TNF-α antagonists and the prevention of hospitalisation for chronic obstructive pulmonary disease

doi:10.1016/j.pupt.2007.03.003

Pulmonary Pharmacology & Therapeutics

Volume 21, Issue 1, February 2008, Pages 234-238

https://doi.org/10.1016/j.pupt.2007.03.003 Get rights and content

Abstract

Background

TNF-α may be important in the pathogenesis of COPD. Consequently, the use of TNF-α antagonists has been advocated for its treatment.

Methods

We conducted an observational study to evaluate the effectiveness of TNF-α antagonists in preventing COPD hospitalisations in a cohort of patients diagnosed with both RA and COPD identified from a health claims database. A nested case-control approach was used to match each case hospitalised to 10 controls on age and cohort entry date. Data on prescribed medications during the year prior to the index date were obtained. Rate ratios (RR) of COPD hospitalisation were estimated by conditional logistic regression, after adjustment for COPD severity and concomitant RA medication use.

Results

The cohort included 15,771 subjects with both RA and COPD, of which 1205 were hospitalised for COPD during follow-up. The adjusted RR of COPD hospitalisation associated with the use of TNF-α antagonists was 0.62 (95% confidence interval (CI) 0.43–0.89). This rate reduction was due to etanercept (RR 0.49, 95% CI 0.29–0.82) but not infliximab (RR 0.95, 95% CI 0.59–1.52).

Conclusion

Our finding of a halving in the rate of COPD hospitalisation associated with the use of etanercept corroborates the potential importance of TNF-α in the pathogenesis of COPD. This study supports the initiation of randomised controlled trials of this TNF-α antagonist among COPD patients at high risk of severe exacerbations.

Introduction

Chronic obstructive pulmonary disease (COPD) is a major health problem whose impact is projected to grow for many years to come [1], [2]. Treatments available to date mainly target symptoms and appear to have little impact on the natural history of the disease [3], [4]. Tumor necrosis factor α (TNF-α) is a multi-functional inflammatory cytokine which is found in excess in the sputum of patients with COPD [5] and appears to drive much of the neutrophilic airway inflammation observed in COPD [6]. In addition, gene promoter polymorphisms for TNF-α are associated with an increase in the incidence of COPD [7] as well as a worsened prognosis [8]. It seems therefore plausible that agents that block the effect of TNF-α might provide benefits to patients with COPD. This inflammatory target has been deemed promising among the novel pharmacological agents to investigate in the treatment of COPD, particularly in patients with systemic symptoms [9].

Despite the general pathophysiological evidence, randomised controlled trials to evaluate the effectiveness of TNF-α antagonists in COPD have been few [10], [11]. We therefore carried out an observational study to indirectly examine this hypothesis. We took advantage of the increasing use of TNF-α antagonists in the treatment of rheumatoid arthritis (RA) to evaluate the effectiveness of TNF-α antagonists in reducing the risk of COPD hospitalisation in a large cohort of patients with both RA and COPD, some of whom were receiving anti-TNF-α agents for their RA.

Section snippets

Data sources

The cohort for this study was formed using the PharMetrics patient-centric outcomes database, a North American insurance claims database [12]. This database consists of standardized information on claims data from 75 different health insurance plans and currently encompasses more than 55 million unique patients. It includes data on all physician visits, hospitalisations and prescribed medications dispensed in these populations. Data spanning the period from January 1995 to December 2003 were

Results

The cohort of RA patients included 235,272 subjects, from which we identified the study cohort of all 15,771 COPD patients with at least 3 visits for COPD. During follow-up, 1205 subjects were hospitalised for COPD and these subjects were matched to 12,050 controls.

Table 1 shows that the cases hospitalised for COPD and their matched controls were 67 years of age at the index date and that the cases occurred on average 14 months after cohort entry. Women represented 69% and 67% of the cases and

Discussion

We found using a large-scale observational approach that TNF-α inhibitors, agents directed against the deleterious effects of the inflammatory cytokine TNF-α, were associated with a reduction in the rate of COPD hospitalisation among patients with COPD receiving these agents to treat their rheumatoid arthritis. This effect, however, was due exclusively to a reduction of 50% in the rate of COPD hospitalisation with etanercept, a soluble receptor fusion protein that binds TNF. The other TNF-α

Acknowledgements

The sponsors did not participate in the design, conduct, analysis or interpretation of the data; and preparation of the manuscript. The authors had full access to all of the data in the study and the first author takes responsibility for the integrity of the data and the accuracy of the data analysis. We thank Dr Juhaeri Juhaeri of Sanofi-Aventis for his assistance with the database acquisition.

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^☆: The study was funded by a grant from the Canadian Institutes of Health Research (CIHR) and the database was provided thanks to a grant from Sanofi-Aventis.

¹: Recipient of a Distinguished Investigator award from the CIHR.

²: The McGill Pharmacoepidemiology Research Unit is funded by an infrastructure grant from the Fonds de la recherché en santé du Québec (FRSQ).

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TNF-α antagonists and the prevention of hospitalisation for chronic obstructive pulmonary disease☆

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Data sources

Results

Discussion

Acknowledgements

Chest

Lancet

Am J Med

The global burden of disease, 1990–2020

Nat Med

Variables related to increased mortality following out-patient pulmonary rehabilitation

Eur Respir J

Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial

Br Med J

Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease

N Engl J Med

Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma

Am J Respir Crit Care Med

Tumor necrosis factor-alpha drives 70% of cigarette smoke-induced emphysema in the mouse

Am J Respir Crit Care Med

Association of tumor necrosis factor alpha gene promoter polymorphism with the presence of chronic obstructive pulmonary disease

Am J Respir Crit Care Med

First study of infliximab treatment in patients with chronic obstructive pulmonary disease

Am J Respir Crit Care Med

The safety and efficacy of infliximab in moderate-to-severe chronic obstructive pulmonary disease

Am J Respir Crit Care Med