Observational UK cohort study to describe intermittent oral corticosteroid prescribing patterns and their association with adverse outcomes in asthma.

INTRODUCTION: Oral corticosteroids (OCS) for asthma are associated with increased risks of developing adverse outcomes (adverse outcomes); no previous study has focused exclusively on intermittent OCS use. METHODS: This historical (2008-2019) UK cohort study using primary care medical records from two anonymised, real-life databases (OPCRD and CPRD) included patients aged≥4 years with asthma receiving only intermittent OCS. Patients were indexed on their first recorded intermittent OCS prescription for asthma and categorised by OCS prescribing patterns: one-off (single), less frequent (≥90 day gap) and frequent (<90 day gap). Non-OCS patients matched 1:1 on gender, age and index date served as controls. The association of OCS prescribing patterns with OCS-related AO risk was studied, stratified by age, Global Initiative for Asthma (GINA) 2020 treatment step, and pre index inhaled corticosteroid (ICS) and short-acting ß2-agonist (SABA) prescriptions using a multivariable Cox-proportional hazard model. FINDINGS: Of 476 167 eligible patients, 41.7%, 26.8% and 31.6% had one-off, less frequent and frequent intermittent OCS prescribing patterns, respectively. Risk of any AO increased with increasingly frequent patterns of intermittent OCS versus non-OCS (HR; 95% CI: one-off 1.19 (1.18 to 1.20), less frequent 1.35 (1.34 to 1.36), frequent 1.42 (1.42 to 1.43)), and was consistent across age, GINA treatment step and ICS and SABA subgroups. The highest risks of individual OCS-related adverse outcomes with increasingly frequent OCS were for pneumonia and sleep apnoea. CONCLUSION: A considerable proportion of patients with asthma receiving intermittent OCS experienced a frequent prescribing pattern. Increasingly frequent OCS prescribing patterns were associated with higher risk of OCS-related adverse outcomes. Mitigation strategies are needed to minimise intermittent OCS prescription in primary care.

Budesonide/Glycopyrrolate/Formoterol for the Management of COPD in a UK Primary Care Population: Real-World Use and Early Medication Success.

Purpose: Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data. Patients and Methods: Patients with a recorded diagnostic COPD code who started BGF with ≥2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥70% (defined a priori). Results: Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV1: 54.5%), were highly symptomatic (mMRC ≥2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting ß2-agonist (SABA) over-use (≥3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period. Conclusion: The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days.

Healthcare Resource Utilization Associated with Intermittent Oral Corticosteroid Prescribing Patterns in Asthma.

Purpose: Oral corticosteroid (OCS) use for asthma is associated with considerable healthcare resource utilization (HCRU) and costs. However, no study has investigated this in relation to patterns of intermittent OCS prescription. Methods: This historical UK cohort study used primary care medical records, linked to Hospital Episode Statistics, from 2008 to 2019, of patients (≥4 years old) with asthma prescribed intermittent OCS. Patients were categorized by OCS prescribing pattern (one-off [single], less frequent [≥90-day gap] and frequent [<90-day gap]) and matched 1:1 (by sex, age and index date) with people never prescribed OCS with/without asthma. HCRU (reported as episodes, except for length of hospital stay [days] and any prescription [records]) and associated costs were compared between intermittent OCS and non-OCS cohorts, and among intermittent OCS prescribing patterns. Results: Of 149,191 eligible patients, 50.3% had one-off, 27.4% less frequent, and 22.3% frequent intermittent OCS prescribing patterns. Annualized non-respiratory HCRU rates were greater in the intermittent OCS versus non-OCS cohorts for GP visits (5.93 vs 4.70 episodes, p < 0.0001), hospital admissions (0.24 vs 0.16 episodes, p < 0.0001), and length of stay (1.87 vs 1.58 days, p < 0.0001). In the intermittent OCS cohort, rates were highest in the frequent prescribing group for GP visits (7.49 episodes; p < 0.0001 vs one-off), length of stay (2.15 days; p < 0.0001) and any prescription including OCS (25.22 prescriptions; p < 0.0001). Mean per-patient non-respiratory related and all-cause HCRU-related costs were higher with intermittent OCS than no OCS (£3902 vs £2722 and £8623 vs £4929, respectively), as were mean annualized costs (£565 vs £313 and £1526 vs £634, respectively). A dose-response relationship existed; HCRU-related costs were highest in the frequent prescribing cohort (p < 0.0001). Conclusion: Intermittent OCS use and more frequent intermittent OCS prescription patterns were associated with increased HCRU and associated costs. Improved asthma management is needed to reduce reliance on intermittent OCS in primary care.

Longitudinal patterns of intermittent oral corticosteroid therapy for asthma in the United Kingdom.

