Incorrect inhaler technique is a common cause of poor asthma control. This two-phase pragmatic study evaluated inhaler technique mastery and maintenance of mastery with DuoResp® (budesonide-formoterol [BF]) Spiromax® compared with Symbicort® (BF) Turbuhaler® in patients with asthma who were receiving inhaled corticosteroids/long-acting β2-agonists.

INTRODUCTION:Ventolin Nebules® (reference product; GlaxoSmithKline) was the first licensed nebulizer solution containing the rapid-onset, short-acting β2-agonist salbutamol. Salbutamol Steri-Neb™ (comparator; Teva Pharmaceuticals, Inc.) has the same chemical composition as the reference product. This study evaluated whether the effectiveness of the comparator is non-inferior to the reference product alongside concomitant medications during real-life clinical management of COPD exacerbations. Safety in terms of adverse events (AEs) was also examined.METHODS:This matched (1:1) historical cohort study evaluated data from 2 UK primary care databases on patients prescribed the salbutamol comparator or reference. The study included a 1-year baseline period, starting 1 year before the index prescription date, and 1-year outcome period. Cohorts were matched for baseline COPD respiratory medications. The primary outcome was analysis of non-inferiority for the comparator versus reference product for the rate of moderate and severe COPD exacerbations. Non-inferiority was satisfied if the 95% confidence interval (CI) upper limit for mean differences in proportions between treatments was <15%. Secondary outcomes were examined through rate ratios (RR) of severe exacerbations and AEs.RESULTS:After matching, 1191 patients were included in each cohort. Adjusted upper 95% CI for the difference in proportion of patients experiencing moderate or severe exacerbations between comparator and reference groups was 0.032 (3.2%), demonstrating non-inferiority. No significant differences were observed in rates of moderate and severe exacerbations (RR: 1.00; 95% CI: 0.91, 1.10), severe exacerbations (RR: 0.76; 95% CI: 0.49, 1.17), or AEs (RR: 0.98; 95% CI: 0.78, 1.22) after adjusting for baseline confounders. No significant differences across cohorts were observed for rates of any AE or death.CONCLUSION:This matched cohort study of real-life management of COPD patients supports the salbutamol comparator as non-inferior to the reference product, providing an effective treatment alternative for COPD exacerbations. Comparator and reference safety profiles were similar.

Objective: The objective of this study was to determine whether the effectiveness of budesonide comparator is non-inferior to budesonide reference in the prevention of asthma exacerbations. Asthma-related hospitalizations and safety were also examined.Methods: This study used a matched, historic cohort design. Data were drawn from the Clinformatics (TM) Data Mart US claims database and included a 1-year baseline, starting 1 year before the index prescription date, and a 1-year outcome period. Patients received budesonide comparator or reference treatment. The primary outcome was the rate of asthma exacerbations. Non-inferiority for budesonide comparator vs budesonide reference was established if the 95% confidence interval (CI) upper limit of mean difference in proportions between treatments was <15%. Secondary outcomes examined rate of asthma-related hospitalizations and adverse events (AEs).Results: The budesonide comparator and reference-matched cohorts each included 3109 patients. The adjusted upper 95% CI for the difference in proportions of patients experiencing asthma exacerbations was 0.035 (3.5%), demonstrating non-inferiority. Cohorts did not significantly differ in the rate of asthma exacerbations (adjusted rate ratio [RR]=1.04, 95% CI: 0.95-1.14) or rate of asthma-related hospitalizations (adjusted RR=1.10, 95% CI: 0.99-1.24) after adjusting for baseline confounders. No asthma exacerbations occurred during the outcome period in 72.9% of budesonide comparator patients and 71.8% of budesonide reference patients. No asthma-related hospitalizations occurred in 77.9% of patients in the budesonide comparator cohort and 79.0% of patients in the budesonide reference cohort. The most frequent AEs were throat irritation (<= 0.4% of patients) and hoarseness/dysphonia (0.02% of patients). AEs did not significantly differ between treatment cohorts.Conclusion: In this real-life study, non-inferiority of the budesonide comparator vs reference was met for the primary end point of asthma exacerbation rates. Asthma-related hospitalization and AE rates did not differ between the two treatment cohorts. The budesonide comparator is an effective and safe treatment alternative for asthma exacerbations.

