Preventing invasive aspergillosis in lung transplant recipients: A cost-utility analysis

Roni Bitterman; Aida Glembocki; Laura N Walti; Shahid Husain; Petros Pechlivanoglou

doi:10.1016/j.healun.2025.12.030

Preventing invasive aspergillosis in lung transplant recipients: A cost-utility analysis

J Heart Lung Transplant. 2026 May;45(5):810-819. doi: 10.1016/j.healun.2025.12.030. Epub 2026 Jan 3.

Authors

Roni Bitterman¹, Aida Glembocki², Laura N Walti³, Shahid Husain⁴, Petros Pechlivanoglou⁵

Affiliations

¹ Transplant Infectious Diseases, Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada. Electronic address: roni.bitterman@uhn.ca.
² Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Department of Paediatric Laboratory Medicine, Division of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada.
³ Transplant Infectious Diseases, Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada; Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁴ Transplant Infectious Diseases, Ajmera Transplant Centre, University Health Network, Toronto, Ontario, Canada.
⁵ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Child Health Evaluative Sciences, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.

PMID: 41490563
DOI: 10.1016/j.healun.2025.12.030

Abstract

Background: Invasive aspergillosis (IA) is a major cause of morbidity and mortality in lung transplant recipients. While most centers use universal prophylaxis, others opt for pre-emptive treatment. The optimal prevention strategy remains uncertain.

Objective: To evaluate the cost-utility of universal antifungal prophylaxis versus pre-emptive therapy for preventing IA during the first post-transplant year, from an Ontario healthcare payer perspective.

Methods: A state transition model with a lifetime horizon was developed. Transition probabilities, utilities, and costs were sourced from the literature as well as individual patient data. The base-case analysis assumed a relative risk of IA of 0.61 (95% CI: 0.33 to1.12) with universal prophylaxis compared to pre-emptive therapy. Outcomes included cumulative IA risk, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Incremental net health benefit (INHB) was calculated using a cost-effectiveness threshold of C$50,000 per QALY. Costs and QALYs were discounted at 1.5%. Deterministic and probabilistic sensitivity analyses were conducted.

Results: The lifetime IA risk was 15.6% with universal prophylaxis and 18.6% with pre-emptive therapy. Universal prophylaxis yielded more QALYs at higher cost, with an ICER of C$30,393 per QALY gained and an INHB of 0.03. Probabilistic sensitivity analysis showed universal prophylaxis was favored at cost-effectiveness thresholds above C$45,000, with considerable uncertainty in the C$35,000-C$45,000 range.

Interpretation: Universal prophylaxis was the preferred strategy in the base-case scenario, with an ICER below the commonly accepted threshold of C$50,000 per QALY. However, results were sensitive to model inputs, emphasizing the need for robust clinical trials directly comparing these strategies.

Keywords: Cost-effectiveness; Invasive aspergillosis; Lung transplant; Pre-emptive therapy; Universal prophylaxis.

MeSH terms

Antifungal Agents* / economics
Antifungal Agents* / therapeutic use
Aspergillosis* / economics
Aspergillosis* / prevention & control
Cost-Benefit Analysis
Female
Humans
Invasive Pulmonary Aspergillosis* / economics
Invasive Pulmonary Aspergillosis* / prevention & control
Lung Transplantation* / adverse effects
Lung Transplantation* / economics
Male
Middle Aged
Ontario
Postoperative Complications* / economics
Postoperative Complications* / prevention & control
Quality-Adjusted Life Years
Transplant Recipients

Substances

Antifungal Agents