MISSISSAUGA, ON (June 17 ) - A second analysis of data from real-world study PATHOS, recently published in the British Medical Journal, shows that treatment of chronic obstructive pulmonary disease (COPD) patients with SYMBICORT® (budesonide/formoterol) was associated with a lower incidence of pneumonia and pneumonia related death, compared to treatment of COPD patients with ADVAIR® (fluticasone/salmeterol).ⅰ PATHOS is the largest real-world study to compare the effectiveness and safety of two commonly prescribed inhaled corticosteroid and long-acting beta agonist (ICS/LABA) combination treatments for COPD with more than one year of patient follow-up.ⅰ
Overall, the ADVAIR® treatment group was associated with a 73% higher pneumonia rate (rate ratio [RR] 1.73 [95% confidence interval [CI] 1.57-1.90]; p<0.001; event-based number needed to treat [NNT]=23 [95% CI18-37]), with event rates of 11.0 per 100 patient-years compared to 6.4 per 100 patient-years for the SYMBICORT® group.ⅰ Similarly, the ADVAIR® treatment group was associated with 74% higher pneumonia-related hospital admissions than the SYMBICORT® treatment group (RR 1.74 [95% CI 1.56-1.94]; p<0.001; event-based number NNT=34 [95% CI 24-59]), with 7.4 hospitalizations per 100 patient-years in the ADVAIR® treatment group compared to 4.3 hospitalizations per 100 patient-years in the SYMBICORT® treatment group.ⅰ A corresponding 82% increase in hospital days (53 versus 29 days per 100 patient-years, respectively; p<0.001) was associated with the ADVAIR® treatment group.ⅰ
The average duration of pneumonia-related hospitalizations was similar for both groupsi but the ADVAIR® treatment group was associated with a higher risk of pneumonia-related death (97 deaths) compared to the SYMBICORT® treatment group (52 deaths) (hazard ratio [HR] 1.76; 95% CI 1.22–2.53; p=0.0025).ⅰ
"As a frequent complication of COPD, pneumonia is associated with considerable health cost and mortality" ⅱ,ⅲ,ⅳ said Dr. Charlie Chan, Professor and Vice-Chair of Medicine, University of Toronto, consultant Respirologist, University Health Network. "This data is significant as it is the first to compare pneumonia rates between two commonly prescribed ICS/LABA combinations in the same matched COPD study population, and can help uncover gaps in care, providing additional information on the efficacy and safety of treatments as experienced in the real-world setting."
A previous analysis of PATHOS data regarding the risk of COPD related moderate and severe exacerbations and hospitalizations was published earlier this year in the Journal of Internal Medicine.ⅴ Together, these analyses of real-world evidence provide insight into the impact of the two treatment combinations in clinical practice, providing healthcare providers, patients and payers with valuable information to further inform their treatment decisions.
The 11-year PATHOS study, led by Uppsala University, retrospectively examined the medical records of 5,468* ICS/LABA-treated patients in Sweden from 1999 to 2009; a total of 19,000 patient years.ⅰ This second published analysis of the data compares the rate of pneumonia associated with two commonly prescribed combinations.ⅰ To allow for a valid comparison, a cohort of patients treated with ADVAIR® were individually matched with an equal number of patients treated with SYMBICORT® a second ICS/LABA.ⅰ Investigators used a statistical technique called "propensity score matching" to minimize bias and ensure the two ICS/LABA-treated groups were comparable in terms of variables including age, gender, and measures of disease severity such as medication use, COPD co-morbidities, previous hospitalizations for any cause and exacerbation rates for COPD, and other conditions like respiratory infections prior to the first ICS/LABA prescription.ⅰ
COPD encompasses two serious lung diseases – emphysema and chronic bronchitis – which result in chronic airway inflammation and progressive loss of lung function, making it difficult to breathe normally.ⅵ Common symptoms of COPD include breathlessness, sputum, and chronic cough.ⅵ People with COPD are likely to experience COPD exacerbations, an acute worsening of symptoms that are a key driver of increased mortality and have been linked to a decline in lung function and worsening overall health.ⅶ Over 750,000 Canadians have been diagnosed with COPD and as many as 1.6 million more people may have COPD, but remain undiagnosed.ⅷ COPD already kills more people worldwide than cancerⅸ and is the fourth leading cause of death in Canada, causing approximately 10,000 deaths a year.ⅹ
PATHOS was a real-world, retrospective study that examined the medical records of 21,361 COPD patients over an 11-year period in Sweden to better understand the evolution of COPD care and the impact of different COPD management strategies on outcomes for patients.ⅰ,ⅴ It is the largest and longest real-world study to compare the effectiveness and safety of two commonly prescribed ICS/LABA combination treatments for COPD. Medical records’ data was linked to national, mandatory Swedish healthcare registries, including hospital, drug, and cause of death register data for 1999-2009, and analyzed by Uppsala University to provide high quality evidence of outcomes in a real-world setting.ⅰ
About Real-World Evidence
Unlike randomized, controlled clinical trials, real-world evidence studies use observational data, such as electronic medical records and healthcare registries, to create deeper insights into unmet clinical need, the burden of illness, the cost of care or the actual, rather than expected, impact of management strategies or treatments in a real-world setting. AstraZeneca is committed to understanding the impact of its medicines in the real-world, beyond what is seen in controlled clinical trials. These insights will help AstraZeneca develop medicines that improve the treatment of disease and help inform healthcare decision-making to ensure effective use of medicines that minimize the burden on patients and healthcare budgets.
