The Role Of A Soluble Tnf-Á Receptor Fusion Protein (Etanercept) In Corticosteroid-Refractory Asthma: A Double Blind, Randomised Placebo-Controlled Trial

Jaymin B Morjaria ^1*, Anoop J Chauhan ², Kesavan S Babu ¹, Riccardo Polosa ³, Donna E Davies ¹ and Stephen T Holgate ¹

¹ University of Southampton, United Kingdom
² Queen Alexandra Hospital, Portsmouth, United Kingdom
³ Universita di Catania, Catania, Italy

^* To whom correspondence should be addressed. E-mail: jbm{at}soton.ac.uk.

Accepted 19 December 2007

Abstract

Rationale: TNF- is a cytokine recognized as a therapeutic target in chronic inflammatory diseases.

Objectives and Methods: We report a randomised double-blind placebo-controlled parallel group trial of etanercept (an IgG1-TNF p75 receptor fusion protein), administered once weekly for 12 weeks in 39 patients with symptomatic corticosteroid refractory asthma. Efficacy was measured by change from the pre-treatment baseline in Asthma Related Quality of Life (AQLQ) and Asthma Control (ACQ) Questionnaires scores (the primary end-points), lung function, PEF and bronchial hyperresponsiveness (BHR). We also assessed sputum and serum inflammatory cells and cytokines, serum albumin and C-reactive protein as biomarkers of inflammation.

Main results: There was a small but significant difference in reduction of ACQ scores between treatment and placebo (-1.11 (95%CI -1.56, -0.75) and -0.52 (95%CI -0.97, -0.07) respectively, p=0.030). There was no significant difference in improvements in AQLQ scores between groups (p=0.084), though sub group analyses restricted to 29 patients not taking antidepressants revealed significant improvements in both AQLQ and ACQ. There were no differences in lung function, PEF, BHR or exacerbation rates between 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.

Keywords: CRP, TNF antagonists, TNF-&[alpha], etanercept, severe asthma

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