Abstract
BACKGROUND:
Provider adherence to clinical treatment guidelines in COPD is low. However, for patients to receive guideline-aligned care, providers not only must prescribe guideline-aligned care, but also must communicate that regimen successfully to patients to ensure medication concordance. The rate of medication concordance between patients and providers and its impact on clinical management is unknown in COPD.
RESEARCH QUESTION:
To examine rates of guideline alignment and medication concordance and to identify patient-level factors that place patients at risk for these types of poor disease management outcomes.
STUDY DESIGN AND METHODS:
This study was a secondary data analysis of the Medication Adherence Research in COPD study (2017–2023). Participants were categorized into 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Medication regimens were classified as aligned or nonaligned with 2017 GOLD guidelines. Nonaligned regimens were stratified further into overuse and underuse categories. Medication concordance between provider-reported and participant-reported regimens was determined. Factors associated with guideline alignment and medication concordance were evaluated using logistic regression.
RESULTS:
Of 191 participants, 51% of provider-reported regimens were guideline aligned, with 86% of nonaligned regimens reflecting overuse with an inhaled corticosteroid (ICS). Thirty-eight percent of participants reported different regimens than their providers, of which > 80% reflected participants not reporting medications their providers reported prescribing. Participants did not report long-acting muscarinic antagonists and long-acting beta-agonists at similar rates as ICSs. Greater symptom burden and absence of a pulmonologist on the care team were associated with both guideline misalignment and medication discordance. Cognitive impairment and Black race additionally were associated with medication discordance.
INTERPRETATION:
Guideline misalignment and medication discordance were common and were driven by overuse of ICSs and unreported medications, respectively. The patient-level factors associated with medication discordance highlight the importance of improving patient-provider communication to improve clinical management in COPD.
Keywords: COPD, GOLD guidelines, guideline adherence, medication concordance, medication agreement, medication understanding
Despite widespread acceptance of clinical treatment guidelines for COPD, provider adherence to these guidelines remains low.1 The most commonly cited treatment guidelines are published by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), a project established in 1997 to create evidence-based guidelines for the prevention, diagnosis, and management of COPD. These guidelines offer specific recommendations for the selection of pharmacologic therapy in COPD based on categories of disease severity.2 Although providers report awareness of these guidelines and general agreement with their recommendations,3 prior studies have described rates of alignment between prescribing patterns and treatment guidelines of approximately 50%.1,4–6
Patients not receiving guideline-aligned care may be at increased risk of poor health outcomes and may be exposed to unnecessary harm. Undertreatment, which for patients with disease severity worse than GOLD stage A involves absence of a long-acting muscarinic antagonist (LAMA), long-acting beta-agonist (LABA), or both, has been associated with worse symptom control7 and, for patients with a history of exacerbations, carries an additional risk of future exacerbations.8,9 Overtreatment, which usually involves prescription of an inhaled corticosteroid (ICS) for patients with GOLD stage B disease, has been associated with an increased risk of pneumonia as well as poor glucose control and risk of fractures.10–13 In addition, overtreatment may complicate patients’ medication regimens unnecessarily and may worsen issues of medication adherence, which for patients with COPD has been shown to be poor.9
Therefore, improving alignment with guidelines has important implications for improving health outcomes.
For patients to receive guideline-aligned care, providers not only must prescribe guideline-aligned treatment, but also must communicate with patients in a way that ensures medication concordance, or agreement between patients and providers about the medication regimen. Although little is known about rates of patient-provider medication concordance in COPD, medication concordance in other chronic diseases has been shown to be poor.14–16 Moreover, patients with COPD face barriers to medication concordance beyond their peers because of disproportionately high rates of cognitive impairment, depression and anxiety, and comorbid disease.17–19 In addition, patients with COPD have been shown to have unique health beliefs about medications that may impair their ability to engage with their treatment plan.20 Understanding rates of medication concordance in COPD and the association of patient-level factors with medication concordance may help to identify patients who need additional support to understand the medication regimen.
