COPD, 11:300–309, 2014 ISSN: 1541-2555 print / 1541-2563 online Copyright © Informa Healthcare USA, Inc. DOI: 10.3109/15412555.2013.841671
ORIGINAL RESEARCH
COPD Exacerbation Frequency, Pharmacotherapy and Resource Use: An Observational Study in UK Primary Care
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
Mike Thomas,1 Amr Radwan,2 Carol Stonham,3 and Sam Marshall4 1
Department of Primary Care Research, University of Southampton, UK
2
Novartis Pharmaceuticals, Frimley, United Kingdom
3
Minchinhampton Surgery, Stroud, United Kingdom
4
pH Associates, Marlow, United Kingdom
Abstract Chronic Obstructive Pulmonary Disease (COPD) management represents a significant health resource use burden. Understanding of current resource use, treatment strategies and outcomes can improve future COPD management, for patient benefit and to aid efficient service delivery. This study aimed to describe exacerbation frequency, pharmacotherapy and health resource use in COPD management in routine UK primary care. A retrospective, observational study using routine clinical records of 511 patients with COPD, was undertaken in 10 General Practices in England. Up to 3 years’ patient data were collected and analysed. 75% (234/314) patients with mild-moderate COPD (≥50% predicted FEV1) received inhaled corticosteroids (ICS). 11% of patients (54/511) received ICS monotherapy. Mean (standard deviation) annual exacerbation frequency was 1.1 (1.2) in mildmoderate, 1.7 (1.6) in severe (30–49% predicted FEV1) and 2.2 (2.0) in very severe (0.1
Low BMI
4 (4%)
24 (7%)
7 (10%)
>0.1
Osteoporosis
9 (9%)
27 (8%)
10 (14%)
>0.1
Depression
5 (5%)
51 (15%)
17 (25%)
0.1
Any of the above co-morbidities
70 (72%)
264 (77%)
62 (90%)
www.copdjournal.com
0.004
303
304
Thomas et al.
Table 5. Resource use, stratified by exacerbation frequency
Table 4. Resource use, stratified by COPD severity
Exacerbation frequency group
COPD severity Mild-moderate (n = 314)
Severe (n = 145)
Very severe (n = 52)
Median (IQR) no. of primary care COPD contacts/year
2.33 (1.45–3.33)
3.33 (2.33–5.00)
3.67 (2.67–6.42)
Median (IQR) no. of secondary care COPD visits/year
0.00 (0.00–0.33)
0.33 (0.00–1.00)
1.00 (0.00–2.08)
Median (IQR) no. of COPD hospitalisations/year
0.00 (0.00–0.00)
0.00 (0.00–0.00)
0.00 (0.00–0.33)
N (%) patients hospitalised for COPD/yeara
13.3 (4%)
14.3 (10%)
8.3 (16%)
Median (IQR) length of hospital stay (days)
5 (2–10)
5 (2–9)
6 (3–11)
NonInfrequentFrequentexacerbators exacerbators exacerbators (n = 97) (n = 345) (n = 69)
ICS were prescribed for 234/314 (75%) of patients with mild-moderate COPD, including 37/53 (70%) of patients with no asthma diagnosis and no recorded exacerbations (Figure 3). LABA, LAMA and ICS use (Table 6) In all, 403 patients (79%) were prescribed a LABA (as either a single agent, combination inhaler with ICS or both) and 295 (58%) a LAMA. And, 393 patients (77%) were prescribed a LABA and/or LAMA in combination with ICS, and 236 (46%) triple therapy (LABA+LAMA+ICS). The proportion of patients prescribed triple therapy was similar in the groups of patients with and without recorded
2.67 (2.00–3.67)
6.67 (5.33–8.67)
Median (IQR) no. of secondary care COPD visits/year
0.00 (0.00–0.00)
0.00 (0.00–0.67)
1.00 (0.33–2.67)
Median (IQR) no. of COPD hospitalisations/year
0.00 (0.00–0.00)
0.00 (0.00–0.00)
0.00 (0.00–0.33)
N (%) patients hospitalised for COPD/yeara
0.7 (1%)
21.0 (6%)
14.3 (21%)
Median (IQR) length of hospital stay (days)
7.00 (6–8)
5.50 (3–10)
5.00 (2–10)
co-morbidities (181/396 (46%) and 55/115 (48%) respectively). Analysis of LABA and LAMA use by exacerbation frequency showed that 10/69 (14%) of frequentexacerbators were not prescribed a LABA, 17 (25%) did not receive a LAMA and 8 (12%) received no ICS during the 3 year study period. 46/69 (67%) of frequentexacerbators received combined treatment with all three (LABA+LAMA+ICS). Chi-squared tests of consistency carried out on the distribution of the number of exacerbations for each type of treatment showed no significant
86%
Contacts for roune COPD management
a
Percentage of primary care contacts
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
Number of patients hospitalised per year is the mean of the number of patients hospitalised in each year of the 3 year observation period, hence not a whole number.
