Chronic Obstructive Pulmonary Disease Maintenance Medication Research Articles

Prediction of treatment nonadherence among older adults with chronic obstructive pulmonary disease using Medicare real-world data.

BACKGROUND: Suboptimal maintenance medication (MM) adherence remains a clinical problem among Medicare beneficiaries with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To inform risk-based personalized decision-making, this study sought to develop and validate prediction models of nonadherence to COPD MMs for Medicare beneficiaries. METHODS: This was a retrospective cohort study of beneficiaries aged 65 years and older with COPD and inhaled MMs. Nonadherence (proportion of days covered < 0.8) was measured in 12 months following the first MM fill after COPD diagnosis. Logistic and least absolute shrinkage selector operator regressions were implemented, and area under the receiver operating characteristic curve (AUROC) evaluated model accuracy, as well as positive predictive values and negative predictive values. Our models evaluated different sets of predictors for two cohorts: those with an MM prescription before COPD diagnosis (prevalent users) and those without (new users). RESULTS: Among 16,157 prevalent and 40,279 new users of MMs, 11,271 (69.8%) and 34,009 (84.4%), respectively, were nonadherent. The best-performing logistic models achieved AUROCs of 0.8714 and 0.881, positive predictive values of 0.881 and 0.881, and negative predictive values of 0.559 and 0.578, respectively, for prevalent and new users. The least absolute shrinkage selector operator models had similar accuracy. Models with baseline-only predictors had average performance (AUROC < 0.72). The most important predictors were initial MM adherence, short-acting bronchodilator use, and asthma. CONCLUSIONS: To our knowledge, this study is the first to develop predictive models of nonadherence to COPD MMs. Generated models achieved good discrimination and underlined the importance of early adherence. Well-performed models can be useful for care decision-making and interventions to improve COPD medication adherence after the first critical few months following a treatment episode. DISCLOSURES: All authors declared no conflicts of interest.

Treatment Patterns for Chronic Obstructive Pulmonary Disease (COPD) in the United States: Results from an Observational Cross-Sectional Physician and Patient Survey.

PurposeThere is a high prevalence of chronic obstructive pulmonary disease (COPD) in the United States (US). Although guidelines are available for the treatment of COPD, evidence suggests that management of COPD in clinical practice is not always aligned with this guidance. This study aimed to further understand the current use of COPD maintenance medication in the US.Patients and MethodsThis study was an analysis of data from the Adelphi Respiratory Disease Specific Programme (DSP™) 2019. Point-in-time data were collected from participating US physicians and their COPD patients. Physicians were either primary care physicians (PCPs) or pulmonologists, with a minimum workload of ≥3 COPD patients per month. Patients were aged ≥18 years with a physician-confirmed diagnosis of COPD.ResultsIn total, 171 physicians completed the survey (92 PCPs and 79 pulmonologists). Mean patient age was 66.4 years, 45% were female, with moderate COPD in 49.4% of patients and severe/very severe in 19.3%. Pulmonologists more frequently prescribed dual bronchodilation and triple therapy than PCPs, whereas inhaled corticosteroid/long-acting β2-agonist was more frequently prescribed by PCPs than pulmonologists. For both physician types, the most common reason for prescribing their patients’ current treatment was 24-hour symptom relief. The majority of PCPs (70.1%) and pulmonologists (71.9%) reported referring to COPD guidelines when making treatment decisions.ConclusionPrescribing patterns for COPD patients were found to differ between PCPs and pulmonologists. Improved physician understanding of how to tailor treatment for each patient, based on current symptoms and exacerbation risk, could help optimize patient care in COPD.

Concordance between reported medication taking behavior and prescription instructions for patients with chronic obstructive pulmonary disease visiting community pharmacies

BackgroundUnderstanding types and frequency of medication taking discrepancies could help design pharmacist interventions to improve adherence, outcomes, and prescribing. ObjectiveThis study aimed to assess concordance between participants' descriptions of chronic obstructive pulmonary disease (COPD) medication taking behaviors and prescription instructions. MethodsContinued analysis of previously collected data. Dispensing data from 35 community pharmacies identified participants at the age of ≥ 40 years, with ≥ 1 COPD maintenance medication in the past year and self-reported COPD. Participants completed a survey of demographics, corticosteroid/antibiotic drug use, and symptom scores. Participants listed each medication and described medication taking behavior. COPD severity was classified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) ABCD categories from exacerbation history and symptoms. Aggregate proportion days covered (PDC) for any 1 maintenance medicine was calculated using 12-month dispensing data. Discrepancies between medication taking and instructions were classified: (1) overuse, (2) underuse, or (3) discontinued by participant (without prescriber knowledge). Descriptive statistics summarized survey results. Chi-square compared discrepancies among long-acting bronchodilators (LABDs), inhaled corticosteroids (ICS), and short-acting bronchodilators (SABDs). ResultsMost participants (N = 709; 27.6% urban, 70.5% rural) were highly symptomatic (GOLD groups B/D = 89.9%) and high risk (groups C/D = 59.2%). Median medication number was 4. Concordance of ICS and LABD taking behavior with prescriber instructions was 80.6% and 81.8%, respectively (P > 0.05). PDC averaged 0.46 ± 0.37; only 28.7% were adherent (i.e., PDC ≥ 0.80). ICS underuse (11.8%) exceeded LABD (5.5%). LABD discontinuation (7.4%) exceeded ICS (2.7%) or SABD (0.6%). SABD overuse (9.3%) exceeded ICS (3.4%) or LABD (4.3%) (P < 0.5 all comparisons). ConclusionAlthough most were highly symptomatic, high risk, and frequently described correct medication taking behavior, overall adherence was very low. Discrepancies included overuse, underuse, and self-discontinuation. Nonadherence and medication taking discrepancies may increase symptoms, exacerbations, and additional medication prescribing. Potential pharmacist strategies include regularly assessing adherence and differentiating intentional versus nonintentional nonadherence to identify and implement patient-specific interventions to encourage medication taking as prescribed.

