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

Eric J. Bow, David J. Vanness, Monica Slavin, Catherine Cordonnier, Oliver A. Cornely, David I. Marks, Antonio Pagliuca, Carlos Solano, Lael Cragin, Alissa J. Shaul, Sonja Sorensen, Richard Chambers, Michal Kantecki, David Weinstein, Haran Schlamm

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Abstract

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.

Original languageEnglish (US)
Article number128
JournalBMC Infectious Diseases
Volume15
Issue number1
DOIs
StatePublished - Mar 17 2015

All Science Journal Classification (ASJC) codes

  • Infectious Diseases

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    Bow, E. J., Vanness, D. J., Slavin, M., Cordonnier, C., Cornely, O. A., Marks, D. I., Pagliuca, A., Solano, C., Cragin, L., Shaul, A. J., Sorensen, S., Chambers, R., Kantecki, M., Weinstein, D., & Schlamm, H. (2015). Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients. BMC Infectious Diseases, 15(1), [128]. https://doi.org/10.1186/s12879-015-0855-6