90%
1.33 (0.67–2.00)
a Number of patients hospitalised per year is the average (mean) of the number of patients hospitalised in each year of the observation period, hence not a whole number.
a
2.
Median (IQR) no. of primary care COPD contacts/year
Contacts for COPD exacerbaon management
80% 70% 58%
60% 50% 40%
39%
30% 20% 13% 10% 3%
1%
0% GP
Nurse or respiratory nurse
Other
b
Personnel seen Figure 2. Distribution of personnel seen during COPD-related primary care contacts for routine or exacerbation management. aPercentage of all recorded primary care contacts occurring during the study period. Includes GP surgery visits, home visits and telephone contacts. b‘Other’ is comprised predominantly of Community Respiratory Team and physiotherapist contacts. Copyright © 2014 Informa Healthcare USA, Inc
Figure 3. Proportion of patients prescribed ICS during the study period, according to COPD severity, presence of asthma and exacerbation frequency. an values show the total number of patients within each sub-group. bThe boxes below the n values show the number (and percentage) of patients within each sub-group who were prescribed ICS during the study period.
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
COPD exacerbation frequency, pharmacotherapy and resource use
www.copdjournal.com
305
306
Thomas et al.
Table 6. Drug treatments prescribed for routine COPD management during the observation period – according to exacerbation frequency Exacerbation frequency group Non-exacerbators (n = 97)
Infrequentexcerbators (n = 345)
Frequentexacerbators (n = 69)
Overall (n = 511)
Drug treatmentsa Any LABA (single agent or combination LABA-ICS device)
64 (66%)
280 (81%)
59 (86%)
403 (79%)
Any LAMA
40 (41%)
203 (59%)
52 (75%)
295 (58%)
Any ICS (single agent or combination LABA-ICS device)
66 (68%)
286 (83%)
61 (88%)
413 (81%)
ICS monotherapy (without LABA or LAMA)
18 (19%)
32 (9%)
4 (6%)
54 (11%)
LABA monotherapy (without LAMA or ICS)
10 (10%)
22 (6%)
1 (1%)
33 (6%)
LAMA monotherapy (without LABA or ICS)
12 (12%)
69 (20%)
14 (20%)
95 (19%)
8 (8%)
13 (4%)
0 (0%)
21 (4%)
Drug combinationsa
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
LABA + LAMA (without ICS) LABA and/or LAMA (without ICS)
23 (24%)
92 (27%)
15 (22%)
130 (25%)
LABA + ICS (without LAMA)
40 (41%)
175 (51%)
35 (51%)
250 (49%)
LAMA + ICS (without LABA)
4 (4%)
12 (3%)
3 (4%)
19 (4%)
LABA+LAMA+ICS
27 (28%)
163 (47%)
46 (67%)
236 (46%)
LABA and/or LAMA (with ICS)
59 (61%)
274 (79%)
60 (87%)
393 (77%)
a
Drug treatments are not mutually exclusive, reflecting the fact that patients may have moved between different combinations of drugs during the observation period.
difference between centres (i.e., all differences could be explained by the expected random variation).