PRS36 Use of Logistic Lasso Regression to Predict Treatment Adherence Among Medicare Beneficiaries with COPD

Adherence to maintenance medications (MMs) remains an issue that is linked to adverse outcomes in older adults with chronic obstructive pulmonary disease (COPD). Prediction studies may identify individuals with future low adherence in order to inform necessary interventions. The objective of this study is to develop and validate predictive models of adherence to inhaled COPD MMs.

Effect of compliance with GOLD treatment recommendations on COPD health care resource utilization, cost, and exacerbations among patients with COPD on maintenance therapy.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report for the management of chronic obstructive pulmonary disease (COPD) focuses on reducing existing symptoms, decreasing the risk of future exacerbations, and improving health status by recommending specific drug therapy based on exacerbation risk and symptoms. However, disparities exist between evidence-based recommendations and clinical practice. Research that quantifies the real-world effect of COPD regimen alignment with the GOLD recommendations on clinical and economic outcomes is needed. OBJECTIVE: To compare COPD-related health care resource utilization (HRU) and costs, as well as exacerbation rates, among patients with COPD on maintenance therapy based on 2017 GOLD treatment recommendation compliance status per GOLD ABCD risk group classification in a U.S. commercially insured/Medicare Advantage population. METHODS: This retrospective cohort study utilized administrative claims data in the HealthCore Integrated Research Database. The COPD population was identified using a previously validated claims-based predictive model. Among this population, patients with ≥ 1 claim for a COPD maintenance medication (earliest maintenance fill-date = index date) between January 1, 2014, and March 31, 2017, were identified. Patients were required to be aged ≥ 40 years, have ≥ 12 months of pre-index and ≥ 30 days of post-index health plan enrollment, with no diagnosis for asthma, cystic fibrosis, and/or lung cancer at any time from January 1, 2013, to March 31, 2018. Patients were categorized into exacerbation risk/symptomatology groups according to the 2017 GOLD ABCD assessment recommendations and were then classified into treatment-compliance status based on their maintenance therapy. Multivariable analyses were conducted to examine post-index COPD-related HRU, costs, and exacerbations by compliance status. RESULTS: The primary analytical study sample included 38,382 patients in the GOLD A/B group and 6,525 in the GOLD C/D group. Patients were further categorized into GOLD A (n = 19,345), B (n = 19,037), C (n = 1,865), and D (n = 4,670). GOLD-compliant regimens were observed in 32.9% of patients in the GOLD A/B group and in 58.9% of patients in the GOLD C/D group. Inhaled corticosteroid-containing regimens were the most commonly observed noncompliant regimen. Patients on compliant regimens had significantly fewer COPD-related inpatient and emergency department visits and therefore had significantly lower COPD-related medical costs in both the GOLD A/B and C/D cohorts. Similar results were observed for individual GOLD cohorts B, C, and D. These savings were offset by increased pharmacy expenditures. Being on GOLD guideline-compliant regimens significantly reduced the risk of exacerbation by 8% (hazard ratio [HR] = 0.92; P < 0.0001) in the GOLD A/B cohort and by 12% (HR = 0.88; P = 0.0005) in the GOLD C/D cohort, and was also associated with a significantly reduced exacerbation rate in the GOLD A/B (rate ratio [RR] = 0.93; P < 0.0001) and GOLD C/D (RR = 0.93; P = 0.0129) groups. CONCLUSIONS: This study suggests a continuing trend of high prevalence of suboptimal prescriber compliance to GOLD treatment recommendations. Treatment regimens compliant with GOLD recommendations were associated with improvement in exacerbations, reduced COPD-related HRU, and COPD-related medical cost offsets. DISCLOSURES: This study was funded by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI). BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations. Palli and Shaikh are employees of BIPI. Willey is an employee of HealthCore, which was contracted by BIPI to conduct this study. Zhou was an employee of HealthCore at the time of study execution. Data were presented in part during an AMCP webinar (recording not made public) held in lieu of the Spring 2020 AMCP conference, which was canceled due to the COVID-19 pandemic.

