Real-life effectiveness of indacaterol-glycopyrronium after switching from tiotropium or salmeterol/fluticasone therapy in patients with symptomatic COPD: the POWER study.
ABSTRACT: Purpose:In contrast to randomized controlled trials (RCTs), changes in maintenance pharmacotherapy in clinical practice occur without a washout period. The Prospective cohort study for the real-life effectiveness evaluation of glycOpyrronium With indacatERol combination in the management of COPD in Canada (POWER) study evaluated the real-life effectiveness of indacaterol/glycopyrronium (IND/GLY) following a direct switch from a long-acting muscarinic antagonist (LAMA, tiotropium) or long-acting ?2-agonist (LABA)/inhaled corticosteroid (ICS) maintenance treatment (salmeterol/fluticasone [SFC]). Methods:POWER was a single-cohort, prospective, multicenter, interventional study in which patients with moderate-to-severe COPD, who remained symptomatic on their current treatment of once-daily (od) tiotropium 18 µg or twice-daily (bid) SFC (any dose), were switched to treatment with open-label IND/GLY 110/50 µg od for 16 weeks. Effectiveness end points were change from baseline in trough FEV1, transition dyspnea index (TDI) total scores, and COPD assessment test (CAT) scores at 16 weeks. Results:Trough FEV1 improved by 175 mL at Week 16 in patients who switched to IND/GLY. The change was 176 mL (95% CI: 135-217) when switched from tiotropium and 172 mL (95% CI: 85-258) when switched from SFC fixed-dose combination (FDC). At Week 16, significant improvements were observed in the mean TDI total scores (?=2.5) and CAT scores (?=-6.5) after the switch to IND/GLY treatment (both P<0.0001). Additionally, IND/GLY was well tolerated in patients with moderate-to-severe COPD, and no safety signal was observed. Conclusion:In clinical practice settings, a direct switch from previous treatment with either tiotropium or SFC to IND/GLY was safe and provided superior clinically significant improvements in lung function and patient-related outcomes in patients with moderate-to-severe COPD. Clinical trial registration:NCT02202616.
Project description:Indacaterol/glycopyrronium (IND/GLY) is approved for maintenance treatment of adult patients with COPD. This post hoc analysis explored the efficacy and safety of IND/GLY versus salmeterol/fluticasone (SFC) in symptomatic (Global Initiative for Chronic Obstructive Lung Disease [GOLD] B and GOLD D) patients with moderate-to-severe COPD.Data from LANTERN and ILLUMINATE studies were pooled and analyzed. In both studies, symptomatic COPD patients were randomized to once-daily IND/GLY 110 ?g/50 ?g or twice-daily SFC 50 ?g/500 ?g. End points were pre-dose trough forced expiratory volume in one second (FEV1), standardized area under the curve for FEV1 from 0 to 12 hours (FEV1 AUC0-12 hours), peak FEV1, peak forced vital capacity (FVC), pre-dose trough FVC, Transition Dyspnea Index (TDI) total score, St George's Respiratory Questionnaire total score, rescue medication use and safety.A total of 1,263 patients were classified as either GOLD B (n=809) or GOLD D (n=454). At week 26, IND/GLY demonstrated statistically significant improvement in all lung function parameters versus SFC in patients in both the GOLD B and GOLD D subgroups. TDI total score and rescue medication use were significantly improved with IND/GLY versus SFC in the overall population and in the GOLD B (TDI total score only) and GOLD D (rescue medication only) subgroups. IND/GLY also reduced the rate of exacerbations in the pooled population. Overall safety profile was comparable with a higher incidence of pneumonia in the SFC-treated group.In this pooled analysis, IND/GLY demonstrated superior efficacy compared with SFC in patients in the GOLD B and GOLD D subgroups and supported its use in symptomatic COPD patients.