Discussion This article reports the results of a retrospective, observational research study of 511 patients with COPD, recruited from 10 primary care practices in England. The mean time from diagnosis to data collection for patients in the study sample was 8 years, showing that the majority had well-established COPD at the time of data collection. The rate of co-morbidities was high, with 77% of patients overall having at least one co-morbidity recorded. The proportion of patients in this study with ischaemic heart disease, type II diabetes, depression and high BMI was 26%, 14%, 14% and 21% (respectively); these proportions were noted to be higher than national estimates (for England) for the prevalence of each disease (coronary heart disease – 20.8% of men and 10% of women aged 65–74 (7); diabetes (type I or type II) – 5.8% aged 17 or over (8); depression – 11.7% aged 18 or over (8); obesity – 10.7% aged 16 or over) (8). Then, 32% of patients in the sample had asthma also diagnosed and recorded. However, as objective supporting evidence of asthma diagnosis was not required, this is likely to be an overestimate of the true rate of concomitant asthma (previously reported at around 13%)(9) and is likely to reflect misdiagnosis in patients with nonspecific respiratory symptoms. A previous diagnosis of asthma can potentially explain the early use of ICS in patients with mild COPD, although we found high use of ICS in patients with mild-moderate COPD regardless of a previous asthma diagnosis. In line with previous research (10,11), the study results confirm that exacerbation frequency increases
with increasing physiological disease severity. However, our data demonstrate that patient all levels of disease severity may be non-exacerbators, infrequent-exacerbators or frequent-exacerbators; 8% of patients with mild-moderate COPD had ≥3 exacerbations/year, 9% with very severe COPD had no exacerbations during the 3-year period and the proportion of infrequentexacerbators was similar across severities. This discrepancy between physiological severity and exacerbation frequency was also observed in the ECLIPSE study (12) and is suggestive of a frequent-exacerbator ‘phenotype’, independent of disease severity. The proportion of non-exacerbators in the current study appears to be slightly lower than in the ECLIPSE study (19% of patients in this study vs 23% of patients in the ECLIPSE study had no exacerbations over the 3-year study period). If this is a true difference, it is difficult to attribute to our study having a more complete method of identifying COPD exacerbations, since we relied on routine documentation whereas in the ECLIPSE study, exacerbation details were specifically collected at study follow-up visits by investigators, with their patients. The difference may be due to the ECLIPSE patients receiving more optimal treatment. We found that a higher proportion of ‘frequentexacerbators’ than ‘non-exacerbators’ had at least one recorded co-morbidity and more patients in this group suffered from depression. Frequent exacerbators had high levels of resource use in all parameters measured, even when lung function was well maintained, and so accrued high direct health costs. An increase in the median number of COPD-related primary care contacts/year (from 1.33 to 2.67 to 6.67) was observed in the non-exacerbator, infrequent-exacerbator and frequentexacerbator groups (respectively); an increase was also Copyright © 2014 Informa Healthcare USA, Inc
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
COPD exacerbation frequency, pharmacotherapy and resource use observed in the proportion of patients hospitalised/year (1%, 6%, 21%, respectively). This observation has considerable economic importance, as a high proportion of medical expenditure for COPD occurs as a direct consequence of exacerbations (13–17). Unsurprisingly, we also found higher resource use in those with more impaired lung function, consistent with the findings of previous research (5, 13, 18–19). Given the economic impact of COPD exacerbations and their impact on patient outcomes, health status and quality of life (20–23), reducing the frequency and severity of exacerbations across all levels of disease severity, should be a key focus of COPD management, and management strategies may need to encompass risk-stratification for exacerbation frequency as well as physiological impairment. In terms of primary care resource use, we found that in UK practice, most routine COPD-related primary care contacts (58%) were with a practice nurse or respiratory nurse, although exacerbations were generally managed by GPs (86% of all contacts for exacerbation management). This suggests that nurse-led management occurs for routine but not for acute care. This study indicates an apparent over-use of inhaled corticosteroids (ICS) in patients with mild-moderate COPD, with 75% of patients in this sub-group prescribed ICS during the study period. The UK 2004 NICE guidelines which were current at the time of the study recommended that patients with an FEV1 ≥50% who are uncontrolled by a short-acting bronchodilator alone, should receive maintenance monotherapy with a LABA or LAMA. Add-on ICS were only recommended in those with FEV1