Consistency of chronic obstructive pulmonary disease regimens for patients visiting community pharmacies with the Global Initiative for Chronic Obstructive Lung Disease recommendations

ObjectiveDespite evidence-based Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations, outcomes are poor. GOLD uses chronic obstructive pulmonary disease (COPD) assessment test (CAT) scores with exacerbation history to categorize COPD severity into A, B, C, and D severity groups. Therapy is group-specific; monotherapy/dual long-acting bronchodilators (LABDs) therapy is preferred to inhaled corticosteroids (ICS). Pharmacist-accessible data could be used to identify evidence-based interventions to improve outcomes. The primary objective was to analyze previously collected data to compare the consistency of patient-described COPD regimens with GOLD therapeutic recommendations to identify potential pharmacist interventions. MethodsCross-sectional, nonrandomized design using a written questionnaire and CAT scores. Dispensing data from 35 Missouri community pharmacies initially identified participants aged 40 years or older with 1 or more COPD medications dispensed in the past year. Those self-reporting COPD, emphysema, or chronic bronchitis completed a demographic survey with medication history, including oral corticosteroid and antibiotic use, and CAT scores. Proportion of days covered (PDC) was calculated for any COPD maintenance medication dispensed over 1 year. The participants’ COPD was categorized into A, B, C, and D severity groups. The reported medication regimens were categorized into consistent with, escalated from, or less than initial first-line/alternative recommended therapy for the A, B, C, and D severity groups. ResultsThe participants totaled 709 (group A: 6%; group B: 35%; group C: 4%; group D: 55%). Of the regimens, 41% were consistent with, 34% were escalated from, and 24% were less than initial first-line/alternative GOLD recommendations. Most (96%) of the participants were highly symptomatic. Regimens containing ICS: (67.5%); ICS plus LABD (37.2%) exceeded dual LABD (4.2%). The average PDC was 0.43 ± 0.37; only 28.7% were adherent (PDC ≥ 0.80). ConclusionsParticipants with self-reported COPD were highly symptomatic and nonadherent; undertreatment was noted. Community pharmacists could provide therapeutic interventions consistent with GOLD A, B, C, and D severity groups, promote dual LABD versus ICS therapies, and optimize adherence.

Initiation of triple therapy maintenance treatment among patients with COPD.

Triple therapy is indicated for patients with very severe chronic obstructive pulmonary disease (COPD). Use of this treatment in the appropriate patient population is important to ensure optimal outcomes. This study quantified the use of triple therapy and assessed concordance with 2013-2016 Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations within a national health plan. Retrospective cohort study using data from a large national health plan. To estimate the prevalence of triple therapy using claims data, patients in the first of 2 cohorts were indexed on their first diagnosis of COPD between January 1, 2012, and December 31, 2014, and required to have 24 months postindex continuous enrollment. To assess concordance with GOLD recommendations, a second cohort was created and indexed on the date of triple therapy initiation between January 1, 2013, and November 30, 2016, and required to have 12 months preindex and 1 month postindex continuous enrollment. For both cohorts, patients were aged 40 years or older, with no International Classification of Diseases code for asthma, cystic fibrosis, or lung cancer during the study period. In the first cohort of 92,248 patients with COPD receiving any COPD maintenance medication, 17% were prescribed triple therapy. In the second cohort (n = 19,645), the majority (60%) of patients on triple therapy were classified as GOLD group A or B (ie, no evidence of any exacerbation or only 1 exacerbation not resulting in hospitalization at baseline). Results showed that triple therapy was often prescribed among patients classified as GOLD group A or B. Additional research is required, however, to further assess whether these patients may have had an exacerbation that was not evident in claims data. Treatment of COPD should be individualized to optimize outcomes and reduce adverse events.

Assessment of symptom burden and adherence to respiratory medications in individuals self-reporting a diagnosis of COPD within a community pharmacy setting

ObjectivesData on symptom burden or medication adherence in patients with chronic obstructive pulmonary disease (COPD) within a community pharmacy setting are limited. This study assessed symptom burden and adherence to respiratory medications in individuals reporting COPD, chronic bronchitis, or emphysema diagnoses visiting community pharmacies. DesignThis cross-sectional study enrolled participants visiting 35 community pharmacies in Missouri (October 2016 to April 2017). ParticipantsEligible participants (aged 40 years or more with a self-reported history of COPD, prescription for at least 1 COPD maintenance medication during the previous 12 months, and able to complete an English questionnaire) were identified from pharmacy dispensing records. Main outcome measuresParticipants completed a questionnaire assessing demographics, clinical characteristics, health literacy, COPD Assessment Test (CAT) modified Medical Research Council (mMRC) dyspnea scale scores, and exacerbation history. Recent spirometry data were obtained, if available, from participants’ physicians. COPD was classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016 criteria. Medication adherence was assessed as proportion of days covered (PDC) from dispensing records. ResultsOf 682 participants (mean age 63.0 years; 57% female) with available pharmacy data, 251 (36.8%) had available spirometry data. Most participants had mMRC scores ≥ 2 (60.9%) and CAT scores ≥ 10 (90.2%); 57.2% reported at least 2 moderate or 1 or more severe exacerbations within the previous 12 months. GOLD classifications varied depending on the scale used (mMRC vs. CAT); more participants were classified as group C/D than group A/B, with the highest proportion classified as group D (higher symptom burden and exacerbation risk). Mean PDC was 0.46 ± 0.37; only 28.7% of participants were adherent (PDC ≥ 80%) to at least 1 COPD maintenance medication. ConclusionIndividuals self-reporting a COPD diagnosis receiving respiratory medications from community pharmacies in Missouri have a high symptom burden and low medication adherence. Further research should determine reasons for low adherence and ways to reduce COPD symptoms.

