Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

Background: Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals.

Methods: In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care.

Mortality after admission with pneumonia is higher than after admission with an exacerbation of COPD.

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Safety data in randomised real-world evidence studies: Salford Lung Study learnings.

Evidence to support clinical decision making must be based on safety data that have been captured, analysed and interpreted in a robust and reliable way. Randomised real-world evidence (RRWE) studies provide the opportunity to evaluate the use of medicines in patients and settings representative of routine clinical practice. However, elements that underpin the design of RRWE studies can have a significant impact upon the analysis, interpretation and implications of safety data.

A structured review evaluating content validity of the Asthma Control Test, and its consistency with U.S. guidelines and patient expectations for asthma control.

Objective: To assess whether the content of the Asthma Control Test (ACT) served as a valid measure of asthma control (i.e., content validity) by mapping ACT items to the National Heart, Lung and Blood Institute (NHLBI) guideline asthma control definitions, and to language used by patients to describe their asthma.

Impact of socioeconomic status on participation and outcomes in the Salford Lung Studies.

COPD and asthma prevalence is associated with socioeconomic status (or "deprivation"), yet deprivation is rarely considered in typical large-scale efficacy randomised controlled trials that recruit highly selected patient populations. In this analysis of the Salford Lung Studies in COPD and asthma (two 12-month, open-label, effectiveness randomised controlled trials conducted in UK primary care), we evaluated the impact of patient deprivation on clinical outcomes with initiating fluticasone furoate/vilanterol continuing usual care. Patients were categorised into deprivation quintiles based on postcode and a countrywide database of indices of deprivation, and trial outcomes by quintile were assessed.

Real-World Data and Randomised Controlled Trials: The Salford Lung Study.

Traditional efficacy double-blind randomised controlled trials (DBRCTs) measure the benefit a treatment produces under near-ideal test conditions in highly selected patient populations; however, the behaviour of patients and investigators in such trials is highly controlled, highly compliant and adherent, and non-representative of routine clinical practice. Pragmatic effectiveness trials measure the benefit a treatment produces in patients in everyday "real-world" practice. Ideally, effectiveness trials should recruit patients as similar as possible to those who will ultimately be prescribed the medicine, and create freedom within the study design to allow normal behaviours of patients and healthcare professionals (HCPs) to be expressed.

Can medicines development improve outcomes in asthma and chronic obstructive pulmonary disease management by driving effectiveness?

Despite the availability of treatment guidelines and inhaled medications for asthma and chronic obstructive pulmonary disease (COPD), much remains to be done to lessen the burden of these respiratory diseases for patients. The challenge of selecting effective and efficacious drugs for patients is a key focus area for healthcare professionals. Here we discuss the concept of "drivers of effectiveness"- features of a medicine which may increase or decrease its effectiveness in the presence of real-world factors - and highlight the importance of considering these drivers in the early stages of drug development, and exploring their impact in carefully designed pragmatic trials.

Fluticasone furoate/vilanterol versus fluticasone propionate in patients with asthma and exercise-induced bronchoconstriction.

: To investigate whether once-daily (OD) fluticasone furoate (FF)/vilanterol (VI) provides greater long-term protection from postexercise fall in forced expiratory volume in 1 s (FEV) than twice-daily (BD) fluticasone propionate (FP) in patients with asthma and exercise-induced bronchoconstriction. : A randomized, double-blind, crossover study was conducted in patients (aged 12-50 years) on low-/mid-dose maintenance inhaled corticosteroid. Following a 4-week run-in period (FP 250 µg BD), patients with a ≥ 20% decrease in postexercise FEV received FF/VI 100/25 µg OD or FP 250 µg BD for 2 weeks.

Patient-reported outcomes with initiation of fluticasone furoate/vilanterol versus continuing usual care in the Asthma Salford Lung Study.

Background: The Asthma Salford Lung Study demonstrated the effectiveness and safety of initiating once-daily inhaled fluticasone furoate/vilanterol (FF/VI) versus continuing usual care (UC) in asthma patients in UK primary care [1]. Here, we report a detailed analysis of patient-reported outcome (PRO) endpoints.

Methods: Adults with symptomatic asthma maintained on inhaled corticosteroids (ICS) ± long-acting beta-agonists (LABA) were randomized 1:1 to initiate FF/VI (100 [200]/25 μg) or continue UC.

Efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI) versus twice-daily inhaled corticosteroids/long-acting β-agonists (ICS/LABA) in patients with uncontrolled asthma: An open-label, randomized, controlled trial.

Background: A variety of different fixed-dose combinations of inhaled corticosteroids/long-acting β-agonists (ICS/LABA) are available for the treatment of asthma. The aim of this 24-week, open-label, multicenter, Phase IIIb randomized controlled trial was to evaluate the efficacy and safety of once-daily fluticasone furoate/vilanterol (FF/VI; 100/25 or 200/25 μg) compared with twice-daily fixed combinations of ICS/LABA (fluticasone propionate/salmeterol [FP/S] and budesonide/formoterol [BUD/F]) as maintenance therapy in patients with uncontrolled asthma treated with ICS alone.

Methods: Adult patients with documented physician-diagnosed asthma ≥1 year with an Asthma Control Test (ACT) score ≥15 and < 20 were included.

Effectiveness of fluticasone furoate/vilanterol versus fluticasone propionate/salmeterol on asthma control in the Salford Lung Study.

Objective: The Asthma Salford Lung Study demonstrated the effectiveness of initiating once-daily fluticasone furoate/vilanterol (FF/VI) versus continuing usual care in asthma patients in UK primary care [ 1 ]. Here, we report a secondary analysis in a subset of patients with fluticasone propionate/salmeterol (FP/Salm) as their baseline intended maintenance therapy, to evaluate the relative effectiveness of initiating FF/VI versus continuing FP/Salm.

Methods: Adults with symptomatic asthma were randomised to initiate FF/VI 100[200]/25 µg or continue FP/Salm.

Once-daily fluticasone furoate/vilanterol versus twice-daily fluticasone propionate/salmeterol in patients with asthma well controlled on ICS/LABA.

Objective: We aimed to demonstrate non-inferiority of once-daily fluticasone furoate/vilanterol 100/25 µg (FF/VI) to twice-daily fluticasone propionate/salmeterol 250/50 µg (FP/SAL) in adults/adolescents with asthma well controlled on inhaled corticosteroid/long-acting β agonist (ICS/LABA).

Methods: This was a randomized, double-blind, double-dummy, parallel-group, 24-week study (NCT02301975/GSK study 201378). Patients whose asthma met study-defined criteria for control were randomized 1:1:1 to receive FF/VI, FP/SAL or twice-daily FP 250 µg for 24 weeks.

Effectiveness of fluticasone furoate plus vilanterol on asthma control in clinical practice: an open-label, parallel group, randomised controlled trial.

Background: Evidence for management of asthma comes from closely monitored efficacy trials done in highly selected patient groups. There is a need for randomised trials that are closer to usual clinical practice.

Methods: We did an open-label, randomised, controlled, two-arm effectiveness trial at 74 general practice clinics in Salford and South Manchester, UK.

Fluticasone furoate/vilanterol once daily improves night-time awakenings in asthma patients with night symptoms: Post hoc analyses of three randomized controlled trials.

Objective: Symptoms, including night-time awakenings, affect the quality of life of people with asthma. Fluticasone furoate/vilanterol (FF/VI) reduces exacerbations, improves lung function, and rescue-free and symptom-free 24-hour periods in patients with asthma. These post hoc analyses compared daytime and night-time symptoms in patients with asthma who received FF/VI, versus FF, fluticasone propionate (FP) or placebo.

Integrated safety and efficacy analysis of once-daily fluticasone furoate for the treatment of asthma.

Background: Fluticasone furoate is a once-daily inhaled corticosteroid. This report provides an overview of safety and efficacy data that support the use of once-daily fluticasone furoate 100 μg or 200 μg in adult and adolescent asthma patients.

Methods: Fourteen clinical studies (six Phase II and eight Phase III) were conducted as part of the fluticasone furoate global clinical development programme in asthma.

Efficacy and safety comparison: Fluticasone furoate and fluticasone propionate, after step down from fluticasone furoate/vilanterol in Japanese patients with well-controlled asthma, a randomized trial.

Background: For patients with well-controlled asthma, 'step down' of therapy is recommended. We evaluated Japanese patients switching from inhaled corticosteroid (ICS)/long-acting beta-agonists (LABA; equivalent to fluticasone propionate [FP]/salmeterol [SAL] 250/50 μg twice daily [BD]) to fluticasone furoate (FF)/vilanterol (VI) 100/25 μg, then stepping down to ICS alone.

