title: Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.
abstract: Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting.
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore.
authors.forename: Ying Jiao
authors.initials: YJ
authors.lastname: Zhao
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore ai_leng_khoo@nhg.com.sg.
authors.forename: Ai Leng
authors.initials: AL
authors.lastname: Khoo
authors.affiliation: Pharmacoeconomics and Drug Utilisation, Health Products Regulation Group, Health Sciences Authority, Singapore.
authors.forename: Gloria
authors.initials: G
authors.lastname: Tan
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore.
authors.forename: Monica
authors.initials: M
authors.lastname: Teng
authors.affiliation: Department of Pharmacy, National University Health System, Singapore.
authors.forename: Caroline
authors.initials: C
authors.lastname: Tee
authors.affiliation: Department of General Internal Medicine and Infectious Diseases, Singapore General Hospital, Singapore.
authors.forename: Ban Hock
authors.initials: BH
authors.lastname: Tan
authors.affiliation: Pharmacoeconomics and Drug Utilisation, Health Products Regulation Group, Health Sciences Authority, Singapore.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ong
authors.affiliation: Pharmacy and Therapeutics Office, Group Corporate Development, National Healthcare Group, Singapore.
authors.forename: Boon Peng
authors.initials: BP
authors.lastname: Lim
authors.affiliation: Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore.
authors.forename: Louis Yi Ann
authors.initials: LY
authors.lastname: Chai
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000191:economics* / Q000627:therapeutic use; D001230:Aspergillus / Q000187:drug effects / Q000254:growth & development; D002175:Candida / Q000187:drug effects / Q000254:growth & development; D003362:Cost-Benefit Analysis; D005260:Female; D015725:Fluconazole / Q000191:economics / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000191:economics / Q000401:mortality; D006801:Humans; D017964:Itraconazole / Q000191:economics / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000191:economics* / Q000382:microbiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018803:Models, Economic; D009181:Mycoses / Q000188:drug therapy* / Q000191:economics* / Q000382:microbiology / Q000401:mortality; D012846:Singapore; D016019:Survival Analysis; D014230:Triazoles / Q000191:economics / Q000627:therapeutic use; D065819:Voriconazole / Q000191:economics / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; D017964:Itraconazole; C101425:posaconazole; D015725:Fluconazole; D065819:Voriconazole