Dataset Information

Effectiveness and Cost-Effectiveness of Prophylactic Voriconazole and Fluconazole Regarding Prevention of Post-hematopoietic Stem Cell Transplantation Invasive Fungal Infection and Its Related Death: A Single Center Experience.

ABSTRACT:

Purpose

Analyzing effectiveness and cost-effectiveness of voriconazole versus fluconazole prophylaxis in hematopoietic stem cell transplantation (HSCT).

Methods

The research included 70 patients; 34 undergoing allogeneic HSCT and 36 undergoing autologous stem cell transplantation (ASCT), alternated to receive either voriconazole or fluconazole prophylaxis for 180 days on a 1:1 basis. Patients were monitored for occurrence of invasive fungal infections (IFI), IFI-related death (IRD) and total death events. Cost-effectiveness of both agents in both groups was also assessed.

Results

Antifungal prophylactic drug had no impact on incidence of IFI and IRD in both allogeneic HSCT and ASCT (P = .452 and P = 1.000; P = .457 and P = .146 respectively). An insignificant difference occurred among patients receiving voriconazole or fluconazole regarding overall survival (OS) and fungal infection-free survival (FFS) in both groups (P = .705 and P = .879; P = .713 and P = .681 respectively). Regarding cost-effectiveness, voriconazole dominated fluconazole regarding prevention of IFI and IRD but was less costly/less effective regarding prevention of total death events and gaining life years in the allogeneic HSCT setting. In the ASCT setting, voriconazole was not cost-effective regarding avoidance of IFI and IRD and was dominated by fluconazole regarding avoidance of total death events and gaining life years.

Conclusions

Voriconazole does not differ from fluconazole regarding its efficacy in prevention of IFI and IRD and does not improve OS and FFS in both allogeneic HSCT and ASCT settings. Voriconazole is cost-effective regarding protection from IFI and IRD in allogeneic HSCT but not cost-effective in ASCT.

SUBMITTER: El-Ghammaz AMS

PROVIDER: S-EPMC7573062 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPatients receiving allogeneic hematopoietic stem cell transplantation (alloHSCT) are at high risk of invasive fungal infections (IFIs), which are associated with high mortality and economic burden. The cost-effectiveness of prophylaxis for the prevention of IFIs in alloHSCT recipients in Mexico has not yet been assessed.MethodsThis analysis modeled a hypothetical cohort of 1,000 patients to estimate costs and outcomes for patients receiving prophylaxis for IFIs following alloHSCT, from the perspective of institutional payers in Mexico. The main prophylaxis agents currently used in Mexican clinical practice are voriconazole, fluconazole, and amphotericin B (AmB). The model accounted for event rates of IFIs during each treatment, assuming IFI causality due to invasive aspergillosis, invasive candidiasis, or other IFIs, and that the outcome for patients during follow-up was IFI-related death, death from other causes, or survival. Clinical efficacies were obtained from published literature; costs were based on local sources. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs). Univariate (assessing the impact of varying each model parameter) and probabilistic sensitivity analyses were performed.ResultsVoriconazole was associated with the lowest number of breakthrough IFIs, IFI-related deaths, and total number of deaths. Total costs were lower for fluconazole (Mexican pesos [MXN] 72,944; US $4,079) than voriconazole (MXN 101,413; US $5,671) or AmB (MXN 110,529; US $6,180). Voriconazole had better clinical outcomes and lower costs than AmB and could be considered cost-effective compared with fluconazole in line with the local ICER threshold. Drug costs, monitoring costs, and duration of prophylaxis were most sensitive to variation from univariate sensitivity analysis. Findings from the probabilistic sensitivity analysis were consistent with the base-case results.ConclusionVoriconazole had the most favorable clinical outcomes, but overall prophylaxis costs were higher than with fluconazole. Overall, based on local ICER thresholds (MXN 184,665; US $10,326), voriconazole was considered a cost-effective option for prophylaxis of IFI in Mexico.

Project description: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.

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