Annie Burden

Asthma control with extrafine‐particle hydrofluoroalkane–beclometasone vs. large‐particle chlorofluorocarbon–beclometasone: a real‐world observational study

Background The extrafine‐particle formulation of hydrofluoroalkane–beclometasone (EF HFA–BDP; Qvar®) demonstrates improved total and small airway deposition compared with large‐particle chlorofluorocarbon (CFC)–BDP. In some short‐term studies, EF HFA–BDP provides greater effects on lung function than CFC–BDP, and hence is recommended to be prescribed at a lower dose, but whether there are differences in asthma outcomes during long‐term treatment is unknown.

Effectiveness of same versus mixed asthma inhaler devices: a retrospective observational study in primary care.

Purpose Correct use of inhaler devices is fundamental to effective asthma management but represents an important challenge for patients. The correct inhalation manoeuvre differs markedly for different inhaler types. The objective of this study was to compare outcomes for patients prescribed the same inhaler device versus mixed device types for asthma controller and reliever therapy. Methods This retrospective observational study identified patients with asthma (ages 4-80 years) in a large primary care database who were prescribed an inhaled corticosteroid (ICS) for the first time. We compared outcomes for patients prescribed the same breath-actuated inhaler (BAI) for ICS controller and salbutamol reliever versus mixed devices (BAI for controller and pressurised metered-dose inhaler [pMDI] for reliever). The 2-year study included 1 baseline year before the ICS prescription (to identify and correct for confounding factors) and 1 outcome year. Endpoints were asthma control (defined as no hospital attendance for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection) and severe exacerbations (hospitalisation or oral corticosteroids for asthma). Results Patients prescribed the same device (n=3,428) were significantly more likely to achieve asthma control (adjusted odds ratio, 1.15; 95% confidence interval [CI], 1.02-1.28) and recorded significantly lower severe exacerbation rates (adjusted rate ratio, 0.79; 95% CI, 0.68-0.93) than those prescribed mixed devices (n=5,452). Conclusions These findings suggest that, when possible, the same device should be prescribed for both ICS and reliever therapy when patients are initiating ICS.

Clinical and cost effectiveness of switching asthma patients from fluticasone-salmeterol to extra-fine particle beclometasone-formoterol: a retrospective matched observational study of real-world patients

Background: Efficacy trials suggest that extra-fine particle beclometasone dipropionate-formoterol (efBDP-FOR) is comparable to fluticasone propionate-salmeterol (FP-SAL) in preventing asthma exacerbations at a clinically equivalent dosage. However, switching from FP-SAL to efBDP-FOR has not been evaluated in real-world asthma patients. Aims: The REACH (Real-world Effectiveness in Asthma therapy of Combination inHalers) study investigated the clinical and cost effectiveness of switching typical asthma patients from FP-SAL to efBDP-FOR. Methods: A retrospective matched (1:3) observational study of 1,528 asthma patients aged 18–80 years from clinical practice databases was performed. Patients remaining on FP-SAL (n=1,146) were compared with those switched to efBDP-FOR at an equivalent or lower inhaled corticosteroid (ICS) dosage (n=382). Clinical and economic outcomes were compared between groups for the year before and after the switch. Non-inferiority (at least equivalence) of efBDP-FOR was tested against FP-SAL by comparing exacerbation rates during the outcome year. Results: efBDP-FOR was non-inferior to FP-SAL (adjusted exacerbation rate ratio 1.01 (95% CI 0.74 to 1.37)). Switching to efBDP-FOR resulted in significantly better (p<0.05) odds of achieving overall asthma control (no asthma-related hospitalisations, bronchial infections, or acute oral steroids; salbutamol ≤200μg/day) and lower daily short-acting β2-agonist usage at a lower daily ICS dosage (mean −130μg/day FP equivalents; p<0.001). It also reduced mean asthma-related healthcare costs by £93.63/patient/year (p<0.001). Conclusions: Asthma patients may be switched from FP-SAL to efBDP-FOR at an equivalent or lower ICS dosage with no reduction in clinical effectiveness but a significant reduction in cost.

