ASTHMA

The role of a soluble TNF receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial

J B Morjaria¹, A J Chauhan², K S Babu¹, R Polosa³, D E Davies¹, S T Holgate¹

¹ Infection, Inflammation and Repair Division, Southampton University Hospitals Trust, Southampton, UK
² Department of Respiratory Medicine, Queen Alexandra Hospital, Portsmouth, UK
³ Dipartimento di Medicina Interna, Universita’ di Catania, Presidio Ospedaliero Ascoli-Tomaselli, Catania, Italy

Dr J B Morjaria, Mailpoint 810, South Academic Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK; jbm{at}soton.ac.uk

Aim: Tumour necrosis factor (TNF) 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 TNF 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 TNF antagonism in subjects with severe refractory asthma.

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