This study used an existing cohort of patients with COPD to examine rates at which providers prescribe GOLD guideline-aligned treatment, rates of patient-provider medication concordance, and the interplay between guideline alignment and medication concordance. We further examined how patient-level factors are associated with both guideline alignment and medication concordance to identify patients at higher risk of these types of poor disease management.
Study Design and Methods
Study Cohort
Medication Adherence Research in COPD Patients (MARC) was a multicenter cohort study conducted between Johns Hopkins Medicine (Baltimore, Maryland) and ChristianaCare (Wilmington, Delaware) from 2017 through 2023 of participants aged ≥ 40 years who received a physician diagnosis of COPD and who were prescribed a long-term daily medication for COPD. Participants were recruited from among former clinical research participants and patient volunteers. All participants provided written informed consent. Institutional review boards at Johns Hopkins Medicine (Identifier: IRB00091482) and ChristianaCare (Identifier: IRB00000479) approved the protocol. The analytical cohort for this study is limited to MARC participants with GOLD stage B, C, or D disease according to 2017 GOLD categorization to ensure that all participants had an indication for a long-term daily medication.
Procedures
At the baseline visit, participants completed self-report surveys on demographics, clinical characteristics, recent exacerbations, prescribed medication regimens, and prescribing provider (s). Exacerbations were defined as any respiratory flare-up requiring the use of antibiotics, systemic corticosteroids, or both or health care use in the prior 12 months. Evaluation included spirometry using pulmonary function testing machines in accordance with American Thoracic Society and European Respiratory Society technical standards.21 Measurements collected included the modified Medical Research Council dyspnea scale score,22 COPD Assessment Test (CAT),23 Montreal Cognitive Assessment-Blind,24 and Beliefs About Medicines Questionnaire, which measures strength of beliefs in the necessity of medications and concerns about their use.25 Because of limitations during the COVID-19 pandemic, participants enrolled from 2020 onward completed spirometry assessment remotely using a lung function monitor. Participants were coached through a minimum of three efforts by research coordinators who had completed the National Institute for Occupational Safety and Health training in spirometry.
Prescribing providers were contacted to provide the patient’s medication regimen. Both patient-reported and provider-reported regimens were categorized into therapeutic classes of LAMA, LABA, and ICS. Alignment of both regimens with 2017 GOLD recommendations was determined, and nonaligned regimens were stratified into underuse and overuse categories (Table 1). Medication concordance was defined as agreement in all therapeutic classes reported by patients and providers.
TABLE 1 ].
Alignment of Medication Regimen With 2017 GOLD Recommendations
| Aligned Regimens | Nonaligned Regimens | |||
|---|---|---|---|---|
| GOLD Stage | First-Line Therapy | Second-Line Therapy | Underuse | Overuse |
| A | SAMA or SABA | SAMA plus SABA or LAMA or LABA | N/A | ICS monotherapy or ICS plus LABA or ICS plus LAMA or ICS plus LAMA plus LABA |
| B | LAMA or LABA | LAMA plus LABA | No inhaler or ICS monotherapy | ICS plus LABA or ICS plus LAMA or ICS plus LAMA plus LABA |
| C | LAMA or LAMA plus LABA | ICS plus LABA | No inhaler or ICS monotherapy or LABA monotherapy | ICS plus LAMA or ICS plus LAMA plus LABA |
| D | LAMA plus LABA or ICS plus LAMA plus LABA | LAMA or ICS plus LABA | No inhaler or ICS monotherapy or LABA monotherapy | N/A |
GOLD = Global Initiative for Chronic Obstructive Lung Disease; ICS = inhaled corticosteroid; LABA = long-acting beta-agonist; LAMA = long-acting muscarinic antagonist; SABA = short-acting beta-agonist; SAMA = short-acting muscarinic antagonist.
Statistical Analysis
Descriptive statistics were generated to characterize participant sample. Differences in guideline alignment and medication concordance status by GOLD group were assessed via χ2 tests using the Fisher exact test to account for low frequency counts. Medication concordance by therapeutic class was determined using a kappa statistic.