Effect of Inhaled Corticosteroid Therapy Step-Down and Dosing Regimen on Measures of Asthma Control

Background: Asthma guidelines recommend stepping down therapy to the lowest dose that maintains asthma control. Objective: We sought to evaluate the effect of dosing frequency and baseline patient and treatment-related factors on database markers of asthma control after inhaled corticosteroid (ICS) dose step-down. Methods: This retrospective observational study evaluated primary care patients (4-80 years old) with asthma prescribed twice-daily (BD) ICS (n=26,834) or ICS/long-acting β-agonist (LABA; n=20,814) for ≥ 1 year before ≥ 50% step-down in ICS dose, when they were switched to once-daily (QD) or remained on BD therapy. Study endpoints included exacerbations (oral corticosteroid prescription, unscheduled asthma-related hospital attendance, or general practice consultation for lower respiratory tract infection) and medication adherence. Results: Significant improvements in most endpoints were recorded during the year after step-down, as compared with the prior year (baseline). The proportion of patients with no exacerbation during the baseline year vs. the year after step-down was as follows (p<0.001 for all comparisons): QD ICS cohort (73% baseline vs. 81% after step-down); BD ICS cohort (67% vs. 77%); QD ICS/LABA cohort (60% vs. 64%); BD ICS/LABA cohort (55% vs. 65%). Adherence improved significantly after step-down for all cohorts, most markedly for QD cohorts; and the average daily ICS dose as consumed by patients was higher for all but the QD ICS/LABA cohort despite the reduction in prescribed dose. Factors predicting loss of asthma control after step-down for patients controlled at baseline in either or both ICS and ICS/LABA populations included obesity, smoking, comorbid rhinitis, comorbid gastroesophageal reflux disease, and, during the baseline year, ≥ 7 short-acting β-agonist prescriptions, mean consumed ICS dose of ≥ 800 μg/day, and ≥ 4 primary care consultations. Conclusion: Stepping down therapy is a valid management option and may improve asthma-related outcomes. Some improvements may result from increased adherence, particularly among patients switched to QD therapy.

Initial step-up treatment changes in asthmatic children already prescribed inhaled corticosteroids : a historical cohort study

Background:When standard doses of inhaled corticosteroids (ICS) fail to control symptoms in children aged >4 years, guidelines recommend the addition of a long-acting β2-agonist (LABA), with other treatment options being available if symptoms persist.Aims:To determine the proportion of initial ‘step-up’ episodes where LABAs were prescribed and to describe characteristics of individuals not stepped up with LABA.Methods:Between 1999 and 2011, initial step-up episodes from ICS monotherapy were identified in children aged 5–12 years with asthma and in receipt of ICS. Data sources were the Clinical Practice Research Datalink and Optimum Patient Care Research Database.Results:Initial step-up episodes were identified in 10,793 children. ICS dose was increased in 6,252 children (58%), LABA was introduced in 3,436 (32%; including 1,107 where fixed dose combination inhaler (FDC) replaced the ICS inhaler), and leukotriene receptor antagonist (LTRA) was added in 1,105 (10%). Compared with children stepped up to any LABA, others were younger and prescribed lower doses of ICS and reliever medication. ICS dose increase was more likely in obese children and LTRA prescribing was more likely in children with rhinitis and in receipt of antibiotics. Compared with FDC, step-up to separate LABA inhaler was more likely in younger, obese children who were using less oral steroids.Conclusions:One-third of initial step-up episodes in children with asthma treated with ICS are to add LABA. Different characteristics of children prescribed therapies other than LABA suggest that prescribers tailor treatment in some clinical settings.

Risk of pneumonia in obstructive lung disease : A real-life study comparing extra-fine and fine-particle inhaled corticosteroids

BACKGROUND Regular use of inhaled corticosteroids (ICS) in patients with obstructive lung diseases has been associated with a higher risk of pneumonia, particularly in COPD. The risk of pneumonia has not been previously evaluated in relation to ICS particle size and dose used. METHODS Historical cohort, UK database study of 23,013 patients with obstructive lung disease aged 12-80 years prescribed extra-fine or fine-particle ICS. The endpoints assessed during the outcome year were diagnosis of pneumonia, acute exacerbations and acute respiratory events in relation to ICS dose. To determine the association between ICS particle size, dose and risk of pneumonia in unmatched and matched treatment groups, logistic and conditional logistic regression models were used. RESULTS 14788 patients were stepped-up to fine-particle ICS and 8225 to extra-fine ICS. On unmatched analysis, patients stepping-up to extra-fine ICS were significantly less likely to be coded for pneumonia (adjusted odds ratio [aOR] 0.60; 95% CI 0.37, 0.97]); experience acute exacerbations (adjusted risk ratio [aRR] 0.91; 95%CI 0.85, 0.97); and acute respiratory events (aRR 0.90; 95%CI 0.86, 0.94) compared with patients stepping-up to fine-particle ICS. Patients prescribed daily ICS doses in excess of 700 mcg (fluticasone propionate equivalent) had a significantly higher risk of pneumonia (OR [95%CI] 2.38 [1.17, 4.83]) compared with patients prescribed lower doses, irrespective of particle size. CONCLUSIONS These findings suggest that patients with obstructive lung disease on extra-fine particle ICS have a lower risk of pneumonia than those on fine-particle ICS, with those receiving higher ICS doses being at a greater risk.

