A Pragmatic RCT of FF/UMEC/VI in Patients with Uncontrolled Asthma: PERFORM Protocol

Background: FULFIL compared once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100μg/62.5μg/25μg via the ELLIPTA ® inhaler with twice-daily budesonide/formoterol (BUD/FOR) 400μg/12μg via the Turbuhaler ® in patients (pts) with advanced COPD, showing statistically significant improvements in lung function and health-related quality of life with FF/UMEC/VI (Lomas et al. ERJ 2016;48:PA4629). We report healthcare resource utilisation and cost data from FULFIL. Methods: Pts recorded unscheduled healthcare contacts (all-cause and COPD-related), including home visits, physician visits, urgent care/outpatient visits, emergency room visits, number of hospitalisation days and contacts for COPD exacerbations. Healthcare costs were calculated from 2016 UK National Health Service Reference Costs ( post hoc ). Results: Over 24 weeks (ITT; FF/UMEC/VI, n=911; BUD/FOR, n=899), slightly fewer pts required overall healthcare contacts in the FF/UMEC/VI arm (19%) than BUD/FOR arm (20%). The proportion requiring contacts for exacerbations was lower for FF/UMEC/VI (8%) vs BUD/FOR (11%). Over 52 weeks (extension population [EXT]; FF/UMEC/VI, n=210; BUD/FOR, n=220), fewer pts in the FF/UMEC/VI arm vs the BUD/FOR arm required overall healthcare contacts or contacts for exacerbations (25% vs 33% and 12% vs 21%, respectively). Based on non-drug healthcare utilisation, non-drug costs per patient per year were lower for FF/UMEC/VI than BUD/FOR in the ITT (£653.80 vs £763.31) and EXT (£749.22 vs £988.03). Conclusion: FF/UMEC/VI resulted in reduced healthcare contacts for exacerbations and non-drug healthcare costs among pts with COPD compared with BUD/FOR. Funding GSK (CTT116853)

Rationale: Clinical remission (CR) is an ambitious and achievable treatment goal in asthma. There is no standardized CR definition; national guidelines and international recommendations assess CR after 52 weeks of treatment with four key components: i) no severe exacerbations; ii) no systemic corticosteroids; iii) asthma control; iv) stable/optimized lung function. Previous post hoc analyses of the CAPTAIN trial demonstrated that patients with uncontrolled moderate-to-severe asthma not yet considered for biologics can achieve CR with both fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) and FF/VI inhaled maintenance therapies. We assessed the attainability of CR in patients taking FF/VI 200/25, FF/UMEC/VI 100/62.5/25, or FF/UMEC/VI 200/62.5/25 versus FF/VI 100/25. Methods: The CAPTAIN Phase 3 trial assessed FF/UMEC/VI versus FF/VI in terms of lung function, asthma control, and exacerbations in patients with uncontrolled moderate-to-severe asthma despite inhaled corticosteroid/long-acting β2-agonist maintenance therapy. In this post hoc analysis, the proportion and odds of patients meeting a composite CR endpoint (oral corticosteroid free, no severe exacerbations, Asthma Control Questionnaire 5-item total score <1.5, change from baseline in forced expiratory volume in 1 second ≥100 mL) were assessed at Week 24 in patients taking FF 200 mcg and adding UMEC to FF/VI (simultaneous step-up) versus FF 100 mcg and dual therapy. Results: With FF/VI 100/25, 19% of patients (n=77/407) met the CR endpoint at Week 24; 26% (n=104/406) met the CR endpoint with increased FF dose (FF/VI 200/25), 31% (n=127/406) when adding UMEC (FF/UMEC/VI 100/62.5/25), and 36% (n=146/408) with simultaneous step-up (FF/UMEC/VI 200/62.5/25). Compared with FF/VI 100/25, odds of meeting the CR endpoint at Week 24 were greater with increased FF dose (FF/VI 200/25: odds ratio [95% confidence interval]: 1.51 [1.08, 2.11], p=0.017) or with addition of UMEC (FF/UMEC/VI 100/62.5/25: 1.93 [1.39, 2.68], p<0.001). The greatest odds of meeting the CR endpoint at Week 24 were obtained with simultaneous step-up (FF/UMEC/VI 200/62.5/25: 2.44 [1.76, 3.37], p<0.001) (Figure). P-values are nominally statistically significant. Conclusions: Both increasing FF dose and adding UMEC contributed to improving clinical outcomes in patients with asthma. These results suggest that the greater odds of meeting the CR endpoint with FF/UMEC/VI 200/62.5/25 versus FF/VI 100/25 were mostly driven by the addition of UMEC. Although data over 52 weeks are needed to confirm achievement of CR, patients not yet considered for biologics with moderate-to-severe asthma uncontrolled on FF/VI 100/25 may gain greater benefits with simultaneous step-up to high-dose triple therapy versus increasing FF dose or adding UMEC alone.

