Reduced rate of COPD-related hospitalizations seen with long-term ICS/LABA combination therapy

Long-term treatment with fixed-combination budesonide/formoterol (Symbicort Turbuhaler, AstraZeneca) was associated with fewer healthcare utilization-defined exacerbations and hospitalizations than fluticasone/salmeterol in patients with moderate and severe chronic obstructive pulmonary disease (COPD), according to a study published online in the Journal of Internal Medicine.  

Data from the real-world study PATHOS found that COPD patients treated with budesonide/formoterol had a reduced risk of exacerbations per patient-year by 26.6% (0.80 vs 1.09; P<.0001) and hospitalizations due to COPD by 29.1% (0.15 vs 0.21; P<.0001) than those treated with salmeterol/fluticasone.

The 11-year-old PATHOS analysis set out to investigate the clinical use and assess the relative effectiveness of budesonide/formoterol and fluticasone/salmeterol-two commonly prescribed inhaled corticosteroid/long-acting beta agonist (ICS/LABA) combinations for the treatment of COPD. It aimed to assess the long-term impact of these treatments on healthcare utilization, including exacerbations, hospitalizations, emergency department visits, and use of antibiotics and oral steroids.

Researchers at Uppsala University in Sweden 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. This first published analysis of the data compares the rate of COPD exacerbations associated with two commonly prescribed combinations. To allow for a valid comparison, a cohort of patients treated with budesonide/formoterol was individually matched with an equal number of patients treated with a second ICS/LABA, fluticasone/salmeterol. 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. Exacerbations were defined in the study as medical interventions such as hospitalizations, emergency room visits, and prescription of oral steroids or antibiotics due to COPD deterioration.

“So called ‘real-world’ studies, such as PATHOS, together with randomized prospective studies, play an important role in answering questions about the value of medicines in delivering better, cost-effective healthcare to patients,” said study lead investigator Kjell Larsson, MD, professor of respiratory medicine at the Karolinska Institute in Stockholm. “These findings can help physicians and the healthcare community to understand disease patterns and create a fuller picture of treatment effects and what patients are experiencing.”

Overall, budesonide/formoterol reduced the annual rate of moderate to severe exacerbations by 26% compared to fluticasone/salmeterol (0.80 vs 1.09 /patient-year; P<.0001). The significant, and clinically relevant reduction in favor of budesonide/formoterol was apparent for all types of exacerbation event (eg, antibiotic use, oral steroid use, or hospital admission). Use of budesonide/formoterol reduced rates of COPD-related hospitalization by 29% (0.15 vs 0.21/patient-year; P<.0001) with 34% fewer hospital days due to COPD exacerbation (0.63 vs 0.95/patient-year; P<.0001) compared with fluticasone/salmeterol.

At present, Symbicort Turbuhaler is not FDA-approved for the management of COPD in the United States, although the pMDI form of Symbicort currently does maintain that indication.