Voriconazole could be the best option for antifungal prophylaxis for patients undergoing hematopoietic stem cell transplantation (HSCT), according to a meta-analysis published in JAMA Network Open.
Investigators searched Medline, EMBASE, and Cochrane Central Register of Controlled Clinical Trials for studies that compared any antifungal with a placebo, no antifungal agent, or another antifungal agent among patients with hematological disease or undergoing HSCT.
The primary outcomes of the study were invasive fungal infections (IFIs) and death. Secondary outcomes included fungal infections, proven IFIs, invasive candidiasis, invasive aspergillosis, fungi-related death, and withdrawal due to adverse effects of the drug. This meta-analysis included 69 studies comparing 12 treatments with a total of 14,789 patients. The surface under the cumulative ranking curve (SUCRA) was used to rank each antifungal for each outcome. A larger SUCRA value indicated a better rank.
For treatment of IFIs, posaconazole ranked highest (SUCRA, 86.7%), followed by caspofungin (SUCRA, 84.2%) and micafungin (SUCRA, 75.0%). Posaconazole was associated with a significant reduction in IFIs (relative risk [RR], 0.57; 95% CI, 0.42-0.79) and invasive aspergillosis infections (RR, 0.36; 95% CI, 0.15-0.85) compared to placebo. Voriconazole was associated with significant reductions in invasive candidiasis compared to placebo (RR, 0.15; 95% CI, 0.09-0.26).
Micafungin ranked highest for mortality (SUCRA, 90.0%), followed by voriconazole (SUCRA, 73.8%) and posaconazole (SUCRA, 68.5%). Caspofungin ranked best for reducing fungal infections (SUCRA, 84.9%) and preventing invasive candidiasis (SUCRA, 88.5%). Amphotericin B was highest in terms of reducing fungi-related deaths (SUCRA, 78.8%). Voriconazole had the lowest incidence of withdrawal (SUCRA, 78.1%), while posaconazole had the highest incidence of withdrawal due to adverse effects (SUCRA, 17.5%).
Based on subgroup analysis of efficacy and tolerance, voriconazole might be the best choice for patients undergoing HSCT, specifically allogenic HSCT. For those with acute myeloid leukemia or myelodysplastic syndrome, posaconazole may be the best option.
Investigators found that the follow-up time in most studies was too short to determine survival benefits. Head-to-head trials of posaconazole and voriconazole were also limited. The subgroup analysis did show different results among varying populations but a more detailed analyses was limited by lack of data.
While caution is needed in interpreting the results, “voriconazole may be the best prophylactic option for patients undergoing HSCT, and posaconazole may be the best prophylactic option for patients with with acute myeloid leukemia or myelodysplastic syndrome,” investigators concluded.
Wang J, Zhou M, Xu JY, Zhou RF, Chen B, Wan Y. Comparison of antifungal prophylaxis drugs in patients with hematological disease or undergoing hematopoietic stem cell transplantation: a systematic review and network meta-analysis. JAMA Netw Open. 2020;3(10):e2017652. doi:10.1001/jamanetworkopen.2020.17652.