Project description:The aim of this study was to evaluate the cost-effectiveness of the long-acting beta-2 agonist (LABA)/long-acting muscarinic antagonist (LAMA) dual bronchodilator indacaterol/glycopyrronium (IND/GLY) as a maintenance treatment for COPD patients from the perspective of health care payer in Taiwan.We adopted a patient-level simulation model, which included a cohort of COPD patients aged ?40 years. The intervention used in the study was the treatment using IND/GLY, and comparators were tiotropium or salmeterol/fluticasone combination (SFC). Data related to the efficacy of drugs, incidence of exacerbation, and utility were obtained from clinical studies. Direct costs were estimated from claims data based on the severity of COPD. The cycle length was 6 months (to match forced expiratory volume in 1 second [FEV1] data), and the time horizons included 1, 3, 5, 10 years, and lifetime. Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the model results. Costs were expressed in US dollars with a discount rate of 3.0%.Compared to tiotropium and SFC, the incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY) gained of patients treated with IND/GLY were US$5,987 and US$14,990, respectively. One-way sensitivity analysis revealed that the improvement in FEV1 provided by IND/GLY, the distribution of patients with regard to the severity of COPD, and acute exacerbation rate ratio were the key drivers behind cost-effectiveness. Adopting a willingness to pay of US$60,000 per QALY gained as the threshold, there was a 98.7% probability that IND/GLY was cost-effective compared to tiotropium. Similarly, there was a 99.9% probability that IND/GLY was cost-effective compared to SFC.As a maintenance treatment for COPD, we consider the dual bronchodilator IND/GLY as a cost-effective strategy when compared to either tiotropium or SFC.
Project description:BACKGROUND AND OBJECTIVE:Indacaterol/glycopyrronium (IND/GLY) 110/50??g once daily (q.d.) has demonstrated greater improvements in lung function, patient-reported outcomes and lower exacerbation rates versus mono long-acting muscarinic antagonists (LAMA) in chronic obstructive pulmonary disease (COPD) patients. However, data are limited on initial treatment with IND/GLY 110/50??g q.d. versus mono LAMA in COPD patients, not previously on maintenance treatment with long-acting bronchodilators (LABD). METHODS:A pooled analysis of ARISE, SHINE and SPARK trials was conducted to evaluate the efficacy of IND/GLY 110/50??g q.d. versus open-label (OL) tiotropium (TIO) 18??g q.d. and GLY 50??g q.d. in COPD patients, not on maintenance treatment with LABD at study entry (LABD-naïve). Efficacy was assessed after 24/26?weeks of treatment. RESULTS:In total, 998 LABD-naïve patients were included (IND/GLY: 353; OL TIO: 328; GLY: 317). Patients treated with IND/GLY 110/50??g q.d. experienced greater improvements in trough forced expiratory volume in 1 s (FEV1 ) versus OL TIO 18??g q.d. (least squares mean treatment difference (?): 0.086?L) and GLY 50??g q.d. (?: 0.080?L) after 24/26?weeks. Improvements in electronic diary (eDiary) symptom scores, transition dyspnoea index (TDI) focal score, St George's Respiratory Questionnaire (SGRQ) total score and rescue medication use were also greater with IND/GLY versus OL TIO and GLY. Greater proportion of patients achieved minimal clinically important difference in trough FEV1 , TDI and SGRQ with IND/GLY versus OL TIO and GLY. CONCLUSION:LABD-naïve patients treated with IND/GLY 110/50??g q.d. achieved improvements in lung function, daily symptoms, dyspnoea, health-related quality of life and rescue medication use versus those who received single LAMA.
Project description:Long-acting bronchodilator monotherapy (long-acting ?2-agonist [LABA] or long-acting muscarinic antagonist [LAMA]) is extensively used for treatment of patients with chronic obstructive pulmonary disease (COPD) with mild-to-moderate airflow limitation. However, a substantial number of patients remain symptomatic despite treatment with a single bronchodilator, necessitating a change in therapy.This 12-week, randomized, multicenter, open-label, phase IV study aims to show that the once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 ?g fixed-dose LABA/LAMA combination results in an improved lung function in symptomatic patients with mild-to-moderate COPD who switch from once-daily tiotropium 18 ?g. The study aims to enroll a total of 404 symptomatic patients in Korea with mild-to-moderate COPD who received tiotropium for at least 12 weeks prior to the study initiation. The primary objective of this study is to demonstrate the superiority of IND/GLY over tiotropium in terms of trough forced expiratory volume in 1 second (FEV1) following 12 weeks of treatment. Secondary endpoints include the pre-dose trough FEV1 after 4 weeks of treatment, transition dyspnea index (TDI) total score, COPD assessment test (CAT) total score, and rescue medication use following the 12-week treatment, and safety assessment over the 12-week treatment.This study intends to establish the use of LABA/LAMA combination therapy in symptomatic patients with mild-to-moderate COPD by demonstrating the superiority of IND/GLY over tiotropium monotherapy.ClinicalTrials.gov, NCT02566031 . Registered on 10 August 2015.
