COPD: Adherence, Persistence to Triple Therapy with Single vs Multiple Inhalers

multiple inhalers on a white background
multiple inhalers on a white background
COPD triple therapy adherence and persistence was assessed among patients using single-inhaler triple therapy vs those using multiple inhalers

In chronic obstructive pulmonary disease (COPD), once-daily, single-inhaler triple therapy improves medication adherence and persistence better than multiple-inhaler triple therapy (MITT), according to a recent study published in Respiratory Medicine. .

Although triple therapy — which consists of an inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting beta 2 agonist — is recommended for patients with COPD at risk of exacerbation, MITT is associated with poor adherence and persistence. Researchers therefore chose to assess the lesser known rates of adherence and persistence for single inhalers containing fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) by comparing rates among the 2 types of triple therapy for COPD.

The current study — a combined US/Canadian retrospective analysis of the IQVIA PharMetrics Plus claims database — involved 9942 individuals, including 2782 on single-inhaler FF/UMEC/VI and 7160 on MITT. Eligible patients were aged 40 years or older and had 12 months or more of continuous insurance coverage pre-index treatment and 6 or more months of coverage post-index treatment.

The researchers used inverse probability weighting to balance baseline characteristics. They assessed adherence using proportion of days covered (PDC) and evaluated risk ratios using linear and log-binomial models. Persistence was computed using Cox models; nonpersistence was defined as a gap of more than 30 days between prescription fills.

The investigators found adherence to be superior for FF/UMEC/VI compared with MITT users (mean PDC, 0.66 vs 0.48; P <.001). Single-inhaler triple therapy users were twice as likely to adhere to therapy (PDC ≥0.8) as MITT users (46.5% vs 22.3%; risk ratio 2.08; 95% CI, 1.85-2.30; P <.001). Single-inhaler triple therapy users also had a significantly higher PDC than MITT users at 12 months (mean [median], 0.60 [0.74] vs 0.40 [0.32]; P <.001).

In terms of persistence, FF/UMEC/VI users had a longer median duration of use (150 days) compared with  MITT users (60 days). After 12 months, many more FF/UMEC/VI users stayed on their medications than did MITT users (35.7% vs 13.9%, respectively; hazard ratio 1.91; 95% CI, 1.81-2.01; P <.001). During follow-up, fewer patients in the single-inhaler triple therapy cohort required other COPD medications (ie, short-acting beta-2 agonists, antibiotics, systemic corticosteroids, and leukotriene modifiers) than those in the MITT group.

Strengths of this study include the use of real-world data, a geographically diverse sample, a short time between patient contact and data availability, and the propensity score-weighted cohort design of the analysis. The study was limited by potentially inaccurate coding of COPD in the database; the unavailability of information on race, socioeconomic status, education, and smoking history; no guarantee that the patient took the medication as prescribed; and medications received during an inpatient stay not being captured in the database.

The finding that adherence and persistence to triple therapy was higher with MITT than with single-inhaler triple therapy has important clinical repercussions, said the investigators. “It has been suggested that proper adherence to therapy is key to improved prognosis in patients with COPD, with adherent patients having a lower risk of death and admission to hospital due to exacerbation,” the authors noted. “Persistence is an important indicator of patients’ long-term behavior and is key for controlling symptoms, reducing exacerbation risk, improving quality of life, and increasing survival rates,” they explained.

Disclosure: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Mannino D, Bogart M, Wu B, et al. Adherence and persistence to once-daily single-inhaler versus multiple-inhaler triple therapy among patients with chronic obstructive pulmonary disease in the USA: a real-world study. Respiratory Medicine. Published online March 18, 2022. doi:10.1016/j.rmed.2022.106807