Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.
Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.
In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.
Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.
The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.
The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.
Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
Findings clarify clinical practice guidelines
“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.
“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.
However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.
“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.
The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.
Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.