Project description:Endpoints that evaluate deterioration rather than improvement of disease may have clinical utility in COPD. In this analysis, we compared the effects of different maintenance treatments on the prevention of clinically important deterioration (CID) in moderate-to-severe COPD patients.Data were analyzed from three 26-week studies comparing indacaterol/glycopyrronium (IND/GLY) with tiotropium (TIO) or salmeterol/fluticasone (SFC). Two definitions of CID were used; each was a composite of three outcome measures typically associated with COPD. Definition 1 (D1) comprised a ?100 mL decrease in forced expiratory volume in 1 second (FEV1), a ?4-unit increase in St George's Respiratory Questionnaire, and a moderate-to-severe COPD exacerbation. In Definition 2 (D2), a ?1-unit decrease in transition dyspnea index replaced FEV1.Using D1, IND/GLY significantly reduced the risk of first or sustained CID versus either TIO (hazard ratio 0.72 [0.61, 0.86], P=0.0003 and 0.73 [0.61, 0.89], P=0.001) or SFC (0.67 [0.57, 0.80] and 0.63 [0.52, 0.77], both P<0.0001). With D2, IND/GLY significantly reduced the risk of first, but not sustained, CID versus TIO (0.80 [0.64 to 0.99], P=0.0359 and 0.85 [0.66, 1.10], P=0.2208) and both first and sustained CID versus SFC (0.73 [0.61, 0.88], P=0.001 and 0.72 [0.58, 0.90], P=0.0036).These data confirm the utility of the CID endpoint as a means of monitoring COPD worsening in patients with moderate-to-severe COPD. Using the CID measure, we demonstrated that dual bronchodilation with IND/GLY significantly reduced the risk of CID versus either long-acting muscarinic antagonist or long-acting ?2-agonist/inhaled corticosteroid treatment, providing further evidence for the benefit of dual bronchodilation in this patient population.
Project description:The FLAME study demonstrated that indacaterol/glycopyrronium (IND/GLY), the fixed-dose combination of a long-acting ?2-agonist (LABA, IND) and a long-acting muscarinic antagonist (LAMA, GLY), was superior to salmeterol/fluticasone combination (SFC) in preventing exacerbations in COPD patients with a high risk of exacerbations. In this study, we report a prespecified analysis of the efficacy and safety of IND/GLY versus SFC in Asian patients from the FLAME study.Patients from Asian centers with moderate-to-very severe COPD and ?1 exacerbation in the previous year from the 52-week, randomized FLAME study were included. IND/GLY was compared versus SFC for effects on exacerbations, lung function (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]), health status (St George's Respiratory Questionnaire [SGRQ]), rescue medication use, and safety.A total of 510 Asian patients (IND/GLY, n=250 or SFC, n=260) were included. Compared to the overall FLAME population, the Asian cohort had more males, a shorter duration of COPD, fewer patients using inhaled corticosteroid (ICS) at screening, fewer current smokers, and more patients with very severe COPD. IND/GLY significantly reduced the rate of moderate/severe exacerbations (rate ratio: 0.75; 95% confidence interval: 0.58-0.97; P=0.027) and prolonged time to first moderate/severe exacerbation versus SFC (hazard ratio: 0.77; 95% confidence interval: 0.59-1.01; P=0.055). Predose trough FEV1 and FVC significantly improved in Asian patients (P<0.001). IND/GLY improved SGRQ for COPD (SGRQ-C score; P=0.006) and reduced rescue medication use (P=0.058) at week 52. Pneumonia incidence was 3.6% with IND/GLY and 7.7% with SFC (P=0.046).In exacerbating Asian COPD patients, IND/GLY was more effective than SFC.
