Discussion
This study retrospectively assessed the characteristics of patients with COPD receiving ICS/LABA therapy in a primary care setting in England. Overall, in the 12 months prior to index, demographics and clinicalcharacteristics in this patient population were generally similar across indexed therapies. Compared with those receiving BDP/FOR or BUD/FOR, incident users indexed on Other ICS/LABA combinations appeared to have more severe disease based on their history of moderate/severe AECOPD and GOLD 2019 categorisation. Patients who had received ICS/LABA therapy prior to index (prevalent users) also showed evidence of more severe disease and had a higher prevalence of comorbidities (including asthma) than those who had not received ICS/LABA therapy prior to index (incident users).
The GOLD strategy report and the UK NICEguidelines suggest that ICS/LABA may be prescribed as IMT for patients with COPD and a history of asthma.3 5 Our finding that over 60% of prevalent users in England had a history of asthma suggests that these patients may frequently be prescribed ICS/LABA. Moreover,approximately 20% of incident users had a current asthma diagnosis, further suggesting that ICS/LABA may have been prescribed for that reason and as per UK NICE guidelines.
The GOLD strategy report recommendsconsideration of ICS/LABA as IMT for patients with a history of asthma or patients with a significant exacerbation history and a blood eosinophil count >300 cells/µL and a stepwise escalation from a LAMA or a LABA toICS/LABA (guided by blood eosinophil count) for patients who continue to experience exacerbations.3 In this study, fewer than 20% of incident users were receiving an LAMA prior to an ICS/LABA and over one-third were IMT users receiving no maintenance therapy for COPD before initiating treatment with an ICS/LABA. Less than half of incident users had an exacerbation during the baseline period, suggesting that ICS/LABA is not being prescribed based on exacerbation history, even though in COPD the primary role of ICS is to reduce the risk of exacerbations.3 19 Furthermore, approximately 50% of patients were not taking any treatment in the 3 months prior to initiating treatment with an ICS/LABA, which also provides evidence that prescribing patterns are not in accordance with the stepwise approach recommended by GOLD. These results suggest that this patientpopulation may not be optimally treated in England, although historical or current asthma may have influenced the prescribing decision. However, we cannot say with certainty that the GOLD strategy reportrecommendations were not being followed. For example, the mean blood eosinophil count <300 cells/µL does not take into account the distribution of eosinophil levels across the population, nor the potential reduction in levels in patients who may have been taking oral corticosteroids when blood tests were taken. This was accounted for within the methodology by only considering bloodeosinophil measurements not within 14 days of an AECOPD or prescription of oral corticosteroids. Conversely, the treatment patterns observed may be consistent with NICE guidelines, which recommend initiatingtreatment with ICS/LABA dual therapy in patients withasthmatic features.5 This is in line with several studies that have shown disparities between international treatment recommendations and national prescribing practices in the UK and in other countries.20–24
Disparities between a particular set ofrecommendations and prescribing practices in primary care may be related to variation in familiarity and implementation across different international, national and localguidelines.23 25 In support of this, we observed geographical variation in prescribing patterns, with most prevalent and incident users located in western regions, likely due to differing practices across local clinical commissioning groups and the greater representation of patients in these regions in the CPRD-Aurum database. In England, it has been identified that referrals, diagnosis andtreatments differ significantly across practices; aspects include quality of spirometry undertaken and interpretation of results, support for self-care and treatment optimisation.26 Furthermore, clinical commissioning groups may lead to different regional pricing and prescription switching, further influencing prescribing patterns in primary care. These patterns represent substantial variation in care given to patients with COPD within England; almost half of non-triple and IMT patients were in the two IMD quintiles indicative of greater deprivation. A recent post-hoc analysis of the Salford Lung Studies in COPD has also shown that 52% of participants included were in the most deprived quintile.27 While the level of deprivation did not influence treatment outcomes in the Salford Lung Studies, it was found to be associated with greater HCRU and costs.27 The geographical variation in prescribing patterns and its effects