Inhalation is the foundational route for administering pharmacological treatments for chronic obstructive pulmonary disease (COPD). Given the relevance of both large and small airways in COPD, lung distribution deposition characteristics of different inhaler options could influence treatment effects. This study evaluated the total deposition of 3 single-inhaler triple therapies in the large and small airways. This study assessed lung deposition of different inhalers using in silico functional respiratory imaging from 20 patients with COPD. The first part evaluated budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) pressurized metered-dose inhaler (pMDI), beclomethasone dipropionate/glycopyrronium/formoterol fumarate dihydrate (BDP/G/F) pMDI, and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) dry powder inhaler (DPI) at 30 L/min. The second part assessed BGF pMDI and FF/UMEC/VI DPI at 60 L/min. All 3 inhalers had different in silico total lung and large and small airways deposition profiles at 30 L/min, with BGF pMDI (54.8% to 57.7%) demonstrating a higher deposition profile across each therapeutic component versus BDP/G/F pMDI (38.6% to 40.5%) and FF/UMEC/VI DPI (24.0% to 36.1%), respectively. Similarly, at 60 L/min, the total deposition of all 3 components of BGF pMDI (57.2% to 58.5%) remained higher compared with FF/UMEC/VI DPI (19.8% to 34.1%). These findings provide quantitative insights into relative lung deposition distribution profiles and efficiency of delivery for 3 inhaler options. Further research is needed to understand if these deposition patterns could translate into real-world clinical effectiveness differences.

BackgroundIn asthma, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) was previously demonstrated to improve forced expiratory volume in 1 s (FEV1) and asthma control, but the mechanism by which this occurs, especially at the level of the small airways, is not well-understood. We asked the question, does FF/UMEC/VI influence asthma control by improving airway structure–function and airway occlusions? Hence, our objective was to measure airway structure–function using 129Xe magnetic resonance imaging (MRI) ventilation defect percentage (VDP), computed tomography (CT) and airwave oscillometry after 6-week single-inhaler FF/UMEC/VI and 1 year later.MethodsParticipants with Global Initiative for Asthma Step 4–5 (GINA4–5) asthma who were poorly controlled on inhaled corticosteroid/long-acting β-2 agonist (ICS/LABA) provided written informed consent to baseline, 6- and 12-week visits as well as an open-extension 1-year visit. All received FF/UMEC/VI (200/62.5/25 µg) at baseline and underwent MRI, spirometry, plethysmography and oscillometry, pre- and post-bronchodilator (BD). The Asthma Control Questionnaire, the Asthma Quality of Life Questionnaire (AQLQ) and St. George's Respiratory Questionnaire (SGRQ) were completed. CT was acquired at baseline and 1 year later.ResultsThirty-one participants (24 females, 54±15 yrs) completed the baseline visit, 28 (21 females, 54±15 yrs) completed the 6-week visit and 15 patients attended the 1-year visit. At 6-weeks, there was significantly improved pre-BD VDP (p=0.02), FEV1 (p=0.008), distal airways resistance (R5–19) (p=0.001), AQLQ (p<0.001) and SGRQ-scores (p=0.001), which persisted at 1 year. VDP improved in participants with elevated mucus score and eosinophil count, while R5–19 improvements were independent of type 2 inflammation. Mean airway mucus score, lumen area and total airway count were significantly improved at 1 year.ConclusionsIn participants with GINA4–5 asthma, who had been poorly controlled on ICS/LABA, single-inhaler FF/UMEC/VI resulted in improved VDP and FEV1 at 6-weeks. These improvements persisted 1-year later when airway markers were also significantly improved, consistent with the reversal of airway remodelling.

