fluticasone and indacaterol

Chronic obstructive pulmonary disease exacerbations accelerate lung function decline, reduce quality of life, and increase mortality. A subset of patients (n = 457) from the FLAME (Effect of Indacaterol Glycopyrronium vs. Fluticasone Salmeterol on COPD Exacerbations) study used the Exacerbations of COPD Tool (EXACT) to capture symptom-defined exacerbations.. To evaluate the effect of indacaterol/glycopyrronium versus salmeterol/fluticasone on symptom-defined exacerbations measured using EXACT, and to assess differences between these events and exacerbations requiring healthcare resource use (HCRU).. All patients in FLAME used an electronic diary to record and detect symptom deteriorations; HCRU-related exacerbations were confirmed by investigators. In patients using the EXACT questionnaire, the onset, recovery, and magnitude of symptom-defined exacerbations were identified by changes in total scores relative to baseline. We analyzed the annualized rate and time to first symptom-defined (EXACT) exacerbation and assessed differences between symptom-defined and HCRU events in terms of number, severity, and concordance.. A nonsignificant 17% reduction in the annualized rate of symptom-defined (EXACT) exacerbations (rate ratio, 0.83; 95% confidence interval [CI], 0.60-1.14; P = 0.242) and a numerically longer time to first symptom-defined exacerbation were observed with indacaterol/glycopyrronium versus salmeterol/fluticasone (hazard ratio, 0.76; 95% CI, 0.56-1.03; P = 0.075). These results were consistent with data from the overall FLAME population. Of the symptom-defined (EXACT) events, 23.5% corresponded to HCRU events, and 22.2% of HRCU events were captured by EXACT (κ index, 0.24; 95% CI, 0.15-0.33).

Topics: Bronchodilator Agents; Disease Progression; Drug Therapy, Combination; Female; Fluticasone; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Risk Factors; Salmeterol Xinafoate; Surveys and Questionnaires

The place of combinations of bronchodilators (longacting beta-agonist / muscarinic agonist or LABA / LAMA) in the prevention of the exacerbations of the chronic obstructive pulmonary disease (COPD) is not still clearly established, and need a comparison with combination of LABA/ inhaled steroids. FLAME was a randomized non-inferiority phase 3 study comparing indacaterol/glycopyrronium 110/50 μg (IND/GLY) once daily with salmeterol/proprionate of fluticasone 50/500 μg (SAL/FC) twice daily. The primary objective of the study was to demonstrate that IND/GLY was non-inferior to SAL/FC in terms of reduction of all COPD exacerbations (mild/moderate/severe) during 52 weeks of treatment in patients having had at least 1 exacerbation in previous 12 months. The combination IND/GLY showed not only non inferiority, but also superiority, to SAL/FC in reducing the annual rate of all COPD exacerbations (mild, moderate, or severe) by 11 % by comparison with SAL/FC (p = 0.003), and by 17 % for the annual rate of moderate or severe exacerbations (p inferior to 0.001). IND/GLY prolonged the time to the first COPD exacerbation by 16 % for mild, 22 % for moderate and 19 % for severe by comparison with SAL/FC (all with p inferior to 0.05). FLAME study showed that IND/GLY, a steroid-free option, is more effective than SAL/FC in preventing COPD exacerbations in patients with one or more exacerbations in the past year.. Résumé : La place des associations de bronchodilatateurs (bêta-2 mimétiques /anticholinergiques à longue durée d’action ou LABA/LAMA) dans la prévention des exacerbations de la broncho-pneumopathie chronique obstructive (BPCO) n’est pas encore clairement établie, et nécessite une comparaison avec les associations de LABA/corticostéroïdes inhalés (CSI). FLAME est une étude randomisée de non-infériorité, de phase 3, comparant l’association indacatérol/glycopyrronium 110/50 μg (IND/GLY) 1/jour au salmétérol/propionate de fluticasone 50/500 μg (SAL/FC) 2/jour, d’une durée de 52 semaines. Le critère d’investigation principal est de démontrer que l’IND/GLY n’est pas inférieur au SAL/FC dans la réduction du taux d’exacerbations (légères/modérées/sévères) de patients BPCO ayant eu au moins une exacerbation dans les 12 mois qui précèdent. L’IND/GLY s’est révélée non seulement non inférieure, mais est aussi supérieure, à l’association SAL/FC dans la réduction du taux des exacerbations (légères, modérées et sévères) avec une réduction de 11 % par rapport à l’association SAL/FC (p 0,003) et de 17 % pour les exacerbations modérées ou sévères (p inférieur à 0,001). L’association IND/ GLY augmente le temps avant la première exacerbation de 16 % pour les légères, de 22 % pour les modérées et de 19 % pour les sévères par rapport au SAL/FC (toutes différences avec un p inférieur à 0,05). L’étude FLAME a montré qu’IND/GLY, une option sans CSI, est plus efficace que l’association SAL/FC pour la prévention des exacerbations de BPCO chez des patients ayant eu au moins une exacerbation l’année qui précède.