should be taken into closeconsideration in future observational studies as a potential confounding factor. This variation in care, along with the specifics of patients’ primary and secondary care, could affect outcomes and subsequently the generalisability of any findings from specific regions of England.Furthermore, this variation highlights how diagnostic andtreatment decisions by primary care physicians also drive prescribing patterns in conjunction with patients’characteristics. Further studies exploring the drivers behind inconsistent implementation and variation in treatment of patients diagnosed with COPD by GPs in primary care will be of interest, as the discrepancies in diagnosis and management suggest that prescribing patterns may be affected.26
Prior COPD-related and all-cause HCRU were similar between non-triple and IMT users and across indexed therapies, even though non-triple users experienced numerically more moderate-to-severe and moderate AECOPDs in the year prior to index and had clinical characteristics potentially indicative of more advanced disease than IMT users. The lack of numerical differences in total healthcare costs may be due to similar inpatient stay costs, which seemed to be the greatest contributor to COPD-related and all-cause healthcare costs among patients who used healthcare services. Inpatient stays seemed to be the main driver of costs even though only approximately one-third of patients had experienced an inpatient visit over the 12-month period prior to index; this is in line with several studies that have shownhospitalisations are the main drivers of direct healthcare costs in patients with COPD.4 28 29 Costs for GP visits werenumerically lower than for inpatient stays, even though nearly all patients (>99%) had GP consultations. In contrast, a previous UK retrospective study showed that GPinteractions contributed more to costs than moderate-to-severe exacerbations and non-COPD hospitalisations.30 This disparity may have arisen because a smaller proportion of patients with severe (FEV1 ≥30%–<50% predicted) or very severe COPD (FEV1 <30% predicted) were included in that study (27%) compared with the present study (approximately 32%–36%), as these patients would be expected to experience more frequent and severeexacerbations than populations with milder disease.
This study has several strengths, including thereal-world insight into prescribing patterns in England and the large cohort which is representative of the UK population. Patients with COPD are largely managed in the primary care setting in the UK and thusCPRD-Aurum adequately captures the majority of a patient’s COPD healthcare journey, even though it does not cover privately insured patients. This study is not without its limitations. First, only medications prescribed in the primary care setting were recorded, so patients may have initiated ICS/LABA therapy earlier than the index date if they received an earlier prescription through secondary care. Second, in this study, over 20% of patients had a current asthma diagnosis. In England, it has been shown that clinicians have difficulties diagnosing up to 19.8% of patients based on clinical presentation and spirometry results, which can lead to inappropriatediagnoses and treatment initiation.31 The approach used in this study does not allow for potential misdiagnosis of asthma as COPD and vice versa to be identified; as such, the potential inclusion of patients with asthma–COPD overlap syndrome cannot be ruled out. Similarly, COPD and COPD-related chronic airflow limitations were not differentiated; however, patients were required to have received a diagnosis of COPD, be at least 35 years of age and have an FEV1/FVC ratio of <0.7, in line with adefinition of COPD which was validated against patient notes.32 Third, approximately 25% of patients were missing MRC score and 25% of patients were missing GOLD status data; however, these were not necessary for inclusion in the study and as such did not impact therepresentativeness of the study sample. In addition, approximately 50% of patients were missing eosinophil count data, which precluded further analysis on whether this treatable trait is taken into account in ICS prescribing in a real-world setting in England. Patients with asthma and COPD may also require a different treatment from those with COPD only and could arguably be classified as having asthma–COPD overlap syndrome rather than asthma and COPD. However, suggested treatment generally involves both ICS and LABA therapy33 and they were considered appropriate to include in this cohort. Additionally, a small percentage of patients in the cohort are neither current nor historical smokers. However, the proportions of smokers in this study are in line with what would be expected in a population of patients with COPD in the UK.34 Finally, direct costs may have been underestimated as some tariffs are negotiated locally and not nationally.