Abstract
Significant variability in adherence to COPD management recommendations has been reported. We aimed to evaluate real-life COPD pharmacotherapy prescribing patterns and adherence to the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy in Switzerland. A questionnaire-based survey was conducted among Swiss general practitioners (GPs) and pulmonologists (PULs) from May 1 to November 30, 2017. Participants were invited to complete a questionnaire on their next 5–10 consecutive patients already receiving a pharmacological treatment for COPD. They were requested to assess dyspnea using the modified Medical Research Council (mMRC) dyspnea scale and to determine whether a treatment adjustment was indicated. Fifty-three PULs and 39 GPs completed questionnaires on 511 COPD patients. Dyspnea with mMRC grade ≥2 was reported in 62.5% of the patients, and 31.9% had had at least two exacerbations (or at least one with hospital admission) in the last 12 months. The vast majority (87.1%) of GOLD A patients were overtreated. In the GOLD B group, 52.2% of prescriptions were concordant with GOLD 2017 recommendations, but 37% of patients were overtreated. Among GOLD C patients, 49.2% received GOLD-adherent treatment and 47.5% were overtreated. In the GOLD D category, 78.8% of the patients received a treatment consistent with recommendations but 15.2% were undertreated. After reassessment of patient status, treatment was modified in 50.3% of the patients. This study confirms that discordance of real-world prescription patterns with international guidance is frequent. Further educational efforts are required to improve adherence to COPD management recommendations.
Introduction
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death, morbidity and healthcare costs worldwide [Citation1]. In the multinational, population-based Burden of Obstructive Lung Disease (BOLD) study (n = 9,425), the prevalence of moderate-to-very-severe COPD was 10.1% overall (11.8% among men and 8.5% among women), and it varied substantially between countries (from 8.5% in Iceland to 18.8% in the Philippines in men) [Citation2]. A cross-sectional single-center Swiss study observed a 9% prevalence of COPD in patients (n = 888) aged ≥45 years who were admitted to tertiary care hospital [Citation3].
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy [Citation1] is considered worldwide as the most reliable guidance document for the management of COPD; however, significant variability in adherence to GOLD recommendations has been reported [Citation4]. A retrospective analysis from a Veterans Administration Medical Center in the US observed that only 19% of 878 COPD patients received a treatment regimen that was compliant with GOLD recommendations; 14% were overtreated, 44% were undertreated, and in 23% the treatment was not consistent with any of the recommendations [Citation5]. A large audit of COPD management during hospital admissions in 13 European countries in 2010–2011 (>16,000 patients from 384 hospitals) found wide variations in adherence to GOLD 2010 recommendations between hospitals and across countries [Citation6]. In Switzerland, a prospective cohort study conducted in seven pulmonary outpatient clinics in 2010–2016 (n = 305) revealed that pharmacological treatment was frequently suboptimal, especially in lower risk groups; prescriptions were consistent with GOLD recommendations at only 59.1% of follow-up visits, and the required escalations or de-escalations in pharmacotherapy were seldom adequately implemented [Citation7].
In many countries, including Switzerland, COPD patients are managed by general practitioners (GPs) in routine practice. An international survey of 1,307 GPs and pulmonologists (PULs) demonstrated that only 58% of GPs were aware of GOLD recommendations, compared with 93% of PULs [Citation8]. In 2010, a questionnaire-based survey of Swiss GPs revealed that 44% of the patients originally diagnosed with COPD did not fulfill GOLD criteria for the condition and that 59% of the patients were prescribed a pharmacological treatment that was not compliant with GOLD recommendations [Citation9]. A recent analysis of the Swiss COPD cohort indicated that 21.5% of the patients treated in primary care did not fulfill spirometric diagnostic criteria for COPD [Citation10].
While patient-reported outcome questionnaires such as the modified Medical Research Council dyspnea scale (mMRC) or the COPD Assessment Test (CAT) are crucial for COPD assessment and treatment selection [Citation1], these tools are not used by most physicians in real-practice settings. A Danish cross-sectional survey among 124 GPs and their 1,716 COPD patients demonstrated that mMRC grade was recorded in only 7% of the patients [Citation11]. Another study in 57 primary care practices (>30,000 COPD patients) in the Balearic Islands, Spain, showed even worse results: mMRC or CAT was recorded in fewer than 0.5% of the patients [Citation12].
