TY - JOUR
T1 - Impact of unresolved neutropenia in patients with neutropenia and invasive aspergillosis
T2 - A post hoc analysis of the SECURE trial
AU - Kontoyiannis, Dimitrios P.
AU - Selleslag, Dominik
AU - Mullane, Kathleen
AU - Cornely, Oliver A.
AU - Hope, William
AU - Lortholary, Olivier
AU - Croos-Dabrera, Rodney
AU - Lademacher, Christopher
AU - Engelhardt, Marc
AU - Patterson, Thomas F.
N1 - Funding Information:
This study was funded by Astellas Pharma, Inc. Medical writing support was also funded by Astellas Pharma, Inc.
Funding Information:
D. P. K. has received support from Astellas, Pfizer and Merck. D. S. has received support from Astellas, Pfizer and Merck. K. M. has received support from Astellas, Anson, Chimerix, Cubist, Optimer, Merck, Rebiotix, ViroPharma and Pfizer. O. A. C. has received support from Astellas, Cubist, Optimer, Pfizer, Gilead, Merck, 3M, Basilea, F2G, ViroPharma, GSK, Actelion, Sanofi Pasteur, Quintiles, Summit, Vifor, Celgene, Genzyme and Miltenyi. W. H. has received support from Astellas, Pfizer, Gilead, F2G, Amplyx and Basilea. O. L. has received support from Astellas, Pfizer, Gilead and Merck. R. C.-D. and C. L. are employees of Astellas Pharma Global Development, Inc. M. E. is an employee of Basilea Pharmaceutica International Ltd, Basel, Switzerland. T. F. P. has received support from Amplyx, Astellas, Basilea, Gilead, Merck, Pfizer, Toyama, Scynexis, Vical and Viamet.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
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U2 - 10.1093/jac/dkx423
DO - 10.1093/jac/dkx423
M3 - Article
C2 - 29194488
AN - SCOPUS:85040098862
VL - 73
SP - 757
EP - 763
JO - Journal of Antimicrobial Chemotherapy
JF - Journal of Antimicrobial Chemotherapy
SN - 0305-7453
IS - 3
ER -