RT Journal Article
SR Electronic
T1 The role of a soluble TNFα receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 584
OP 591
DO 10.1136/thx.2007.086314
VO 63
IS 7
A1 J B Morjaria
A1 A J Chauhan
A1 K S Babu
A1 R Polosa
A1 D E Davies
A1 S T Holgate
YR 2008
UL http://thorax.bmj.com/content/63/7/584.abstract
AB Aim: Tumour necrosis factor α (TNFα) is a cytokine recognised as a therapeutic target in chronic inflammatory diseases.Methods: A randomised, double blind, placebo controlled parallel group trial is reported of etanercept (an IgG1-TNF p75 receptor fusion protein), administered once weekly for 12 weeks in 39 patients with severe corticosteroid refractory asthma. Efficacy was measured by change from the pretreatment baseline in Asthma Related Quality of Life (AQLQ) and Asthma Control (ACQ) Questionnaire scores (the primary endpoints), lung function, peak expiratory flow (PEF) and bronchial hyperresponsiveness (BHR). Sputum and serum inflammatory cells and cytokines, serum albumin and C reactive protein (CRP) as biomarkers of inflammation were also assessed.Results: There was a small but significant difference in reduction of ACQ scores between treatment and placebo (−1.11 (95% CI −1.56 to −0.75) and −0.52 (95% CI −0.97 to −0.07), respectively, p = 0.037). There was no significant difference in improvements in AQLQ scores, lung function, PEF, BHR or exacerbation rates between the groups. Minor adverse events, including injection site pain and skin rashes, were more frequent with etanercept. There was a significant reduction in sputum macrophages and CRP, and increases in serum TNFα and albumin following treatment, but not in other laboratory parameters.Conclusion: Etanercept therapy over 12 weeks demonstrated only a small but significant improvement in asthma control and systemic inflammation, as measured by serum albumin and CRP. Larger randomised, placebo controlled trials are required to clarify the role of TNFα antagonism in subjects with severe refractory asthma.