BACKGROUND: Previous studies have reported reduced acute exacerbation rates and improved symptom control in asthma patients treated using inhaled corticosteroids plus formoterol maintenance and reliever therapy (MART). Fluticasone furoate (FF) and vilanterol (VIL) also provide rapid bronchodilation and sustained anti-inflammatory effects, however no studies have investigated FF/VIL as MART for asthma control.
METHODS: From October 1, 2021 to September 30, 2023, this retrospective study included asthma patients classified as step 3 or 4 according to the Global Initiative for Asthma guidelines, who were then divided into two groups. One group received BUD/FOR as MART, while the other received FF/VIL as MART. Pulmonary function tests, exacerbation rates, Asthma Control Test (ACT), fractional exhaled nitric oxide (FeNO) levels, and blood eosinophil counts were measured before and after 12 months of treatment.
RESULTS: A total of 161 patients were included, of whom 36 received BUD/FOR twice daily as MART, and 125 received FF/VIL once daily as MART. After 12 months of treatment, the FF/VIL group showed a significant increase in ACT scores by 1.57 (p < 0.001), while the BUD/FOR group had an increase of 0.88 (p = 0.11). In terms of FeNO levels, the BUD/FOR group experienced a decline of -0.2 ppb (p = 0.98), whereas the FF/VIL group had a mild increase of + 0.8 ppb (p = 0.7). Notably, there was a significant difference in the change of FeNO between the two groups (∆ FeNO: -0.2 ppb in BUD/FOR; + 0.8 ppb in FF/VIL, p < 0.001). There were no significant alterations observed in FEV1, blood eosinophil count, or acute exacerbation decline in either group.
CONCLUSIONS: In the current study, patients treated with FF/VIL as MART showed improvements in ACT scores, while those treated with BUD/FOR as MART exhibited a reduction in FeNO levels. However, the difference between the two treatment groups did not reach clinical significance. Thus, FF/VIL as MART showed similar effectiveness to BUD/FOR as MART.

BACKGROUND: The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR).
METHODS: Reduction in reliever medication use (puffs/24 h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12 months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phase III/IV clinical studies.
RESULTS: Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3 months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24 h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01).
CONCLUSIONS: We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.
In this study we looked at how different factors affect the response to asthma treatment in people with moderate to severe asthma who are taking regular medication. Specifically, we wanted to quantify how much asthma duration, differences in the degree of symptom control and lung function, as well as smoking habit, body weight, and sex influence how well someone responds to regular maintenance therapy. Using computer simulations based on models obtained from data in a large patient population with moderate–severe asthma, we explored scenarios that reflect real-life management of patients undergoing treatment with inhaled corticosteroids alone or in combination with long-acting beta agonists over a 12-month period. We looked at how much reliever inhaler they use, how well they rate their asthma control, and how often they have asthma attacks. By considering these results together, we evaluated how well the treatments work on ongoing symptoms and/or reduce the risk of future asthma attacks. Our simulations showed that smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. This was linked to a higher risk of having asthma attacks and worse symptom control. Switching those patients who do not respond well to their initial treatment with corticosteroid to combination therapy reduced how much reliever inhaler they need. Also, the effects of fluticasone propionate/salmeterol combination therapy were greater than budesonide/formoterol. In conclusion, our study found that certain patient characteristics can predict how well someone responds to asthma treatment.

BACKGROUND: Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs) offer an alternative, but concerns exist whether DPIs provide an effective relief during an obstructive event.
OBJECTIVE: We aimed to show non-inferiority of Salbutamol Easyhaler DPI compared to pMDI with spacer in treating methacholine-induced bronchoconstriction. Applicability of Budesonide-formoterol Easyhaler DPI as a reliever was also assessed.
METHODS: This was a randomized, parallel-group trial in subjects sent to methacholine challenge (MC) test for asthma diagnostics. Participants with at least 20 % decrease in forced expiratory volume in 1 s (FEV1) were randomized to receive Salbutamol Easyhaler (2 × 200 μg), Ventoline Evohaler with spacer (4 × 100 μg) or Budesonide-formoterol Easyhaler (2 × 160/4.5 μg) as a reliever. The treatment was repeated if FEV1 did not recover to at least -10 % of baseline.
RESULTS: 180 participants (69 % females, mean age 46 yrs [range 18-80], FEV1%pred 89.5 [62-142] %) completed the trial. Salbutamol Easyhaler was non-inferior to pMDI with spacer in acute relief of bronchoconstriction showing a -0.083 (95 % LCL -0.146) L FEV1 difference after the first dose and -0.032 (-0.071) L after the last dose. The differences in FEV1 between Budesonide-formoterol Easyhaler and Salbutamol pMDI with spacer were -0.163 (-0.225) L after the first and -0.092 (-0.131) L after the last dose.
CONCLUSIONS: The study confirms non-inferiority of Salbutamol Easyhaler to Ventoline Evohaler with spacer in relieving acute bronchoconstriction, making Easyhaler a sustainable and safe reliever for MC test and supports its use during asthma attacks.

