Inhaler Formulary Change in COPD and the Association with Exacerbations, Health Care Utilization, and Costs.

Rationale: Prescription formularies specify which medications are available to patients. Formularies change frequently, potentially forcing patients to switch medications for nonclinical indications (nonmedical switching). Nonmedical switching is known to impact disease control and adherence. The consequences of nonmedical switching have not been rigorously studied in COPD. Methods: We conducted a cohort study of Veterans with COPD on inhaler therapy in January 2016 when formoterol was removed from the Department of Veterans Affairs (VA) national formulary. A 2-point difference-in-differences analysis using multivariable negative binomial and generalized linear models was performed to estimate the association of the formulary change with patient outcomes in the 6 months before and after the change. Our primary outcome was the number of COPD exacerbations in 6 months, with secondary outcomes of total health care encounters and encounter-related costs in 6 months. Results: We identified 10,606 Veterans who met our inclusion criteria, of which 409 (3.9%) experienced nonmedical switching off formoterol. We did not identify a change in COPD exacerbations (-0.04 exacerbations; 95% confidence interval [CI] -0.12, 0.03) associated with the formulary change. In secondary outcome analysis, we did not observe a change in the number of health care encounters (-0.12 visits; 95% CI -1.00, 0.77) or encounter-related costs ($369; 95% CI -$1141, $1878). Conclusions: Among COPD patients on single inhaler therapy, nonmedical inhaler switches due to formulary discontinuation of formoterol were not associated with changes in COPD exacerbations, encounters, or encounter-related costs. Additional research is needed to confirm our findings in more severe disease and other settings.

Trends and Rural-Urban Differences in the Initial Prescription of Low-Value Inhaled Corticosteroids among U.S. Veterans with Chronic Obstructive Pulmonary Disease.

Rationale: Guidelines recommend inhaled corticosteroids (ICS) for patients with chronic obstructive pulmonary disease (COPD) and select indications, including asthma history, high exacerbation risk, or high serum eosinophils. ICS are commonly prescribed outside of these indications, despite evidence of harm. We defined a "low-value" ICS prescription as the receipt of an ICS without evidence of a guideline-recommended indication. ICS prescription patterns are not well characterized and could inform health system interventions to reduce low-value practices. Objectives: To evaluate the national trends in initial low-value ICS prescriptions in the U.S. Department of Veterans Affairs and to determine whether rural-urban differences in low-value ICS prescribing exist. Methods: We performed a cross-sectional study between January 4, 2010, and December 31, 2018, identifying veterans with COPD who were new users of inhaler therapy. We defined low-value ICS as prescriptions in patients with 1) no asthma, 2) low risk of future exacerbation (Global Initiative for Chronic Obstructive Lung Disease group A or B), and 3) serum eosinophils <300 cells/µl. We performed multivariable logistic regression to evaluate trends in low-value ICS prescription over time, adjusting for potential confounders. We performed fixed effects logistic regression to assess rural-urban prescribing patterns. Results: We identified a total of 131,009 veterans with COPD starting inhaler therapy, 57,472 (44%) of whom were prescribed low-value ICS as initial therapy. From 2010 to 2018, the probability of receiving low-value ICS as initial therapy increased by 0.42 percentage points per year (95% confidence interval, 0.31-0.53). Compared with urban residence, rural residence was associated with a 2.5-percentage-point (95% confidence interval, 1.9-3.1) higher probability of receiving low-value ICS as initial therapy. Conclusions: The prescription of low-value ICS as initial therapy is common and increasing slightly over time for both rural and urban veterans. Given the widespread and persistent nature of low-value ICS prescribing, health system leaders should consider system-wide approaches to address this low-value prescribing practice.

Low-Value Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease and the Association with Healthcare Utilization and Costs.