The association of patient-level factors at baseline with guideline alignment and medication concordance at baseline was evaluated using logistic regression. Logistic regression models controlling for (1) age, (2) sex, and (3) race were fit for the following additional variables: (4) insurance status, (5) educational attainment, (6) smoking status, (7) CAT score, (8) modified Medical Research Council dyspnea scale score, (9) exacerbation history, (10) comorbidity count,26 (11) Montreal Cognitive Assessment-Blind score, (12) GOLD stage, and (13) presence of a pulmonologist on the care team. Models for guideline alignment additionally were fit for (14) self-reported history of asthma to control for comorbid asthma in the prescription of inhaled corticosteroids. Models for medication concordance additionally were fit for (15) Beliefs About Medicines Questionnaire scores. Results of the univariable and multivariable logistic regressions are presented as OR and adjusted ORs (aORs), respectively, with corresponding 95% CIs and P values. Statistical significance was defined as P < .05. Analyses were performed using Stata version 17.1 software (StataCorp).
Results
Participant Characteristics
As shown in e-Figure 1, 191 participants with complete data on provider-reported regimens and GOLD stage B, C, and D disease were included in this analysis, of whom 188 patients also had complete data on patient-reported regimens. Of these 191 participants, the average age was 68.4 years, 44% were male, 71% were White, and 29% were currently smoked with a median of 39 pack-years of smoking (Table 2). At baseline, 58.6% of participants (n = 112) were classified with GOLD stage B disease, 2.1% of participants (n = 4) were classified with GOLD stage C disease, and 39.3% of participants (n = 75) were classified with GOLD stage D disease. Self-reported history of asthma ranged from 36% in the GOLD stage B group to 50% in the GOLD stage C group.
TABLE 2 ].
Baseline Patient Characteristics
| GOLD Stage | ||||
|---|---|---|---|---|
| Characteristic | Full Cohort | B | C | D |
| No. of patients | 191 | 112 (58.6) | 4 (2.1) | 75 (39.3) |
| Age, y | 68.4 ± 9.1 | 68.1 ± 9.3 | 76.6 ± 7.8 | 68.4 ± 8.8 |
| At diagnosis | 55.5 ± 12.5 | 55.9 ± 12.6 | 55 ± 8.7 | 55.0 ± 12.7 |
| Male sex | 83 (43.5) | 53 (47.3) | 4 (100) | 26 (34.7) |
| Race | ||||
| White | 135 (71.1) | 81 (72.3) | 4 (100) | 50 (67.6) |
| Black | 51 (26.8) | 29 (25.9) | 0 | 22 (29.7) |
| Other | 4 (2.1) | 2 (1.8) | 0 | 2 (2.7) |
| Socioeconomic status | ||||
| Public insurance only | 149 (78.8) | 90 (81.8) | 4 (100.0) | 55 (73.3) |
| Highest education | ||||
| High school or less | 58 (30.4) | 33 (29.5) | 1 (25) | 24 (32.0) |
| Some college | 59 (30.9) | 33 (29.5) | 0 | 26 (34.7) |
| College degree or more | 74 (38.7) | 46 (41.1) | 3 (75) | 25 (33.3) |
| Current tobacco user | 53 (30.8) | 31 (30.1) | 2 (100) | 22 (32.8) |
| Pack-years | 39 (26–54) | 39 (24–53) | 40 (25–54) | 39 (26–56) |
| FEV1, % predicted (SD)a | 55.2 (22.8) | 55.6 (20.8) | 61.2 (33.4) | 54.1 (25.1) |
| Exacerbations in prior year | ||||
| None | 95 (49.5) | 95 (84.8) | 0 | 0 |
| 1 | 39 (20.3) | 17 (15.2) | 0 | 22 (29.3) |
| ≥ 2 | 57 (2.7) | 0 | 4 (100) | 53 (70.7) |