Health Care Resource Utilization and Exacerbation Rates in Patients with COPD Stratified by Disease Severity in a Commercially Insured Population.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality and is associated with substantial economic burden. There is a lack of data regarding COPD outcomes and costs in a real-world setting, particularly by Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity. To (a) characterize a commercially insured U.S. population with COPD and (b) assess prevalence of exacerbations, health care resource utilization (HCRU), costs, and treatment patterns in a cohort of patients with confirmed COPD, overall and stratified by GOLD stage. This retrospective observational cohort study used administrative claims data from the HealthCore Integrated Research Database to identify patients with ≥ 1 inpatient, emergency room (ER), or office visit claim for COPD between January 1, 2012, and November 30, 2013, and continuous enrollment for 1 year before and 2 years after the first COPD diagnosis date. Patients with a spirometry claim within 12 months were eligible for medical record abstraction to confirm COPD diagnosis (forced expiratory volume in 1 second [FEV1]/forced vital capacity ratio < 0.7) and GOLD 1-4 classification (based on postbronchodilator FEV1 percent predicted). HCRU, costs, treatment patterns, and rate of moderate/severe exacerbation were identified from diagnosis up to 24 months. Outcomes were analyzed by univariate analysis stratified by GOLD classification. Multivariable analysis was conducted to assess associations between GOLD classification and outcomes of interest. 53,484 patients newly diagnosed with COPD were identified who met initial inclusion criteria: 14,293 (27%) had a qualifying spirometry claim, and 1,505 had confirmed COPD (GOLD 1, 333 [22%]; GOLD 2, 823 [55%]; GOLD 3, 317 [21%]; GOLD 4, 32 [2%]). Patients with greater disease severity had higher rates of moderate/severe COPD exacerbations (GOLD 1 and 2, 40.4 and 48.9 per 100 person-years, respectively; GOLD 3 and 4, 83.6 and 89.1 per 100 person-years, respectively). All-cause and COPD-related inpatient admissions, COPD-related office visits, and COPD-related ER visits were more prevalent with more severe GOLD classification. Mean annual COPD-related medical costs increased with GOLD classification ($5,945 for GOLD 1 patients, $18,070 for GOLD 4). COPD maintenance medication was filled by 42%, 56%, 73%, and 75% of patients in GOLD 1-4 (57% overall), respectively; combination corticosteroid/long-acting beta2-agonist inhalers were the most commonly used medication, regardless of GOLD classification. Patients with more severe disease had greater adherence (range 44%-68% of days covered for GOLD 1-4) and persistence (range 107-209 days for GOLD 1-4). Trends toward increases in exacerbations, HCRU, and costs were observed as airflow limitation worsened. Adherence and persistence with COPD maintenance therapy was suboptimal even with severe disease. This study was supported by Boehringer Ingelheim Pharmaceuticals (Ridgefield, CT), which was given the opportunity to review the manuscript for medical and scientific accuracy, as well as intellectual property considerations. Willey and Singer are employees of HealthCore (parent company Anthem), which received funding from Boehringer Ingelheim to complete this study. Wallace and Shinde were employed by HealthCore at the time of this study. Wallace and Singer report stock ownership in Anthem. Napier is an employee of Anthem. Kaila, Bayer, and Shaikh are employees of Boehringer Ingelheim Pharmaceuticsls. Portions of this research were presented at the following conferences: (a) A. Wallace, S. Kaila, V. Zubek, A. Shaikh, M. Shinde, V. Willey, M. Napier, and J. Singer, Healthcare resource utilization, costs, and exacerbation rates in patients with COPD stratified by GOLD airflow limitation classification in a US commercially insured population, presented at AMCP Nexus 2017; October 16-19, 2017; Dallas, TX; and (b) A.E. Wallace, V. Zubek, S. Kaila, A. Shaikh, M. Shinde, V. Willey, M.B. Napier, and J.R. Singer, Real-world treatment patterns among newly diagnosed COPD patients according to GOLD airflow limitation severity classification in a U.S. commercially insured/Medicare Advantage population, presented at CHEST 2017 Annual Meeting; October 28-November 1, 2017; Toronto, Ontario, Canada.