IntroductionFew studies have utilized 24-h serial spirometry to compare the effects of inhaled chronic obstructive pulmonary disease (COPD) therapies on lung function. The FULFIL study previously reported significant lung function improvements with once-daily single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus twice-daily single-inhaler budesonide/formoterol (BUD/FOR) in patients with symptomatic COPD at risk of exacerbations.MethodsThis prespecified analysis evaluated 24-h serial spirometry data from a subgroup of 406 patients in FULFIL. BUD/FOR twice-daily dosing was maintained during 24-h spirometry. A post hoc analysis evaluated serial forced expiratory volume in 1 s (FEV1) at day 1 and week 24 by disease severity at screening (FEV1 < 50% predicted and no moderate or severe exacerbation in prior year, FEV1 < 50% predicted and ≥ 1 moderate or severe exacerbation in prior year, and FEV1 ≥ 50% and < 80% predicted and ≥ 2 moderate or ≥ 1 severe exacerbations in prior year).ResultsOdds of achieving a ≥ 100-mL increase from baseline in FEV1 within the first 6 h post dose on day 1 were significantly greater with FF/UMEC/VI than BUD/FOR [odds ratio 2.79 (95% confidence interval 1.56–4.98); p < 0.001]. FF/UMEC/VI led to greater improvements in weighted mean FEV1 over 0–6, 0–12, 0–24, and 12–24 h on day 1 and at week 24, with the greatest between-group differences at week 24 (range 196–210 mL; all p < 0.001). Significant between-treatment differences in FEV1 and forced vital capacity (FVC) in favor of FF/UMEC/VI versus BUD/FOR were seen at all time points at week 24 (FEV1 range 156–231 mL, all p < 0.001; FVC range 139–309 mL, all p ≤ 0.002). Serial FEV1 results were consistent irrespective of disease severity at screening.ConclusionThese findings further demonstrate sustained lung function benefits with once-daily FF/UMEC/VI single-inhaler triple therapy in patients with symptomatic COPD at risk of exacerbations across a range of disease severities.

BackgroundThis analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy.MethodsIMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death.ResultsBaseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments.ConclusionsIn a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10–11% and 1–3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI.Trial registrationNCT02164513 (GSK study number CTT116855).

BackgroundCompared with multiple-inhaler triple therapy (MITT), single-inhaler triple therapy (SITT) with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) demonstrated improved lung function and meaningful improvements in chronic obstructive pulmonary disease (COPD) Assessment Test score....

