TNFα Antagonists for Acute Exacerbations of COPD: A Randomised Double-Blind Controlled Trial
Open accessAbstract
BACKGROUND: The purpose of this randomised double-blind double-dummy placebo-controlled trial was to investigate whether etanercept, a tumour necrosis factor α (TNFα) antagonist, would provide more effective anti-inflammatory treatment for acute exacerbations of chronic obstructive pulmonary disease (COPD) than prednisone. METHODS: We enrolled 81 patients with acute exacerbations of COPD and randomly assigned them to treatment with either 40 mg oral prednisone given daily for 10 days or to 50 mg etanercept given subcutaneously at randomisation and 1 week later. Both groups received levofloxacin for 10 days plus inhaled bronchodilators. The primary endpoint was the change in the patient's forced expiratory volume in 1 s (FEV(1)) 14 days after randomisation. Secondary endpoints included 90-day treatment failure rates and dyspnoea and quality of life. RESULTS: At 14 days the mean±SE change in FEV(1) from baseline was 20.1±5.0% and 15.2±5.7% for the prednisone and etanercept groups, respectively. The mean between-treatment difference was 4.9% (95% CI -10.3% to 20.2%), p=0.52. Rates of treatment failure at 90 days were similar in the prednisone and etanercept groups (32% vs 40%, p=0.44), as were measures of dyspnoea and quality of life. Subgroup analysis revealed that patients with serum eosinophils >2% at exacerbation tended to experience fewer treatment failures if treated with prednisone compared with etanercept (22% vs 50%, p=0.08). CONCLUSIONS: Etanercept was not more effective than prednisone for treatment of acute exacerbations of COPD. Efficacy of prednisone was most apparent in patients who presented with serum eosinophils >2%. CLINICAL TRIALS: gov number NCT 00789997.
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Therapies against TNF-α have not proven effective for outcomes such as dyspnea or exacerbations, suggesting that TNF-α is not the primary or at least the sole driver of COPD inflammation.
“therapies against TNF-α have not proven to be effective for various outcomes such as dyspnea or a number of exacerbations [43], suggesting that this cytokine is not the primary or at least the sole driver of COPD inflammation.”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [43]
The Secondary outcomes section (page unavailable) reports that dyspnoea improved in both groups, with no significant difference between etanercept and prednisone. The Discussion (page unavailable) also reports no benefit of etanercept over prednisone for treating acute exacerbations and cites a separate trial finding no dyspnoea benefit from infliximab in stable COPD. This paper does not establish that TNF-α therapies reduce the number of exacerbations; its own trial studied treatment of an exacerbation, not prevention of future ones. (LLM, conf=0.86)
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Cites
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- Chronic obstructive pulmonary disease on July 20, 2023 by guest. Protected by copyright. http://thorax.bmj.com/ Thorax: first published as 10.1136/thoraxjnl-2012-202432 on 17 November 2012. Downloaded from REFERENCES
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Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting
Henrot, P., Dupin, I., Schilfarth, P., Esteves, P., Blervaque, L., Zysman, M., Gouzi, F., Hayot, M., Pomiès, P., & Berger, P. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076454 · Cited by 85 · see citing works
“Of note, therapies against TNF-α have not proven to be effective for various outcomes such as dyspnea or a number of exacerbations [43], suggesting that this cytokine is not the primary or at least the sole driver of COPD inflammation.”
Background
- Authors
- Aaron, S. D., Vandemheen, K. L., Maltais, F., Field, S. K., Sin, D. D., Bourbeau, J., Marciniuk, D. D., FitzGerald, J. M., Nair, P., & Mallick, R.
- Affiliations
- University of Ottawa (CA)
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- University of Calgary (CA)
- University of British Columbia (CA)
- McGill University (CA)
- University of Saskatchewan (CA)
- Corresponding author
- Aaron, Shawn D
- ORCID
- Venue
- Thorax
- Publisher
- BMJ
- Published
- 2012-11-17
- Volume
- 68
- Issue
- 2
- Pages
- 142-148
- ISSN
- 0040-6376 (ISSN-L)
- 1468-3296
- OpenAlex
- W2096651238
- Cited by
- 103
- References
- 3
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 12 · 2022: 8 · 2021: 7 · 2020: 4 · 2019: 6 · 2018: 9 · 2017: 7 · 2016: 11 · 2015: 7 · 2014: 8 · 2013: 5
- FWCI
- 5.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Thorax (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Fetzer Institute
- McGill University
- University of Saskatchewan
- Ottawa Hospital Research Institute
- McGill University Health Centre
- Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval
- Canadian Institutes of Health Research (MCT-901676)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Keywords
- COPD exacerbations, etanercept, TNF-alpha inhibitors, prednisone, corticosteroid therapy, serum eosinophils, FEV1, treatment failure, dyspnea, quality of life, levofloxacin, anti-inflammatory therapy
- MeSH terms
- Etanercept, Aged, Anti-Inflammatory Agents, Non-Steroidal, Double-Blind Method, Female, Forced Expiratory Volume, Glucocorticoids, Humans, Immunoglobulin G, Male, Middle Aged, Prednisone, Tumor Necrosis Factor-alpha, Ofloxacin, Treatment Outcome, Receptors, Tumor Necrosis Factor, Disease Progression, Pulmonary Disease, Chronic Obstructive, Levofloxacin
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