Posaconazole for salvage treatment of invasive aspergillosis in refractory patients

Anita H. Sung*1, Francois Bourhis 2, Alexander Hirst 3.

Author address: 

1 Merck & Co., Inc.; 2 Mapi; Rwsa; 3 Mapi Group.

Abstract: 

Background: Invasive aspergillosis (IA) has become a major source of morbidity and mortality over
the past three decades with greater difficulty achieving successful treatment in patients with refractory IA. The population at risk for fungal disease has increased due to advances in chemotherapy,
transplantation, and the use of immunosuppressive treatments for many medical ailments. This study
aimed to identify estimates of the efficacy, cost, and utility of salvage IA treatments in order to assess
these outcomes in refractory IA through a modelling approach.
Material/methods: To support the development of a cost-effectiveness model, a systematic review of
English-language studies in patients who were refractory to first-line antifungal therapy was conducted
via MEDLINE. Potentially relevant studies were screened using pre-defined eligibility criteria.
A semi-Markov cost-effectiveness model was developed to evaluate the potential health benefits and
costs of posaconazole for salvage treatment of IA. The model consisted of two health states, alive and
dead; within the alive health state patients could either be receiving treatment or have treatment
success. A lifetime horizon and UK NHS perspective were adopted. Comparators for posaconazole
were based on the recommendations from ECIL-5 guidelines and include liposomal amphotericin B,
voriconazole (if not used as first-line therapy), and caspofungin. Model efficacy was based on overall
survival and treatment success rates found in the literature.
Based on the literature, utilities of 0.500 and 0.605 were considered for patients receiving treatment
and for whom treatment succeeded, respectively. Costs were obtained from the British National
Formulary and the NHS reference costs and included medication, management of IA related events,
and hospitalisations.
Treatment efficacy was evaluated in quality-adjusted life-years (QALY) and total life-years (LY) and
the economic impact was assessed using incremental cost-effectiveness ratios (ICER). Uncertainty
around the model parameters was explored in univariate sensitivity analyses.
Results: The systematic review identified 1,024 studies. After screening, only 14 studies met the
inclusion criteria and provided outcomes data for incorporation into the model. Posaconazole was a
dominant strategy (i.e., cost-saving and more effective strategy) against liposomal amphotericin B and
voriconazole. Posaconazole was a cost-effective strategy against caspofungin with an ICER of £5,638
per QALY and an ICER of £3,092 per LY saved.
Conclusions: Further studies are required to determine the clinical and economic impact of IA
treatments in the refractory setting. Based on the information available for use in the model,
posaconazole may be cost-effective or even cost-saving in salvage treatment of IA that is refractory to
other antifungal therapy. Posaconazole improved treatment success rates and QALYs compared to all
comparators considered within the cost-effectiveness model. Additionally posaconazole was
associated with reduced total cost when compared to liposomal amphotericin B and voriconazole.

2017

abstract No: 

P1743

Full conference title: 

27th European Congress of Clinical Microbiology and Infectious Diseases (2017, Vienna)
    • ECCMID 27th (2017)