Affordable treatment alternatives are needed to prevent and treat chronic obstructive pulmonary disease (COPD) exacerbations and reduce the economic burden of COPD. This study evaluated whether the effectiveness of Steri-Neb™ (Teva Pharmaceuticals, Inc.), the comparator ipratropium/salbutamol (I/S) nebulizer solution, is non-inferior to DuoNeb® (Mylan Specialty L.P.), the originator with the same chemical composition, the first FDA-approved product of this kind, for the prevention of COPD exacerbations. I/S comparator versus originator safety also was examined. Both the I/S comparator and the originator are indicated (EU/USA) for bronchospasm management in patients with COPD.

Chronic obstructive pulmonary disease (COPD), a complex progressive disease, is currently the third leading cause of death worldwide. One recommended treatment option is fixed-dose combination therapy of an inhaled corticosteroid (ICS)/long-acting β-agonist. Clinical trials suggest pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) show similar efficacy and safety profiles in COPD. Real-world observational studies have shown that combination therapy has significantly greater odds of achieving asthma control when delivered via pMDIs. Our aim was to compare effectiveness, in terms of moderate/severe COPD exacerbations and long-acting muscarinic antagonist (LAMA) prescriptions, for COPD patients initiating fluticasone propionate (FP)/salmeterol xinafoate (SAL) via pMDI versus DPI at two doses of FP (500 and 1,000 μg/d) using a real-life, historical matched cohort study. COPD patients with ≥2 years continuous practice data, ≥2 prescriptions for FP/SAL via pMDI/DPI, and no prescription for ICS were selected from the Optimum Patient Care Research Database. Patients were matched 1:1. Rate of moderate/severe COPD exacerbations and odds of LAMA prescription were analyzed using conditional Poisson and logistic regression, respectively. Of 472 patients on 500 μg/d, we observed fewer moderate/severe exacerbations in patients using pMDI (99 [42%]) versus DPI (115 [49%]) (adjusted rate ratio: 0.71; 95% confidence interval: 0.54, 0.93), an important result since the pMDI is not licensed for COPD in the UK, USA, or China. At 1,000 μg/d, we observed lower LAMA prescription for pMDI (adjusted odds ratio: 0.71; 95% confidence interval: 0.55, 0.91), but no difference in exacerbation rates, potentially due to higher dose of ICS overcoming low lung delivery from the DPI.

BACKGROUND: Guidelines recommend reducing treatment in patients with well-controlled asthma after 3 months of stability. However, there is inadequate real-life data to guide physicians on therapy change in daily practice.OBJECTIVE: To assess asthma control after change to and step-down of fluticasone propionate/formoterol fumarate dihydrate (FP/FOR) in real-life patients.METHODS: In a randomized controlled, pragmatic, open-label trial, 225 well-controlled patients with asthma were randomized (1: 2) to maintain high-dose fluticasone propionate/salmeterol xinafoate (FP/SAL, 1000/100 mu g) or switch to FP/FOR (1000/40 mu g) daily for 12 weeks (phase 1). One hundred sixteen patients stable on FP/FOR at week 12 were subsequently randomized (1: 1) to maintain this therapy, or stepped down to FP/FOR (500/20 mu g) daily for 12 weeks (phase 2). The primary end point was the 7-question Asthma Control Questionnaire (ACQ7) score.RESULTS: In phase 1, FP/FOR (1000/40 mu g) (n = 126) was noninferior to FP/SAL (1000/100 mu g) (n = 73) for ACQ7 (difference in means, -0.12; 95% CI, -0.32 to 0.09). In phase 2, FP/FOR (500/20 mu g) (n = 52) was noninferior to FP/FOR (1000/40 mu g) (n = 52) for ACQ7 (difference in means, 0.01; 95% CI, -0.20 to 0.22). There was no significant difference in exacerbation rate between the groups in either phase. However, 1 to 2 exacerbations in 12 months before phase 1 were associated with the occurrence of an exacerbation after step-down (P = .007).CONCLUSIONS: In patients with well-controlled asthma, a change from FP/SAL to FP/FOR did not compromise asthma control. Step-down of FP/FOR was well tolerated; however, in contrast to current guidelines, our data suggest caution in stepping down patients uncontrolled in the last 12 months. Larger step-down studies are required to confirm these findings. (C) 2017 American Academy of Allergy, Asthma & Immunology