Lack of appropriate symptom assessment might be associated with the fact that many physicians underestimate symptoms as a driver to therapeutic adjustments. In fact, exacerbations are the main factor leading to treatment escalation and many patients continue to have symptoms while being treated [Citation13]. A study of current COPD management using a large UK primary-care database (n = 24,957) revealed that most of treated COPD patients receive inhaled corticosteroids (ICS) irrespective of severity of airflow limitation, asthma diagnosis, and exacerbation history [Citation14].
In a major revision of the GOLD report published in 2017, spirometric assessment was separated from symptom evaluation and ABCD groups were defined exclusively by patient symptoms and history of exacerbations [Citation15]. Also, some novel approaches and new classes of COPD medications, such as fixed combinations of long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA), have been introduced into COPD management during the last decade.
The aim of this study was to evaluate real-life COPD pharmacotherapy prescribing patterns among Swiss physicians (both GPs and PULs) and to assess adherence to 2017 GOLD recommendations, with a focus on treatment changes guided by symptom assessment.
Methods
A questionnaire-based survey was conducted among physicians (PULs and GPs) from all over Switzerland from May 1 to November 30, 2017. Among the 7,800 GPs and 320 PULs active in Switzerland, 1,473 GPs and 120 private practice PULs were identified by Boehringer Ingelheim representatives as potential participants. Subsequently, 168 GPs and 104 PULs from three language zones (German, French, and Italian) were randomly selected and were approached to inquire about their interest in participating in the survey. The physicians who confirmed their participation (23.2% of invited GPs and 60% of invited PULs) were asked to complete a paper questionnaire with data on their next 5–10 consecutive patients with a previously confirmed diagnosis of COPD and already receiving a pharmacological treatment for this condition.
The questionnaire included the following patient-related variables: age, sex, time since COPD diagnosis, smoking status, GOLD status, method used previously (if any) to assess dyspnea, number and severity of COPD exacerbations during the previous 12 months, current COPD therapy, use of rescue medication, comorbidities (hypertension, diabetes, ischemic heart disease, or other), and concomitant medications. In addition, the physician was asked to assess dyspnea using the mMRC scale during the appointment, to reevaluate GOLD status and to determine whether a treatment adjustment (escalation, de-escalation) was indicated considering GOLD 2017 recommendations. Potential reasons for modifying the current treatment were prespecified: GOLD 2017 assessment, lack of effectiveness of the current treatment, adverse effects of the current treatment, difficulties with the current inhaler, and patient’s preference. As LAMA/LABA fixed-dose combinations were the newest treatment options and were licensed as second-line treatments in Switzerland, the reasons for selecting a LAMA/LABA combination were specifically evaluated.
The patients had to sign an informed consent form prior to participation. Data records were pseudonymized. Patient data were evaluated and categorized by exacerbation status and symptoms to categories A, B, C, D according to the GOLD 2017 report. The concordance of current pharmacological treatment with GOLD 2017 recommendations was defined as follows:
Group A: short-acting beta-agonist or short-acting muscarinic antagonist;
Groups B and C: LABA, LAMA, or LAMA/LABA combination;
Group D: any treatment regimen including LAMA/LABA combination (fixed or free).
The use of ICS was categorized as incorrect for GOLD groups A, B, and C.
As the study was exploratory, statistical analyses were mainly descriptive and no adjustments for multiple comparisons were made. A p value <.05 was considered statistically significant. The main planned subgroup analysis was the comparison of patients managed by PULs GPs and the prescribing patterns of both physician groups. Data were analyzed according to the character of the variables (continuous or categorical) and presented as mean ± standard deviation (SD), or median and interquartile range, or proportion. This questionnaire-based survey was approved by the Northwest and Central Switzerland ethics committee (ENKZ BASEC 2016-01156).
Results
Ninety-two physicians (53 PULs and 39 GPs) participated in the survey and completed questionnaires on a total of 511 COPD patients (320 and 191, respectively).