UNASSIGNED: There is currently limited evidence for the optimal timing of triple therapy initiation in Japan, which is crucial for optimizing strategies for the effective treatment of chronic obstructive pulmonary disease (COPD). This study assessed the impact of prompt vs delayed initiation of triple therapy following a COPD exacerbation on clinical and economic outcomes in patients in Japan.
UNASSIGNED: Retrospective cohort study of patients in the Medical Data Vision Co., Ltd. database initiating triple therapy as single-inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol or budesonide/glycopyrronium/formoterol) or multiple-inhaler triple therapy within 180 days of a moderate-to-severe exacerbation (index). For the main analysis, patients were categorized as prompt or delayed initiators, initiating triple therapy within 0-30 days or 31-180 days of index, respectively. Inverse probability of treatment weighting based on propensity scores was used to adjust for measured confounders between prompt and delayed cohorts.
UNASSIGNED: For the main analysis, 610 (60.3%) and 402 (39.7%) patients were prompt and delayed initiators, respectively. The rate of subsequent moderate-to-severe exacerbations following index exacerbation was numerically lower in prompt vs delayed initiators (weighted rate ratio 0.95, 95% confidence interval [CI]: 0.74-1.21; P = 0.6603). Time-to-first subsequent moderate-to-severe exacerbation increased significantly in prompt vs delayed initiators (weighted hazard ratio 0.77, 95% CI: 0.64-0.93; P = 0.0053). In patients indexed on a severe exacerbation, delayed initiation resulted in significantly higher 90-day all-cause readmissions vs prompt initiation (42.1% vs 30.6%; P = 0.0329 [weighted estimates]). Weighted healthcare resource utilization rates were numerically lower in prompt vs delayed initiators, and weighted direct costs (all cause and COPD-related) were significantly lower in prompt initiators.
UNASSIGNED: This real-world study demonstrated that earlier initiation of triple therapy resulted in several benefits in clinical outcomes for COPD and may also reduce the economic burden of COPD management in Japan.

Aim: Inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combination therapy is used for the effective control of asthma. Aim of this study was to collect data on the effectiveness, safety, quality of life, and patient satisfaction from a fixed dose combination of budesonide/formoterol administered with the Elpenhaler® device following 3-months\' treatment.Methods: A 3-month real-life, multicentre, one-arm, prospective observational study (SKIRON study-NCT03055793) was conducted, using the following questionnaires: Asthma Control Questionnaire (ACQ-6) for asthma control assessment, MiniAQLQ questionnaire for QoL assessment, and Feeling of Satisfaction with Inhaler questionnaire (FSI-10) for patients\' satisfaction with the inhaler device. Comorbidities and safety data were also recorded during the study.Results: We enrolled 1,174 asthmatic patients following standard clinical practice in primary care from 126 sites in urban and rural areas of Greece. The majority of patients (71.5%) had at least one comorbidity. A statistically significant improvement in the ACQ-6 score was noted at 3 months compared to the baseline evaluation (mean ± SD 2.19 ± 0.97 at baseline vs. 0.55 ± 0.56 at 3 months; mean change -1.64 (95%CI -1.69, -1.57), p < 0.0001). MiniAQLQ score was statistically and clinically significantly improved, compared to baseline, (4.55 ± 1.04 at baseline vs. 6.37 ± 0.64 at 3 months; mean change 1.82 (95%CI 1.75, 1.87), p < 0.0001). The mean FSI-10 score of 44.2 ± 5.4 indicated patient satisfaction and ease-of-use of the Elpenhaler® device.Conclusions: In this large real-world study of inadequately-controlled asthma patients in primary care settings, the treatment with budesonide/formoterol FDC with the Elpenhaler® device was associated with significant improvement in patients\' asthma control and quality of life.