Clinical remission (CR) is an emerging treatment goal in asthma. However, evidence showing whether CR is achievable with inhaled therapy is lacking. This post hoc analysis of CAPTAIN evaluated attainability of a composite CR endpoint with inhaled fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) or FF/VI. CAPTAIN (GSK 205715) was a Phase IIIA, randomized, controlled, 24-52-week trial comparing once-daily single-inhaler FF/UMEC/VI versus FF/VI in adults with uncontrolled moderate-to-severe asthma despite ICS/LABA. CR was defined as a composite endpoint comprising no systemic corticosteroids, no severe exacerbations, ACQ-5 total score < 1.50, and either change from baseline in FEV1 ≥ 0ml (lung function stabilization) or ≥ 100ml (lung function optimization), assessed for patients meeting the CR endpoint at Week 24 (W24) and achieving CR at W52 with FF/UMEC/VI (100/62.5/25, 200/62.5/25μg) versus FF/VI (100/25, 200/25μg). Additional analyses assessed the CR endpoint at W24/W52 using ACQ-5 ≤ 0.75 and ≤ 1.00 thresholds. Adjusted odds/risk ratios for CR were calculated for W24. More patients met the CR endpoint (lung function stabilization/optimization) with FF/UMEC/VI versus FF/VI at W24 (stabilization: 42-47% vs 31-36%; optimization: 31-36% vs 19-26%) and W52 (stabilization: 43-47% vs 33-34%; optimization: 30-38% vs 21-24%). Using more stringent ACQ-5 thresholds, fewer patients met the CR endpoint with ACQ ≤ 0.75 versus < 1.50 across treatment arms and timepoints. The odds and probability of meeting the CR endpoint versus not meeting the CR endpoint at W24 were greater with FF/UMEC/VI versus FF/VI, regardless of FF dose. The results of this post hoc analysis demonstrate that CR is achievable with inhaled therapy in moderate-to-severe asthma and is more likely with FF/UMEC/VI than FF/VI. CR should be considered an attainable treatment goal for patients with asthma, irrespective of disease severity or treatment history. ClinialTrials.gov identifier, NCT02924688.

Rationale: In the IMPACT (Informing the Pathway of COPD Treatment) trial, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy reduced exacerbation risk versus FF/VI and UMEC/VI and mortality risk versus UMEC/VI. However, pneumonia incidence was higher in the inhaled corticosteroid (FF)–containing arms, raising questions about the relative benefit of exacerbation reduction compared with the increased risk of pneumonia.Objectives: Determine benefit–risk of the three treatments by evaluating time-to-first and rates of composite exacerbation or pneumonia outcomes.Methods: We evaluated time-to-first (prespecified) and rates (post hoc) of investigator-reported pneumonia, serious pneumonia leading to hospitalization or death, and the composite endpoints of 1) moderate (required antibiotics/corticosteroids)/severe (hospitalized) exacerbation or pneumonia and 2) severe exacerbation or serious (hospitalized) pneumonia. Analyses were repeated for radiographically confirmed pneumonia (post hoc).Results: Moderate/severe exacerbations occurred in 47%, 49%, and 50% of patients randomized to FF/UMEC/VI, FF/VI and UMEC/VI, and pneumonias in 8%, 7%, and 5%, respectively. FF/UMEC/VI reduced the risk of combined moderate/severe exacerbation or pneumonia (time-to-first) versus FF/VI (hazard ratio, 0.87 [95% confidence interval (CI), 0.82–0.92]) and UMEC/VI (0.87 [0.81–0.94]), as well as the risk of combined severe exacerbation or serious pneumonia versus UMEC/VI (0.83 [0.72–0.96]). FF/UMEC/VI reduced the rate of combined moderate/severe exacerbation or pneumonia (rate ratio, 0.78 [0.72–0.84]) and combined severe exacerbation or serious pneumonia (rate ratio, 0.76 [0.65–0.89]) versus UMEC/VI. Results were similar for radiographically confirmed pneumonia endpoints.Conclusions: Despite higher incidence of pneumonia in FF-containing arms, these composite exacerbation/pneumonia outcomes support a favorable benefit–risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.