| CAT scoreb | ||||
| Median (IQR) | 18 (13–23) | 17 (12–23) | 7 (6–8) | 19 (16–24) |
| ≥ 10 | 154 (81.5) | 89 (80.2) | 0 | 65 (87.8) |
| mMRC dyspnea scale scorec | ||||
| Median (IQR) | 2 (2–3) | 2 (2–3) | 1 (1–1) | 2 (2–3) |
| ≥ 2 | 158 (83.6) | 92 (83.6) | 0 | 66 (88.0) |
| Comorbidity count | ||||
| Median (IQR) | 3 (2–5) | 3 (2–5) | 4 (4–5) | 3 (2–4) |
| ≥ 3 | 125 (65.5) | 74 (66.1) | 4 (100) | 47 (62.8) |
| MoCA-Blind scored | ||||
| Median (IQR) | 18 (17–20) | 18 (17–20) | 18 (16–20) | 18 (16–19) |
| ≤ 17 | 71 (37.8) | 42 (38.5) | 2 (50) | 27 (36.0) |
| BMQ scoree | ||||
| Necessity scale | 10 (6–13) | 10 (6–13) | 8 (6–11) | 9 (6–11) |
| Concerns scale | 17 (13–20) | 17 (13–20) | 17 (16–18) | 17 (13–19) |
| History of asthma | 70 (37.6) | 40 (36.0) | 2 (50.0) | 28 (39.4) |
| Managed by pulmonologist | 112 (58.6) | 59 (52.7) | 2 (50.0) | 51 (68.0) |
Data are presented as No. (%), No., mean ± SD, or median (interquartile range), unless otherwise indicated. BMQ = Beliefs About Medicines Questionnaire; CAT = COPD Assessment Test; GOLD = Global Initiative for Chronic Obstructive Lung Disease; IQR = interquartile range; mMRC = modified Medical Research Council; MoCA = Montreal Cognitive Assessment.
Assessments before bronchodilator administration were used in these summary statistics because participants who completed spirometry remotely did not undergo testing after bronchodilator administration.
Higher scores indicate greater symptom burden.
Higher scores indicate greater dyspnea.
Lower scores indicate greater cognitive impairment.
Lower scores indicate stronger beliefs about the necessity of medications or higher concerns about their use.
Provider-Reported Medication Regimens
Complete data on provider-reported medication regimens is presented in e-Table 1. The most prevalent regimen was triple therapy with ICSs, LABAs, and LAMAs (44% [n = 84]), followed by ICSs and LABAs (27% [n = 51]) and LABAs and LAMAs (14% [n = 27]). These distributions were relatively consistent across GOLD stage groups, with the exception of the GOLD stage C group, which was an outlier given the overall low number of participants (n = 4).
Alignment With 2017 GOLD Guidelines
Overall, 51.3% of provider-reported regimens were in alignment with 2017 GOLD guidelines. The proportion of aligned regimens increased as GOLD group worsened in severity (P < .001), with 22.3% of regimens (n = 25) in alignment for participants in the GOLD stage B group, 75.0% (n = 3) in the GOLD stage C group, and 93.3% (n = 70) in the GOLD stage D group (Fig 1).Rates of alignment by year of enrollment into MARC from 2017 through 2021 did not differ significantly.
Figure 1 –
Bar graph showing alignment of provider-reported regimens with 2017 GOLD guidelines by GOLD group. GOLD = Global Initiative for Chronic Obstructive Lung Disease.
Of the nonaligned regimens, 86.0% (n = 80) reflected overuse of pharmacotherapy. In GOLD stage B and C groups, all cases of overuse, by definition, involved prescription of an ICS that was not recommended. Of these cases, 59% (n = 47) involved triple-therapy regimens with ICSs, LAMAs, and LABAs, 38% (n = 30) involved ICSs and LABAs, and 4% (n = 3) involved ICS monotherapy.