Project description:<b>Background</b>: QVA149 is a dual bronchodilator combining the long-acting ?<sub>2</sub>-agonist(LABA) indacaterol and the long-acting muscarinic antagonist (LAMA) glycopyrronium, for maintenance treatment of COPD. This post hoc analysis evaluated the improvements in lung function, dyspnea, and health status in subgroups of patients based on prior medication use, disease severities, baseline cough score, and baseline rescue medication use, achieved with QVA149 compared with placebo and other active comparators in 2 phase III clinical studies. <b>Methods</b>: In both the SHINE (NCT01202188) and ILLUMINATE (NCT01315249) studies, symptomatic patients aged ?40 years with moderate-to-severe COPD were randomized to once-daily QVA149 (110/50 µg), indacaterol (150 µg), glycopyrronium (50 µg), tiotropium (18 ?g), or placebo (2:2:2:2:1) and once-daily QVA149 (110/50 µg) or twice-daily salmeterol/fluticasone ([SFC]; 50/500 µg), respectively for 26 weeks. Here, we present the improvements in lung function, transition dyspnea index (TDI) and St. George's Respiratory Questionnaire (SGRQ) total score by prior medication use and COPD disease severity separately from both studies. <b>Results</b>: In total, 2144 and 523 patients were randomized in the SHINE and ILLUMINATE studies; 89.1% and 82.6%, respectively, completed the study. QVA149 showed significant improvements in lung function compared with placebo (SHINE study) and SFC (ILLUMINATE study) regardless of prior medication, disease severity, baseline cough score, and rescue medication use. TDI and SGRQ total scores were also improved with QVA149 compared with placebo and SFC in most of the analyzed subgroups. <b>Conclusion:</b> QVA149 showed improvements in lung function, dyspnea, and health status in both moderate and severe COPD patients independent of previous medication use and baseline cough score.
Project description:BACKGROUND:Dual bronchodilation combining a long-acting ?2-agonist (LABA) and a long-acting muscarinic antagonist (LAMA) is the preferred choice of treatment recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 guidelines for the management of patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). The once-daily (q.d.) fixed-dose combination (FDC) of LABA, indacaterol 110 ?g and LAMA, glycopyrronium 50 ?g (IND/GLY 110/50 ?g q.d.) demonstrated superior improvements in lung function, dyspnoea and overall health status and better tolerability against LABA or LAMA monotherapies and combination of LABA and inhaled corticosteroid (ICS) in more than 11,000 patients with moderate-to-severe COPD in several randomised controlled clinical trials. METHODS:The CRYSTAL study was the first, 12-week, randomised, open-label trial that evaluated the efficacy and safety of a direct switch from previous treatments to IND/GLY 110/50 ?g q.d. on lung function and dyspnoea in patients with moderate COPD and a history of up to one exacerbation in the previous year. Patients were divided into 2 groups according to their background therapy and symptom scores and were randomised (3:1) to IND/GLY or to continue with their previous treatments. RESULTS:The study included 4389 randomised patients, of whom 2160 were in groups switched to IND/GLY (intention-to-treat population). The effect of IND/GLY was superior to LABA + ICS on trough forced expiratory volume in 1 s (FEV1; treatment difference, ? = +71 mL) and transition dyspnoea index (TDI; [? = 1.09 units]), and to LABA or LAMA on trough FEV1 (? = +101 mL) and a TDI (? = 1.26 units). Improvements in health status and lower rescue medication use were also observed with IND/GLY. The safety profile of the study medication was similar to that observed in previous studies. CONCLUSIONS:IND/GLY demonstrated superior improvements in lung function and dyspnoea after direct switch from previous treatments. TRIAL REGISTRATION:ClinicalTrials.gov number: NCT01985334 .
