TY - JOUR
T1 - Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo - A post-hoc analysis of the BACE randomized controlled trial
AU - Vermeersch, Kristina
AU - Belmans, Ann
AU - Bogaerts, Kris
AU - Gyselinck, Iwein
AU - Cardinaels, Nina
AU - Gabrovska, Maria
AU - Aumann, Joseph
AU - Demedts, Ingel K.
AU - Corhay, Jean Louis
AU - Marchand, Eric
AU - Slabbynck, Hans
AU - Haenebalcke, Christel
AU - Vermeersch, Stefanie
AU - Verleden, Geert M.
AU - Troosters, Thierry
AU - Ninane, Vincent
AU - Brusselle, Guy G.
AU - Janssens, Wim
AU - Ninane, Vincent
AU - Aumann, Joseph
AU - Demedts, Ingel K.
AU - Slabbynck, Hans
AU - Haenebalcke, Christel
AU - Peché, Rudi
AU - Brusselle, Guy G.
AU - Vincken, Walter
AU - Corhay, Jean Louis
AU - Haerens, Michiel
AU - Fremault, Antoine
AU - Lauwerier, Tine
AU - Debrock, Alix
AU - Lamont, Jan
AU - Tits, Geert
AU - Jordens, Paul
AU - Delobbe, Alain
AU - Martinot, Jean Benoît
N1 - Funding Information:
-NC has nothing to disclose. -MG has nothing to disclose. -JA has nothing to disclose. -IKD has nothing to disclose. -JLC has received speaker and consultancy fees from Boehringer-Ingelheim, AstraZeneca, Novartis, Chiesi and GlaxoSmithKline. -EM has, within the last 5 years, received honoraria for lectures from Boehringer-Ingelheim, Chiesi and Novartis; he is a member of advisory boards for AstraZeneca, Chiesi, Boehringer-Ingelheim and Novartis. -HS has received consultancy fees from Boehringer-Ingelheim and GlaxoSmithKline. -CH has received speaker and consultancy fees from Boehringer-Ingelheim, Chiesi, AstraZeneca, GlaxoSmithKline and Novartis. -SV has nothing to disclose. -GMV has nothing to disclose. -TT is vice president of the European Respiratory Society (2018–2019). His institute received speaker and consultancy fees from Boehringer-Ingelheim, AstraZeneca and Chiesi. -VN has received speaker and consultancy fees from Boehringer-Ingelheim, AstraZeneca, Novartis, MSD, GlaxoSmithKline and Chiesi. -GB has, within the last 5 years, received honoraria for lectures from AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Pfizer, Teva, UCB Pharma and Zambon; he is a member of advisory boards for AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Novartis, Sanofi/Regen-eron and Teva. -WJ is supported as a senior clinical researcher by the Fund for Scientific Research Flanders (Belgium); and has received research funding, speaker and consultancy fees from Boehringer-Ingelheim, AstraZeneca, Novartis, Chiesi and GlaxoSmithKline. WJ is co-founder of ArtIQ.
Funding Information:
This work is part of The Belgian trial with Azithromycin for acute COPD Exacerbations requiring hospitalizations (BACE trial) which is funded by the Flemish Government Agency for Innovation by Science and Technology (IWT, grant number: IWT-TBM130233). The IWT was not involved in the study design, in the collection, analysis, and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication.
Funding Information:
We would like to thank the Flemish Government Agency for Innovation by Science and Technology (IWT) for funding the BACE trial through the
Funding Information:
-KV is supported as a doctoral candidate by the Flemish Government Agency for Innovation by Science and Technology (Belgium). -AB’s institute received consultancy fees from Boehringer-Ingelheim and UCB Pharma. -KB’s institute received consultancy fees from Boehringer-Ingelheim and UCB Pharma. -IG has nothing to disclose.
Funding Information:
(TBM) program: IWT-TBM number 130233. The trial was also approved and supported by the Belgian Thoracic Society (BVP-SBP) which provided logistic support for the organization of the investigator meetings. Financial support for study logistics was also received from TEVA, Belgium. Neither the IWT, BVP-SBP nor TEVA were involved in the study design, in the collection, analysis and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. We thank the BACE trial patients for their participation, and the BACE trial investigators and supporting staff for their contributions in the Consortium: Vincent Ninane (CHU St.-Pierre – Brussel), Joseph Aumann (Jessa ziekenhuis – Hasselt), Ingel K Demedts (AZ Delta – Roeselare-Menen), Hans Slabbynck (ZNA Middelheim – Antwerpen), Eric Marchand (CHU-UCL Namur – Yvoir), Christel Haenebalcke (AZ St-Jan ziekenhuis – Brugge), Rudi Peché (CHU de Charleroi – Charleroi), Guy G Brusselle (UZ Gent - Gent), Walter Vincken (UZ Brussel – Brussel), Jean-Louis Corhay (CHU de Liège – Luik), Michiel Haerens (AZ Groeninge – Kortrijk), Antoine Fremault (Grand Hôpital de Charleroi – Charleroi), Tine Lauwerier (Imelda ziekenhuis – Bonheiden), Alix Debrock (St-Augustinus ziekenhuis – Antwerpen), Jan Lamont (Maria Middelares zieken-huis – Gent), Geert Tits (St-Andriesziekenhuis – Tielt), Paul Jordens (Onze-Lieve-Vrouwziekenhuis – Aalst), Alain Delobbe (Clinique Reine Astrid – Mal-medy), Jean-Benoît Martinot (Clinique Ste.-Elisabeth – Namur).
Publisher Copyright:
© 2019 The Author(s).
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/10/29
Y1 - 2019/10/29
N2 - BACKGROUND: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality.OBJECTIVES: (1) To investigate the intervention's effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions.METHODS: Enrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time.RESULTS: Azithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97, p = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81, p = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80; p = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60, p = 0.005), or low blood eosinophil count (<300cells/μL, RR = 0.33, 95%CI:0.17;0.64, p = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses.CONCLUSIONS: This post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy.TRIAL REGISTRATION: ClinicalTrials.gov number. NCT02135354 .
AB - BACKGROUND: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality.OBJECTIVES: (1) To investigate the intervention's effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions.METHODS: Enrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time.RESULTS: Azithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97, p = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81, p = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80; p = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60, p = 0.005), or low blood eosinophil count (<300cells/μL, RR = 0.33, 95%CI:0.17;0.64, p = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses.CONCLUSIONS: This post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy.TRIAL REGISTRATION: ClinicalTrials.gov number. NCT02135354 .
KW - CRP
KW - Eosinophil count
KW - Macrolide
KW - Readmission
KW - Recurrent event
UR - http://www.scopus.com/inward/record.url?scp=85074323927&partnerID=8YFLogxK
U2 - 10.1186/s12931-019-1208-6
DO - 10.1186/s12931-019-1208-6
M3 - Article
C2 - 31665017
AN - SCOPUS:85074323927
SN - 1465-9921
VL - 20
SP - 237
JO - Respiratory Research
JF - Respiratory Research
IS - 1
M1 - 237
ER -