Randomized trial of micafungin versus fluconazole as prophylaxis against invasive fungal infections in hematopoietic stem cell transplant recipients

Park, Silvia; Kım, Kihyun; Jang, Jun Ho; Kim, Seok Jin; Kim, Won Seog; Chung, Doo Ryeon; Kang, Cheol-In; Peck, Kyong Ran; Jung, Chul Won

doi:10.1016/j.jinf.2016.06.011

Cited by 37 publications

(47 citation statements)

References 38 publications

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“…In a study of 113 adult patients receiving stem cell transplants from matched sibling donors, a reduced dose of fluconazole with 100 mg per day did not result in an increased rate of invasive fungal infections . While clinical research studies in adults investigating newer antifungal substances including micafungin, voriconazole or low‐dose liposomal amphotericin B have not yet demonstrated a clear advantage over fluconazole in situations with a low frequency of probable and proven mould infections; however, posaconazole has been shown to significantly reduce the rate of invasive aspergillosis and IFD‐related mortality in adult patients with severe GvHD …”

Section: Discussionmentioning

confidence: 99%

Epidemiology, utilisation of healthcare resources and outcome of invasive fungal diseases following paediatric allogeneic haematopoietic stem cell transplantation

Linke

Ehlert

Ahlmann

et al. 2019

Mycoses

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Summary Background Epidemiology and management practices of invasive fungal diseases (IFD) after allogeneic haematopoietic stem cell transplantation (HSCT) are a subject of constant change. We investigated the contemporary incidence, diagnostics, antifungal management and outcome at a major paediatric transplant centre in Germany. Methods The single‐centre retrospective observational study included all paediatric allogeneic HSCT patients (pts) transplanted between 2005 and 2015. Patient‐related data were assessed up to 365 days post‐transplant. The primary endpoint was the incidence of possible, probable and proven IFDs. Secondary endpoints included diagnostics and antifungal treatment; analysis of risk factors; and overall survival with the last follow‐up in January 2017. Results A total of 221 first (196), second (21) or third (4) procedures were performed in 200 pts (median age: 9 years, range, 0.5‐22) for leukaemia/lymphoma (149) and non‐malignant disorders (72). Prophylaxis was administered in 208 HSCT procedures (94%; fluconazole, 116, mould‐active agents, 92). At least one computed tomography scan of the chest was performed in 146, and at least one galactomannan antigen assay in 60 procedures. There were 15 cases of proven (candidemia, 4; aspergillosis, 4) or probable (aspergillosis, 7) IFDs, accounting for an incidence rate of 6.8%. Overall mortality at last follow‐up was 30%; the occurrence of proven/probable IFDs was associated with a reduced survival probability (P < .001). Conclusion Morbidity and mortality from IFDs at our institution were consistent with data reported from other centres. Utilisation of healthcare resources for prevention, diagnosis and management of IFDs was considerable.

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Section: Discussionmentioning

confidence: 99%

Epidemiology, utilisation of healthcare resources and outcome of invasive fungal diseases following paediatric allogeneic haematopoietic stem cell transplantation

Linke

Ehlert

Ahlmann

et al. 2019

Mycoses

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“…In addition, antifungal resistance has become a global problem, especially with Candida glabrata , which may be responsible for as many as 18.2% IC infections worldwide [37, 38]. Numerous trials have demonstrated the benefit of micafungin prophylaxis in HSCT recipients [16, 36, 39, 40]. In a prospective, randomized, double-blind comparative study of micafungin versus fluconazole, administered as antifungal prophylaxis during the neutropenic phase of HSCT, treatment success of micafungin was 80.0% versus 73.5% for fluconazole (95% CI: 0.9–12; P = 0.03) [36].…”

Section: Discussionmentioning

confidence: 99%

“…In a prospective, randomized, double-blind comparative study of micafungin versus fluconazole, administered as antifungal prophylaxis during the neutropenic phase of HSCT, treatment success of micafungin was 80.0% versus 73.5% for fluconazole (95% CI: 0.9–12; P = 0.03) [36]. In HSCT recipients, prophylaxis with micafungin has also been shown to have similar efficacy to fluconazole [16]. In the current study, micafungin was effective for prophylaxis in patients at risk of IFI (90.5%).…”

Section: Discussionmentioning

confidence: 99%

“…Several clinical trials involving micafungin have demonstrated its efficacy in IC, reporting response rates ranging from 71–90% [12–15]. Micafungin has also shown efficacy when used as a prophylactic agent for fungal infections in neutropenic patients [6, 16]. In addition, micafungin has a favorable safety and tolerability profile with a low potential for drug-drug interactions compared with caspofungin and fluconazole [17–19].…”