Background: Selecting the most appropriate asthma therapy for individual patients can be challenging owing to limited data on real-life effectiveness of inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combinations available. Various factors, such as ease of use of the device and speed of onset of the LABA, can influence inhaler technique and adherence, thereby affecting clinical outcomes in real-life patients. Further studies are needed to evaluate whether efficacy of new asthma therapies demonstrated in clinical trials translate to effectiveness in a pragmatic setting.To compare the real-life effectiveness of switching to Flutiform® 250 (250 mcg fluticasone/10 mcg formoterol) from Seretide® 250 Evohaler® (250 mcg fluticasone/25 mcg salmeterol) in adult patients with asthma. Methods: This was the first phase of a pragmatic, open label, randomised controlled, non-inferiority trial in adult patients with asthma. Key eligibility criteria included prescription for Seretide® 250 Evohaler® for at least 6 months and no asthma exacerbations in the 3 months prior to enrolment. In addition, at the baseline visit, patients had to demonstrate controlled or partially controlled asthma according to Global Initiative for Asthma (GINA) criteria. Overall, 225 patients from 27 sites in the UK were randomised 2:1 to Flutiform® 250 or Seretide® 250 Evohaler® for 12 weeks. The primary outcome was asthma control assessed using the 7-item Asthma Control Questionnaire (ACQ7). Non-inferiority limit on the ACQ7 was set at 0.3. Patients were eligible for the non-inferiority analysis if they stayed on the randomised treatment for at least 8 weeks and did not change treatment during the follow-up period. Secondary outcomes included the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ), Forced Expiratory Volume in 1 second (FEV1) % predicted, perception of asthma symptoms assessed with a Visual Analog Scale (VAS), asthma control (GINA) and absence of exacerbations during outcome period. Analyses of secondary outcomes included all randomised patients [Full Analysis Set (FAS)]. Results: Of the 207 patients who completed the study 90 (43%) were male, the mean (standard deviation) age was 53 (13) years, and 152 (73%) had not had an exacerbation in the year prior to the study. Of those randomised to Flutiform® 250 126 (83%) were eligible for the non-inferiority analysis compared to 73 (99%) randomised to Seretide® 250 Evohaler® (see figure for details of the FAS). At Week 12, Flutiform® 250 was non-inferior to Seretide® 250 Evohaler® in terms of asthma control assessed by ACQ7 with an upper confidence limit of 0.09, which is less than the pre-defined limit of 0.3 [mean difference −0.11; 95% confidence interval (CI), −0.31 to 0.09]. The odds of being more controlled according to GINA criteria were significantly higher in the Flutiform® 250 group (odds ratio 2.04; 95% CI, 1.16 to 3.59; P=0.01). No significant differences between the groups were found for exacerbations, Mini-AQLQ, VAS or FEV1% predicted (see table). Although there was no significant difference in the distribution of adherence between the groups (P=0.51 using Fisher’s Exact Test), a greater proportion of patients in the Flutiform® 250 group had adherence of 100% or more [34 (33%) compared with 13 (24%)]. Conclusions: Real-life patients previously controlled on Seretide® 250 Evohaler® can be switched to Flutiform® 250 and maintain good asthma control. Moreover, patients on Flutiform® 250 were significantly better controlled than patients on Seretide® 250 Evohaler® when asthma control was assessed according to GINA criteria.

Background Previous studies reported a high burden of uncontrolled asthma in Europe. The relationship between treatment step, smoking status and control, however, remain underreported. Aim To evaluate the distribution of asthma control across guideline-recommended management steps, and the association between control and smoking status of real-life patients within a primary care setting in the UK. Methods Patient data were extracted from the Optimum Patient Care Research Database and prospectively followed for at least 1 year. Patient-reported outcomes and practice data characterised patients9 control status as defined by the Global INitiative for Asthma (GINA), current treatment management step and smoking status. Results Of 91,393 eligible patients, 28% had GINA controlled asthma, 58% partially controlled and 14% uncontrolled. Control was weakly correlated with GINA management steps (Spearman9s rho=0.26), with 21%, 31%, 24%, 23% and 1.4% achieving control across steps 1 to 5, respectively. During the 1-year follow-up, 11% of patients experienced at least 1 exacerbation. This proportion of patients increased across the ascending GINA steps from 5% at step 1 to 67% at step 5 (p<0.01). Non-smokers were significantly more likely to achieve control than current or ex-smokers (p<0.001). Conclusion The majority of patients in this real-life cohort failed to achieve GINA-defined asthma control within a UK primary care setting. GINA management step was only weakly correlated with control status, but higher step management was associated with a greater risk of exacerbations. Non-smokers were significantly more likely to achieve control than current and ex-smokers.

