'Real-World' Study Shows Two Drugs Better Than One for COPD

Norra MacReady

September 17, 2014

For older adults with chronic obstructive pulmonary disease (COPD), combination therapy with long-acting β-agonists (LABAs) and inhaled corticosteroids (ICSs) produces better outcomes than treatment with LABAs alone, a new study suggests.

In a retrospective, population-based analysis of 11,872 people aged 66 years or older, rates of mortality or hospitalization for COPD were lower among new users of LABAs plus ICSs than new users of LABAs alone. The differences were modest but statistically significant, Andrea S. Gershon, MD, from the Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada, and colleagues write in an article published in the September 17 issue of JAMA.

The salutary effect of LABAs and ICSs was even more pronounced in subgroups of patients who had asthma or who were not taking long-acting anticholinergic drugs (LAAs).

These findings could have a real effect on everyday clinical practice, the authors write. "Our finding of an association between LABAs and ICSs and outcomes helps clarify the management of patients with COPD and asthma, as many studies of COPD medications have excluded people with asthma and vice versa," the authors write. "In addition, practice guidelines for COPD recommend that LABAs be considered first-line treatment while asthma guidelines warn against use of LABAs without ICSs. Our findings also offer insight into the optimal treatment of COPD patients without asthma — those who would not be considered especially corticosteroid responsive."

The authors used multiple linked population healthcare databases to identify all residents of Ontario, Canada, who were aged 66 years or older, who had physician-diagnosed COPD, and who were new users of LABAs or LABA-ICS combination therapy between September 1, 2003, and March 31, 2011. They defined new users as patients who had not filled a prescription for LABAs or ICSs either in combination or alone within the previous year. The authors used propensity score matching to compare patients with similar characteristics. After matching, there were 3160 new users of LABAs alone and 8712 new users of both LABAs and ICSs, who were followed for a median of 2.5 and 2.7 years, respectively.

The primary outcome measure was a composite of all-cause mortality and COPD hospitalization. Secondary outcomes included hospitalization for pneumonia or fragility fractures of the spine, hip, pelvis, or forearm, all of which may be adverse effects of ICSs. The authors adjusted for all the baseline characteristics, such as age, sex, socioeconomic status, duration of and hospitalization history for COPD, and number of physician or emergency room visits within the previous year.

The primary outcome occurred in 5594 (64.2%) of patients receiving the LABA-ICS combination, including 5010 (57.5%) who died or were hospitalized for COPD within 5 years. Of the patients using LABA alone, the primary outcome occurred in 2129 (67.4%), including 1933 (61.2%) within 5 years. Use of the combination therapy was associated with a hazard ratio of 0.92 (95% confidence interval [CI], 0.88 - 0.96) for the primary outcome compared with people taking LABAs alone (P < .001). The hazard ratio for death associated with combination therapy was 0.92 (95% CI, 0.87 - 0.97; P < .001) compared with LABAs only, and for hospitalization for COPD, it was 0.91 (95% CI, 0.85 - 0.98; P = .01). There were no significant differences in secondary outcomes.

In the subset of patients with asthma, use of the LABA-ICS combination was associated with a hazard ratio of 0.84 (95% CI, 0.77 - 0.91) for primary outcomes compared with LABAs alone (P < .001). Similarly, combination therapy for patients with asthma who did not take LAAs was associated with a hazard ratio of 0.79 (95% CI, 0.73 - 0.86; P < .001) compared with LABAs alone. Receipt of LAAs was not associated with any significant differences between the groups.

These data represent important findings from a real-world clinical setting, Peter M.A. Calverley, MBChB, DSc, writes in an accompanying editorial. Randomized clinical trials (RCTs) "provide evidence that a drug works in a specific patient population, [but] what happens when treatment is used in the general patient population seen in daily practice remains uncertain."

Dr. Calverley, from the Institute of Ageing and Chronic Disease, University of Liverpool, United Kingdom, adds that "[l]arge administrative health care databases, statistical methods needed to interrogate these complex data sets, and, in some countries like Canada, comprehensive health care provision that reduces confounding due to socioeconomic treatment choices all provide the opportunity to study the effect of clinicians' prescribing choices."

The data presented in this study suggest that the overlap of asthma and COPD "is a common clinical problem among older COPD patients and merits treatment with a LABA-ICS combination. Conversely, patients without an asthma history taking a long-acting antimuscarinic agent may not benefit from ICS use," Dr. Calverley writes.

However, the study's most significant feature may be the validation of data obtained in RCTs in this broader "real-world" population, Dr. Calverley notes. The outcomes may have a bit better than those seen in RCTs, "but the patients were also much more diverse and often sicker." These data show "that findings from appropriately conducted database analyses complement data from RCTs and should be considered when determining treatment algorithms."

The authors have disclosed no relevant financial relationships. Dr. Calverley reports board membership for GlaxoSmithKline, Boehringer Ingelheim, Takeda, and the UK Department of Health Respiratory Programme Board; lecture/speaker fees from Novartis, GlaxoSmithKline, Boehringer Ingelheim, and AstraZeneca; and travel reimbursement from Boehringer Ingelheim.

JAMA. 2014;312:1101-1102, 1114-1121. Article abstract, Editorial extract

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