Patient characteristics
The patients’ baseline characteristics are summarized in . The proportion of male patients was 56.4% and the distribution by age was as follows: 20.4% <60 years, 37.8% between 61 and 70 years and 41.8% >70 years. Only 7% of the patients were nonsmokers. Dyspnea with mMRC grade ≥2 was reported in 62.5% of the patients, and 31.9% had had at least two exacerbations (or at least one with hospital admission) in the last 12 months. The majority of patients were symptomatic (GOLD group B, 36.0%; group D, 23.1%), while a relatively high proportion of patients were classified in group A (27.4%). Comorbidities, mainly hypertension, heart disease, and diabetes, were present in 81.2% of the patients. The proportion of frequent exacerbators was similar among patients managed by GPs and PULs. However, patients in PUL practices had a more severe symptom burden, with 29% of patients in the GOLD D category compared with 14% in GP practices.
Table 1. Patients’ baseline characteristics.
Previous use of symptom assessment tools (mMRC scale or CAT score) was more than twice as frequent among PULs than among GPs; the mMRC scale was used in 47.8% and 20.4% of the patients, respectively (p < .0001) and the CAT score was used in 26.6% and 10.5% of the patients, respectively (p < .0001) (). Overall, physicians used neither the mMRC scale nor the CAT score in 53% of the cases, both the mMRC scale and the CAT score in 11.2%, the mMRC scale but not the CAT score in 26.4%, and the CAT score but not the mMRC scale in 9.4%.
Table 2. Previous use of symptom assessment tools.
Pharmacological treatment at the time of the visit
Pharmacological treatments according to GOLD 2017 categories at the time of the visit are shown in . Overall, according to the treating physician’s own evaluation, treatments were concordant with GOLD 2017 recommendations and GOLD status was correct in 53.2% of the patients, GOLD status was incorrect in 4.3%, treatment escalation without GOLD status change was required in 24.7%, treatment de-escalation without GOLD status change was indicated in 11.9%, and the information was missing for 5.9%. The vast majority (87.1%) of GOLD A patients were overtreated with LABA, LAMA, ICS, or combinations of these medications. In the GOLD B group, about half (52.2%) of prescriptions were concordant with GOLD 2017 recommendations, but 37.0% of patients were overtreated with ICS. Among GOLD C patients, 49.2% received GOLD-adherent treatment and 47.5% were overtreated. In the GOLD D category, 78.8% of the patients received a treatment consistent with recommendations, but 15.2% were undertreated.
Figure 1. Baseline pharmacological treatment according to GOLD 2017 category. LAMA, monotherapy with LAMA; LABA, monotherapy with LABA; LAMA/LABA, fixed or free combinations of LAMA and LABA; LAMA/LABA/ICS, any triple combinations; ICS (+ other), ICS-containing regimens other than triple combinations (LAMA/LABA/ICS); other, regimens without ICS, LAMA, and LABA. Missing data are not shown.
Adherence to GOLD recommendations was better among PULs than among GPs; 56.9% of their patients were treated appropriately, compared with 47% of the patients managed by GPs. Compared with patients in PUL practices, patients managed by GPs were more likely to be undertreated and less likely to be overtreated.
Treatment decisions made during the visit
After reassessment of patient status in light of the updated GOLD report, treatment was modified in 257 (50.3%) patients, including in 45 (8.8%) patients for which previous treatment were concordant with GOLD 2017 recommendations according to the physician’s own evaluation (). The proportion of patients whose treatment was modified was 48.4% for PULs compared with 53.4% for GPs (the difference was not statistically significant). In patients managed by PULs, treatment adjustment rates according to ABCD categories were as follows: group A, 26.9%; group B, 46.2%; group C, 32%; and group D, 23.9%.
Table 3. Actual treatment adjustments versus adjustments required according to GOLD 2017 recommendations.
Both groups of physicians stated that the main reason for adjusting the COPD treatment was its reevaluation according to GOLD 2017 recommendations, followed closely by insufficient efficacy of the previous treatment (). The decision was considered at odds with the GOLD 2017 global strategy if the treatment regimen was changed although it was not required by GOLD, or if there were no changes although an adjustment would have been required according to GOLD. PULs made GOLD-discordant decisions more frequently than GPs (19.1% vs. 4.7%; see ).