UNASSIGNED: In the FULFIL trial, once-daily single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) resulted in reduced moderate/severe exacerbation rates and conferred significant improvements in lung function and health status in patients with chronic obstructive pulmonary disease (COPD) versus twice-daily budesonide/formoterol (BUD/FOR) dual therapy.
UNASSIGNED: FULFIL was a Phase III, randomized, double-blind, double-dummy, parallel-group study. Patients ≥40 years of age with symptomatic COPD were randomized 1:1 to FF/UMEC/VI 100/62.5/25 mcg or BUD/FOR 400/12 mcg. In this post hoc analysis, patients were categorized by exacerbation history in the year prior to study entry (≥1 moderate/severe exacerbation [recent exacerbation] versus no recent exacerbation). Endpoints included annual rate of on-treatment moderate/severe exacerbations up to Week 24, annual rate of on-treatment severe exacerbations up to Week 24, change from baseline in trough forced expiratory volume in 1 second at Week 24, and change from baseline in health status as measured by St George\'s respiratory questionnaire total score at Week 24.
UNASSIGNED: Of the 1810 patients in the intent-to-treat population, 1180 (65%) had one or more moderate/severe exacerbation in the year prior to entry, while 630 (35%) patients did not. FF/UMEC/VI versus BUD/FOR significantly reduced moderate/severe exacerbation rates in the recent exacerbation subgroup (mean annualized rate: 0.19 vs 0.29; rate ratio [95% confidence interval [CI]]: 0.64: [0.45, 0.91]; p=0.014) and numerically reduced moderate/severe exacerbation rates in the no recent exacerbation subgroup (mean annualized rate: 0.29 vs 0.43; rate ratio [95% CI]: 0.67 [0.43, 1.04]; p=0.073). Severe exacerbation rates were numerically reduced with FF/UMEC/VI versus BUD/FOR treatment across both subgroups. FF/UMEC/VI conferred significant improvements in lung function and health status versus BUD/FOR, regardless of recent exacerbation history.
UNASSIGNED: FF/UMEC/VI reduced moderate/severe and severe exacerbation rates and improved lung function and health status versus BUD/FOR in patients with symptomatic COPD, regardless of recent exacerbation history.

BACKGROUND: Asthma is a chronic inflammatory disease of the airways that causes recurring episodes of wheezing, breathlessness, chest tightness and coughing. Inhaled drugs on a daily basis are the cornerstone of asthma treatment, therefore, patient adherence is very important.
METHODS: We performed a multicenter, open, non-interventional, observational, prospective study of 716 adult patients diagnosed with asthma receiving FDC (Fixed-dose combination) budesonide/formoterol via the Elpenhaler device. We assessed the adherence to treatment at 3 and 6 months (based on the MMAS-8: 8-item Morisky Medication Adherence Scale), the quality of life and change in forced expiratory volume in 1 s (FEV1) from baseline to follow-up.
RESULTS: Approximately 80% of the patients showed medium to high adherence throughout the study. The mean (SD) MMAS-8 score at 6 months was 6.85 (1.54) and we observed a statistically significant shift of patients from the low adherence group to the high adherence group at 6 months. Moreover, after 6 months of treatment with FDC budesonide/formoterol, we observed an increase in the patients\' quality of life that as expressed by a change 2.01 (95%CI 1.93-2.10) units in Mini AQLQ (p < 0.0001) that was more pronounced in the high adherence group. The same trend was also observed in terms of spirometry (mean FEV1 2.58 L (0.85) at the end of the study, increased by 220 mL from baseline) with a higher improvement in the medium and high adherence groups.
CONCLUSIONS: Treatment with FDC of budesonide/formoterol via the Elpenhaler device was associated with improvement in asthma-related quality of life and lung function over 6 months that were more prominent in patients with higher adherence.
BACKGROUND: 2017-HAL-EL-74 (ClinicalTrials.gov Identifier: NCT03300076).

To determine treatment persistence and exacerbations in patients initiating inhaler treatment with fixed-dose combinations of inhaled corticosteroids/long-acting beta-2-adrenergic agonists (ICS/LABA) for the treatment of asthma.
Retrospective observational study conducted by review of electronic medical records (database: Fundación RediSS).
Retrospective cohort study. The follow-up period was 1 year.
The study included patients aged ≥18 years who started treatment with ICS/LABA and met the inclusion/exclusion criteria.
The study groups were fluticasone propionate/salmeterol (FP/SAL), beclomethasone/formoterol (BDP/FORM), budesonide/formoterol (BUD/FORM), fluticasone furoate/vilanterol (FF/VI) and fluticasone propionate/formoterol (FP/FORM). The main measurements were persistence, medication possession ratio (MPR) and exacerbations. Statistical significance was established as p<0.05.
In total, 3203 patients were recruited for the study. By groups, 31.1% FP/SAL, 28.6% BDP/FORM, 25.0% BUD/FORM, 8.2% FF/VI and 7.0% FP/FORM. The mean age was 52.2 years, 60.8% were female and 44.9% had persistent-moderate asthma. Treatment persistence was 61.7% (95% CI 60.0% to 63.4%) and by study group it was FP/SAL: 60.7%, BDP/FORM: 61.2%, BUD/FORM: 60.3%, FF/VI: 66.7% and FP/FORM: 67.6% (p=0.046). MPR by study group was FP/SAL: 74.3%, BDP/FORM: 73.8%, BUD/FORM: 74.6%, FF/VI: 79.4% and FP/FORM: 80.6% (p=0.028). The mortality rate was 2.9%. By treatment group, exacerbations were FP/SAL: 21.9% (95% CI 19.3% to 24.5%), BDP/FORM: 22.2% (95% CI 19.5% to 24.9%), BUD/FORM: 22.8% (95% CI 19.9% to 25.7%), FF/VI: 17.9% (95% CI 14.9% to 20.7%) and FP/FORM: 16.0% (95% CI 12.2% to 19.3%), p=0.036.
Patients undergoing treatment with FP/FORM and FF/VI versus FP/SAL, BDP/FORM and BUD/FORM were associated with greater treatment adherence (persistence, MPR) and lower rates of exacerbations. However, further studies will be needed to strengthen the consistency of the results.