Topics: Administration, Inhalation; Aged; Bronchodilator Agents; Female; Fluticasone; Forced Expiratory Volume; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate; Treatment Outcome

Topics: Adrenergic beta-2 Receptor Agonists; Double-Blind Method; Drug Combinations; Fluticasone; Glycopyrrolate; Guideline Adherence; Humans; Indans; Muscarinic Antagonists; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate

Topics: Administration, Inhalation; Drug Therapy, Combination; Fluticasone; Forced Expiratory Volume; Glycopyrrolate; Indans; Lung Volume Measurements; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate

Indacaterol/glycopyrronium (IND/GLY) is a once-daily inhaled fixed-dose combination of indacaterol (IND), a long-acting β2-adrenergic agonist (LABA), and glycopyrronium (GLY), a long-acting muscarinic antagonist (LAMA) for use as maintenance treatment to relieve symptoms of chronic obstructive pulmonary disease (COPD) in adults.. To determine the economic benefits of IND/GLY compared with the free combination of indacaterol and glycopyrronium (IND + GLY), and with the fixed-dose combination of salmeterol/fluticasone (SFC), in a moderate-to-severe COPD population with low-exacerbation risk. The model-based analysis extrapolated results up to lifetime time horizon and calculated costs per quality-adjusted life year.. Assuming equal efficacy, a cost-minimisation analysis compared IND/GLY vs IND + GLY using model inputs from the double-blind, randomised SHINE trial. The double-blind, randomised ILLUMINATE and TORCH trials were used to analyse cost-effectiveness versus SFC. To consider ICS-related pneumonia events, published odds ratio comparing an ICS-exposed group to a control group of COPD patients was used. Direct and indirect drug costs as well as drug acquisition costs (in Swedish Krona [SEK]) were derived from published Swedish sources. Cost and effects were discounted with 3%. Uncertainty was assessed by one-way and probabilistic sensitivity analyses (PSA).. IND/GLY was cost-saving vs IND + GLY with incremental savings of SEK (EUR) 768 (85), and 3309 (368) per patient over one and five years. IND/GLY was found to be less costly and more effective compared to SFC with cost savings of SEK (EUR) 2744 (303), 8854 (976), 13,938 (1536), 27,495 (3031) and 43,033 (4744) over one, three, five, ten years and lifetime. The PSA indicated that all iterations produced dominant results for IND/GLY.. IND/GLY is cost-minimising vs IND + GLY and dominates SFC in the maintenance treatment of COPD patients in Sweden. Encouraging dual bronchodilator therapy over an ICS-containing combination results in lower total costs and better outcomes compared to combination therapy including fluticasone in moderate-to-severe COPD patients with low exacerbation risk.

Topics: Aged; Albuterol; Androstadienes; Bronchodilator Agents; Cost-Benefit Analysis; Double-Blind Method; Drug Combinations; Drug Costs; Drug Therapy, Combination; Female; Fluticasone; Forced Expiratory Volume; Glycopyrrolate; Humans; Indans; Male; Middle Aged; Monte Carlo Method; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate; Sweden

