Safety analysis of glecaprevir/pibrentasvir in patients with markers of advanced liver disease in clinical and real-world cohorts.

Chronic hepatitis C virus (HCV) infection has the greatest health impact in patients with advanced liver disease. The direct-acting antiviral (DAA) regimen glecaprevir/pibrentasvir (G/P) is approved for treatment of HCV-infected patients without cirrhosis and with compensated cirrhosis. However, events of liver decompensation/failure have been reported in patients treated with protease-inhibitor-containing DAA regimens, often in patients with advanced liver disease.

Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension.

Introduction: High efficacy and safety of 8-week glecaprevir/pibrentasvir (G/P) therapy was seen in hepatitis C (HCV)-infected, treatment-naïve (TN), compensated cirrhosis (CC) patients in EXPEDITION-8. To provide further understanding of the efficacy of G/P treatment in HCV-infected TN patients with CC and clinical evidence of portal hypertension (PHT), this analysis focused on differences in sustained virologic response at post-treatment week 12 (SVR12) between 8-week and 12-week G/P treatment groups in patients with PHT, and on differences in safety outcomes between PHT and non-PHT groups.

Methods: Data were derived from an ad hoc subgroup analysis of the EXPEDITION-8 study for patients receiving 8 weeks of G/P therapy, and pooled patient-level data from nine clinical studies for patients receiving 12 weeks of therapy.

Safety of Patients with Hepatitis C Virus Treated with Glecaprevir/Pibrentasvir from Clinical Trials and Real-World Cohorts.

Introduction: More than 70 million people are estimated to be infected with hepatitis C virus (HCV) globally. If left untreated, HCV infection can lead to complications such as extensive liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Evolution of treatments has resulted in highly effective and well-tolerated all-oral direct-acting antivirals.

A randomized, controlled, repeat-dose study of batefenterol/fluticasone furoate compared with placebo in the treatment of COPD.

Background: Batefenterol (BAT) is a bi-functional molecule with both muscarinic antagonist and β-adrenoceptor agonist pharmacology. This Phase II, randomized, placebo-controlled, double-blind study evaluated the safety and tolerability of BAT 300 μg with fluticasone furoate (FF) 100 μg administered via the ELLIPTA inhaler (BAT/FF 300/100).

Methods: Subjects with stable chronic obstructive pulmonary disease were randomized 2:1 to receive BAT/FF 300/100 or placebo once daily for 6 weeks.

A Patient-Centered Walking Program for COPD.

Pulmonary rehabilitation programs improve dyspnea and health status associated with chronic obstructive pulmonary disease (COPD), but benefits wane when patients return to a sedentary lifestyle. This study tested a simple, low-resource, low-cost home walking program. In this single center, 3-month study, 115 COPD patients were randomized to a control cohort or a goal setting cohort.

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone.

Background: The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate.

Efficacy and safety of fluticasone furoate/vilanterol or tiotropium in subjects with COPD at cardiovascular risk.

Background: Fluticasone furoate/vilanterol (FF/VI) is a novel, once-daily, inhaled corticosteroid/long-acting β2-agonist combination approved for the treatment of COPD and asthma. We compared the safety and efficacy of FF/VI and tiotropium (TIO) in subjects with moderate-to-severe COPD with greater risk for comorbid cardiovascular disease (CVD).

Methods: This randomized, blinded, double-dummy, parallel-group study compared a once-daily morning dose of FF/VI 100/25 mcg delivered via ELLIPTA™ with TIO 18 mcg via HandiHaler(®) for 12 weeks in subjects with diagnosed COPD, forced expiratory volume in 1 second (FEV1) 30%-70% predicted, and CVD or CVD risk.

Fluticasone propionate/salmeterol 250/50 μg versus salmeterol 50 μg after chronic obstructive pulmonary disease exacerbation.

Background: Inhaled long-acting beta2 agonists used alone and in combination with an inhaled corticosteroid reduce the risk of exacerbations in patients with stable COPD. However, the relative efficacy of these agents in preventing recurrent exacerbations in those recovering from an initial episode is not known. This study compared the rate of COPD exacerbations over the 26 weeks after an initial exacerbation in patients receiving the combination of fluticasone propionate and salmeterol (FP/SAL) or SAL alone.