Background: Airway inflammation is the fundamental mechanism in asthma and can be measured non-invasively by means of fractional exhaled nitric oxide (FeNO). Both, The National Institute for Health and Care Excellence (NICE) diagnostics guidance 12 and British guideline on the management of asthma, are recommending the inclusion of FeNO testing as part of diagnosis in patients that have an intermediate probability of having asthma. Furthermore, FeNO testing is recommended as an option for monitoring response to corticosteroid treatment in patients with increased FeNO. However, there is a need for establishing routine data predictors for individuals with increased FeNO, to identify those that would benefit from FeNO measurement as a tool for aiding asthma diagnosis and monitoring treatment responsiveness. To provide a real-life predictive model for the identification of individuals at risk of asthma that have increased FeNO. Methods: An analysis of real-life standard care and FeNO data derived from a randomised, multi-centre, double-blind, placebo-controlled study entitled: ‘The evaluation of FeNO for predicting response to an inhaled corticosteroid in subjects with non-specific respiratory symptoms’ was carried out. Data from study participants with non-specific respiratory symptoms and an Asthma Control Questionnaire (ACQ) score ≥1 were analysed cross-sectionally. Logistic regression was used to investigate the relationship between FeNO levels, categorised in normal (≤25 ppb) and intermediate (>25 and <40 ppb)/high (≥40 ppb), and a number of determinants, including demographic variables, smoking status, history of atopy, number of short acting beta agonist (SABA) inhalers in the year preceding study participation, symptoms of cough, wheeze and dyspnoea, prior history of oral steroid use, blood eosinophil count (cut off 0.2×109/L) and forced expiratory volume in the first second percent predicted (FEV1% pred). Results: Overall, 90 individuals were assessed, with a mean ± standard deviation (SD) age of 46±17.1, 50 (56%) were female, and 59 (67%) were non-smokers. Sixty individuals (67%) had normal FeNO levels compared to 30 (33%) with intermediate/high levels. From univariate analyses, the odds ratio (OR) and 95% confidence interval (CI) of being in the intermediate/high FeNO group were increased if individuals were male [4.00 (1.58, 10.14)], had a history of atopy [4.3 (1.6, 11.54)], eosinophils >0.2×109/L [3.07 (1.10, 8.61)] and decreased with age [0.97 (0.94, 0.99)]. Finally, in a multivariable model, only male gender and history of atopy remained significant, independent factors, 4.32 (1.61, 11.68) and 4.65 (1.63, 13.26), respectively. Conclusions: Our research shows that a history of atopy and being male are the strongest, independent predictors for increased FeNO levels in individuals at risk of asthma, while an eosinophil count >0.2×109/L and young age also retain some predictive ability.

Background: Questionnaire-based surveys report that uncontrolled asthma is common in Europe, and associated with high healthcare costs. The relationship between treatment step control are less well described. To quantify the asthma burden within routine primary care in the UK, specifically the distribution of asthma control across guideline-recommended management steps and the association between patients' control and smoking status.Methods: Patients were retrospectively identified using the Optimum Patient Care Research Database and prospectively followed-up for at least 1-year. Patients' routine clinical data and self reports were used to assess GINA control status; clinical records were used to categorise current treatment by GINA management steps and patients' smoking status.Results: A total of 105,018 eligible asthma patients were identified, mean (SD) age 45 (23) years; 55% female; 15% current and 24% ex-smokers. Only 20% of patients were controlled, 59% were partially controlled and 21% were uncontrolled. Control was only weakly correlated to GINA management steps (Spearman's rho=0.15, P<0.001), 27.5%, 21.5%, 20.3%, 15.1% and 12.1% achieving control across Step 1 to 5, respectively. Similarly, the proportion with uncontrolled asthma rose across higher GINA steps (12.6%, 18.2%, 19.6%, 29.2% and 36.6%). About 13% of patients experienced at least one exacerbation in the 1-year follow-up period. Frequent exacerbations (2 or more per year) were very uncommon at lower treatment steps (step 1 11.6%, step 2 12.8%) but were significantly more common at steps 3 and 4 at 18.8% and 28.2% respectively (P<0.001 for trend with ascending treatment step).Conclusions: In this cohort of UK primary care asthma patients, the majority failed to achieve GINA defined control. GINA management step was only weakly correlated with control status, but higher step management was associated with a greater risk of exacerbation.

