TNF-α antagonists and the prevention of hospitalisation for chronic obstructive pulmonary disease☆
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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2018, Journal of Allergy and Clinical ImmunologyCitation Excerpt :It is possible that a more responsive population of patients with COPD in whom the safety signal is attenuated is present; biomarkers, such as C-reactive protein, might be useful for this purpose. For example, a health claims database observational study suggested that TNF-α antagonists given to treat rheumatoid arthritis prevented exacerbations, resulting in hospitalization in patients with both rheumatoid arthritis and COPD.55 However, this effect was exclusively due to a reduction of 50% in the rate of COPD-related hospitalization with etanercept.
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2018, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :The confounding by indication could have occurred if patients with more severe COPD, and thus at greater risk of being hospitalised for COPD, preferentially received a TNF-α antagonist. Moreover, the confounding by contraindication could also have biased the results of the observational study, since COPD patients with more severe rheumatoid arthritis, who were more likely to receive an anti-TNF-α agent, were less likely to be labelled as COPD when they were hospitalised [37]. The previously reported lack of effectiveness of the IL-1β antagonist canakinumab, IL-1R1 antagonist MEDI8986, and IL-8 antagonist ABX-IL8 [2] has been confirmed by this meta-analysis, at least with regard to the impact on the risk of exacerbation, lung function and health-related QoL in COPD patients.
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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).