Using Multiple Long-Acting Inhalers Linked to Poor COPD Outcomes

Patients with COPD who used two or more long-acting inhalers had more exacerbations, worse adherence and persistence, and greater healthcare resource utilization and costs than patients who used a single long-acting inhaler.


VANCOUVER, Among patients with COPD, concomitant use of more than one long-acting inhaler is associated with a number of adverse outcomes, according to research presented at Chest 2010. Specifically, multiple-inhaler users experienced more COPD exacerbations, experienced their first exacerbation more quickly, were less persistent and adherent, and had greater utilization of and spending on healthcare resources than single-inhaler users during a one-year study period, even after controlling for proxies of disease severity.

Using a single cohort, Andrew P. Yu, PhD, of the Analysis Group Inc, Boston, and colleagues conducted three retrospective studies that compared the outcomes of COPD patients treated with multiple long-acting inhalers versus those treated with a single long-acting inhaler. A long-acting inhaler contains a long-acting 2-agonist (LABA), a long-acting muscarinic antagonist, an inhaled corticosteroid (ICS), or a fixed-dose combination of a LABA and an ICS.

One study focused on COPD exacerbations (defined as a medical claim with a COPD exacerbation diagnosis, a medical claim for hospitalization or an emergency department [ED] visit with a COPD diagnosis, or a prescription for an antibiotic or corticosteroid filled within a week after an outpatient visit with a COPD diagnosis). Another focused on persistence (time to a treatment gap of more than 30 days) and adherence (proportion of days covered [PDC] and dichotomized adherence). The third study focused on resource utilization (hospitalizations, ED visits, urgent care, and outpatient visits) and costs.

In all three studies, the researchers retrieved information on 23,494 patients, ages 40 and older, from the Thomson MarketScan Commercial Claims and Encounters and Medicare Supplemental Database. Half of the patients used multiple long-acting inhalers and half used a single long-acting inhaler. Pairs of patients from each treatment group were matched by age, sex, index year, COPD subtype, comorbidities, number of exacerbations during the six months before the study period, and prior COPD treatments.

Exacerbations

In the exacerbation study, after adjustment for confounding factors, multiple-inhaler users experienced significantly more exacerbations and shorter times to first exacerbation. During the study period, 46.4% of multiple-inhaler users and 36.5% of single-inhaler users experienced an exacerbation, and the mean number of exacerbations was 1.55 among multiple-inhaler users and 1.03 among single-inhaler users.

Multiple-inhaler use is associated with a greater risk of exacerbations than single-inhaler use, the researchers concluded. This may be partially explained by a complicated medication regimen. Simplified inhaler regimens may improve COPD outcomes.

Persistence and Adherence

In the persistence and adherence study, multiple-inhaler users were significantly more likely to discontinue their index treatment (hazard ratio, 1.40 after adjustment for confounding factors). Index treatments were discontinued by 86.7% of multiple-inhaler users and 78.6% of single-inhaler users. The association remained when the researchers looked only at patients who had well-controlled COPD (no exacerbations during the study period) and only at those who had poorly controlled disease (at least one exacerbation during the study period).

In addition, multiple-inhaler users were 34% less likely than single-inhaler users to adhere to their treatment. The PDC was 0.51 for multiple-inhaler users compared with 0.55 for single-inhaler users, and the rates of non-adherence were 79.2% among multiple-inhaler users compared with 71.5% among single-inhaler users. Single-inhaler users continued to show significantly higher adherence among patients with well-controlled disease (PDC was 10.1% higher for single-inhaler users) and among patients with poorly-controlled disease (PDC was 5.7% higher for single-inhaler users).

Reduced medication burden with long-acting inhalers may increase treatment adherence and reduce the risk of treatment discontinuation for COPD patients, the researchers stated.

Resource Utilization and Costs

The resource utilization and costs study estimated patients adjusted incidence rate ratios for resource use a negative binomial model and estimated their incremental costs using a generalized nonlinear model.

After adjustment for confounding factors, multiple-inhaler users had significantly more all-cause inpatient days, COPD-related inpatient days, inpatient admissions, outpatient visits, other medical service visits, and urgent care visits than single-inhaler users. In addition, multiple-inhaler users incurred higher costs, with incremental cost differences of $3,319 for all-cause healthcare, $1,586 for medical care, and $1,776 for pharmacy care.

Previous work has shown that multiple-inhaler use is associated with lower adherence than single-inhaler use, which may partially explain the increased healthcare resource utilization and costs for multiple healthcare users, the researchers concluded. Reducing the inhaler burden for COPD patients may reduce healthcare resource utilization and associated costs.