indacaterol is a novel, inhaled once-daily ultra-long-acting β(2)-agonist for the treatment of chronic obstructive pulmonary disease (COPD).. this study compared the onset of action of single doses of indacaterol 150 and 300 μg with salbutamol 200 μg, salmeterol-fluticasone 50/500 μg, and placebo in moderate-to-severe COPD patients.. this was a multicenter, randomized, double-blind, placebo-controlled crossover study. The primary variable was forced expiratory volume in one second (FEV(1)) at five minutes postdose.. out of 89 patients randomized (mean age 62 years), 86 completed the study. At five minutes postdose, both indacaterol doses were statistically and clinically superior to placebo (P < 0.001), with treatment-placebo differences in FEV(1) of 100 (95% confidence interval [CI] 70-130) mL and 120 (95% CI 90-150) mL for indacaterol 150 and 300 μg, respectively. FEV(1) at five minutes postdose with both indacaterol doses was numerically higher than for salbutamol (10 and 30 mL for indacaterol 150 and 300 μg, respectively) and significantly higher than for salmeterol-fluticasone (50 mL, P = 0.003; 70 mL, P < 0.001, respectively). Moreover, both indacaterol doses showed significantly higher FEV(1) than placebo (P < 0.001) at all postdose time points. The numbers of patients with an FEV(1) increase of at least 12% and 200 mL at five minutes postdose were 16 (18.8%), 24 (27.6%), 20 (23.3%), 8 (9.1%), and 3 (3.4%) for indacaterol 150 and 300 μg, salbutamol 200 μg, salmeterol-fluticasone 50/500 μg, and placebo, respectively.. single doses of indacaterol 150 and 300 μg demonstrated a fast onset of action similar to that for salbutamol and faster than that for salmeterol-fluticasone.

Topics: Adult; Aged; Albuterol; Androstadienes; Bronchodilator Agents; Cross-Over Studies; Female; Fluticasone; Humans; Indans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate

Asthma is a chronic inflammatory airway disease induced by many environmental factors. The inhalation of allergens and pollutants promotes the production of reactive oxygen species (ROS) leading to airway inflammation, hyper-responsiveness, and remodeling in allergic asthma. The effects of asthma medications on ROS production are unclear. The present study investigated the anti-ROS effects of current asthma medications including inhaled corticosteroid (ICS; budesonide and fluticasone), leukotriene receptor antagonist (LTRA; montelukast), long-acting β2 agonists (LABAs; salmeterol and formoterol), and a new extra-LABA (indacaterol).. The human monocyte cell line THP-1 cells were pre-treated with different concentrations of the asthma medications at different time points after hydrogen peroxide (H. Montelukast, fluticasone, and salmeterol suppressed H. Different asthma medications have different anti-ROS effects on monocytes. The combination therapy with LABA and ICS seemed not to be the only choice for asthma control. Montelukast may also be a good supplemental treatment for the poorly controlled asthma because of its powerful anti-ROS effects. Our findings provide a novel therapeutic view in asthma.

Topics: Acetates; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Albuterol; Anti-Asthmatic Agents; Budesonide; Cyclopropanes; Fluticasone; Formoterol Fumarate; Humans; Indans; Leukotriene Antagonists; Monocytes; Quinolines; Quinolones; Reactive Oxygen Species; Salmeterol Xinafoate; Sulfides; THP-1 Cells

Topics: Fluticasone; Humans; Indans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate

The objective of this study was to assess the cost effectiveness of the dual bronchodilator indacaterol/glycopyrronium (IND/GLY) compared with salmeterol/fluticasone combination (SFC) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who had a history of one or no exacerbations in the previous year, in Canada, France, Italy, and Portugal.. A patient-level simulation was developed to compare the costs and outcomes of IND/GLY versus SFC based on data from the LANTERN trial (NCT01709903). Monte-Carlo simulation methods were employed to follow individual patients over various time horizons. Population and efficacy inputs were derived from the LANTERN trial. Considering the payers' perspective, only direct costs were included. Costs and health outcomes were discounted annually at 3.0 % for all countries. Unit costs were taken from publically available sources with all costs converted to euros (€). The cost base year was 2015. Deterministic and probabilistic sensitivity analyses were undertaken to test the robustness of the model results.. IND/GLY was found to be the dominant (more effective and less costly) treatment option compared with SFC in all four countries. The use of IND/GLY was associated with mean total cost savings per patient over a lifetime of €6202, €1974, €1611, and €220 in Canada, France, Italy, and Portugal, respectively. Sensitivity analysis showed that exacerbation rates had the largest impact on incremental costs and quality-adjusted life-years (QALYs). The probability of IND/GLY being cost effective was estimated to be >95 % for thresholds above €5000/QALY.. In patients with moderate to severe COPD, IND/GLY is likely to be a cost-effective treatment alternative compared with SFC.

Topics: Administration, Inhalation; Aged; Bronchodilator Agents; Canada; Cost-Benefit Analysis; Drug Costs; Drug Therapy, Combination; Fluticasone; France; Glycopyrrolate; Health Care Costs; Humans; Indans; Italy; Male; Portugal; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate

Topics: Adrenergic beta-2 Receptor Agonists; Asthma; Bronchodilator Agents; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Fluticasone; Humans; Indans; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Quinolones; Salmeterol Xinafoate