Background: Increasing frequency of intermittent oral corticosteroid (OCS) prescription and cumulative OCS exposure increase the risk of OCS-related adverse outcomes. Objective: We sought to describe the evolution and trajectory of intermittent OCS prescription patterns in patients with asthma and investigate risk factors independently associated with transitioning to a frequent prescription pattern. Methods: This historical cohort study included patients with active asthma managed in UK primary care and included in the Optimum Patient Care Research Database (OPCRD; opcrd.co.uk). Intermittent OCS prescription patterns were categorized as sporadic, infrequent, moderately frequent, or frequent. Prescription pattern sequences were described for those who had a frequent sequence in their final year of prescribing. We examined associations between OCS prescription pattern and the hazard of transitioning into a frequent intermittent OCS prescription pattern using multivariable Cox regression with a 10-year look-back period. Results: Of 105,229 patients with intermittent OCS prescriptions, 57.1% (n = 60,083) had a frequent OCS prescription pattern at some point. Irrespective of baseline pattern, most patients transitioned to frequent prescription during the look back. The strongest risk factors were a more frequent prescription pattern at the start of look-back period, a lower percentage peak expiratory flow rate, and higher Global Initiative for Asthma treatment step. Older age, female sex, obesity, and active smoking were also associated with a higher risk of transitioning. Conclusion: Our findings help identify those most at risk of transitioning to frequent intermittent OCS receipt and encourage earlier intervention with OCS-sparing treatments.

Data-Resource Profile: United Kingdom Optimum Patient Care Research Database.

Introduction: Electronic medical records (EMRs) maintained in primary care in the UK and collected and stored in EMR databases offer a world-leading resource for observational clinical research. We aimed to profile one such database: the Optimum Patient Care Research Database (OPCRD). Methods and Participants: The OPCRD, incepted in 2010, is a growing primary care EMR database collecting data from 992 general practices within the UK. It covers over 16.6 million patients across all four countries within the UK, and is broadly representative of the UK population in terms of age, sex, ethnicity and socio-economic status. Patients have a mean duration of 11.7 years' follow-up (SD 17.50), with a majority having key summary data from birth to last data entry. Data for the OPCRD are collected incrementally monthly and extracted from all of the major clinical software systems used within the UK and across all four coding systems (Read version 2, Read CTV3, SNOMED DM+D and SNOMED CT codes). Via quality-improvement programmes provided to GP surgeries, the OPCRD also includes patient-reported outcomes from a range of disease-specific validated questionnaires, with over 66,000 patient responses on asthma, COPD, and COVID-19. Further, bespoke data collection is possible by working with GPs to collect new research via patient-reported questionnaires. Findings to Date: The OPCRD has contributed to over 96 peer-reviewed research publications since its inception encompassing a broad range of medical conditions, including COVID-19. Conclusion: The OPCRD represents a unique resource with great potential to support epidemiological research, from retrospective observational studies through to embedded cluster-randomised trials. Advantages of the OPCRD over other EMR databases are its large size, UK-wide geographical coverage, the availability of up-to-date patient data from all major GP software systems, and the unique collection of patient-reported information on respiratory health.

Application of an algorithm to analyze patterns of intermittent oral corticosteroid use in asthma.

An algorithm to describe patterns of intermittent oral corticosteroid use in the UK (n = 476,167) found that one-third of patients receiving intermittent oral corticosteroids for asthma only had short gaps (<90 days) between oral corticosteroid prescriptions sometime during follow-up. The increasing frequency pattern was more likely in patients with greater asthma severity and with more short-acting ß2-agonist use at baseline. Our approach may provide a clinically relevant representation of intermittent oral corticosteroid use in asthma.

Potential Severe Asthma Hidden in UK Primary Care.

BACKGROUND: Severe asthma may be underrecognized in primary care. OBJECTIVE: Identify and quantify patients with potential severe asthma (PSA) in UK primary care, the proportion not referred, and compare primary care patients with PSA with patients with confirmed severe asthma from UK tertiary care. METHODS: This was a historical cohort study including patients from the Optimum Patient Care Research Database (aged ≥16 years, active asthma diagnosis pre-2014) and UK patients in the International Severe Asthma Registry (UK-ISAR aged ≥18 years, confirmed severe asthma in tertiary care). In the OPCRD, PSA was defined as Global INitiative for Asthma 2018 step 4 treatment and 2 or more exacerbations/y or at Global INitiative for Asthma step 5. The proportion of these patients and their referral status in the last year were quantified. Demographic and clinical characteristics of groups were compared. RESULTS: Of 207,557 Optimum Patient Care Research Database patients with asthma, 16,409 (8%) had PSA. Of these, 72% had no referral/specialist review in the past year. Referred patients with PSA tended to have greater prevalence of inhaled corticosteroid/long-acting ß2-agonist add-ons (54.1 vs 39.8%), and experienced significantly (P < .001) more exacerbations per year (median, 3 vs 2/y), worse asthma control, and worse lung function (% predicted postbronchodilator FEV1/forced vital capacity, 0.69 vs 0.72) versus nonreferred patients. Confirmed patients with severe asthma (ie, UK patients in the International Severe Asthma Registry) were younger (51 vs 65 years; P < .001), and significantly (P < .001) more likely to have uncontrolled asthma (91.4% vs 62.5%), a higher exacerbation rate (4/y [initial assessment] vs 3/y), use inhaled corticosteroid/long-acting ß2-agonist add-ons (67.7% vs 54.1%), and have nasal polyposis (24.2% vs 6.8) than referred patients with PSA. CONCLUSIONS: Large numbers of patients with PSA in the United Kingdom are underrecognized in primary care. These patients would benefit from a more systematic assessment in primary care and possible specialist referral.