Background: Global Initiative for Asthma (GINA) guidelines recommend a gradual step-down of asthma therapy if asthma has been well-controlled for at least 3 months. In real life, however, many well-controlled patients are prescribed high doses of inhaled corticosteroids (ICS), and are therefore unnecessarily at risk of systemic side effects associated with long-term ICS use. To encourage and facilitate step-down in a clinical setting, further pragmatic studies are required to demonstrate that good control of asthma can be maintained with a lower dose of ICS in stable and controlled patients, and to explore potential predictors for response to step-down.To test if good control of asthma can be maintained in adult patients previously stable on Flutiform® 250 (250 mcg fluticasone/10 mcg formoterol) for 12 weeks, after step-down to Flutiform® 125 (250 mcg fluticasone/5 mcg formoterol). Methods: This was the second phase of a pragmatic, open-label, randomised controlled, non-inferiority trial in adult patients with asthma. Patients eligible for this phase had been on Flutiform® 250 for 12 weeks, had had no exacerbations during this period and were considered suitable for step-down by their GP. A total of 116 patients from 23 sites in the UK were randomised 1:1 to continue on Flutiform® 250 or to step down to Flutiform® 125. The primary outcome was asthma control assessed using the 7-item Asthma Control Questionnaire (ACQ7). Non-inferiority limit on the ACQ7 was set at 0.3. Patients were eligible for the non-inferiority analysis if they stayed on the randomised treatment for at least 8 weeks and did not change treatment before outcome visit. Secondary outcomes included forced expiratory volume in the first second (FEV1) % predicted, the Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ), asthma control (according to GINA) and absence of exacerbations during outcome period. Analyses of secondary outcomes included all randomised patients [Full Analysis Set (FAS)]. Adherence was calculated based on dose counter values for patients who returned the study inhalers. Results: Of the 107 patients who completed the study 48 (45%) were male and the mean [standard deviation (SD)] age was 54 (13) years. Of those randomised, 52 (90%) patients in each arm were eligible for the non-inferiority analysis (see figure for details of the FAS). At week 12, Flutiform® 125 was non-inferior to Flutiform® 250 in terms of asthma control assessed by ACQ7, with an upper confidence limit of 0.22, which is less than the pre-defined limit of 0.3 [mean difference 0.01; 95% confidence interval (CI), −0.20 to 0.22]. No significant differences between the groups were found for GINA asthma control, absence of exacerbations, Mini-AQLQ, or FEV1% predicted (see Table for treatment effect estimates). Adherence was high in both groups [median (inter-quartile range) 94% (88% to 106%) and 98% (77% to 103%) for the Flutiform® 125 and Flutiform® 250 groups, respectively] and there was no significant difference in distribution of adherence between the groups (P=0.20, Mann-Whitney U-test). Conclusions: This study showed that real-life patients previously controlled on Flutiform® 250 can be stepped down to Flutiform® 125 and maintain good asthma control. Additional analyses are ongoing to investigate biomarkers [blood eosinophils, fractional exhaled nitric oxide (FeNO)] and other factors that might predispose patients to exacerbations or worsening of asthma control following ICS step-down. In the future, such predictors could help physicians to make more informed decisions on stepping down therapy in a real-life setting.

