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Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients.

Bow EJ, Vanness DJ, Slavin M, Cordonnier C, Cornely OA, Marks DI, Pagliuca A, Solano C, Cragin L, Shaul AJ, Sorensen S, Chambers R, Kantecki M, Weinstein D, Schlamm H - BMC Infect. Dis. (2015)

Bottom Line: Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99), and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall proven/probable IFI.All-cause mortality was similar across all mould-active agents.The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.

View Article: PubMed Central - PubMed

Affiliation: CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, Canada. EJBow@cancercare.mb.ca.

ABSTRACT

Background: Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making.

Methods: Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC.

Results: Five eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99), and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17-0.58) and voriconazole (OR: 0.33; IQR: 0.17-0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42-1.12). All-cause mortality was similar across all mould-active agents.

Conclusion: As expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.

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Evidence network of randomized controlled trials (RCTs) included into the mixed treatment comparison (MTC).
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Fig2: Evidence network of randomized controlled trials (RCTs) included into the mixed treatment comparison (MTC).

Mentions: The systematic literature search identified 5 published RCTs that met predefined criteria for inclusion into the MTC [10,26-29]. Our literature search identified 6 additional RCTs that were not able to directly or indirectly inform a comparison of fluconazole, itraconazole, posaconazole, and voriconazole [30-35]. A flow chart of search results and a summary of each trial’s characteristics and patient populations are shown in the online Additional file 1. The 5 head-to-head studies [10,26-29] constituting the evidence network (Figure 2) for the MTC randomized a total of 2147 patients, with individual study sample sizes ranging from 140–600 patients. Four studies were multicentre trials, 3 studies had an open-label design, and 2 had a double-blind design. Fluconazole (with a total of 813 randomized patients) was a comparator in 4 RCTs, itraconazole (n = 485) was a comparator in 3, voriconazole (n = 548) in 2, and posaconazole (n = 301) was a comparator in a single trial. The data extracted from these studies for each outcome are shown in Table 1. The overall estimates of heterogeneity were large, particularly in the main analysis using a non-informative prior (see online Additional file 1).Figure 2


Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients.

Bow EJ, Vanness DJ, Slavin M, Cordonnier C, Cornely OA, Marks DI, Pagliuca A, Solano C, Cragin L, Shaul AJ, Sorensen S, Chambers R, Kantecki M, Weinstein D, Schlamm H - BMC Infect. Dis. (2015)

Evidence network of randomized controlled trials (RCTs) included into the mixed treatment comparison (MTC).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4374298&req=5

Fig2: Evidence network of randomized controlled trials (RCTs) included into the mixed treatment comparison (MTC).
Mentions: The systematic literature search identified 5 published RCTs that met predefined criteria for inclusion into the MTC [10,26-29]. Our literature search identified 6 additional RCTs that were not able to directly or indirectly inform a comparison of fluconazole, itraconazole, posaconazole, and voriconazole [30-35]. A flow chart of search results and a summary of each trial’s characteristics and patient populations are shown in the online Additional file 1. The 5 head-to-head studies [10,26-29] constituting the evidence network (Figure 2) for the MTC randomized a total of 2147 patients, with individual study sample sizes ranging from 140–600 patients. Four studies were multicentre trials, 3 studies had an open-label design, and 2 had a double-blind design. Fluconazole (with a total of 813 randomized patients) was a comparator in 4 RCTs, itraconazole (n = 485) was a comparator in 3, voriconazole (n = 548) in 2, and posaconazole (n = 301) was a comparator in a single trial. The data extracted from these studies for each outcome are shown in Table 1. The overall estimates of heterogeneity were large, particularly in the main analysis using a non-informative prior (see online Additional file 1).Figure 2

Bottom Line: Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99), and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall proven/probable IFI.All-cause mortality was similar across all mould-active agents.The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.

View Article: PubMed Central - PubMed

Affiliation: CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, Canada. EJBow@cancercare.mb.ca.

ABSTRACT

Background: Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making.

Methods: Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC.

Results: Five eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99), and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17-0.58) and voriconazole (OR: 0.33; IQR: 0.17-0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42-1.12). All-cause mortality was similar across all mould-active agents.

Conclusion: As expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.

Show MeSH
Related in: MedlinePlus