Objective To review the evidence for the use of open-inhaler (inhaled corticosteroid [ICS] plus long-acting β2-agonist [LABA] with separate add-on long-acting muscarinic antagonist [LAMA]) versus single-inhaler triple therapy (ICS/LABA/LAMA combination) and the merits of add-on LAMA to ICS/LABA in patients with uncontrolled asthma. Data Sources Original research articles were identified from PubMed using the search term “triple therapy asthma.” Information was also retrieved from the ClinicalTrials.gov website. Study Selections Articles detailing the use of add-on LAMA to ICS plus LABA (open-inhaler triple therapy), and closed triple therapy compared with ICS plus LABA dual therapy, addressing patient symptoms, exacerbations, and health-related quality of life. Results Open-inhaler triple therapy was associated with a significantly reduced incidence of hospitalizations and emergency department visits and a decrease in ICS dose, oral corticosteroids use, and antibiotics use. Exacerbations and acute respiratory events were also reduced. Single-inhaler triple therapy showed a greater improvement in lung function, asthma control, and health status and was noninferior to open-inhaler triple therapy for Asthma Quality of Life Questionnaire scores. Single-inhaler triple therapy may also lead to improved therapy adherence. Conclusion Add-on LAMA to ICS plus LABA (open- or single-inhaler triple therapy) improves the response in patients who remain symptomatic and provides a reasonable alternative to ICS dose escalation in treatment-refractory patients.

Improving Medical and Psychiatric Outcomes Among Individuals With Bipolar Disorder: A Randomized Controlled Trial

Background: IMPACT (InforMing the PAthway of COPD Treatment, NCT02164513), showed superior exacerbation reduction and lung function improvement with single inhaler, once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/22μg vs once-daily FF/VI 100/22μg, for patients with moderate/severe COPD. Objectives: The cost-effectiveness of FF/UMEC/VI vs FF/VI was assessed, from a Canadian public payer perspective. Methods: A validated linked risk equation model (Briggs, Med Decis Making 37;4 2017), which predicts COPD disease progression, associated healthcare costs and health outcomes, was populated with baseline characteristics, efficacy and medication use from IMPACT. Canadian healthcare resource unit costs and drug costs were applied, with future costs and health outcomes discounted at 1.5% annually. Analysis was probabilistic, with a lifetime horizon and outputs including exacerbation rates, costs (2017 CAD), quality-adjusted life years (QALYs) gained and incremental cost effectiveness ratio (ICER) per QALY. Results: Compared with FF/VI, FF/UMEC/VI treatment resulted in fewer moderate and severe exacerbations (10.52 and 3.38 vs 11.13 and 3.48), mean (95% CI) incremental costs and QALYs of $2,598 ($2,010, $3,268) and 0.13 (0.09, 0.18), and an ICER of $19,649 per QALY ($15,406, $26,454). The probability of FF/UMEC/VI being cost-effective vs FF/VI was 100% at a willingness-to-pay threshold of $50,000 per QALY. Results were most sensitive to time horizon, and efficacy of treatment post-discontinuation. Conclusions: FF/UMEC/VI was predicted to improve health outcomes and to be a cost-effective option for treatment of moderate/severe COPD compared with FF/VI, in Canada.

Objective: Two single-center, four-way, single-dose, crossover studies assessed the systemic exposure, systemic pharmacodynamics (PD), and safety profile of the closed triple fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) therapy compared with dual therapies. These are the first studies where pharmacokinetic (PK) profile assessment was possible for this inhaled triple fixed-dose combination product. Methods: Healthy volunteers were randomized to receive 4 consecutive inhalations (each administered as a single dose) via a single ELLIPTA® dry powder inhaler: in study 1 (CTT116415/NCT01691547), FF/UMEC/VI at total doses of 400/500/100 μg, FF/UMEC 400/500 μg, UMEC/VI 500/100 μg, or FF/VI 400/100 μg; in study 2 (200587/NCT01894386), FF/UMEC/VI at total doses of 400/500/100 μg or 400/250/100 μg, FF/VI 400/100 μg, or UMEC/VI 250/100 μg. PK and PD parameters and safety were assessed. Results: Of 88 subjects, 95% completed both studies and received all planned treatments. Total systemic exposure was similar for FF, UMEC, and VI when administered as a triple therapy compared with FF/VI and UMEC/VI. No clinically significant systemic PD findings were detected. The incidence of adverse events was low and similar across treatment arms. Conclusions: Systemic exposure to all three components of the closed triple therapy, following single-dose delivery, was similar to that seen with the dual therapies FF/VI and UMEC/VI. The delivered lung dose and safety profile of all three agents, delivered via a single inhaler, are expected to be similar to those of the dual therapies.