Introduction and objectives Technical errors in the use of inhalers are associated with poor asthma control. This study evaluated achievement of mastery in a training environment using a randomised cross-over design (stage 1), followed by randomization into a prospective 12-week trial to assess maintenance of mastery in patients receiving inhaled corticosteroids (ICS)/long-acting β2-agonists (LABA) via SPIROMAX versus ICS/LABA received via TURBOHALER (stage 2). Methods Patients with asthma were randomised to a 6-step training protocol using empty Spiromax and empty Turbohaler devices. The proportion of patients achieving and maintaining inhaler mastery, respectively defined as the absence of health care professional (HCP)-observed errors by training step 3 (instructional video) in stage 1, and the absence of HCP-observed errors after 12 weeks of inhaler use in stage 2, were analysed using logistic regression. The maintenance of independent expert video-observed inhaler mastery was analysed using logistic regression. Total observed errors (HCP and technology) were analysed using a negative binomial regression model. Vitalograph Pneumatic Spirometry results were compared using a Mann Whitney U test. Results A total of 493 (89.1%) patients (stage 1) and 305 (61.9%) (stage 2) were eligible for the full analysis set. The odds of maintaining inhaler mastery were not significantly different for patients using either inhaler, although achieving inhaler mastery was significantly greater in patients using Spiromax compared with Turbohaler at baseline. A higher, non-significant percentage of patients using Spiromax maintained inhaler mastery (assessed by HCPs). This result was supported by significantly higher odds of maintaining mastery when HCP errors were calibrated using independent video assessment in patients using Spiromax (consented videos available for 243/305 patients [79%]). Maintaining inhaler mastery improved asthma control in both treatment groups and was not significantly different (Table 1).Abstract P154 Table 1 Inhaler technique variables Spiromax Turbohaler p-value‡ Odds ratios(95% CI)§ Rate ratios(95% CI) Treatment difference(95% CI)# Inhaler mastery achievement, stage 1, n (%)* Yes 454 (94) 418 (87) <0.001 3.77(2.05−6.95) — — No 27 (6) 63 (13) Inhaler mastery maintenance, stage 2, n (%) † Yes 89 (59) 82 (53) 0.316 1.26(0.80−1.98) — — No 62 (41) 72 (47) — — Total HCP-observed errors, mean (SD) — 0.50 (0.67) 0.81 (1.10) — — 0.61(0.44− 0.84) — HCP-observed mastery assessed by independent video review, n (%) Yes 122 (81) 92 (60) ˂0.001 2.84(1.69−4.76) — — No 29 (19) 62 (40) — Change in 6-item Asthma Control Questionnaire, week 12, mean (SD) — -0.22 (0.95) -0.36 (1.05) — — — 0.13(-0.10−0.37) *In stage 1, 493 patients were randomly assigned to either empty Spiromax followed by empty Turbohaler or empty Turbohaler followed by empty Spiromax. Achieving inhaler mastery was defined as the absence of HCP-observed errors by the end of step 3 of a 6-step standardised inhaler training protocol for empty Spiromax compared to empty Turbohaler inhalers; †In stage 2, 305 out of 395 patients (61.9%) patients were eligible for the full analysis set. Maintaining inhaler mastery was defined as the absence of HCP-observed errors after 12 weeks of inhaler use; ‡The p-value for the treatment comparison is based on chi-square. p < 0.05 considered statistically significant; §Logistic regression; Negative binomial regression; #Analysis of variance; CI: confidence interval; HCP: Health care professional; SD, standard deviation. Conclusions The proportion of patients achieving inhaler mastery at baseline was significantly greater for Spiromax compared with Turbohaler; no significant difference was found in inhaler mastery at 12 weeks. Patients using Spiromax made significantly fewer errors overall (HCP-observed and HCP- and technology-observed) than patients using Turbohaler. Maintaining inhaler mastery improved asthma control in both treatment groups. Independent video assessment can assist HCPs in evaluating device mastery, and is proposed as the gold standard in such studies.