Section: Introductionmentioning

confidence: 99%

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Effectiveness and Safety of Micafungin in Managing Invasive Fungal Infections among Patients in Greece with Hematologic Disorders: The ASPIRE Study

et al. 2019

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Introduction Invasive candidiasis (IC) can be a life-threatening infection in immunocompromised patients, particularly those with cancer, hematologic diseases and/or hematopoietic stem cell transplantation (HSCT) recipients. The objective of this study was to evaluate the effectiveness of micafungin in patients with hematologic malignancies or HSCT recipients, relevant to clinical presentation of IC, in real-life practice in Greece. Methods ASPIRE was a phase IV, multicenter, non-interventional, prospective cohort study, conducted at ten tertiary hospitals in Greece, in adults with hematologic disease. Micafungin treatment for IC or prophylaxis for Candida infection was administered per standard clinical practice until a clinical outcome (success or failure) was reached. Treatment success was defined by the EORTC/MSG criteria for invasive fungal infections (IFI) and was assessed by the investigator. Treatment discontinuation and safety were also evaluated. Results One hundred forty-three patients were enrolled. Median age was 62; 85 (59.4%) patients were male, and 133 (93.0%) had Greek ethnicity. One hundred twenty-six (88.1%) patients had hematologic malignancies, and 21 (14.7%) had received HSCT. Prophylaxis was administered to 74 (51.7%) patients [median (range) dose: 50 (50–150) mg/day] with no signs of IFI. Overall, 52 (36.4%) patients with possible IFI at baseline received micafungin treatment [100 (50–125) mg/day] versus 12 (17.2%) with probable [100 (75–150) mg/day] and 5 (3.5%) with confirmed [125 (100–150) mg/day] IFI. Treatment success was 91.6% (95% CI 85.80–95.59; n = 131) overall and 90.5% ( n = 67) in patients receiving prophylaxis. Median time on treatment was 13 days. Treatment discontinuation ( n = 26; 18.2%) was not related to adverse events. No treatment-related serious adverse events were reported. Conclusion Micafungin treatment for IC or prophylaxis for Candida infection was effective and well tolerated in patients with hematologic disorders in clinical practice in Greece. These results demonstrate that micafungin could be used more widely for prophylaxis. Further work is required to determine the efficacy and safety of micafungin for the management of IFIs in hematologic settings. Funding Astellas Pharma Inc.

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“…We assumed that the daily mortality rate due to death from other causes was constant each day. The model was calibrated so that the 100‐day overall survival was 85% . Model calibration results are available in the Data S1.…”

Section: Methodsmentioning

confidence: 99%

Cost‐effectiveness of antifungal prophylaxis, preemptive therapy, or empiric treatment following allogeneic hematopoietic stem cell transplant

Walker

Schmidt

Tantravahi

et al. 2019

Transplant Infectious Dis

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Background: Invasive fungal infection (IFI) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) that is also associated with excess healthcare costs. Current approaches include universal antifungal prophylaxis, preemptive therapy based on biomarker surveillance, and empiric treatment initiated in response to clinical signs/symptoms. However, no study has directly compared the cost-effectiveness of these treatment strategies for an allogeneic HSCT patient population. Methods:We developed a state transition model to study the impact of treatment strategies on outcomes associated with IFIs in the first 100 days following myeloablative allogeneic HSCT. We compared three treatment strategies: empiric voriconazole, preemptive voriconazole (200 mg), or prophylactic posaconazole (300 mg) for the management of IFIs. Preemptive treatment was guided by scheduled laboratory surveillance with galactomannan (GM) testing. Endpoints were cost and survival at 100 days post-HSCT. Results: Empiric treatment was the least costly ($147 482) and was equally effective (85.2% survival at 100 days) as the preemptive treatment strategies. Preemptive treatments were slightly more costly than empiric treatment (GM cutoff ≥ 1.0 $147 910 and GM cutoff ≥ 0.5 $148 108). Preemptive therapy with GM cutoff ≥ 1.0 reduced anti-mold therapy by 5% when compared to empiric therapy. Posaconazole prophylaxis was the most effective (86.6% survival at 100 days) and costly ($152 240) treatment strategy with a cost of $352 415 per life saved when compared to empiric therapy. Conclusions: One preemptive treatment strategy reduced overall anti-mold drug exposure but did not reduce overall costs. Prevention of IFI using posaconazole prophylaxis was the most effective treatment strategy and may be cost-effective, depending upon the willingness to pay per life saved. K E Y W O R D S antifungal therapy, cost-effectiveness, fungal infection, galactomannan, hematopoietic stem cell transplantation S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Walker BS, Schmidt RL, Tantravahi S, Kim K, Hanson KE. Cost-effectiveness of antifungal prophylaxis, preemptive therapy, or empiric treatment following allogeneic hematopoietic stem cell transplant. Transpl Infect Dis. 2019;21:e13148. https ://doi.

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Randomized trial of micafungin versus fluconazole as prophylaxis against invasive fungal infections in hematopoietic stem cell transplant recipients

Cited by 37 publications

References 38 publications

Epidemiology, utilisation of healthcare resources and outcome of invasive fungal diseases following paediatric allogeneic haematopoietic stem cell transplantation

Epidemiology, utilisation of healthcare resources and outcome of invasive fungal diseases following paediatric allogeneic haematopoietic stem cell transplantation

Effectiveness and Safety of Micafungin in Managing Invasive Fungal Infections among Patients in Greece with Hematologic Disorders: The ASPIRE Study

Cost‐effectiveness of antifungal prophylaxis, preemptive therapy, or empiric treatment following allogeneic hematopoietic stem cell transplant

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