Effect of fluticasone propionate/salmeterol on arterial stiffness in patients with COPD.

Background: COPD is associated with increased arterial stiffness which may in part explain the cardiovascular morbidity observed in the disease. A causal relationship between arterial stiffness and cardiovascular events has not been established, though their strong association raises the possibility that therapies that reduce arterial stiffness may improve cardiovascular outcomes. Prior studies suggest that fluticasone propionate/salmeterol (FSC) may improve cardiovascular outcomes in COPD and we hypothesized that FSC would reduce arterial stiffness in these patients.

Safety and efficacy of fluticasone propionate/salmeterol hydrofluoroalkane 134a metered-dose-inhaler compared with fluticasone propionate/salmeterol diskus in patients with chronic obstructive pulmonary disease.

Purpose: To provide information on the efficacy and safety of Fluticasone Propionate/Salmeterol Hydrofluoroalkane 134a Metered-Dose-Inhaler 230/42mcg (FSC MDI) and its comparable dose of Fluticasone Propionate/Salmeterol DISKUS 250/50mcg (FSC DISKUS) in patients with COPD.

Methods: This multicenter, randomized, double-blind, 12 week study was designed to evaluate FSC MDI treatment responses as compared with FSC DISKUS. The primary comparison of interest was non-inferiority between the FSC MDI treatment group and the FSC DISKUS treatment group assessed in terms of 2-hour post-dose FEV(1) change from baseline at endpoint.

Disease severity and symptoms among patients receiving monotherapy for COPD.

Aim: To examine the burden of respiratory symptoms, quality of life and co-morbid illness in COPD patients receiving maintenance treatment in a real world setting.

Methods: In a single visit, patients with a physician's diagnosis of COPD who were receiving monotherapy with a long-acting bronchodilator (LABD) performed spirometry, completed symptom questionnaires, and reported their treatments, history of exacerbations and co-morbidities.

Results: We enrolled 1084 patients of whom 1072 had acceptable spirometry.

Effect of increased body mass index on asthma risk, impairment and response to asthma controller therapy in African Americans.

Objective: To explore whether obesity alters the risk, impairment and response to treatment in African Americans with asthma.

Methods: The data used for this secondary analysis are from a 1-year study in African American subjects comparing fluticasone propionate/salmeterol 100/50 microg combination (FSC) and fluticasone propionate 100 microg (FP). Subjects were retrospectively stratified by body mass index (BMI) <20 [underweight], 20-24.

Comparative effect of body mass index on response to asthma controller therapy.

Increases in body mass index (BMI) are reported to influence asthma severity and response to treatment. This analysis was designed to explore whether increasing BMI altered the comparative response to treatment with either fluticasone propionate (FP) or montelukast. Two double-blind, randomized, parallel-group trials of 12-weeks duration comparing FP, 88 micrograms, twice daily or montelukast, 10 mg, daily were evaluated.

Body mass index and response to asthma therapy: fluticasone propionate/salmeterol versus montelukast.

We studied the relationship between body mass index (BMI) on responses to asthma therapy using a retrospective analysis of four previously reported clinical trials. Fluticasone propionate (FP)/salmeterol via Diskus 100/50 microg twice daily and montelukast (MON) 10 mg daily were compared. BMI was classified as underweight (less than 20 kg/m(2)), normal (20-24.

Beta2-receptor polymorphisms in patients receiving salmeterol with or without fluticasone propionate.

Rationale: Retrospective pharmacogenetic studies have questioned whether patients with asthma who are arginine homozygous at the beta(2-)adrenergic receptor (position 16) should use long-acting beta-agonists.

Objectives: To examine whether the response to salmeterol alone or in combination with an inhaled corticosteroid is influenced by beta- receptor polymorphisms.

Methods: Subjects using only as-needed albuterol were screened and completed two sequential open-label run-in periods (8 wk on as-needed albuterol; 8 wk on as-needed ipratropium).