Rationale: Inhaled corticosteroids (ICS) are not first-line therapy for patients with chronic obstructive pulmonary disease (COPD) at low risk of exacerbations, but they are commonly prescribed despite evidence of harm. We consider ICS prescription in this population to be of "low value." The association of low-value ICS with subsequent healthcare utilization and costs is unknown. Understanding this relationship could inform efforts to reduce the delivery of low-value care. Objectives: To determine whether low-value ICS prescribing is associated with higher outpatient healthcare utilization and costs among patients with COPD who are at low risk of exacerbation. Methods: We performed a cohort study between January 1, 2010, and December 31, 2018, identifying a cohort of veterans with COPD who performed pulmonary function tests (PFTs) at 21 Veterans Affairs medical centers nationwide. Patients were defined as having low exacerbation risk if they experienced less than two outpatient exacerbations and no hospital admissions for COPD in the year before PFTs. Our primary exposure was the receipt of an ICS prescription in the 3 months before the date of PFTs. Our primary outcomes were outpatient utilization and outpatient costs in the 1 year after PFTs. For inference, we generated negative binomial models for utilization and generalized linear models for costs, adjusting for confounders. Results: We identified a total of 31,551 patients with COPD who were at low risk of exacerbation. Of these patients, 9,742 were prescribed low-value ICS (mean [standard deviation (SD)] age, 69 [9] yr), and 21,809 were not prescribed low-value ICS (mean [SD] age, 68 [9] yr). Compared with unexposed patients, those exposed to low-value ICS had 0.53 more encounters per patient per year (95% confidence interval CI, 0.23-0.83) and incurred $154.72 higher costs/patient/year (95% CI, $45.58-$263.86). Conclusions: Low-value ICS prescription was associated with higher subsequent outpatient healthcare utilization and costs. Potential mechanisms for the observed association are that 1) low-value ICS may be a marker of poor respiratory symptom control, 2) there is confounding by indication, or 3) low-value ICS results in increased drug costs or utilization. Health systems should identify low-value ICS prescriptions as a target to improve value-based care.

Association of Guideline-Recommended COPD Inhaler Regimens With Mortality, Respiratory Exacerbations, and Quality of Life: A Secondary Analysis of the Long-Term Oxygen Treatment Trial.

BACKGROUND: Although inhaled therapy reduces exacerbations among patients with COPD, the effectiveness of providing inhaled treatment per risk stratification models remains unclear. RESEARCH QUESTION: Are inhaled regimens that align with the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy associated with clinically important outcomes? STUDY DESIGN AND METHODS: We conducted secondary analyses of Long-term Oxygen Treatment Trial (LOTT) data. The trial enrolled patients with COPD with moderate resting or exertional hypoxemia between 2009 and 2015. Our exposure was the patient-reported inhaled regimen at enrollment, categorized as either aligning with, undertreating, or potentially overtreating per the 2017 GOLD strategy. Our primary composite outcome was time to death or first hospitalization for COPD. Additional outcomes included individual components of the composite outcome and time to first exacerbation. We generated multivariable Cox proportional hazard models across strata of GOLD-predicted exacerbation risk (high vs low) to estimate between-group hazard ratios for time to event outcomes. We adjusted models a priori for potential confounders, clustered by site. RESULTS: The trial enrolled 738 patients (73.4% men; mean age, 68.8 years). Of the patients, 571 (77.4%) were low risk for future exacerbations. Of the patients, 233 (31.6%) reported regimens aligning with GOLD recommendations; most regimens (54.1%) potentially overtreated. During a 2.3-year median follow-up, 332 patients (44.9%) experienced the composite outcome. We found no difference in time to composite outcome or death among patients reporting regimens aligning with recommendations compared with undertreated patients. Among patients at low risk, potential overtreatment was associated with higher exacerbation risk (hazard ratio, 1.42; 95% CI, 1.09-1.87), whereas inhaled corticosteroid treatment was associated with 64% higher risk of pneumonia (incidence rate ratio, 1.64; 95% CI, 1.01-2.66). INTERPRETATION: Among patients with COPD with moderate hypoxemia, we found no difference in clinical outcomes between inhaled regimens aligning with the 2017 GOLD strategy compared with those that were undertreated. These findings suggest the need to reevaluate the effectiveness of risk stratification model-based inhaled treatment strategies.