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Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial

Clinical and experimental allergy, 2012-07, Vol.42 (7), p.1097-1103 [Peer Reviewed Journal]

2012 Blackwell Publishing Ltd ;2015 INIST-CNRS ;2012 Blackwell Publishing Ltd. ;Copyright © 2012 Blackwell Publishing Ltd ;ISSN: 0954-7894 ;EISSN: 1365-2222 ;DOI: 10.1111/j.1365-2222.2012.04014.x ;PMID: 22702508

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Title:
Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial
Author: Nair, P. ; Gaga, M. ; Zervas, E. ; Alagha, K. ; Hargreave, F. E. ; O'Byrne, P. M. ; Stryszak, P. ; Gann, L. ; Sadeh, J. ; Chanez, P.
Subjects: Adolescent ; Adult ; Aged ; Asthma ; Asthma - drug therapy ; Asthma - metabolism ; Asthma - pathology ; Benzamides - administration & dosage ; Benzamides - adverse effects ; Biological and medical sciences ; Biomarkers - metabolism ; Blood ; Cell activation ; Cell Count ; Clinical trials ; CXCR2 ; CXCR2 protein ; Cyclobutanes - administration & dosage ; Cyclobutanes - adverse effects ; Double-Blind Method ; Elastase ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; IL-8 ; Interleukin 8 ; Interleukin-8 - metabolism ; Inventories ; Leukocytes (neutrophilic) ; Male ; Middle Aged ; Neutrophil Activation - drug effects ; Neutrophils - metabolism ; Neutrophils - pathology ; Pancreatic Elastase - metabolism ; Peroxidase ; Peroxidase - metabolism ; Receptors, Interleukin-8B - antagonists & inhibitors ; Respiratory tract ; severe asthma ; Severity of Illness Index ; Sputum ; sputum neutrophils ; Statistical analysis
Is Part Of: Clinical and experimental allergy, 2012-07, Vol.42 (7), p.1097-1103
Description: Summary Background Increased numbers of neutrophils are reported in the airways of patients with severe asthma. It is not clear if they contribute to the lack of control and severity. There are currently no strategies to investigate this by decreasing neutrophil numbers in the airways. Objective To investigate the safety and efficacy of SCH527123, a selective CXCR2 receptor antagonist, in patients with severe asthma and increased number of neutrophils in sputum. Methods In a randomized, double‐blind, parallel study, patients with severe asthma and sputum total cell count < 10 × 106/g and neutrophils > 40% were randomized to SCH527123, 30 mg daily PO (n = 22) or placebo (n = 12) for 4 weeks. Primary end‐points were safety and change in sputum and blood neutrophil counts. Secondary end‐points were change in asthma control questionnaire (ACQ) score, minor and major exacerbations, spirometry and sputum neutrophil activation markers. Results The SCH 527123 caused a mean reduction of 36.3% in sputum neutrophil percentage compared to a 6.7% increase in the placebo arm (P = 0.03). The mean absolute neutrophil count in blood was reduced by 14% at the end of 4 weeks, but recovered by the 5th week. There were no differences in the overall rates of adverse events among the groups. There were fewer mild exacerbations (1.3 vs. 2.25, P = 0.05) and a trend towards improvement in the ACQ score (mean difference between groups of 0.42 points, P = 0.053). No statistically significant changes were observed in forced expiratory volume in 1 s (FEV 1), sputum myeloperoxidase, IL8 or elastase. Conclusions The SCH527123 is safe and reduces sputum neutrophils in patients with severe asthma. Clinical Relevance This new treatment provides an opportunity to investigate the role of neutrophils in severe asthma with potential clinical benefits. Larger studies of longer duration are needed to evaluate the impact on other outcomes of asthma including exacerbations.
Publisher: Oxford: Blackwell Publishing Ltd
Language: English
Identifier: ISSN: 0954-7894
EISSN: 1365-2222
DOI: 10.1111/j.1365-2222.2012.04014.x
PMID: 22702508
Source: MEDLINE
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Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial

2012 Blackwell Publishing Ltd ;2015 INIST-CNRS ;2012 Blackwell Publishing Ltd. ;Copyright © 2012 Blackwell Publishing Ltd ;ISSN: 0954-7894 ;EISSN: 1365-2222 ;DOI: 10.1111/j.1365-2222.2012.04014.x ;PMID: 22702508

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