Medication Concordance
Kappa statistics for medication concordance between provider-reported and patient-reported medication regimens by inhaler class ranged from 0.33 (LABA) to 0.66 (LAMA) (Table 3). Overall, 38% of participants (n = 71) reported a different regimen than their provider. Of these discordant regimens, 83% (n = 59) reflected participants not reporting at least one of the prescribed inhaler classes. Of these patients, 40% (n = 23) reported not taking one medication, 56% (n = 33) reported not taking two medications, and 5% (n = 3) reported not taking three medications. The number of unreported medications stratified by the number of medications prescribed is presented in e-Figure 2. Of the total number of unreported medications, 40% (n = 39) were LABAs, 40% (n = 39) were ICSs, and 20% (n = 20) were LAMAs. Overall, 29% of participants prescribed a LABA, LAMA, or both and 27% of participants prescribed an ICS reported not taking those medications. Although less common, 9% of participants (n = 17) reported taking at least one additional inhaler class beyond what their provider reported. These added inhaler classes were roughly evenly distributed among the three classes (36% ICS, 36% LAMA, 28% LABA).
TABLE 3 ].
Patient-Provider Medication Concordance by Therapeutic Class
| Drug Class | Patient-Provider Concordance | Percent Positive Agreement | Kappa Statistic (95% CI) | ||
|---|---|---|---|---|---|
| ICS | Patient report (+) | Patient report (−) | 69 | 0.42 (0.30–0.55) | |
| Provider report (+) | 105 | 39 | |||
| Provider report (−) | 9 | 35 | |||
| LAMA | Patient report (+) | Patient report (−) | 79 | 0.66 (0.55–0.77) | |
| Provider report (+) | 108 | 20 | |||
| Provider report (−) | 9 | 51 | |||
| LABA | Patient report (+) | Patient report (−) | 73 | 0.33 (0.19–0.47) | |
| Provider report (+) | 122 | 39 | |||
| Provider report (−) | 7 | 20 | |||
ICS = inhaled corticosteroid; LABA = long-acting beta-agonist; LAMA = long-acting muscarinic antagonist.
Interplay Between Guideline Alignment and Medication Concordance
Of the 38% of participants (n = 71) who reported a discordant medication regimen, only 15% (n = 11) reported discrepancies that brought them into alignment with GOLD guidelines, with the remainder either not changing the alignment (63% [n = 45]) or bringing them out of alignment (21% [n = 15]). Most participants being brought into alignment (n = 10) were in the GOLD stage B group because these participants did not report an ICS, which is considered overuse for that group.
Overall rates of medication concordance did not differ significantly either by GOLD group or by category of guideline alignment. However, participants prescribed overuse regimens reported not taking medications at higher rates than participants prescribed guideline-aligned regimens, with 36% of participants (n = 29) in the overuse category not reporting at least one medication as compared with 28% of participants (n = 27) prescribed guideline-aligned regimens, although this difference was not statistically significant.
Factors Associated With Alignment and Concordance
The results from logistic regression models are presented in Table 4. In a multivariable model of factors associated with guideline alignment, having GOLD stage D disease was positively associated significantly with guideline alignment (aOR, 352.9; 95% CI, 20.3–6138.2; P < .001). Higher CAT score was associated significantly with guideline nonalignment (aOR, 0.88; 95% CI, 0.80–0.97; P < .01), suggesting that participants reporting greater symptom burden were more likely to be prescribed nonaligned regimens. Having a pulmonologist on the care team also was associated significantly with guideline alignment (aOR, 3.04; 95% CI, 1.03–8.92; P < .05).
TABLE 4 ].