Applying UK real-world primary care data to predict asthma attacks in 3776 well-characterised children: a retrospective cohort study

Current understanding of risk factors for asthma attacks in children is based on studies of small but well-characterised populations or pharmaco-epidemiology studies of large but poorly characterised populations. We describe an observational study of factors linked to future asthma attacks in large number of well-characterised children. From two UK primary care databases (Clinical Practice Research Datalink and Optimum Patient Care research Database), a cohort of children was identified with asthma aged 5–12 years and where data were available for ≥2 consecutive years. In the “baseline” year, predictors included treatment step, number of attacks, blood eosinophil count, peak flow and obesity. In the “outcome” year the number of attacks was determined and related to predictors. There were 3776 children, of whom 525 (14%) had ≥1 attack in the outcome year. The odds ratio (OR) for one attack was 3.7 (95% Confidence Interval (CI) 2.9, 4.8) for children with 1 attack in the baseline year and increased to 7.7 (95% CI 5.6, 10.7) for those with ≥2 attacks, relative to no attacks. Higher treatment step, younger age, lower respiratory tract infections, reduced peak flow and eosinophil count >400/μL were also associated with small increases in OR for an asthma attack during the outcome year. In this large population, several factors were associated with a future asthma attack, but a past history of attacks was most strongly associated with future attacks. Interventions aimed at reducing the risk for asthma attacks could use primary care records to identify children at risk for asthma attacks.Childhood asthma: prediction from past attacksA past history of asthma attacks in young children is a strong predictor for future attacks and should be factored into treatment regimes. Childhood asthma attacks take considerable toll on sufferers and their carers, yet risk factors for future attacks are unclear. David Price at the Observational and Pragmatic Research Institute in Singapore and co-workers searched UK primary care databases to find at least two years’ worth of consecutive data on children with asthma aged 5 to 12. The team analyzed data from 3,776 children. Their results showed that past attacks are the strongest predictor for future attacks; of 638 patients who experienced more than one asthma attack during the first year, 240 (38%) had attacks in the second year. Other risk factors included reduced peak flow, lower respiratory tract infections and younger age.

Performance of database-derived severe exacerbations and asthma control measures in asthma: responsiveness and predictive utility in a UK primary care database with linked questionnaire data

Background Observational research is essential to evaluate the real-life effectiveness of asthma treatments and can now make use of outcomes derived from electronic medical records. Aim The aim of this study was to investigate the utility of several database outcome measures in asthma. Methods This study identified cohorts of patients with active asthma from a UK primary care database – Optimum Patient Care Research Database – approximately 10% of which was prospectively supplemented with questionnaire data. The “Questionnaire cohort” included patients aged 18–60 years with valid questionnaire data and 1 year of continuous primary care data. Separate “ICS initiation” and “ICS step-up” cohorts included patients aged 5–60 years initiated on inhaled corticosteroids (ICSs), who had 1 year of continuous primary care data before, and after, this index visit. Database measures of asthma symptom control and exacerbations were identified in the Optimum Patient Care Research Database and cross-tabulated with corresponding patient-reported (questionnaire) data. Responsiveness of the database outcomes was analyzed, using McNemar’s and Wilcoxon’s signed rank tests, and Poisson regression was used to estimate the association between database outcomes and future risk of database exacerbations, in the ICS initiation cohort. Results The final study included 2,366 Questionnaire cohort patients and 51,404 ICS initiation patients. Agreement between patient-reported and database-recorded exacerbations was fair (kappa 0.35). Following the initiation of ICS, database risk domain asthma control (based on exacerbations) improved (proportion of patients with uncontrolled asthma decreased from 24.9% to 18.6%; P<0.001) and mean number of database exacerbations decreased from 0.09 to 0.08 per patient per year (P=0.001). However, another measure of asthma control which includes short-acting beta-agonist prescription as part of the definition did not show this improvement. Patients with prior exacerbations had a higher risk of future exacerbation (rate ratio [95% confidence interval], 3.23 [3.03–3.57]). Conclusion Asthma control and exacerbations derived from primary care databases were responsive, with the exception of short-acting beta-agonist prescriptions, and useful for risk prediction.