Impact of unresolved neutropenia in patients with neutropenia and invasive aspergillosis: A post hoc analysis of the SECURE trial

Dimitrios P. Kontoyiannis, Dominik Selleslag, Kathleen Mullane, Oliver A. Cornely, William Hope, Olivier Lortholary, Rodney Croos-Dabrera, Christopher Lademacher, Marc Engelhardt, Thomas F. Patterson

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: Historically, baseline neutropenia and lack of neutrophil recovery have been associated with poor outcomes in invasive aspergillosis (IA). It is unclear how treatment with the new Aspergillus-active triazoles isavuconazole and voriconazole affects outcomes in neutropenic patients with IA. Methods: A post hoc analysis of the Phase 3 SECURE trial assessed patients with neutropenia (neutrophil count <0.5×10 9 /L for >10 days at baseline) with IA (proven/probable) who had received either isavuconazole or voriconazole. The primary endpoint was all-cause mortality (ACM) through day 42. ACM in patients with resolved versus unresolved neutropenia at day 7 and overall success at end of treatment (EOT) were also assessed. Results: One hundred and forty-two patients with neutropenia and IA were included (isavuconazole n=78, voriconazole n=64). ACM through day 42 (primary endpoint), day 7 and EOT were higher for patients with unresolved versus resolved neutropenia at each timepoint (day 42, unresolved: 45.0% isavuconazole, 45.2% voriconazole; resolved: 5.0% isavuconazole, 5.9% voriconazole; day 7, unresolved: 31.0% isavuconazole, 29.8% voriconazole; resolved: 5.0% isavuconazole, 5.9% voriconazole; EOT, unresolved: 48.6% isavuconazole, 36.4% voriconazole; resolved: 5.0% isavuconazole, 14.3% voriconazole). ACM was significantly higher for isavuconazoletreated patientswith unresolved versus resolved neutropenia (day 7, P=0.031; day 42, P<0.001; EOT, P<0.001). In voriconazole-treated patients, ACM was significantly higher among patients with unresolved versus resolved neutropenia at day 42 (P=0.002) and numerically higher at day 7 and EOT (P>0.05 for both). Conclusions: Isavuconazole had comparable efficacy and safety to voriconazole in neutropenic patients with IA. Resolution of neutropenia was associated with improved outcomes.

Original languageEnglish (US)
Pages (from-to)757-763
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume73
Issue number3
DOIs
StatePublished - Mar 1 2018

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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    Kontoyiannis, D. P., Selleslag, D., Mullane, K., Cornely, O. A., Hope, W., Lortholary, O., Croos-Dabrera, R., Lademacher, C., Engelhardt, M., & Patterson, T. F. (2018). Impact of unresolved neutropenia in patients with neutropenia and invasive aspergillosis: A post hoc analysis of the SECURE trial. Journal of Antimicrobial Chemotherapy, 73(3), 757-763. https://doi.org/10.1093/jac/dkx423