ORIGINAL RESEARCH
COPD Exacerbation Frequency, Pharmacotherapy and Resource Use: An Observational Study in UK Primary Care
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
Mike Thomas,1 Amr Radwan,2 Carol Stonham,3 and Sam Marshall4 1
Department of Primary Care Research, University of Southampton, UK
2
Novartis Pharmaceuticals, Frimley, United Kingdom
3
Minchinhampton Surgery, Stroud, United Kingdom
4
pH Associates, Marlow, United Kingdom
Abstract Chronic Obstructive Pulmonary Disease (COPD) management represents a significant health resource use burden. Understanding of current resource use, treatment strategies and outcomes can improve future COPD management, for patient benefit and to aid efficient service delivery. This study aimed to describe exacerbation frequency, pharmacotherapy and health resource use in COPD management in routine UK primary care. A retrospective, observational study using routine clinical records of 511 patients with COPD, was undertaken in 10 General Practices in England. Up to 3 years’ patient data were collected and analysed. 75% (234/314) patients with mild-moderate COPD (≥50% predicted FEV1) received inhaled corticosteroids (ICS). 11% of patients (54/511) received ICS monotherapy. Mean (standard deviation) annual exacerbation frequency was 1.1 (1.2) in mildmoderate, 1.7 (1.6) in severe (30–49% predicted FEV1) and 2.2 (2.0) in very severe (0.1
Low BMI
4 (4%)
24 (7%)
7 (10%)
>0.1
Osteoporosis
9 (9%)
27 (8%)
10 (14%)
>0.1
Depression
5 (5%)
51 (15%)
17 (25%)
0.1
Any of the above co-morbidities
70 (72%)
264 (77%)
62 (90%)
www.copdjournal.com
0.004
303
304
Thomas et al.
Table 5. Resource use, stratified by exacerbation frequency
Table 4. Resource use, stratified by COPD severity
Exacerbation frequency group
COPD severity Mild-moderate (n = 314)
Severe (n = 145)
Very severe (n = 52)
Median (IQR) no. of primary care COPD contacts/year
2.33 (1.45–3.33)
3.33 (2.33–5.00)
3.67 (2.67–6.42)
Median (IQR) no. of secondary care COPD visits/year
0.00 (0.00–0.33)
0.33 (0.00–1.00)
1.00 (0.00–2.08)
Median (IQR) no. of COPD hospitalisations/year
0.00 (0.00–0.00)
0.00 (0.00–0.00)
0.00 (0.00–0.33)
N (%) patients hospitalised for COPD/yeara
13.3 (4%)
14.3 (10%)
8.3 (16%)
Median (IQR) length of hospital stay (days)
5 (2–10)
5 (2–9)
6 (3–11)
NonInfrequentFrequentexacerbators exacerbators exacerbators (n = 97) (n = 345) (n = 69)
ICS were prescribed for 234/314 (75%) of patients with mild-moderate COPD, including 37/53 (70%) of patients with no asthma diagnosis and no recorded exacerbations (Figure 3). LABA, LAMA and ICS use (Table 6) In all, 403 patients (79%) were prescribed a LABA (as either a single agent, combination inhaler with ICS or both) and 295 (58%) a LAMA. And, 393 patients (77%) were prescribed a LABA and/or LAMA in combination with ICS, and 236 (46%) triple therapy (LABA+LAMA+ICS). The proportion of patients prescribed triple therapy was similar in the groups of patients with and without recorded
2.67 (2.00–3.67)
6.67 (5.33–8.67)
Median (IQR) no. of secondary care COPD visits/year
0.00 (0.00–0.00)
0.00 (0.00–0.67)
1.00 (0.33–2.67)
Median (IQR) no. of COPD hospitalisations/year
0.00 (0.00–0.00)
0.00 (0.00–0.00)
0.00 (0.00–0.33)
N (%) patients hospitalised for COPD/yeara
0.7 (1%)
21.0 (6%)
14.3 (21%)
Median (IQR) length of hospital stay (days)
7.00 (6–8)
5.50 (3–10)
5.00 (2–10)
co-morbidities (181/396 (46%) and 55/115 (48%) respectively). Analysis of LABA and LAMA use by exacerbation frequency showed that 10/69 (14%) of frequentexacerbators were not prescribed a LABA, 17 (25%) did not receive a LAMA and 8 (12%) received no ICS during the 3 year study period. 46/69 (67%) of frequentexacerbators received combined treatment with all three (LABA+LAMA+ICS). Chi-squared tests of consistency carried out on the distribution of the number of exacerbations for each type of treatment showed no significant
86%
Contacts for roune COPD management
a
Percentage of primary care contacts
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
Number of patients hospitalised per year is the mean of the number of patients hospitalised in each year of the 3 year observation period, hence not a whole number.