Effect of fluticasone propionate/salmeterol (250/50) on COPD exacerbations and impact on patient outcomes.

Prevention and treatment of COPD exacerbations are recognized as key goals in disease management. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/salmeterol 250 mcg/50 mcg (FSC 250/50) and salmeterol 50 mcg (SAL) twice-daily on moderate/severe exacerbations. Subjects received treatment with FSC 250/50 during a one month run-in, followed by randomization to FSC 250/50 or SAL for 52 weeks.

Prevalence of COPD among symptomatic patients in a primary care setting.

Objective: Spirometry is recognized as the gold standard assessment for the diagnosis of COPD. However, spirometry continues to be underused, perpetuating the underdiagnosis of COPD. The aim of this study was to evaluate the prevalence of COPD in a primary care setting in patients with a smoking history and self-reported chronic bronchitis symptoms.

Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations.

Objectives: COPD exacerbations are associated with significant morbidity and mortality. This randomized, double-blind, parallel-group, multicenter study evaluated the effect of fluticasone propionate/salmeterol 250/50 and salmeterol 50 microg twice daily on moderate to severe exacerbations.

Methods: Patients received standardized treatment with fluticasone propionate/salmeterol 250/50 during a 1-month run-in, followed by randomization to fluticasone propionate/salmeterol 250/50 or salmeterol for 12 months.

Lung function and symptom improvement with fluticasone propionate/salmeterol and ipratropium bromide/albuterol in COPD: response by beta-agonist reversibility.

This retrospective analysis of data from two multi-center, randomized, double-blind, parallel group studies compared the efficacy of fluticasone propionate/salmeterol (FSC) 250/50 mcg twice daily with ipratropium bromide/albuterol (IB/ALB) 36/206 mcg four times daily in albuterol-reversible (n=320 [44%]) and non-reversible (n=399 [56%]) patients with COPD. In reversible and non-reversible patients, both treatments significantly increased FEV(1)AUC(0-6h) from baseline and the magnitude of improvement was larger in reversible patients. FSC increased FEV(1)AUC(0-6h) by 1.

Variability in asthma severity in pediatric subjects with asthma previously receiving short-acting beta2-agonists.

Objective: An analysis of 5 double-blinded, randomized, 12-week asthma trials was undertaken to evaluate pediatric subjects (4 to 11 years; n=276) who were previously receiving short-acting beta2-agonists alone and subsequently received treatment with placebo. At baseline, all subjects met National Asthma Education and Prevention Program criteria for moderate/severe asthma.

Study Design: Asthma severity was categorized individually for symptoms, albuterol use, and morning peak expiratory flow and then overall taking into account all three parameters.

Determining economic feasibility of fluticasone propionate-salmeterol vs montelukast in the treatment of persistent asthma using a net benefit approach and cost-effectiveness acceptability curves.

Background: The choice of treatment can have a major impact on the total costs associated with asthma care.

Objective: To determine the relative cost-effectiveness of twice-daily treatment with inhaled fluticasone propionate-salmeterol via Diskus, 100/50 microg, with that of once-daily treatment with oral montelukast as initial maintenance therapy in patients with persistent asthma uncontrolled with a short-acting beta2-agonist alone.

Methods: Data from a randomized, double-blind, double-dummy, 12-week clinical trial were analyzed.

The efficacy and safety of inhaled fluticasone propionate/salmeterol and ipratropium/albuterol for the treatment of chronic obstructive pulmonary disease: an eight-week, multicenter, randomized, double-blind, double-dummy, parallel-group study.

Background: The pathology of chronic obstructive pulmonary disease (COPD) includes both obstructive and inflammatory components.

Objective: The aim of this study was to confirm the findings of a previous study that compared the efficacy of a combination of 2 short-acting bronchodilators with the use of an inhaled corticosteroid and a long-acting beta-agonist in the treatment of COPD.

Methods: We conducted an 8-week, multicenter, randomized, double-blind, double-dummy, parallel-group study of subjects with moderate to severe COPD to compare fluticasone propionate/salmeterol 250/50 microg BID (FSC) with ipratropium/albuterol 36/206 microg QID (IB/ALB).