Real-World Data on COPD Combo Inhalers Favor LAMA-LABAs

Chronic obstructive pulmonary disease (COPD) patients starting on a combination maintenance inhaler had better outcomes if they were prescribed one containing a long-acting muscarinic antagonist and long-acting beta-agonist (LAMA-LABA), a large study of claims data suggested.

In a propensity score-matched analysis involving over 60,000 COPD patients, the group initially prescribed LAMA-LABA inhalers had an 8% reduction in the rate of first moderate or severe exacerbation compared with those started on an inhaled corticosteroid (ICS) plus LABA inhaler (HR 0.92, 95% CI 0.89-0.96), reported researchers led by William Feldman, MD, DPhil, MPH, of Brigham and Women's Hospital in Boston.

LAMA-LABA therapy was also associated with a 20% reduction in first pneumonia hospitalization rates (HR 0.80, 95% CI 0.75-0.86), a finding that was consistent across prespecified subgroup and sensitivity analyses, according to their findings in JAMA Internal Medicine.

Guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommend LAMA-LABA inhalers as combination therapy for COPD, though randomized trials have offered up conflicting evidence, the researchers noted.

The IMPACT and ETHOS trials, for example, showed lower COPD exacerbation rates with ICS-LABA inhalers, despite more cases of pneumonia. Results of FLAME, meanwhile, were more in line with the current study, demonstrating a 22% reduction in the rate of first moderate or severe exacerbation with LAMA-LABA therapy.

"Patients in our study appear to have substantially lower baseline risk than in all three of the other trials," Feldman and co-authors wrote in their discussion.

"Because physicians frequently prescribe inhalers to patients who would not meet entry criteria for inclusion in COPD trials, the relative effectiveness of LAMA-LABA therapy compared with ICS-LABA therapy may differ in routine clinical practice," they continued. "Our study should not be interpreted as a decisive verdict on the conflicting clinical trial data in FLAME, IMPACT, and ETHOS, but rather as one piece of additional evidence to help shape clinical guidelines."

Feldman's group pointed out that caution must be applied given the different study populations as well. Participants in those three trials had spirometry and a moderate to severe exacerbation in the prior year as a requirement for enrollment, while in the current cohort fewer than half had spirometry and only one-third had a moderate or severe exacerbation in the prior year. Other differences included that few in the cohort had received prior maintenance inhaler therapy.

For their study, the researchers looked at a total of 137,833 COPD patients in Optum's Clinformatics Data Mart who from 2014 to 2019 received a prescription for a first combination inhaler. Of these, 30,829 were LAMA-LABA and 107,004 were ICS-LABA inhalers. Each patient was followed for up to 1 year, until a therapy switch or discontinuation, or until death or end of insurance coverage.

Among the total eligible cohort, patients initiated on an ICS-LABA inhaler had more moderate or severe exacerbations and more pneumonia hospitalizations, and they were more likely to have GOLD stage E disease at baseline (16.7% vs 12.5% for the LAMA-LABA group). Women were more commonly prescribed ICS-LABAs than men.

Patients prescribed LAMA-LABAs were more likely to have spirometry measurements at baseline than those prescribed ICS-LABAs (50.2% vs 30.7%) and were more likely to have received an index prescription from a pulmonologist (11.4% vs 4.5%).

After propensity-score matching, the 30,216 matched pairs were well-balanced: patients had an average age of 70 years and were evenly split between men and women. Common comorbidities included hypertension in 78%, coronary heart disease in 36%, diabetes in 31%, and gastroesophageal reflux disease and peripheral vascular disease in about 29%, among a host of other conditions. At baseline, 9.6% had a moderate or severe exacerbation in the prior 30 days.

Incidence of first moderate or severe exacerbation events was 320.6 per 1,000 person-years for the LAMA-LABA group and 363.6 per 1,000 person-years for the ICS-LABA group. For pneumonia hospitalizations, incidence rates were 82.1 versus 104.0 per 1,000 person-years, respectively.

Looking at differences in the rate of first moderate and severe exacerbations separately, LAMA-LABA inhaler use was associated with a 7% reduction of a moderate exacerbation compared with ICS-LABA therapy (HR 0.93, 95% CI 0.90-0.97) and a 15% reduction of a severe exacerbation (HR 0.85, 95% CI 0.77-0.94).

Study limitations included the short follow-up timeframe, the reliance on prescription fills, and the fact that ICS-LABA patients tended to have a more severe COPD status at baseline and less access to specialty care, "which may have led to worse outcomes," despite all attempts to adjust for residual confounders, the researchers said.

Comment