Figure 2. Reasons for treatment adjustments decided by GPs (n = 102) and PULs (n = 155). Multiple choices were possible.
In patients who were prescribed a LAMA/LABA combination, the reasons for selecting a specific combination were evaluated (). Clinical data on the active substance and personal experience with the medication were important factors for both GPs and PULs, although the inhaler appeared to be the main driver for PULs when selecting a LAMA/LABA combination.
Figure 3. Reasons for choosing a LAMA/LABA combination (in patients who are prescribed LAMA or LABA) by GPs (n = 140) and PUL (n = 212). Multiple choices were possible.
Discussion
This questionnaire-based survey of PULs and GPs provides important information on the characteristics of COPD patients and treatment patterns in real-life settings in Switzerland. PULs and GPs followed GOLD 2017 recommendations in 57% and 47% of their prescriptions, respectively. The main discordance with GOLD recommendations was overtreatment, predominantly with ICS (and/or long-acting bronchodilators in group A), as 87.1% of patients in group A, 37.0% in group B, and 47.5% in group C were overtreated. Treatment was concordant with the GOLD global strategy in the majority of patients in group D; however, 15.2% of these patients were undertreated. In our study, a treatment adjustment was decided during the visit for half of the patients, with no difference between PULs and GPs. Changes were driven mainly by patient status evaluation and treatment reassessment according to the GOLD 2017 global strategy and insufficient efficacy of the previous treatment.
This study confirms that discordance of real-world prescription patterns with international guidance is frequent, as reported previously in Switzerland and other countries. Bourbeau et al. observed that prescriptions of Canadian GPs in COPD patients matched guideline recommendations only in 35% of the cases [Citation16]. Discrepancies between reported and recommended treatment included nonprescription of long-acting bronchodilators for patients with moderate (27%) and severe (21%) COPD, nonprescription of both LAMA and LABA for patients with severe COPD (51%), and overtreatment with ICS (63%) or long-acting bronchodilators (47%) for patients with mild COPD. Factors that might explain the gap between treatment recommendations and real-world practice include inadequate familiarity with published recommendations, time constraints (making it difficult, for instance, to perform spirometry at each visit) and low self-efficacy of physicians, that is, poor confidence in their ability to perform the recommended behavior [Citation7, Citation17].
Adherence of Swiss GPs to GOLD recommendations has not improved since 2010, when a previous questionnaire-based study showed that 47% of prescriptions were at odds with current guidance [Citation9]. In an international survey using patient scenarios, Davis et al. found that COPD recommendations may present a challenge not only for GPs but for also respiratory specialists [Citation8]. While 93% of PULs were aware of the GOLD 2011 report compared with 58% of GPs, both groups of physicians were found to have insufficient knowledge levels regarding the pharmacological management of COPD in some clinical situations. Whereas a GOLD-concordant response was provided by more PULs (67%) than of GPs (38%) for a GOLD group B patient scenario, PULs and GPs performed similarly when presented with GOLD groups C and D patient scenarios (40% and 38%, respectively, for group C, and 58% and 57%, respectively, for group D). Better performance in group D might be explained by the fact that different combinations of ICS, LAMA, and LABA, including triple combinations, are considered appropriate for these patients.
In the present study, similar proportions (29–39%) of patients were treated with LAMA/LABA across all ABCD categories and a progressive increase was observed in the use of LAMA/LABA/ICS triple therapy, which is incorrectly prescribed in 14% and 15% of non-exacerbating patients in groups A and B, respectively, and up to half of the patients in group D. Overprescription of ICS and triple therapy remains one of the main issues of concern in COPD management. Studies on COPD treatment in general practice have reported ICS prescription rates of 76% in patients with mild COPD in Denmark [Citation11] and 38% in GOLD stage I or II patients in the UK [Citation18].
