Impact of unresolved neutropenia in patients with neutropenia and invasive aspergillosis: a <i>post hoc</i> analysis of the SECURE trial

Kontoyiannis, Dimitrios P, Selleslag, Dominik, Mullane, Kathleen, Cornely, Oliver A, Hope, William ORCID: 0000-0001-6187-878X, Lortholary, Olivier, Croos-Dabrera, Rodney, Lademacher, Christopher, Engelhardt, Marc and Patterson, Thomas F (2018) Impact of unresolved neutropenia in patients with neutropenia and invasive aspergillosis: a <i>post hoc</i> analysis of the SECURE trial. JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 73 (3). pp. 757-763.

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Abstract

<h4>Background</h4>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.<h4>Methods</h4>A post hoc analysis of the Phase 3 SECURE trial assessed patients with neutropenia (neutrophil count <0.5 × 109/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.<h4>Results</h4>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 isavuconazole-treated patients with 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).<h4>Conclusions</h4>Isavuconazole had comparable efficacy and safety to voriconazole in neutropenic patients with IA. Resolution of neutropenia was associated with improved outcomes.

Item Type:	Article
Uncontrolled Keywords:	Humans, Aspergillus, Neutropenia, Nitriles, Triazoles, Pyridines, Antifungal Agents, Treatment Outcome, Adult, Aged, Middle Aged, Female, Male, Invasive Pulmonary Aspergillosis, Voriconazole
Depositing User:	Symplectic Admin
Date Deposited:	12 Feb 2018 08:32
Last Modified:	13 Feb 2024 12:47
DOI:	10.1093/jac/dkx423
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3016381