Zhao, Y.J., Khoo, A.L., Tan, G., Teng, M., Tee, C., Tan, B.H., . . . Chai, L.Y. (2016). Network meta-analysis and pharmacoeconomic evaluation of fluconazole, itraconazole, posaconazole, and voriconazole in invasive fungal infection prophylaxis. Antimicrobial Agents and Chemotherapy, 60, 376–386.

DOI Link

doi: 10.1128/AAC.01985-15

Purpose

STUDY PURPOSE: To examine the efficacy and cost-effectiveness of various azoles for antifungal prophylaxis in patients with hematologic malignancies undergoing chemotherapy or cell transplantation

TYPE OF STUDY: Meta-analysis and systematic review

Search Strategy

DATABASES USED: PubMed and Cochrane Collaboration

INCLUSION CRITERIA: Randomized controlled trials comparing one triazole against another or against placebo for antifungal prophyaxis

EXCLUSION CRITERIA: Patients with graft-versus-host disease (GVHD), or patients who received multiple chemotherapy cycles

Literature Evaluated

TOTAL REFERENCES RETRIEVED: 1,261

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane assessment tool for quality evaluation. Studies were of moderate quality, and two-third were deemed to be at risk of biases, as they were industry-sponsored.

Sample Characteristics

FINAL NUMBER STUDIES INCLUDED = 21
TOTAL PATIENTS INCLUDED IN REVIEW = 5,505
SAMPLE RANGE ACROSS STUDIES: Not provided
KEY SAMPLE CHARACTERISTICS: Duration of antifungal prophylaxis and follow-up ranged from 70–100 days; 39% underwent hematopoietic cell transplantation (HCT), and the most common disease was acute myeloid leukemia (AML).

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Results

Overall, proven or probable fungal infection occurred in 5% of the study population—45% were Candida and 49% were Aspergillus. All triazoles were better than placebo, except for itraconazole. Various triazoles differed in terms of tolerability and specific treatment-related side effects. Comparative efficacy analysis was in favor of posaconazole based on numerous outcomes evaluated. Itraconazole was associated with more study withdrawals but was also the least costly. Incremental cost-effectiveness ratios (ICER) were calculated for each agent. This analysis showed that posaconazole had a higher ICER than comparators. All triazoles except for intraconazole capsules were found to be effective in reducing fungal infection.

Conclusions

The findings suggest that posaconazole may more cost-effective for antifungal prophylaxis than the other triazoles examined. Itraconazole capsules were not shown to be effective.

Limitations

Low sample sizes
Did not include patients of other high risk groups, such as GVHD. No direct head-to-head comparison of individual azoles, though the network meta-analysis approach was used to enable this comparison. The study was done in Singapore, so cost, etc., information may not be applicable in other areas.

Nursing Implications

The findings showed that all azoles other than itraconzole capsules were effective for antifungal prophylaxis, and that posaconazole may be the most cost-effective agent.

Legacy ID

6054