GOLD 2017 treatment pathways in 'real life': An analysis of the DACCORD observational study.

The 2017 update to the Global Initiative for Obstructive Lung Disease (GOLD) strategy document includes recommendations for treatment intensification or step-down in chronic obstructive pulmonary disease (COPD), although recognises that limited supporting information is available. DACCORD is an ongoing observational, non-interventional study, recruiting patients following COPD maintenance treatment change or initiation, a subset of whom were receiving a long-acting β2-agonist (LABA) plus a long-acting muscarinic antagonist (LAMA) fixed-dose combination (FDC) on entry. Since there were no requirements in terms of prior medication (and no washout before commencing LABA/LAMA FDC), this provides an opportunity to generate 'real world' data to test the GOLD 2017 recommendations. To reduce heterogeneity, the current analyses include patients receiving indacaterol/glycopyrronium at baseline, and who, prior to the study, were receiving no COPD maintenance medication ('none'), LABA or LAMA monotherapy ('mono'), LABA plus inhaled corticosteroid (ICS; 'LABA/ICS'), or triple therapy ('triple'). At the baseline visit, data collected included: demographic and disease characteristics; COPD Assessment Test (CAT); and exacerbations in the 6 months prior to entry. At 3, 6, 9 and 12 months data on exacerbations were collected, with CAT recorded at 3 and 12 months. A total of 2724 patients were included in the baseline analyses: 795, 954, 598 and 377 in the 'none', 'mono', 'LABA/ICS' and 'triple' subgroups, respectively. There were no clinically relevant differences in baseline demographics between the four groups. In terms of disease characteristics, the 'triple' group had the highest proportion of patients with a disease duration of more than 1 year since diagnosis and with severe/very severe airflow limitation, but a similar percentage of non-exacerbators compared to the 'none' group. Over the 1-year follow-up, the majority of patients in all four subgroups did not exacerbate (exacerbation rates 0.16, 0.19, 0.21, and 0.26 in the 'none', 'mono', 'LABA/ICS' and 'triple' groups, respectively). At 12 months, 61.4%, 65.0%, 71.0% and 52.4% of patients had a clinically relevant improvement in CAT score. Overall, the results support the GOLD recommendations in suggesting that a switch from a mono-bronchodilator or LABA plus ICS to LABA/LAMA FDC is a valid treatment option for patients with COPD. The results also validate the use of a LABA/LAMA FDC as initial maintenance treatment for COPD, and provide first 'real world' evidence to support the newly added 'step down' recommendation (from triple to LABA/LAMA FDC).

Adherence and healthcare utilization among older adults with COPD and depression

Background and objectiveAdherence to chronic obstructive pulmonary disease (COPD) maintenance medications and antidepressants may reduce healthcare utilization among multimorbid individuals with COPD and depression. We quantified the independent effects of adherence to antidepressants and COPD maintenance medications on healthcare utilization among individuals co-diagnosed with COPD and depression. ProceduresWe conducted a retrospective cohort study using a 2006–2012 5% random sample of Medicare beneficiaries co-diagnosed with COPD and depression who had two or more prescription fills of both COPD maintenance medications and antidepressants. We measured adherence to medications using the proportion of days covered per 30-day period. The primary outcomes were all-cause emergency department (ED) visits and hospitalizations. Beneficiaries were followed over a minimum 12-month follow-up period. ResultsOf the 16,075 beneficiaries meeting inclusion criteria, 21% achieved adherence ≥80% to COPD maintenance medications and 55% achieved adherence ≥80% to antidepressants. Compared to no use and controlling for antidepressant adherence and potential confounders, higher (≥80%) levels of adherence to COPD maintenance medications were associated with decreased risk of ED visits (hazard ratio (HR) 0.79; 95% CI 0.74, 0.83) and hospitalizations (HR 0.82; 95% CI 0.78, 0.87). Similarly, higher levels (≥80%) of adherence to antidepressants resulted in decreased risk of ED visits (HR 0.74; 95% CI 0.70, 0.78) and hospitalizations (HR 0.77; 95% CI 0.73, 0.81) compared to no use. ConclusionsClinicians can assist in the improved management of their multimorbid patients' health by treating depression among patients with COPD and monitoring and encouraging adherence to the regimens they prescribe.