Objective. To evaluate the impact of uncontrolled asthma on the absenteeism and health-related quality of life (HRQOL) of adults and children with asthma and the caregivers of pediatric patients. Patients and methods. Patient information was obtained from datasets maintained by National Jewish Health for this cross-sectional study. Participants in the study were 12 years of age or older. Participants younger than 18 years had their information provided by caregivers. Caregivers also provided 6 months of absenteeism and QOL data. Participants were classified as having uncontrolled asthma based on a treatment and symptom guideline-based algorithm. Absenteeism was assessed from the self-reported number of work or school days missed due to asthma during the previous 6 months. HRQOL among adults was measured using the validated Marks Asthma Quality of Life Questionnaire (Marks-AQLQ) and among caregivers using the validated Pediatric Asthma Caregivers Quality of Life Questionnaire (PACQLQ). To account for the positive skew in absenteeism data, a zero-inflated Poisson regression model was used to compare group differences. HRQOL was analyzed for adults and caregivers using the Wilcoxon-Mann-Whitney test. Results. A total of 15,149 patients met the inclusion criteria for the study and were included in the analysis. Adults with uncontrolled asthma and caregivers of children with uncontrolled asthma reported significantly higher absenteeism than their controlled counterparts: 43% vs 24% adults reported missing days of work, with a median 6 days vs 3 days missed; 31% vs 16% of caregivers reported missing days of work, with 4 days vs 2 days missed; and caregivers reported that more than 70% vs 45% pediatric patients missed school, with a median of 6 days vs 4 days missed (uncontrolled vs controlled asthma, respectively). Adult uncontrolled asthmatics and caregivers of uncontrolled pediatric patients had significantly lower HRQOL as indicated by the Marks-AQLQ (scores 1.5 points higher, p < 0.001) and PACQLQ (scores < 0.5 points lower, p < 0.001), respectively. Conclusions. Uncontrolled asthma has far-reaching impact on the productivity and quality of life of asthma patients and their caregivers. Proper assessment, treatment, and disease management to improve asthma control may reduce the impact of uncontrolled asthma on asthmatic adults, children, and the caretakers of pediatric asthmatic patients.

Triple therapy with inhaled corticosteroids and dual bronchodilator therapy is recommended for chronic obstructive pulmonary disease (COPD) patients who have exacerbations and eosinophilia. It can be administered by single inhaler triple therapy (SITT) or by multiple inhaler triple therapy (MITT). There is a lack of evidence of the benefits of SITT over MITT in the Chinese population, especially on switching from existing MITT to SITT. A total of 70 Chinese patients with COPD were recruited in this open-label, double-arm clinical trial to investigate the number of critical inhaler errors, the modified Medical Research Council (mMRC) dyspnea scale, the Medication Adherence Report Scale for Asthma (MARS-A) score, and a satisfaction score upon switching from MITT to SITT. The mean number of critical inhaler errors was 0.4±1.0 in the SITT group and 1.1±1.8 in the MITT group( p=0.038) at the first visit; and 0.2±0.6 in the SITT group and 0.8±1.1 in the MITT group (p=0.007) at the second visit. The mean change in MARS-A from baseline to first visit was +3.76±7.48 in the SITT group and -1.27±7.76 in the MITT group (p-value 0.008). A total of 22 (59.5%) and 8 (24.2%) of the patients in the SITT and the MITT group respectively, had an increase in MARS-A score from baseline to first visit, with an adjusted odds ratio of 6.23 (95% confidence interval=1.63-23.77, p=0.007), favoring SITT. There was no significant difference in the change in the mMRC dyspnea scale and the satisfaction score between the 2 groups. Switching from MITT to SITT in Chinese COPD patients may have the benefits of having fewer critical inhaler errors and a higher MARS-A score.