Factors Associated With Guideline Alignment and Medication Concordance
| Variable | Guideline Alignment Models | Medication Concordance Models | ||
|---|---|---|---|---|
| OR (95% CI) | aOR (95% CI) | OR (95% CI) | aOR (95% CI) | |
| Age | … | 0.94 (0.87–1.00) | … | 1.00 (0.95–1.06) |
| Male sex | … | 2.71 (0.97–7.51) | … | 0.78 (0.34–1.82) |
| Racea | ||||
| Black | … | 0.41 (0.11–1.57) | … | 0.35 (0.13–0.97)b |
| Other/missing | … | 1.02 (0.03–41.8) | … | 1.54 (0.13–18.8) |
| Public insurancec | 0.84 (0.41–1.69) | 1.38 (0.38–5.04) | 1.16 (0.56–2.43) | 1.66 (0.61–4.51) |
| Highest educationd | ||||
| Some college | 0.91 (0.44–1.90) | 0.45 (0.12–1.64) | 1.72 (0.77–3.83) | 1.83 (0.62–5.40) |
| College or more | 0.84 (0.41–1.73) | 0.53 (0.13–2.09) | 1.05 (0.49–2.24) | 0.59 (0.20–1.73) |
| Current tobacco usee | 1.20 (0.58–2.49) | 1.09 (0.33–3.61) | 0.87 (0.41–1.85) | 1.51 (0.56–4.03) |
| Comorbidity count | 1.04 (0.89–1.21) | 1.24 (0.94–1.63) | 1.02 (0.86–1.21) | 1.08 (0.86–1.35) |
| CAT scoref | 1.00 (0.96–1.05) | 0.88 (0.80–0.97)g | 0.95 (0.91–0.99)b | 0.92 (0.86–0.99)b |
| mMRC dyspnea scale scoreh | 1.10 (0.82–1.48) | 1.52 (0.91–2.53) | 0.71 (0.51–0.98)b | 0.67 (0.43–1.03) |
| Exacerbation historyi | 5.44 (3.39–8.72)j | 0.56 (0.13–2.39) | 0.83 (0.58–1.17) | 0.94 (0.37–2.39) |
| History of asthmak | 0.68 (0.37–1.26) | 0.46 (0.14–1.56) | … | … |
| MoCA-Blind scorel | 0.98 (0.87–1.11) | 1.05 (0.83–1.33) | 1.18 (1.03–1.35)b | 1.21 (1.02–1.44)b |
| GOLD stagem | ||||
| C | 7.88 (0.73–85.08) | 3.31 (0.05–230.1) | 0.49 (0.06–3.81) | Omittedn |
| D | 77.4 (24.5–244.4)j | 352.9 (20.3–6138.2)j | 0.89 (0.47–1.68) | 0.77 (0.16–3.74) |
| BMQ scoreo | ||||
| Necessity | … | … | 0.95 (0.88–1.03) | 0.90 (0.81–1.00) |
| Concern | … | … | 1.03 (0.95–1.11) | 0.98 (0.88–1.09) |
| Pulmonologistp | 2.41 (1.30–4.49)g | 3.04 (1.03–8.92)b | 2.94 (1.54–5.62)j | 4.76 (1.86–12.2)j |
aOR = adjusted OR; BMQ = Beliefs About Medicines Questionnaire; CAT = COPD Assessment Test; GOLD = Global Initiative for Chronic Obstructive Lung Disease; mMRC = modified Medical Research Council; MoCA = Montreal Cognitive Assessment.
Reference group is White.
P < .05.
Reference group is private insurance.
Reference group is high school or less.
Reference group is no current tobacco use.
Higher score indicates greater symptom burden.
P < .01.
Higher score indicates greater dyspnea.
Defined as the number of exacerbations in the last year.
P < .001.
Reference group is no history of asthma.
Lower score indicates greater cognitive impairment.
Reference group is stage B.
Omitted because of low variability (n = 4) contributing to perfect prediction failure.
Lower score indicates stronger beliefs about the necessity of medications or higher concerns about their use.
Defined as the presence of a pulmonologist on the patient’s care team.
In a multivariable model of factors associated with medication concordance, higher CAT score was found to be associated significantly with medication discordance (aOR, 0.92; 95% CI, 0.86–0.99; P < .05), even after controlling for GOLD group. In addition, Montreal Cognitive Assessment-Blind score was associated significantly with medication concordance (aOR, 1.21; 95% CI, 1.02–1.44; P < .05), indicating that patients with cognitive impairment are less likely to be concordant with their providers. Beliefs About Medicines Questionnaire Necessity score was on the border of statistical significance (aOR, 0.90; 95% CI, 0.81–1.00; P = .51), potentially suggesting that patients who hold stronger beliefs about the necessity of medications are more likely to be concordant with their providers. Black race also was associated negatively with medication concordance (aOR, 0.35; 95% CI, 0.13–0.97; P < .05). Being treated by a pulmonologist was associated with medication concordance (aOR, 4.76; 95% CI, 1.86–12.2; P < .001).