A two-year evaluation of the ‘real life’ impact of COPD on patients in Germany: The DACCORD observational study

IntroductionDACCORD is an observational, non-interventional study being conducted in German primary and secondary care centres. The study aims to describe the impact of disease (including exacerbations) and treatments over 2 years on ‘real-life’ patients with chronic obstructive pulmonary disease (COPD). Materials and methodsPatients had a clinical and spirometry diagnosis of COPD, were aged ≥40 years and, on recruitment, were initiating or changing COPD maintenance medication. The only exclusion criteria were asthma and randomised clinical trial participation. Exacerbations data were collected every 3 months. COPD medication, COPD Assessment Test (CAT) and forced expiratory volume in 1 s (FEV1) were recorded at baseline and after 1 and 2 years. ResultsA total of 6122 patients were recruited, 3137 (51.2%) of whom completed the 2-year visit. The mean age of these patients was 65.6 years, 59% were male, 69% had mild or moderate airflow limitation, and their mean COPD Assessment Test (CAT) total score was 20.3. Overall, there was a trend towards decreasing COPD exacerbation rates over the 2-year follow-up period, with rates of 0.390 during Year 1 and 0.347 during Year 2. Rates were lower in patients with no exacerbation during the 6 months prior to entry (0.263 and 0.251 during Years 1 and 2, respectively), with 51.6% of patients having no exacerbation during the 6 months prior to entry and over the 2-year follow-up. Approximately 50% of the overall population experienced a clinically relevant improvement from baseline in CAT total score at Year 1 and 2. When assessed by treatment class (or classes), persistence to medication was high (77.8% in Year 1 and 71.4% in Year 2). ConclusionsOverall, the 2-year follow-up data from DACCORD suggest that for most patients with COPD exacerbations are a rare event. For the majority of patients, the focus should be on managing symptoms, and the impact that these symptoms have on their daily lives. Even for those patients who do exacerbate, although prevention of exacerbations is an important factor, management of symptoms should be a key consideration. DACCORD also suggests that COPD disease progression is not inevitable – providing patients are receiving pharmacological treatment.

"Real-life" inhaled corticosteroid withdrawal in COPD: a subgroup analysis of DACCORD.

Many patients with chronic obstructive pulmonary disease (COPD) receive inhaled corticosteroids (ICSs) without a clear indication, and thus, the impact of ICS withdrawal on disease control is of great interest. DACCORD is a prospective, noninterventional 2-year study in the primary and secondary care throughout Germany. A subgroup of patients were taking ICS prior to entry – 1,022 patients continued to receive ICS for 2 years; physicians withdrew ICS on entry in 236 patients. Data from these two subgroups were analyzed to evaluate the impact of ICS withdrawal. Patients aged ≥40 years with COPD, initiating or changing COPD maintenance medication were recruited, excluding patients with asthma. Demographic and disease characteristics, prescribed COPD medication, COPD Assessment Test, exacerbations, and lung function were recorded. There were few differences in baseline characteristics; ICS withdrawn patients had shorter disease duration and better lung function, with 74.2% of ICS withdrawn patients not exacerbating, compared with 70.7% ICS-continued patients. During Year 1, exacerbation rates were 0.414 in the withdrawn group and 0.433 in the continued group. COPD Assessment Test total score improved from baseline in both groups. These data suggest that ICS withdrawal is possible with no increased risk of exacerbations in patients with COPD managed in the primary and secondary care.

Predictors of Appropriate Pharmacotherapy Management of COPD Exacerbations and Impact on 6-Month Readmission.

Suboptimal treatment of exacerbations is a major concern in management of chronic obstructive pulmonary disease (COPD). The Pharmacotherapy Management of COPD Exacerbation (PCE) Healthcare Effectiveness Data and Information Set (HEDIS) measure is a quality measure included by the National Committee for Quality Assurance that focuses on appropriate use of steroids and bronchodilators during an acute COPD exacerbation. There is limited evidence evaluating predictors of this quality measure, as well as its association with hospital readmission and cost outcomes. To (a) describe characteristics of patients hospitalized for COPD, (b) evaluate factors associated with appropriate receipt of pharmacotherapy upon discharge, and (c) evaluate factors associated with the rate of readmission. In this retrospective, observational, event-based study of COPD-related hospital and ED visits, events were identified between 2007 and 2013 from a Central Texas health plan using administrative claims data. The index date was defined as the date of admission. Subjects were included if they were aged ≥ 40 years and had a medical claim with a primary diagnosis for COPD or a pharmacy claim for a COPD maintenance medication during the 1-year pre-index period. Study groups were identified based on the receipt of PCE within the time frame specified by HEDIS: (a) a systemic corticosteroid within 14 days of discharge (PCE-C) or (b) a bronchodilator within 30 days of discharge (PCE-D). Bivariate analyses of potential factors associated with the receipt of PCE were performed using t-tests for continuous data and chi-square tests for categorical data. Generalized estimating equations, including significant predictors from the bivariate analyses, were used to determine factors associated with receipt of PCE-C and/or PCE-D, as well association with COPD-related and all-cause readmission within 6 months of discharge. Of 375 identified index admissions, 254 (68%) patients received PCE-C; 299 (80%) received PCE-D; and 229 (61%) received both. Patients were more likely to receive PCE with an index inpatient visit as compared with an ED visit (PCE-C: RR = 2.25, 95% CI = 1.21-4.17, P = 0.010; PCE-D: RR = 1.90, 95% CI = 1.01-3.58, P = 0.048). Those with previous use of rescue medication were also more likely to receive PCE (PCE-C: RR = 1.88, 95% CI = 1.12-3.17, P = 0.018; PCE-D: RR = 2.11, 95% CI = 1.16-3.83, P = 0.014). Patients with greater adherence (proportion of days covered [PDC] ≥ 75%) to COPD maintenance medication before admission (RR = 8.67, 95% CI = 1.60-46.78, P = 0.012) were also more likely to receive PCE-D. Older patients were more likely to have a COPD-related readmission (RR = 1.07, 95% CI = 1.01-1.13, P = 0.028), while use of maintenance medication before admission was associated with lower risk of an all-cause readmission (RR = 0.49, 95% CI = 0.30-0.79, P = 0.004). In addition, patients with higher medical and pharmacy costs before the index event were more likely to have all-cause readmission (RR = 1.01, 95% CI = 1.00-1.02, P = 0.013). Receipt of PCE was not shown to be a significant predictor of all-cause or COPD-related readmission. The use of bronchodilators and systemic corticosteroids after a COPD-related inpatient or ED visit may be related to the severity of the index COPD exacerbation or patients' previous pattern of bronchodilator use. However, the use of maintenance medication before the index event was associated with a significant reduction in all-cause readmission, so proper treatment of the underlying disease may be an effective strategy in reducing readmission. Funding for this study was provided by GlaxoSmithKline (HO-14-15081). Tran was a Fellow at Scott & White Health Plan (SWHP) during year 1 of this study and a Fellow at Novartis during year 2 of this study. Novartis did not have any input in this study nor did it contribute any funding or support for this research. Tran, Xiang, Godley, and Stock were employed by SWHP at the time of this study. Rascati is employed by the University of Texas at Austin and also by the Journal of Managed Care & Specialty Pharmacy and has received consulting fees from GlaxoSmithKline. Coleman, Bogart, and Stanford are GlaxoSmithKline employees and shareholders. Study design was created by Rascati, Tran, and Godley, with assistance from Stock, Coleman, Bogart, and Stanford. Tran and Xiang collected the data, with data analysis and interpretation performed by Stock and Rascati. The manuscript was written by Tran, Rascati, and Xiang and revised by Godley, Stock, Coleman, Bogart, and Stanford.