Overuse ICS is also observed among PULs. In a Spanish nationwide clinical audit of more than 4,500 COPD patients from outpatient respiratory clinics (EPOCONSUL), ICS-containing regimens were overprescribed in non-exacerbating GOLD groups (45% in group A, 61% in group B) [Citation19]. Moreover, triple therapy was the leading treatment option in all GOLD groups (35% in group A, 53% in group B, 53% in group C, 71% in group D), followed by double bronchodilator therapy. Higher rates of guideline-discordant ICS prescriptions were observed in the EPOCONSUL audit than in the present study, which might be explained by objective assessment by independent experts, contrary to subjective self-reporting by physicians in this survey.
Use of ICS in patients with COPD is associated with a number of important adverse effects, including an increased risk of severe pneumonia [Citation20]. The latest GOLD report recommends reserving ICS use as part of initial treatment for COPD group D patients with two or more moderate exacerbations or one exacerbation leading to hospitalization in the preceding year and a blood eosinophil count greater than 300 cells/µL, or as part of follow-up treatment in COPD patients with persistent exacerbations on long-acting bronchodilator monotherapy or LABA/LAMA combination therapy and a blood eosinophil count greater than 100 cells/µL [Citation1]. Various algorithms for ICS withdrawal have been proposed [Citation21, Citation22].
This study has several limitations. As physicians were not randomly selected and participated on a voluntary basis, the sample might be biased toward self-motivation and knowledge of COPD management, particularly for GPs. In addition, patient selection was not randomized; therefore, the study sample may not necessarily reflect the characteristics of the whole population of COPD patients in Switzerland.
Conclusions
In this questionnaire-based survey, 92 physicians (53 PULs and 39 GPs) provided information on the characteristics and management of 511 COPD patients in Switzerland. Overall, 53% of COPD patients were not treated consistently with GOLD 2017 recommendations, although 57% of the physicians were PULs. Overprescription of ICS remained frequent. However, a simple reassessment of the patients’ treatments using the GOLD algorithm (assessing dyspnea and risk of exacerbations) was a trigger for many participating physicians to adjust the treatment regimen or to withdraw ICS. Further educational efforts are required to improve adherence to COPD management guidance. GOLD recommendations should be discussed more intensively at professional and interdisciplinary meetings.
Declaration of Interest
JLM, PG, and AT have disclosed no potential conflicts of interest. JPD is an employee of Boehringer Ingelheim. CD has received speaker fees from AstraZeneca and Mundipharma. TD has received research grants and speaker fees from Novartis Pharma and Vifor Pharma. PNC has received speaker fees or honoraria from Boehringer Ingelheim, Cipla, Insignia Learning, and Lupin. JDL has received unrestricted grants from AstraZeneca, Boehringer Ingelheim, GSK, Mundipharma, Novartis, and Sanofi.
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Funding
References
- GOLD. 2019 Global Strategy for Prevention, Diagnosis and Management of COPD. Fontana, WI, USA: Global Initiative for Chronic Obstructive Lung Disease, Inc.; 2019 [cited 2019 July 1]. Available from: https://goldcopd.org/gold-reports/
- Buist AS, McBurnie MA, Vollmer WM, et al. International variation in the prevalence of COPD (the BOLD Study): a population-based prevalence study. Lancet. 2007;370(9589):741–750. DOI:10.1016/S0140-6736(07)61377-4
- Tschopp J, Dumont P, Hayoz D. True prevalence of COPD and its association with peripheral arterial disease in the internal medicine ward of a tertiary care hospital. Swiss Med Wkly. 2017;147:w14460.
- Sehl J, O'Doherty J, O'Connor R, et al. Adherence to COPD management guidelines in general practice? A review of the literature. Ir J Med Sci. 2018;187(2):403–407. DOI:10.1007/s11845-017-1651-7
- Foda HD, Brehm A, Goldsteen K, et al. Inverse relationship between nonadherence to original GOLD treatment guidelines and exacerbations of COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:209–214. DOI:10.2147/COPD.S119507
- Roberts CM, Lopez-Campos JL, Pozo-Rodriguez F, et al. European hospital adherence to GOLD recommendations for chronic obstructive pulmonary disease (COPD) exacerbation admissions. Thorax. 2013;68(12):1169–1171. DOI:10.1136/thoraxjnl-2013-203465
- Grewe FA, Sievi NA, Bradicich M, et al. Compliance of pharmacotherapy with GOLD guidelines: a longitudinal study in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2020;15:627–635. DOI:10.2147/COPD.S240444
- Davis KJ, Landis SH, Oh YM, et al. Continuing to confront COPD international physician survey: physician knowledge and application of COPD management guidelines in 12 countries. Int J Chron Obstruct Pulmon Dis. 2015;10:39–55.