Discussion
In this analysis, > 50% of provider-reported medication regimens were not in alignment with GOLD guidelines in effect at the time of the study. More than 85% of nonaligned regimens reflected overuse of medications, primarily driven by use of ICSs for patients at low risk of exacerbations. Underuse was driven primarily by absence of any long-acting inhaler. These findings demonstrate continued poor provider uptake of clinical treatment guidelines in COPD.
In an assessment of medication concordance, nearly 40% of participants were found to report a different medication regimen than their provider, and kappa statistics by therapeutic class ranged from low to moderate. Although a small proportion of instances of medication discordance brought patients into guideline alignment, most medication discrepancies represented participants not reporting at least one guideline-recommended medication. Less than 10% of participants reported more medications than their provider, likely representing additional prescriptions from sources other than the provider primarily managing the COPD, for example, urgent care or ED physicians. These results demonstrate that medication discordance is common in COPD and is characterized primarily by patients not reporting guideline-recommended medications that their providers reported prescribing.
Having GOLD stage D disease was associated significantly with guideline alignment after controlling for other factors, which is consistent with prior research demonstrating that rates of guideline alignment increase by GOLD stage severity.1,27 This finding reflects the fact that > 70% of participants in all three GOLD stage groups were receiving ICS-containing double therapy or triple therapy, which for patients with GOLD stage B disease is considered overuse, whereas for patients with GOLD stage D disease is considered guideline-aligned treatment. Higher CAT scores also were found to be associated significantly with guideline nonalignment even after controlling for GOLD stage group, raising the possibility that providers may escalate therapy beyond guideline recommendations by adding an ICS for patients who remain highly symptomatic with fewer medications. However, participants who were prescribed overuse regimens also were found not to report medications at higher rates than participants prescribed guideline-aligned regimens, although this difference was not statistically significant. In addition, participants were found to not report a LAMA, LABA, or both as frequently as an ICS. Taken together, these findings raise concern that patients whose treatment is escalated because of a high symptom burden may not take all medications prescribed and are just as likely not to report an aligned LAMA, LABA, or both as compared with a nonaligned ICS. Being cared for by a pulmonologist also was associated significantly with guideline alignment, suggesting that specialists may be more familiar with guidelines or may be more likely to adopt them into their practice.
It is possible that some instances of overuse reflect patients who previously were categorized with GOLD stage D disease being escalated to an ICS-containing regimen for a history of exacerbations and later being recategorized as having GOLD stage B disease because of improvement in their condition as a result of that medication. However, the high rates of unreported medications among this group are at odds with this explanation. Moreover, this explanation does not apply to escalations to ICS-containing regimens for high symptom burden, because GOLD guidelines do not recommend escalation to ICSs for severe or persistent symptoms. Notably, history of asthma was not associated significantly with guideline alignment, suggesting that comorbid asthma also does not account for the observed overuse of ICSs.
For medication concordance, higher CAT score was associated significantly with medication discordance after controlling for other factors. This finding suggests either that patients who are more symptomatic are less confident in the ability of medications to relieve symptoms and as a result are discordant at higher rates, or that patients who do not adhere to the medication regimen as prescribed are more symptomatic as a result. However, given that this model controlled for strength of beliefs in the necessity of medication, the latter interpretation seems more likely.
Cognitive impairment was negatively associated significantly with medication concordance, which is consistent with prior research that patients with cognitive impairment are at higher risk of nonadherence.28 Stronger belief in the necessity of medication also was associated with medication concordance, although this finding was on the border of statistical significance (P = .51). Black race was associated negatively with medication concordance, whereas other demographic factors and socioeconomic indicators were not. Prior studies have suggested that this association may be mediated through worse communication by health care providers with patients from racial and ethnic minority groups29 as well as lower trust in the health care system or in the positive effect of medications.30 It is also possible that the other socioeconomic factors used in this study do not capture the ways in which Black and patients from racial and ethnic minority groups face systematic bias in health care. Having a pulmonologist on the care team was associated with medication concordance, suggesting that specialists may have more training or time to communicate with patients about inhaler regimens or may have access to an experienced multidisciplinary team that assists with communication.