Adherence to Maintenance Medications among Older Adults with Chronic Obstructive Pulmonary Disease. The Role of Depression.

Among individuals with chronic obstructive pulmonary disease (COPD), depression is one of the most common yet underrecognized and undertreated comorbidities. Although depression has been associated with reduced adherence to maintenance medications used in other conditions, such as diabetes, little research has assessed the role of depression in COPD medication use and adherence. The objective of this study was to assess the impact of depression on COPD maintenance medication adherence among a nationally representative sample of Medicare beneficiaries newly diagnosed with COPD. We used a 5% random sample of Medicare administrative claims data to identify beneficiaries diagnosed with COPD between 2006 and 2010. We included beneficiaries with 2 years of continuous Medicare Parts A, B, and D coverage and at least two prescription fills for COPD maintenance medications after COPD diagnosis. We searched for prescription fills for inhaled corticosteroids, long-acting β-agonists, and long-acting anticholinergics and calculated adherence starting at the first fill. We modeled adherence to COPD maintenance medications as a function of new episodes of depression, using generalized estimated equations. Our primary outcome was adherence to COPD maintenance medications, measured as proportion of days covered. The exposure measure was depression. Both COPD and depression were assessed using diagnostic codes in Part A and B data. Covariates included sociodemographics, as well as clinical markers, including comorbidities, COPD severity, and depression severity. Of 31,033 beneficiaries meeting inclusion criteria, 6,227 (20%) were diagnosed with depression after COPD diagnosis. Average monthly adherence to COPD maintenance medications was low, peaking at 57% in the month after first fill and decreasing to 35% within 6 months. In our adjusted regression model, depression was associated with decreased adherence to COPD maintenance medications (odds ratio, 0.93; 95% confidence interval, 0.89-0.98). New episodes of depression decreased adherence to maintenance medications used to manage COPD among older adults. Clinicians who treat older adults with COPD should be aware of the development of depression, especially during the first 6 months after COPD diagnosis, and monitor patients' adherence to prescribed COPD medications to ensure best clinical outcomes.

A year in the life of German patients with COPD: the DACCORD observational study.