Methods: 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).

Efficacy and safety evaluation of once-daily fluticasone furoate/vilanterol in Asian patients with asthma uncontrolled on a low- to mid-strength inhaled corticosteroid or low-dose inhaled corticosteroid/long-acting beta2-agonist.

Background: Response to inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combinations varies across ethnic groups.

Objective: To investigate the efficacy and safety of the ICS/LABA combination fluticasone furoate/vilanterol (FF/VI) 100/25 μg in Asian patients with asthma.

Methods: A randomized (1:1), 12-week, double-blind, placebo-controlled, parallel group, multicenter phase III study of once-daily FF/VI 100/25 μg versus placebo in patients of Asian ancestry ages ≥12 years with asthma, uncontrolled on a low- to mid-strength ICS or low-dose ICS/LABA.

Ethnic sensitivity assessment of fluticasone furoate/vilanterol in East Asian asthma patients from randomized double-blind multicentre Phase IIb/III trials.

Background: Fluticasone furoate (FF)/vilanterol (VI) is a once daily (OD) inhaled corticosteroid/long-acting β2-agonist combination asthma therapy approved in Japan and the EU. FF/VI efficacy and safety data from asthma studies including patients in East Asia were evaluated to assess ethnic sensitivity.

Methods: Randomized, double-blind, multicenter Phase IIb/III trials were assessed.

Fluticasone furoate (FF)/vilanterol (100/25 mcg or 200/25 mcg) or FF (100 mcg) in persistent asthma.

Objectives: Fluticasone furoate (FF; inhaled corticosteroid) combined with vilanterol (VI; long-acting beta(2) agonist) is a once-daily therapy for asthma and chronic obstructive pulmonary disease. This 12-week phase III study compared the efficacy and safety of once-daily (evening dosing) FF/VI 100/25 mcg versus FF 100 mcg (primary objective) and FF/VI 100/25 mcg versus FF/VI 200/25 mcg (descriptive comparison only) in patients (n = 1039) ≥12 years with moderate-to-severe persistent asthma.

Methods: The primary end point was weighted mean (wm) 0-24-h serial forced expiratory volume in 1 s (FEV(1)) at week 12.

Fluticasone furoate/vilanterol 200/25 mcg in Asian asthma patients: a randomized trial.

Background: This study investigated the efficacy and safety of the inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) combination fluticasone furoate (FF)/vilanterol (VI) in Asian asthma patients.

Methods: A 12-week, double-blind, double-dummy, active-comparator, parallel-group, multicenter study. 309 Asian asthma patients (≥12 years, uncontrolled with high-strength ICS or mid-dose ICS/LABA) were randomized (1:1) and included in the intent-to-treat population; 155 received once-daily FF/VI 200/25 mcg and 154 received twice-daily fluticasone propionate (FP) 500 mcg.

Fluticasone furoate-vilanterol 100-25 mcg compared with fluticasone furoate 100 mcg in asthma: a randomized trial.

Background: The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2-agonist vilanterol (VI) is under development for the treatment of asthma and chronic obstructive pulmonary disease.

Objective: To compare the efficacy and safety of FF-VI and FF in patients (≥ 12 years old) with persistent asthma.

Methods: In a randomized, double-blind, parallel-group study, patients (n = 609) (intent-to-treat population) received FF-VI 100-25 mcg, FF 100 mcg, or placebo once daily (evening) by using a dry powder inhaler for 12 weeks.

Measurement properties of an asthma symptom and rescue medication use diary.

Introduction: Assessment of symptoms and rescue medication use are well-established endpoints for clinical trials evaluating asthma treatment.

Objective: To evaluate the measurement properties of an asthma symptom and rescue medication use (ASRMU) diary for clinical trials involving asthma patients aged ≥12 years.

Methods: Interviews with 35 patients were conducted to confirm the importance of key concepts in the ASRMU diary.

Efficacy and safety of once-daily fluticasone furoate 50 mcg in adults with persistent asthma: a 12-week randomized trial.

Background: Fluticasone furoate (FF) is a novel, once-daily inhaled corticosteroid (ICS) that has been shown to improve lung function vs. placebo in asthma patients. This study evaluated the efficacy and safety of FF 50 mcg compared with placebo in asthma patients uncontrolled by non-ICS therapy.