These findings suggest that providers routinely should assess medication concordance, particularly before further escalation to nonaligned treatment regimens. Providers should pay specific attention to patient groups at risk of medication discordance and should explore underlying reasons for this discordance, such as confusion and medication beliefs. Our research is consistent with prior literature suggesting that improving communication between patients and providers is critical to addressing racial disparities in COPD and improving clinical management.31 Although additional research is needed on the best strategies to improve this communication, future work should focus on interventions that have shown promise in other disease areas or care settings, such as using pictograms and involvement of the multidisciplinary team.32–34 Additional research also should focus on identifying the reasons pulmonologists have higher rates of medication concordance to implement better those factors in the generalist setting.
The most recent GOLD guidelines published in 2023 collapse GOLD stages C and D into a new stage E defined by a history of frequent or severe exacerbations.35 These recommendations remove ICSs entirely from the guidelines for initial pharmacotherapy and recommend escalation to an ICS-containing regimen for patients with persistent exacerbations, elevated blood eosinophil counts, or comorbid asthma. This further de-emphasis of the role of ICSs highlights the importance of understanding the drivers of overuse of this medication, particularly because recent research has shown that ICS overuse has increased over time.36 Our findings also underscore the importance of ensuring medication concordance to address this problem because we must minimize the likelihood that patients drop a LAMA, LABA, or both rather than an ICS.
This study has several limitations. Like other similar studies, we were unable to account for confounding by indication. Exacerbation history was collected via self-report, which may be subject to information and recall bias. This study did not include data collection on blood eosinophil levels, which may have affected prescribing decisions. The participant sample was affected by the inclusion criteria for MARC, which stipulated a prescription for a long-term daily medication. Although this medication was not required to be an inhaler, this criterion likely affected our sample in ways that underestimated the rate of underuse. For this reason, the analytical cohort for this study was limited to GOLD stages B, C, and D to ensure that all participants had an indication for a controller inhaler. The number of participants with GOLD stage C disease also was low (n = 4), which is consistent with other studies showing overall low prevalence of this disease category.37 Additional research is needed to confirm our findings in a larger sample size, in a more generalizable population, and in a longitudinal analysis. Despite these limitations, the data collection performed within this cohort enables this study to be the first that we are aware of to estimate rates of medication concordance in COPD using both patient-reported and physician-reported regimens and to examine patient-level factors associated with medication concordance.
Interpretation
In conclusion, approximately one-half of provider-reported regimens were in alignment with clinical treatment guidelines, with most nonaligned regimens reflecting overuse. Nearly 40% of patients reported different medication regimens than their providers, which predominantly reflected patients dropping medications. Certain patient-level factors, including higher symptom burden, cognitive impairment, Black race, and not being managed by a pulmonologist, were associated with medication discordance. These findings highlight the importance of increasing provider adherence to clinical treatment guidelines and enhancing patient-provider communication about medication efficacy to improve clinical management in COPD.
Supplementary Material
Funding/Support
The MARC trial was supported by the National Heart, Lung, and Blood Institute [Grant R01HL128620]. M. A. C. was supported by the National Heart, Lung, and Blood Institute [Grants T32HL007534 and F32HL167418]. N. N. H. is supported by the COPD Foundation.
Financial/Nonfinancial Disclosures
The authors have reported to CHEST the following: N. N. H. reports receiving financial support from AstraZeneca and GlaxoSmithKline. None declared (M. A. C., E. P. B., E. R., M. T. V., N. P., M. N. E.).
ABBREVIATIONS:
- aOR
adjusted OR
- CAT
COPD Assessment Test
- GOLD
Global Initiative for Chronic Obstructive Lung Disease
- ICS
inhaled corticosteroid
- MARC
Medication Adherence Research in COPD Patients
- LABA
long-acting beta-agonist
- LAMA
long-acting muscarinic antagonist
Footnotes
Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.
Additional information: The e-Figures and e-Table are available online under “Supplemental Data.”
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