Introduction and objectives Fluticasone propionate/salmeterol (FP/SAL), can be delivered by metered-dose inhaler (MDI) or dry powder inhaler (DPI). The choice of device may affect adherence to and effectiveness of treatment. Although only 1000 mcg/day DPI is licensed for the treatment of COPD in the UK, the MDI and lower doses are regularly used in real-world practice. The aim of this study was to compare the effectiveness and safety of FP/SAL MDI or DPI at two doses (500 and 1000 mcg/day) in COPD patients. Methods Historical, matched cohort study using the Optimum Patient Care Research Database in patients with COPD, aged ≥35 years and initiating with FP/SAL via either MDI or DPI. Conditional Poisson regression and conditional logistic regression were used respectively to compare the rate of moderate/severe COPD exacerbations and the odds of diagnosis of pneumonia and diabetes mellitus (including anti-diabetic drug prescriptions) between MDI and DPI during one year outcome period. Models were adjusted for the respective baseline values of the outcome variable of interest where possible. Addition of LAMA therapy during the outcome period was compared using conditional logistic regression. Results 472 and 1172 patients initiated on FP/SAL at 500 mcg/day and 1000 mcg/day, respectively. The rate of moderate/severe COPD exacerbations was significantly lower for patients prescribed MDI versus DPI initiating with 500 mcg/day of FP/SAL; no significant difference was observed between MDI and DPI for those initiating at 1000 mcg/day. There were no significant differences in the odds of diagnosis of diabetes mellitus or pneumonia between MDI and DPI, irrespective of the initiation dose of FP/SAL (Table 1). LAMA prescription during the outcome period was significantly lower for patients prescribed MDI versus DPI initiating at 1000 mcg/day; no significant difference was observed between MDI and DPI for those initiating at 500 mcg/day. Conclusions This study showed greater reduction in exacerbations for patients using MDI than those using DPI when initiating with FP/SAL 500 mcg/day; no differences in exacerbation reduction and safety were seen for FP/SAL at 1000 mcg/day. Fewer patients using MDIs than DPIs at 1000 mcg/day were prescribed LAMAs, suggesting less need for treatment intensification.

Introduction and objectives Technical errors in the use of inhalers are associated with poor asthma control. This study evaluated achievement of mastery in a training environment using a randomised cross-over design (stage 1), followed by randomization into a prospective 12-week trial to assess maintenance of mastery in patients receiving inhaled corticosteroids (ICS)/long-acting β2-agonists (LABA) via SPIROMAX versus ICS/LABA received via TURBOHALER (stage 2). Methods Patients with asthma were randomised to a 6-step training protocol using empty Spiromax and empty Turbohaler devices. The proportion of patients achieving and maintaining inhaler mastery, respectively defined as the absence of health care professional (HCP)-observed errors by training step 3 (instructional video) in stage 1, and the absence of HCP-observed errors after 12 weeks of inhaler use in stage 2, were analysed using logistic regression. The maintenance of independent expert video-observed inhaler mastery was analysed using logistic regression. Total observed errors (HCP and technology) were analysed using a negative binomial regression model. Vitalograph Pneumatic Spirometry results were compared using a Mann Whitney U test. Results A total of 493 (89.1%) patients (stage 1) and 305 (61.9%) (stage 2) were eligible for the full analysis set. The odds of maintaining inhaler mastery were not significantly different for patients using either inhaler, although achieving inhaler mastery was significantly greater in patients using Spiromax compared with Turbohaler at baseline. A higher, non-significant percentage of patients using Spiromax maintained inhaler mastery (assessed by HCPs). This result was supported by significantly higher odds of maintaining mastery when HCP errors were calibrated using independent video assessment in patients using Spiromax (consented videos available for 243/305 patients [79%]). Maintaining inhaler mastery improved asthma control in both treatment groups and was not significantly different (Table 1). Conclusions The proportion of patients achieving inhaler mastery at baseline was significantly greater for Spiromax compared with Turbohaler; no significant difference was found in inhaler mastery at 12 weeks. Patients using Spiromax made significantly fewer errors overall (HCP-observed and HCP- and technology-observed) than patients using Turbohaler. Maintaining inhaler mastery improved asthma control in both treatment groups. Independent video assessment can assist HCPs in evaluating device mastery, and is proposed as the gold standard in such studies.

