The role of a soluble TNFalpha receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial.
OBJECTIVE
Tumour necrosis factor alpha (TNFalpha) 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 TNFalpha and albumin following treatment, but not in other laboratory parameters.


CONCLUSIONS
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 TNFalpha antagonism in subjects with severe refractory asthma.
Morjaria
J B
JB
Infection, Inflammation and Repair Division, Southampton University Hospitals Trust, Southampton, UK. jbm@soton.ac.uk
Chauhan
A J
AJ
Babu
K S
KS
Polosa
R
R
Davies
D E
DE
Holgate
S T
ST
D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D016535:Bronchial Hyperreactivity / Q000503:physiopathology; D004311:Double-Blind Method; D004351:Drug Resistance; D000068800:Etanercept; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013183:Sputum / Q000737:chemistry; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D018927:Anti-Asthmatic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept