials in meta‐analysis, no head to head comparison has been undertaken 148 . Based on voriconazole's more favourable toxicity profile and ease of administration as compared to liposomal amphotericin B and the above data, liposomal amphotericin is recommended with moderate support as an alternative treatment regimen in patients who develop IA while receiving a mould‐active azole or those intolerant to voriconazole ( Moderate recommendation, Level II evidence ; Table 5).…”

Section: Question 9: What Recommendations Should Guide the First‐line Antifungal Treatment Of Ia In Haematology/oncology Patients?mentioning

confidence: 99%

Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021

Douglas

Smibert

Bajel

et al. 2021

Internal Medicine Journal

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Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID‐19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological‐based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non‐culture methods employing fungal biomarkers in pre‐emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first‐line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological‐based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations.

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Section: Question 9: What Recommendations Should Guide the First‐line Antifungal Treatment Of Ia In Haematology/oncology Patients?mentioning

confidence: 99%

Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021

Douglas

Smibert

Bajel

et al. 2021

Internal Medicine Journal

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“…A systematic review on clinical outcomes associated with isavuconazole versus comparators for patients with IA suggested that isavuconazole is superior to AmB deoxycholate and comparable to both liposomal AmB and voriconazole. 231 As distinction between aspergillosis and mucormycosis is not always easy at early stage of the disease, the activity of isavuconazole against Mucorales is an additional advantage for the use as preemptive therapy of a suspected mold infection. 232 Guidelines suggested that therapeutic drug monitoring of isavuconazole could be useful in case of nonresponse to treatment, unexpected toxicity, potential drug-to-drug interactions, treatment of pathogens with elevated MICs or treatment of central nervous system infections.…”

Section: Eortc/msg Criteria For Severely Immunosuppressed Patientsmentioning

confidence: 99%

Invasive Pulmonary Aspergillosis

Ledoux

Guffroy

Nivoix

et al. 2020

Semin Respir Crit Care Med

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Invasive pulmonary aspergillosis (IPA) remains difficult to diagnose and to treat. Most common risk factors are prolonged neutropenia, hematopoietic stem cell or solid organ transplantation, inherited or acquired immunodeficiency, administration of steroids or other immunosuppressive agents including monoclonal antibodies and new small molecules used for cancer therapy. Critically ill patients are also at high risk of IPA. Clinical signs are unspecific. Early computed tomography (CT)-scan identifies the two main aspects, angioinvasive and airway invasive aspergillosis. Although CT-scan findings are not fully specific they usually allow early initiation of therapy before mycological confirmation of the diagnosis. Role of 18F-fludeoxyglucose positron emission tomography with computed tomography (18F-FDG PET/CT) is discussed. Confirmation is based on microscopy and culture of respiratory samples, histopathology in case of biopsy, and importantly by detection of Aspergillus galactomannan using an immunoassay in serum and bronchoalveolar lavage fluid. Deoxyribonucleic acid detection by polymerase chain reaction is now standardized and increases the diagnosis yield. Two point of care tests detecting an Aspergillus glycoprotein using a lateral flow assay are also available. Mycological results allow classification into proven (irrespective of underlying condition), probable or possible (for cancer and severely immunosuppressed patients) or putative (for critically ill patients) IPA. New antifungal agents have been developed over the last 2 decades: new azoles (voriconazole, posaconazole, isavuconazole), lipid formulations of amphotericin B (liposomal amphotericin B, amphotericin B lipid complex), echinocandins (caspofungin, micafungin, anidulafungin). Results of main trials assessing these agents in monotherapy or in combination are presented as well as the recommendations for their use according to international guidelines. New agents are under development.

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“…No pharmacokinetic studies have so far formally addressed whether the use of a moderate rather than a strong CYP3A4 inhibitor, like isavuconazole, may allow a lower reduction of ibrutinib dosage. An alternative treatment for filamentous fungi invasive disease could be based on the use of either liposomal amphotericin B, which has no effects on ibrutinib metabolism [155].…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of ibrutinib: Reducing the barrier against fungal infections

et al. 2020

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The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is increasingly used in the treatment of chronic lymphocytic leukemia (CLL). Moreover, very promising results have been reported in other B-cell malignancies, including primary central nervous system lymphoma (PCNSL). Although well-tolerated in the majority of patients, ibrutinib demonstrates in some cases troublesome toxicities, including invasive fungal infections (IFIs). In the present review, we summarize clinical manifestations of IFIs in patients treated with ibrutinib, generally characterized by an early onset, mild clinical manifestations, asymptomatic/low symptomatic pulmonary localization and high incidence of central nervous system (CNS) involvement. IFI risk appears particularly increased in patients receiving ibrutinib associated with other immune modulator agents, especially with steroids or immune-chemotherapy. Moreover, the immunomodulatory effect of ibrutinib is described, pointing the attention on the involvement of specific molecules targeted by ibrutinib in innate and adaptive response to fungal infection. Overall, the findings indicate the ibrutinib may rapidly impair innate immune cell functions, while concomitantly restoring an effective protective potential of adaptive immune compartment. A correct awareness, especially when other predisposing factors are present, is warranted about the potential risk of IFIs in ibrutinibtreated patients.

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Systematic review and network meta-analysis of clinical outcomes associated with isavuconazole versus relevant comparators for patients with invasive aspergillosis

Abstract: This data suggests that the efficacy of isavuconazole for treatment of IA is superior to AmB-D and comparable with both L-AmB and voriconazole.

Cited by 12 publications

References 26 publications

Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021

Consensus guidelines for the diagnosis and management of invasive aspergillosis, 2021

Invasive Pulmonary Aspergillosis

Immunomodulatory effect of ibrutinib: Reducing the barrier against fungal infections

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