Introduction and objectives Cardiovascular comorbidity is common in COPD. Retrospective health informatics studies have shown putative benefits of beta-blockers (BB) in reducing both mortality and exacerbations in COPD.1 BB are established in heart failure (HF) guidelines including those patients who have concomitant COPD. However, there remain concerns regarding bronchoconstriction in COPD even with cardio-selective BB. For example, 55% of patients with COPD, who had a myocardial infarction (MI), were not prescribed a BB.2 We wished to assess the use of BB for patients with HF who also have COPD. Methods The Optimum Patient Care Research Database was used to identify QOF codes for 104,945 patients with COPD, 24,413 with HF and 13,421 with both conditions, where there was at least 1 year of data. We evaluated co-prescribing of BB with either ACE-inhibitor (ACEI) or Angiotensin-2 receptor blockers (ARB) in patients with HF/COPD and their association with inhaler therapy. Heart failure treatments were compared between groups using multinomial logistic regression. Results In patients with HF/COPD, mean age was 79 years, 60% males and 27% had prior MI. 21.6% of patients with HF and COPD (n = 2,984) were taking a BB in conjunction with either ACEI/ARB as compared to 42.2% of patients with HF alone (n = 10,303) (p < 0.001). In HF/COPD patients on triple inhaler therapy with ICS/LABA/LAMA there were 46.5% taking ACEI/ARB without BB (n = 1,292) verses 29.3% taking ACEI/ARB with BB (n = 813) (odds ratio [OR] = 1.59, 95% CI 1.46, 1.74, p < 0.001). Corresponding figures for those patients on dual inhaler therapy with ICS/LABA were 47.3% (n = 1,275) verses 22.2% (n = 599) respectively (OR = 2.13, 95% CI 1.93, 2.35, p < 0.001). Conclusions Taken together these data therefore provide strong evidence of an unmet need in COPD patients who should be prescribed beta-blockers more often for concomitant HF. References 1 Short PM, Lipworth SI, Elder DH, Schembri S, Lipworth BJ. Effect of beta blockers in treatment of chronic obstructive pulmonary disease: a retrospective cohort study. BMJ 2011;342:d2549 2 Quint JK, Herrett E, Bhaskaran K, et al. Effect of β blockers on mortality after myocardial infarction in adults with COPD: population based cohort study of UK electronic healthcare records. BMJ 2013;347:f6650

Background: Asthma guidelines recommend extrafine (EF)-ICS be prescribed at the same dose as fluticasone and half dose of beclomethasone [standard-particle (SP)-ICS]. Aim: To compare real-life prescribed doses of ciclesonide (EF-ICS) vs SP-ICS and evaluate their effect on treatment outcomes for patients receiving asthma therapy in The Netherlands. Methods: Pharmacy/hospital records from the PHARMO Database Network (20% of the Dutch population) were collected over 1-year before and 1-year after patients (12-60 years, not on long-acting muscarinic-antagonists) initiated EF or SP-ICS therapy. Initial ICS doses and adjusted rate/odds ratios (RR/OR) of severe exacerbations (hospital admissions/acute oral steroids), changing therapy (additional therapy/increased ICS dose) and increasing short-acting β2-agonists (SABA) doses (categorised) were compared between treatment groups. To avoid bias by severity, patients were exact-matched on key baseline differences. Results: The table shows RR/OR for EF vs SP-ICS matched patients (median age 45 years, 35% males in each group). Median prescribed doses were 120 vs 500mcg for EF (actual dose) vs SP-ICS (FP equivalents). Conclusions: For matched patients ciclesonide was prescribed at one-third of the dose of SP-ICS, yet patients prescribed ciclesonide had lower exacerbation rates and lower odds of changing therapy and receiving higher SABA doses.

Real-world research can use observational or clinical trial designs, in both cases putting emphasis on high external validity, to complement the classical efficacy randomized controlled trials (RCTs) with high internal validity. Real-world research is made necessary by the variety of factors that can play an important a role in modulating effectiveness in real life but are often tightly controlled in RCTs, such as comorbidities and concomitant treatments, adherence, inhalation technique, access to care, strength of doctor-caregiver communication, and socio-economic and other organizational factors. Real-world studies belong to two main categories: pragmatic trials and observational studies, which can be prospective or retrospective. Focusing on comparative database observational studies, the process aimed at ensuring high-quality research can be divided into three parts: preparation of research, analyses and reporting, and discussion of results. Key points include a priori planning of data collection and analyses, identification of appropriate database(s), proper outcomes definition, study registration with commitment to publish, bias minimization through matching and adjustment processes accounting for potential confounders, and sensitivity analyses testing the robustness of results. When these conditions are met, observational database studies can reach a sufficient level of evidence to help create guidelines (i.e., clinical and regulatory decision-making).