IntroductionRandomized interventional trials generally recruit highly selected patients. In contrast, long-term, noninterventional studies can reflect standard of care of real-life populations. DACCORD (Die ambulante Versorgung mit langwirksamen Bronchodilatatoren: COPD-Register in Deutschland [Outpatient Care With Long-Acting Bronchodilators: COPD Registry in Germany]) is an ongoing observational study, conducted in primary and secondary care in Germany, aiming to describe the impact of disease and treatments on real-life patients with chronic obstructive pulmonary disease (COPD).MethodsPatients had a clinical and spirometry diagnosis of COPD, were aged ≥40 years, and were initiating or changing COPD maintenance medication. The only exclusion criteria were asthma and participation in a randomized clinical trial. Exacerbation data were collected every 3 months. COPD medication, COPD Assessment Test, and forced expiratory volume in 1 second (FEV1) were recorded at the end of the 1 year period.ResultsIn the 6 months prior to baseline, 26.5% of the 3,974 patients experienced ≥1 exacerbation, compared with 26.1% over the 1-year follow-up (annualized rate 0.384). Importantly, only previous exacerbations and not poor lung function alone predicted an increased exacerbation risk. There was a general shift to lower disease severity from baseline to 1 year, predominantly as a consequence of a lower proportion of patients considered at high risk due to exacerbations. COPD Assessment Test mean change from baseline was −1.9, with 48.9% of patients reporting a clinically relevant improvement. Overall persistence to medication was high, with 77.2% of patients still receiving the same class of medication at 1 year.ConclusionDACCORD suggests that in clinical practice, the large majority of COPD patients are symptomatic but seldom exacerbate and that widely used tools and treatment recommendations do not reflect this fully.

Investigating the association between medication adherence and health-related quality of life in COPD: Methodological challenges when using a proxy measure of adherence

BackgroundThe association between non-adherence to medication and health-related quality-of-life (HRQoL) in Chronic Obstructive Pulmonary Disease (COPD) remains poorly understood. Different ways to deal with methodological challenges to estimate this association have probably contributed to conflicting results. AimTo investigate the association between medication adherence and HRQoL, thereby illustrating methodological challenges that need to be addressed. MethodsWe used longitudinal patient-level data from a cluster-randomized controlled trial (i.e. RECODE) including three-year data on type and dose of COPD maintenance medication prescribed and HRQoL (Clinical COPD Questionnaire [CCQ], st. George Respiratory Questionnaire [SGRQ], EuroQol 5-dimensions [EQ-5D]) of 511 patients. A linear mixed model was used to assess the association between adherence and HRQoL using a fixed cut-off of 80% of the proportion of days covered (PDC) to define adherence. Subsequently, we investigated the impact of differences in disease severity; lifestyle; and reversed causality, representing the methodological challenges. Additionally, we investigated the impact of changing the definition of adherence. ResultsIn unadjusted analyses, and analyses adjusting for demographic characteristics only, SGRQ score was worse in the adherent compared to the non-adherent group. This association disappeared when correcting for disease severity and/or lifestyle. A better SGRQ score was predictive of decreased adherence in the following year. However, accounting for the previous HRQoL did not result in positive associations between adherence and HRQoL. When defining four categories of adherence, patients with a PDC between 80 and 99% had a significantly worse SGRQ score compared to patients with a PDC <60%, even after correction for lifestyle. There was no significant association between adherence and CCQ or EQ-5D. ConclusionThis study showed persistent methodological challenges in the investigation of the effect of medication adherence on HRQoL in COPD. A positive association of adherence and HRQoL was not found, even after adjusting for lifestyle, disease severity, and previous HRQoL.

Impact and factors associated with nighttime and early morning symptoms among patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms. While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood. Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011. Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week. Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met. Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures. Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels. Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom. Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms. Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without. Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD.

A score to predict short-term risk of COPD exacerbations (SCOPEX).

BackgroundThere is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year.MethodsPredictive variables were selected using Cox regression for time to first severe COPD exacerbation. We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment. The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0–100 to predict an exacerbation within 6 months. Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables.ResultsThe best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex. Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX). Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting β2-agonist (salbutamol).ConclusionSCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk.

Association between depression and maintenance medication adherence among Medicare beneficiaries with chronic obstructive pulmonary disease

Depression is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD). Although comorbid depression is associated with low use and poor adherence to medications treating other chronic conditions, evidence of the relationship between depression and COPD management is limited. This study estimated the association between depression and COPD maintenance medication (MM) adherence among patients with COPD. This cross-sectional study used a 5% random sample of 2006-2007 Chronic Condition Warehouse data. Medicare beneficiaries enrolled in Parts A, B, and D plans with diagnosed COPD who survived through 2006 were included (n = 74,863). COPD MM adherence was measured as medication discontinuation and proportion of days covered (PDC). Depression was identified through the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Multivariable models with modified generalized estimating equations were used to estimate adjusted association between depression diagnosis and medication adherence, controlling for sociodemographics, comorbidities, and disease severity. Among the sample, about one third (33.6%) had diagnosed depression. More than half (61.8%) of beneficiaries with COPD filled at least one COPD MM prescription. Depressed beneficiaries had a higher likelihood of using COPD MM than non-depressed beneficiaries (adjusted prevalence ratios [PR] = 1.02; 95% confidence intervals [CI] = 1.01, 1.03). Among COPD MM users, depressed beneficiaries were more likely to discontinue medications (PR = 1.09; 95% CI = 1.04, 1.14) and less likely to exhibit PDC ≥ 0.80 (PR = 0.89; 95% CI = 0.86, 0.92) than non-depressed beneficiaries. Depression is prevalent in Medicare beneficiaries with COPD and independently associated with lower COPD MM adherence. Interventions to improve medication adherence for COPD patients may consider management of comorbidities such as depression.