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

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Asthma
The role of a soluble TNFα receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial
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  1. J B Morjaria1,
  2. A J Chauhan2,
  3. K S Babu1,
  4. R Polosa3,
  5. D E Davies1,
  6. S T Holgate1
  1. 1Infection, Inflammation and Repair Division, Southampton University Hospitals Trust, Southampton, UK
  2. 2Department of Respiratory Medicine, Queen Alexandra Hospital, Portsmouth, UK
  3. 3Dipartimento di Medicina Interna, Universita’ di Catania, Presidio Ospedaliero Ascoli-Tomaselli, Catania, Italy
  1. Dr J B Morjaria, Mailpoint 810, South Academic Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK; jbm{at}soton.ac.uk

Abstract

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.

https://doi.org/10.1136/thx.2007.086314

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    Footnotes

    • See Editorial, page 571

    • The appendix is published online only at http://thorax.bmj.com/content/vol63/issue7

    • Normal range: The normal ranges of serum C reactive protein and albumin described in this study are <7.5 mg/l and 35–48 g/l in healthy adults.

    • JBM and AJC contributed equally to the study.

    • Contributors: STH, DED, AJC, JM and KSB contributed to the concept and design of the study. JM, AJC, RP, DED and STH contributed to the analysis and interpretation of data. STH was principal investigator; DED, RD, JM and AJC were coinvestigators. AJC, JM, RP and STH drafted the article and revised it critically for intellectual content. JM and AJC conducted and supervised the study at the clinical sites.

    • Funding: This study was supported by an educational grant from Wyeth Pharmaceuticals, UK, and they were not sponsors of the study. The trial was investigator initiated and the sponsors were not involved in the study design, data collection, analysis or interpretation of the data. A copy of the manuscript was nonetheless sent to Wyeth before submission. STH is a UK Medical Research Council funded Clinical Professor.

    • Competing interests: This study was performed with an educational grant from Wyeth Pharmaceuticals. All authors confirm (except JM and STH, see below) that they are not involved in any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript. JM was funded by the educational grant to conduct this study. AJC in the past 5 years has received research funding, honoraria for lectures and educational grants from Astra Zeneca, GlaxoSmithKline, Boehringer Ingelheim and Merck, and has been on advisory boards for Astra Zeneca and GlaxoSmithKline. STH is a consultant for Novartis, Synairgen, Merck, Wyeth and Centocor. STH has received lecture fees from their companies. RP is a consultant for Cardiovascular Therapeutics, Duska Therapeutics and NeuroSearch, and has received lecture fees from Merck and Novartis.

    • Ethics approval: The trial was approved by the SE Hampshire and Isle of Wight Research Ethics Committee.

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