90%
1.33 (0.67–2.00)
a Number of patients hospitalised per year is the average (mean) of the number of patients hospitalised in each year of the observation period, hence not a whole number.
a
2.
Median (IQR) no. of primary care COPD contacts/year
Contacts for COPD exacerbaon management
80% 70% 58%
60% 50% 40%
39%
30% 20% 13% 10% 3%
1%
0% GP
Nurse or respiratory nurse
Other
b
Personnel seen Figure 2. Distribution of personnel seen during COPD-related primary care contacts for routine or exacerbation management. aPercentage of all recorded primary care contacts occurring during the study period. Includes GP surgery visits, home visits and telephone contacts. b‘Other’ is comprised predominantly of Community Respiratory Team and physiotherapist contacts. Copyright © 2014 Informa Healthcare USA, Inc
Figure 3. Proportion of patients prescribed ICS during the study period, according to COPD severity, presence of asthma and exacerbation frequency. an values show the total number of patients within each sub-group. bThe boxes below the n values show the number (and percentage) of patients within each sub-group who were prescribed ICS during the study period.
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
COPD exacerbation frequency, pharmacotherapy and resource use
www.copdjournal.com
305
306
Thomas et al.
Table 6. Drug treatments prescribed for routine COPD management during the observation period – according to exacerbation frequency Exacerbation frequency group Non-exacerbators (n = 97)
Infrequentexcerbators (n = 345)
Frequentexacerbators (n = 69)
Overall (n = 511)
Drug treatmentsa Any LABA (single agent or combination LABA-ICS device)
64 (66%)
280 (81%)
59 (86%)
403 (79%)
Any LAMA
40 (41%)
203 (59%)
52 (75%)
295 (58%)
Any ICS (single agent or combination LABA-ICS device)
66 (68%)
286 (83%)
61 (88%)
413 (81%)
ICS monotherapy (without LABA or LAMA)
18 (19%)
32 (9%)
4 (6%)
54 (11%)
LABA monotherapy (without LAMA or ICS)
10 (10%)
22 (6%)
1 (1%)
33 (6%)
LAMA monotherapy (without LABA or ICS)
12 (12%)
69 (20%)
14 (20%)
95 (19%)
8 (8%)
13 (4%)
0 (0%)
21 (4%)
Drug combinationsa
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
LABA + LAMA (without ICS) LABA and/or LAMA (without ICS)
23 (24%)
92 (27%)
15 (22%)
130 (25%)
LABA + ICS (without LAMA)
40 (41%)
175 (51%)
35 (51%)
250 (49%)
LAMA + ICS (without LABA)
4 (4%)
12 (3%)
3 (4%)
19 (4%)
LABA+LAMA+ICS
27 (28%)
163 (47%)
46 (67%)
236 (46%)
LABA and/or LAMA (with ICS)
59 (61%)
274 (79%)
60 (87%)
393 (77%)
a
Drug treatments are not mutually exclusive, reflecting the fact that patients may have moved between different combinations of drugs during the observation period.
difference between centres (i.e., all differences could be explained by the expected random variation).