- Jochmann A, Neubauer F, Miedinger D, et al. General practitioner's adherence to the COPD GOLD guidelines: baseline data of the Swiss COPD Cohort Study. Swiss Med Wkly. 2010;140:w13053.
- Urwyler P, Abu Hussein N, Bridevaux PO, et al. Predictive factors for exacerbation and re-exacerbation in chronic obstructive pulmonary disease: an extension of the Cox model to analyze data from the Swiss COPD cohort. Multidiscip Respir Med. 2019;14(1):7. DOI:10.1186/s40248-019-0168-5
- Ulrik CS, Hansen EF, Jensen MS, et al. Management of COPD in general practice in Denmark – participating in an educational program substantially improves adherence to guidelines. Int J Chron Obstruct Pulmon Dis. 2010;5:73–79.
- Román-Rodríguez M, Pardo MG, López LG, et al. Enhancing the use of Asthma and COPD Assessment Tools in Balearic Primary Care (ACATIB): a region-wide cluster-controlled implementation trial. NPJ Prim Care Respir Med. 2016;26:16003. DOI:10.1038/npjpcrm.2016.3
- López-Campos JL, Abad Arranz M, Calero Acuña C, et al. Determinants for changing the treatment of COPD: a regression analysis from a clinical audit. Int J Chron Obstruct Pulmon Dis. 2016;11:1171–1178. DOI:10.2147/COPD.S103614
- Price D, West D, Brusselle G, et al. Management of COPD in the UK primary-care setting: an analysis of real-life prescribing patterns. Int J Chron Obstruct Pulmon Dis. 2014;9:889–904. DOI:10.2147/COPD.S62750
- Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease 2017 report. GOLD executive summary. Am J Respir Crit Care Med. 2017;195(5):557–582. DOI:10.1164/rccm.201701-0218PP
- Bourbeau J, Sebaldt RJ, Day A, et al. Practice patterns in the management of chronic obstructive pulmonary disease in primary practice: the CAGE study. Can Respir J. 2008;15(1):13–19. DOI:10.1155/2008/173904
- Perez X, Wisnivesky JP, Lurslurchachai L, et al. Barriers to adherence to COPD guidelines among primary care providers. Respir Med. 2012;106(3):374–381. DOI:10.1016/j.rmed.2011.09.010
- White P, Thornton H, Pinnock H, Georgopoulou S, et al. Overtreatment of COPD with inhaled corticosteroids – implications for safety and costs: cross-sectional observational study. PLoS One. 2013;8(10):e75221. DOI:10.1371/journal.pone.0075221
- Lopez-Campos JL, Navarrete BA, Soriano JB, et al. Determinants of medical prescriptions for COPD care: an analysis of the EPOCONSUL clinical audit. Int J Chron Obstruct Pulmon Dis. 2018;13:2279–2288. DOI:10.2147/COPD.S160842
- Ernst P, Saad N, Suissa S. Inhaled corticosteroids in COPD: the clinical evidence. Eur Respir J. 2015;45(2):525–537. DOI:10.1183/09031936.00128914
- Kaplan AG. Applying the wisdom of stepping down inhaled corticosteroids in patients with COPD: a proposed algorithm for clinical practice. Int J Chron Obstruct Pulmon Dis. 2015;10:2535–2548. DOI:10.2147/COPD.S93321
- Miravitlles M, Cosio BG, Arnedillo A, et al. A proposal for the withdrawal of inhaled corticosteroids in the clinical practice of chronic obstructive pulmonary disease. Respir Res. 2017;18(1):198. DOI:10.1186/s12931-017-0682-y