As-needed low-dose combination budesonide-formoterol is recommended by asthma guidelines in many countries as an alternative to maintenance inhaled corticosteroids (ICS) for treatment of mild asthma, but there are few data on patient attitudes toward these regimens. This study explored the comparative implementation experiences and future treatment preferences of mild asthma patients who had experienced these two treatment regimens.
A subgroup of adults randomised to maintenance ICS or as-needed ICS-formoterol in a multinational, 52-week open-label randomised controlled trial (NovelSTART) in mild asthma patients were interviewed to explore their motivations for treatment use during the study and their preferences for future treatment.
Semistructured interviews were conducted with 74 participants (Maintenance group: n=39, As-needed group n=35, mean age 38 (range 19-69)) and thematically analysed from transcribed audiorecordings.
Emergent themes from analysis comprised: \'How much my asthma affects me\' (how their asthma\'s impact affected their self-management motivation); \'What I know about asthma\' (limited knowledge impeded appropriate self-management decision making); \'How much effort this treatment regimen involves for me\' (treatment complexity and/or difficulty establishing a medication routine impeded implementation, particularly in the Maintenance group); and \'My beliefs about the benefits and risks of this treatment\' (patients who considered their treatment as ineffective, eg, limited difference in symptoms relative to salbutamol (both groups) or slower onset of relief (As-needed group) had poor motivation to use the treatment). Due to the simplicity of the as-needed combination strategy, this was the preferred future regimen, even by patients who had not yet tried it.
Key patient perspectives on the implementation of preventer treatments for mild asthma included factors relating to perceived asthma burden, disease knowledge, treatment complexity and treatment usefulness or safety. The as-needed budesonide-formoterol regimen was preferred to maintenance ICS treatment in mild asthma though patient education is urgently needed to address implementation motivation.
ACTRN12615000999538.

In the phase III, 52-week ETHOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF), at two inhaled corticosteroid dose levels, resulted in significantly lower moderate/severe exacerbation rates versus glycopyrrolate/formoterol fumarate (GFF) and budesonide/formoterol fumarate (BFF). Here, we report results from the ETHOS pulmonary function test (PFT) sub-study, which assessed lung function in a subset of ETHOS patients.
ETHOS (NCT02465567) was a randomized, double-blind, multi-center, parallel-group study in patients with moderate to very severe COPD who had experienced ⩾1 moderate/severe exacerbation in the previous year. Patients received BGF 320/18/9.6 µg, BGF 160/18/9.6 μg, GFF 18/9.6 µg, or BFF 320/9.6 µg twice daily via a single metered dose Aerosphere inhaler for 52 weeks. A subset of patients participated in the 4-hour PFT sub-study; primary endpoints were change from baseline in morning pre-dose trough forced expiratory volume in one second (FEV1) versus GFF and FEV1 area under the curve from 0 to 4 hours (AUC0-4) versus BFF at week 24.
The PFT modified intent-to-treat population included 3088 patients (mean age 64.4 years; mean reversibility post-albuterol 16.7%; mean post-albuterol FEV1% predicted 42.8). BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved morning pre-dose trough FEV1 at week 24 versus GFF (p ⩽ 0.0035 for both). Improvements in trough FEV1 were also observed at week 52 for BGF 320/18/9.6 µg and 160/18/9.6 µg versus GFF (p ⩽ 0.0005 for both). For FEV1 AUC0-4 at week 24, BGF 320/18/9.6 µg and 160/18/9.6 µg showed significant improvements versus BFF (p < 0.0001 for both). Improvements were maintained at week 52 (p < 0.0001).
BGF 320/18/9.6 µg and 160/18/9.6 µg significantly improved trough FEV1versus GFF and FEV1 AUC0-4versus BFF at week 24. The lung function benefits with both doses of BGF were maintained following 52 weeks of treatment.The reviews of this paper are available via the supplemental material section.