Project description:The objective of the FAVOR study was to evaluate the effect of indacaterol/glycopyrronium (IND/GLY) versus tiotropium on peak forced expiratory volume in 1 s (FEV1) and also to investigate patient satisfaction and treatment preference.Patients with moderate-to-severe airflow limitation (FEV1/forced vital capacity ratio of <0.70), those with a COPD assessment test score of ?10, and those who were maintained on tiotropium HandiHaler® therapy prior to enrollment were recruited for the study, and randomized (1:1) to receive either 4 weeks open-label IND/GLY (110/50 ?g) once daily followed by 4 weeks of tiotropium (18 ?g) once daily or vice versa. The primary endpoint was FEV1 1 h post-inhalation after 4 weeks of treatment. Other endpoints included patient's and physician's preference for treatment, patient's satisfaction evaluated using a study-specific questionnaire and the abbreviated Treatment Satisfaction Questionnaire for Medication, and safety and tolerability.Eighty-seven out of 88 randomized patients completed the study and showed significantly higher FEV1 1 h post-inhalation after 4 weeks of treatment with IND/GLY versus tiotropium (treatment difference =0.081 L; p=0.0017). IND/GLY was preferred over tiotropium among the patients (69.4% versus 30.6%, p=0.0004) and the physicians (81.6% versus 18.4%, p<0.0001). A higher proportion of the patients stated they were very satisfied or satisfied with IND/GLY versus tiotropium with regard to dyspnea reduction (79.3% versus 58.0%, respectively) and reduction of dyspnea on exertion (72.4% versus 43.2%, respectively). Patients treated with IND/GLY showed significant improvement in Treatment Satisfaction Questionnaire for Medication domain scores versus tiotropium. IND/GLY demonstrated a good safety and tolerability profile.This study indicated that, beyond FEV1, important patient-reported outcomes improved with the open-label dual bronchodilator IND/GLY when compared with tiotropium. This study suggests that individual patients felt the lung function benefits with IND/GLY compared with tiotropium, which, in turn, may also have contributed to the preference for IND/GLY.
Project description:Background:Current pharmacological therapies for COPD improve quality of life and symptoms and reduce exacerbations. Given the progressive nature of COPD, it is arguably more important to understand whether the available therapies are able to delay clinical deterioration; the concept of "clinically important deterioration" (CID) has therefore been developed. We evaluated the efficacy of the single-inhaler triple combination beclometasone dipropionate, formoterol fumarate, and glycopyrronium (BDP/FF/G), using data from three large 1-year studies. Methods:The studies compared BDP/FF/G to BDP/FF (TRILOGY), tiotropium (TRINITY), and indacaterol/glycopyrronium (IND/GLY; TRIBUTE). All studies recruited patients with symptomatic COPD, FEV1 <50%, and an exacerbation history. We measured the time to first CID and to sustained CID, an endpoint combining FEV1, St George's Respiratory Questionnaire (SGRQ), moderate-to-severe exacerbations, and death. The time to first CID was based on the first occurrence of any of the following: a decrease of ?100 mL from baseline in FEV1, an increase of ?4 units from baseline in SGRQ total score, the occurrence of a moderate/severe COPD exacerbation, or death. The time to sustained CID was defined as: a CID in FEV1 and/or SGRQ total score maintained at all subsequent visits, an exacerbation, or death. Results:Extrafine BDP/FF/G significantly extended the time to first CID vs BDP/FF (HR 0.61, P<0.001), tiotropium (0.72, P<0.001), and IND/GLY (0.82, P<0.001), and significantly extended the time to sustained CID vs BDP/FF (HR 0.64, P<0.001) and tiotropium (0.80, P<0.001), with a numerical extension vs IND/GLY. Conclusion:In patients with symptomatic COPD, FEV1 <50%, and an exacerbation history, extrafine BDP/FF/G delayed disease deterioration compared with BDP/FF, tiotropium, and IND/GLY. Trial registration:The studies are registered in ClinicalTrials.gov: TRILOGY, NCT01917331; TRINITY, NCT01911364; TRIBUTE, NCT02579850.