*9,893 ICS/LABA-treated patient records were analyzed and propensity-matched, a common means of balancing study groups to minimize bias when randomization is not possible or appropriate. Matching of these 9,893 patients (7,155 budesonide/formoterol; 2,738 fluticasone/salmeterol) yielded two matched cohorts each of 2,734 patients.ⅰ
About SYMBICORT® (budesonide/formoterol)
SYMBICORT® (budesonide/formoterol) provides both the anti-inflammatory corticosteroid budesonide and the rapid and long-lasting bronchodilator formoterol in the same device – the SYMBICORT® Turbuhaler®. SYMBICORT® (budesonide/formoterol) is indicated for the treatment of COPD in 88 countries worldwide.
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. AstraZeneca’s Canadian headquarters are located in Mississauga, Ontario. For more information, please visit the company’s website at www.astrazeneca.ca.
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ⅰPneumonia and pneumonia related mortality in patients with COPD treated with fixed combinations of inhaled corticosteroid and long acting β2 agonist: observational matched cohort study (PATHOS). British Medical Journal. Available from:http://www.bmj.com/content/346/bmj.f3306. Last accessed June 4, 2013.
ⅱCalverley PM, Stockley RA, Seemungal TA, et al. Reported pneumonia in patients with COPD: findings from the INSPIRE study. Chest 2011;139:505-12.
ⅲEwig S, Birkner N, Strauss R, et al. New perspectives on community-acquired pneumonia in 388 406 patients. Results from a nationwide mandatory performance measurement programme in healthcare quality. Thorax 2009;64:1062-9.
ⅳHolguin F, Folch E, Redd SC, et al. Comorbidity and mortality in COPD-related hospitalizations in the United States, 1979 to 2001. Chest 2005;128:2005-11.
ⅴLarsson K, Janson C, Lisspers K, et al. Combination of budesonide/formoterol more effective than fluticasone/salmeterol in preventing exacerbations in chronic obstructive pulmonary disease: the PATHOS study. J Intern Med 2013 Mar 15 [Epub ahead of print].
ⅵWorld Health Organization (WHO). COPD Fact Sheet Number 315. Available from:http://www.who.int/mediacentre/factsheets/fs315/en/index.html. Last accessed February, 2013.
ⅶPapi A, Luppi F, Franco F, et al. Pathophysiology of Exacerbations of Chronic Obstructive Pulmonary Disease. Proc Am Thorac Soc 2006; 3:245–251.
ⅷThe Lung Association. The Challenge of Lung Disease in Canada. Available from:http://www.lung.ca/involved-impliquez/federalelection-electionfederale/background-contexte/index_e.php#s4. Last reviewed June 4, 2013.
ⅸWorld Health Organization (WHO). The Global Burden of Disease. 2004 Update. Available from: http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf. Last accessed June 4, 2013.
ⅹBC Medical Journal. A Snapshot of Chronic Obstructive Pulmonary Disease in British Columbia and Canada. Available from: http://www.bcmj.org/article/snapshot-chronic-obstructive-pulmonary-disease-british-columbia-and-canada. Last accessed June 4, 2013.