Discussion This article reports the results of a retrospective, observational research study of 511 patients with COPD, recruited from 10 primary care practices in England. The mean time from diagnosis to data collection for patients in the study sample was 8 years, showing that the majority had well-established COPD at the time of data collection. The rate of co-morbidities was high, with 77% of patients overall having at least one co-morbidity recorded. The proportion of patients in this study with ischaemic heart disease, type II diabetes, depression and high BMI was 26%, 14%, 14% and 21% (respectively); these proportions were noted to be higher than national estimates (for England) for the prevalence of each disease (coronary heart disease – 20.8% of men and 10% of women aged 65–74 (7); diabetes (type I or type II) – 5.8% aged 17 or over (8); depression – 11.7% aged 18 or over (8); obesity – 10.7% aged 16 or over) (8). Then, 32% of patients in the sample had asthma also diagnosed and recorded. However, as objective supporting evidence of asthma diagnosis was not required, this is likely to be an overestimate of the true rate of concomitant asthma (previously reported at around 13%)(9) and is likely to reflect misdiagnosis in patients with nonspecific respiratory symptoms. A previous diagnosis of asthma can potentially explain the early use of ICS in patients with mild COPD, although we found high use of ICS in patients with mild-moderate COPD regardless of a previous asthma diagnosis. In line with previous research (10,11), the study results confirm that exacerbation frequency increases
with increasing physiological disease severity. However, our data demonstrate that patient all levels of disease severity may be non-exacerbators, infrequent-exacerbators or frequent-exacerbators; 8% of patients with mild-moderate COPD had ≥3 exacerbations/year, 9% with very severe COPD had no exacerbations during the 3-year period and the proportion of infrequentexacerbators was similar across severities. This discrepancy between physiological severity and exacerbation frequency was also observed in the ECLIPSE study (12) and is suggestive of a frequent-exacerbator ‘phenotype’, independent of disease severity. The proportion of non-exacerbators in the current study appears to be slightly lower than in the ECLIPSE study (19% of patients in this study vs 23% of patients in the ECLIPSE study had no exacerbations over the 3-year study period). If this is a true difference, it is difficult to attribute to our study having a more complete method of identifying COPD exacerbations, since we relied on routine documentation whereas in the ECLIPSE study, exacerbation details were specifically collected at study follow-up visits by investigators, with their patients. The difference may be due to the ECLIPSE patients receiving more optimal treatment. We found that a higher proportion of ‘frequentexacerbators’ than ‘non-exacerbators’ had at least one recorded co-morbidity and more patients in this group suffered from depression. Frequent exacerbators had high levels of resource use in all parameters measured, even when lung function was well maintained, and so accrued high direct health costs. An increase in the median number of COPD-related primary care contacts/year (from 1.33 to 2.67 to 6.67) was observed in the non-exacerbator, infrequent-exacerbator and frequentexacerbator groups (respectively); an increase was also Copyright © 2014 Informa Healthcare USA, Inc
COPD Downloaded from informahealthcare.com by Lakehead University on 10/28/14 For personal use only.
COPD exacerbation frequency, pharmacotherapy and resource use observed in the proportion of patients hospitalised/year (1%, 6%, 21%, respectively). This observation has considerable economic importance, as a high proportion of medical expenditure for COPD occurs as a direct consequence of exacerbations (13–17). Unsurprisingly, we also found higher resource use in those with more impaired lung function, consistent with the findings of previous research (5, 13, 18–19). Given the economic impact of COPD exacerbations and their impact on patient outcomes, health status and quality of life (20–23), reducing the frequency and severity of exacerbations across all levels of disease severity, should be a key focus of COPD management, and management strategies may need to encompass risk-stratification for exacerbation frequency as well as physiological impairment. In terms of primary care resource use, we found that in UK practice, most routine COPD-related primary care contacts (58%) were with a practice nurse or respiratory nurse, although exacerbations were generally managed by GPs (86% of all contacts for exacerbation management). This suggests that nurse-led management occurs for routine but not for acute care. This study indicates an apparent over-use of inhaled corticosteroids (ICS) in patients with mild-moderate COPD, with 75% of patients in this sub-group prescribed ICS during the study period. The UK 2004 NICE guidelines which were current at the time of the study recommended that patients with an FEV1 ≥50% who are uncontrolled by a short-acting bronchodilator alone, should receive maintenance monotherapy with a LABA or LAMA. Add-on ICS were only recommended in those with FEV1
