fluticasone-propionate--salmeterol-xinafoate-drug-combination and fluticasone-furoate

Fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg is a once-daily inhaled corticosteroid (ICS)/long-acting beta2 agonist (LABA) treatment approved in the United States, Canada and Europe for the long-term maintenance therapy of COPD. We report data from mixed treatment comparisons (MTC) of once-daily FF/VI against established twice-daily ICS/LABA combination therapies on clinical efficacy outcomes.. Data from 33 parallel-group randomised controlled trials (RCTs) of ICS/LABAs, of ≥8 weeks' duration in patients ≥12 years of age with COPD, identified by systematic review, were analysed using covariate-adjusted Bayesian hierarchical models for three efficacy outcomes. Lung function, assessed by change from baseline in forced expiratory volume in one second (FEV1), was the outcome of primary interest (n = 28 studies). Secondary objectives were assessment of annual rate of moderate/severe exacerbations (n = 15) and patient-reported health status, measured by change from baseline in St George's Respiratory Questionnaire (SGRQ) Total score (n = 20). Overall, 25 different treatments were included in the MTC; we report findings, including probabilities of non-inferiority, for comparisons of once-daily FF/VI 100/25 mcg with twice-daily fluticasone propionate (FP)/salmeterol (SAL) 500/50 mcg and budesonide (BUD)/formoterol (FORM) 400/12 mcg.. For FEV1, FF/VI 100/25 mcg demonstrated >99% probability of non-inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg using a 50 mL margin. For annual rate of moderate/severe exacerbations, FF/VI 100/25 mcg demonstrated 73% and 77% probability of non-inferiority to FP/SAL 500/50 mcg and BUD/FORM 400/12 mcg, respectively, using a 10% rate ratio margin. For SGRQ Total score, the corresponding probabilities of non-inferiority were 99% and 98%, respectively, on a 2-unit margin. Significant covariate effects were identified: increased age was associated with deterioration in FEV1 and reduced exacerbation frequency; shorter study duration was associated with reduced exacerbation frequency.. FF/VI 100/25 mcg was comparable with corresponding doses of FP/SAL and BUD/FORM on lung function and health status outcomes. Non-inferiority on moderate/severe exacerbation rate was not demonstrated to the same degree of confidence, though observed rates were similar. Model limitations include a weak treatment network for the exacerbation analysis and variability across the included studies. Our data support previous RCT findings suggesting that the efficacy of FF/VI 100/25 mcg on lung function and health status in COPD is comparable with twice-daily ICS/LABAs.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Androstadienes; Bayes Theorem; Benzyl Alcohols; Bronchodilator Agents; Budesonide, Formoterol Fumarate Drug Combination; Chlorobenzenes; Disease Progression; Drug Administration Schedule; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Lung; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Randomized Controlled Trials as Topic; Recovery of Function; Risk Factors; Time Factors; Treatment Outcome

Topics: Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Androstadienes; Asthma; Benzyl Alcohols; Bronchodilator Agents; Child; Chlorobenzenes; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Equivalence Trials as Topic; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Young Adult

This phase III trial had two treatment periods (P): P1, patients with well-controlled asthma on FP/SAL 250/50 μg BD equivalent stepped across to once daily (OD) FF/VI 100/25 μg (open-label, eight weeks); P2, patients remaining 'well controlled' after P1 stepped down to FF 100 μg OD/FP 100 μg BD/FP 250 μg BD (randomized 1:1:1, double-blind, 12 weeks). Co-primary P2 endpoints: percentage of patients with well-controlled asthma; time to withdrawal due to poorly controlled asthma requiring step-up therapy. Adverse events (AEs) were monitored.. At the end of P1 (n = 430), 373 (90.5%; 95% confidence interval 87.29-93.18) patients' asthma remained well controlled with FF/VI; in P2 (n = 371), control was maintained in 89.5% (FF 100 μg)/79.5% (FP 100 μg)/83.8% (FP 250 μg) of patients. In P2, 4.9-7.3% of patients were withdrawn due to worsening asthma (time-to-withdrawal cumulative incidence curves were comparable). AEs were reported by 37% of patients during P1; and by 36% (FF 100 μg)/48% (FP 100 μg)/49% (FP 250 μg) of patients in P2.. For patients with well-controlled asthma on mid dose ICS/LABA (equivalent to FP/SAL 250/50 μg BD), control can be maintained when they are stepped across to FF/VI 100/25 μg OD. FF 100 μg OD is an effective step-down therapy from FF/VI 100/25 μg OD with similar efficacy to FP 100 μg BD and FP 250 μg BD.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Adult; Androstadienes; Asthma; Benzyl Alcohols; Chlorobenzenes; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Japan; Male; Middle Aged; Peak Expiratory Flow Rate; Prevalence; Smoking; Treatment Outcome

Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is important because patients with ACOS have significantly worse outcomes compared with those with asthma or chronic obstructive pulmonary disease (COPD) alone. Inhaled corticosteroids (ICS), together with a long-acting β2 agonist (LABA), are recommended, but no therapeutic studies for ACOS have been conducted. Recently, fluticasone furoate/vilanterole (FF/VI) has been approved as the first once-daily ICS/LABA combination therapy for asthma and COPD.. A 12-week, randomized, open-label cross-over study was conducted in 16 patients with ACOS to compare the effectiveness of once-daily FF/VI 200/25 μg vs. twice-daily fluticasone propionate/salmeterol (FP/SAL) 500/50 μg. The study period included a 4-week run-in, the first 4-week treatment, and the second 4-week treatment. Respiratory functions, including forced expiratory volume in 1 s (FEV1) and respiratory impedance using the forced oscillation technique (FOT), were measured, as was fractional exhaled nitric oxide (FeNO). A COPD assessment test (CAT) scores and asthma control test (ACT) scores were recorded 0, 4, and 8 weeks after randomization.. The mean values for the FEV1 were 1.33 (±0.29) L in the run-in period, 1.38 (±0.39) L after the FP/SAL treatment period, and 1.47 (±0.38) L after the FF/VI treatment period. The FEV1 value after the FF/VI treatment was significantly greater than the value after the run-in period (p < 0.01). FOT parameters, FeNO levels, CAT scores, ACT scores, and other blood tests were not significantly different during the run-in period, the FP/SAL treatment period, and the FF/VI treatment period.. FF/VI, the first once-daily ICS/LABA, can provide substantial improvement in lung functions, indicating that FF/VI should be considered for the regular treatment of ACOS.

Topics: Aged; Aged, 80 and over; Androstadienes; Anti-Asthmatic Agents; Asthma; Benzyl Alcohols; Chlorobenzenes; Cross-Over Studies; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Nitric Oxide; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests

Fluticasone furoate/vilanterol trifenatate (FF/VI) is a once-daily inhaled corticosteroid/long-acting β₂-agonist combination in development for chronic obstructive pulmonary disease (COPD) treatment. We compared the efficacy and safety of FF/VI versus fluticasone propionate/salmeterol (FP/SAL) twice daily over 12 weeks. Moderate to very severe COPD patients received FF/VI 100/25 μg once daily in the morning (n=266) or FP/SAL 500/50 μg twice daily (n=262). The primary end-point was a change from baseline in 0-24 h weighted mean forced expiratory volume in 1 s (wmFEV₁) at 12 weeks. Additional end-points included time to 100 mL improvement from baseline on day 1 and a change from baseline in St George's Respiratory Questionnaire (SGRQ). Safety was also assessed. wmFEV₁ (mean 130 mL) was greater and time to 100 mL improvement shorter (median 16 min) with FF/VI than FP/SAL (weighted mean 108 mL, median 28 min). Health status (SGRQ total score) improved in both groups (FF/VI -4.3 units, FP/SAL -3.0 units). Differences between treatments were not statistically significant. Six patients in the FF/VI (2%) and three in the FP/SAL (1%) arm experienced serious adverse events, none of which were considered to be drug related. Improvements in lung function and health status were not significantly different between FF/VI 100/25 μg once daily and FP/SAL 500/50 μg twice daily; there was no apparent difference between the safety profiles of either therapy.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adult; Aged; Albuterol; Androstadienes; Anti-Inflammatory Agents; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Severity of Illness Index; Smoking; Surveys and Questionnaires; Treatment Outcome

Fluticasone furoate/vilanterol (FF/VI) is an inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA), recently approved as once-daily maintenance therapy for COPD. We compared the lung function effects of FF/VI with those of twice-daily fluticasone propionate/salmeterol (FP/SAL).. Three 12 week studies comparing FF/VI and FP/SAL were conducted. Patients aged ≥40 years with moderate-to-very severe COPD were randomized to receive double-blind, double-dummy FF/VI 100/25 mcg once-daily, or FP/SAL 250/50 mcg twice-daily for 12 weeks following a 2 week placebo run-in period. The primary endpoint of each study was change from baseline trough in 0-24 h weighted mean FEV(1) (wmFEV(1)) on Day 84. Safety was also assessed.. In Study 1 (HZC113109) (intent-to-treat n: FF/VI = 260; FP/SAL = 259), the increase from baseline in 0-24 h wmFEV(1) was significantly greater with FF/VI than FP/SAL (Δ80 mL, P < 0.001). In Study 2 (HZC112352) (intent-to-treat n: FF/VI = 259; FP/SAL = 252) and Study 3 (RLV116974) (intent-to-treat n: FF/VI = 412; FP/SAL = 416), the increase from baseline in 0-24 h wmFEV(1) was not significantly greater with FF/VI than FP/SAL (Δ29 mL, P = 0.267; Δ25 mL, P = 0.137). The treatment difference was statistically but not clinically significant in a pooled analysis (Δ41 mL, P < 0.001). Pooled adverse events (FF/VI 27%; FP/SAL 28%) and serious adverse events (FF/VI 2%; FP/SAL 3%) were similar between treatments.. Our data suggest that once-daily FF/VI 100/25 mcg provides FEV(1) improvement in COPD that is at least comparable with that conferred by twice-daily FP/SAL 250/50 mcg, although interpretation is limited by differences in individual study outcomes. The safety profiles of FF/VI 100/25 mcg and FP/SAL 250/50 mcg are similar.. clinicaltrials.gov: NCT01323634; NCT01323621; NCT01706328. GlaxoSmithKline study codes: HZC113109; HZC112352; RLV116974.

Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Albuterol; Androstadienes; Benzyl Alcohols; Chlorobenzenes; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Dry Powder Inhalers; Female; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Glucocorticoids; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; Treatment Outcome; Vital Capacity

The combination of fluticasone furoate (FF), a novel inhaled corticosteroid (ICS), and vilanterol (VI), a long-acting β2 agonist, is under development as a once-daily treatment of asthma and COPD. The aim of this study was to compare the efficacy of FF/VI with fluticasone propionate (FP)/salmeterol (SAL) in patients with persistent asthma uncontrolled on a medium dose of ICS.. In a randomized, double-blind, double-dummy, parallel group study, 806 patients received FF/VI (100/25 μg, n = 403) once daily in the evening delivered through ELLIPTA (GlaxoSmithKline) dry powder inhaler, or FP/SAL (250/50 μg, n = 403) bid through DISKUS/ACCUHALER (GlaxoSmithKline). The primary efficacy measure was 0- to 24-h serial weighted mean (wm) FEV1 after 24 weeks of treatment.. Improvements from baseline in 0- to 24-h wmFEV1 were observed with both FF/VI (341 mL) and FP/SAL (377 mL); the adjusted mean treatment difference was not statistically significant (-37 mL; 95% CI, -88 to 15, P = 0.162). There were no differences between 0- to 4-h serial wmFEV1, trough FEV1, and asthma control and quality-of-life questionnaire scores. There was no difference in reported exacerbations between treatments. Both treatments were well tolerated, with no clinically relevant effect on urinary cortisol excretion or vital signs and no treatment-related serious adverse events.. The efficacy of once-daily FF/VI was similar to bid FP/SAL in improving lung function in patients with persistent asthma. No safety issues were identified.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albuterol; Androstadienes; Asthma; Benzyl Alcohols; Child; Chlorobenzenes; Double-Blind Method; Drug Combinations; Female; Fluticasone-Salmeterol Drug Combination; Humans; Male; Middle Aged; Young Adult

In recent years, the combination of fluticasone furoate and vilanterol (FF/VI) has emerged as an alternative therapy, since it is administered every 24 h, in contrast to other ICS/LABAs such as fluticasone propionate plus salmeterol (FP/Salm), which requires administration every 12 h. Concerns have arisen over whether the benefit generated by FF/VI justifies the additional costs it involves over FP/Salm. This study aimed at assessing the health and economic consequences of FF/VI in patients with moderate-severe persistent asthma.. A probabilistic Markov model was created to estimate the cost and quality-adjusted life-years (QALYs) of patients with persistent asthma. Total costs and QALYs for FF/VI and FP/Salm were calculated over a lifetime horizon. Multiple sensitivity analyses were conducted. Cost-effectiveness was evaluated at a willingness-to-pay value of $19,000.. We estimated a gain of 16.8 and 10.7 QALYs per patient per year on FF/VI and FP/Salm, respectively. At the same time, we observed a difference of US$216 in total discounted cost per person-year on FF/VI with respect to FP/Salm. The incremental cost-effectiveness ratio (ICER) of FF/VI was USD $70 per QALY with respect to FP/Salm. In the deterministic and probabilistic sensitivity analyses, our base-case results were robust to variations in all assumptions and parameters.. FF/VI is more cost-effective than FP/Salm. The evidence supports using FF/VI therapy in Colombia, and the study should be replicated in other middle-income countries.

Topics: Administration, Inhalation; Androstadienes; Asthma; Benzyl Alcohols; Chlorobenzenes; Cost-Benefit Analysis; Drug Combinations; Fluticasone; Fluticasone-Salmeterol Drug Combination; Humans; Treatment Outcome