Dataset Information

Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease.

ABSTRACT: Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD).Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks. At the start and end of treatment, inflammation biomarkers (sputum and serum), lung function, and health status (COPD Assessment Test [CAT] questionnaire) were measured.Although a numerical decrease in differential neutrophil count was observed from baseline, SFC 250 did not significantly reduce sputum neutrophils compared with placebo, nor were there significant changes from baseline in the other biomarkers (sputum or serum), lung function, or CAT, versus placebo. Squamous epithelial cell contamination in some sputum samples rendered them unacceptable for analysis, which reduced the sample size to n=19 (SFC 250) and n=10 (placebo). However, inclusion of contaminated samples did not affect the overall trend of the outcome. Ad hoc bootstrap statistical analysis showed a 27.9% (SFC 250) and 1.3% (placebo) decrease in sputum neutrophils. Sputum IL-8 decreased by 43.2% after SFC 250 but increased by 48.3% with placebo. Responder analyses showed 42% of patients had ?20% decrease in neutrophils from baseline; and 47% of patients had a ?200 pg/mL change in sputum IL-8 following SFC 250 versus 20% after placebo; both changes are considered clinically relevant.This study provides additional information about inflammation in Japanese COPD patients and is the first to study the anti-inflammatory effects of SFC 250 in this context and population. In the primary analysis, SFC 250 did not produce significant changes from baseline in sputum neutrophil levels or other sputum or serum inflammatory markers compared with placebo. Secondary ad hoc statistical analysis showed that SFC 250 reduced the number of sputum neutrophils and IL-8 compared with placebo.

SUBMITTER: Asai K

PROVIDER: S-EPMC4407765 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease.

Asai Kazuhisa K Kobayashi Akihiro A Makihara Yukio Y Johnson Malcolm M

International journal of chronic obstructive pulmonary disease 20150417

<h4>Purpose</h4>Using sputum neutrophils as the primary measure, and other inflammation biomarkers, this study evaluated the anti-inflammatory effects of the combination salmeterol 50 mcg and fluticasone propionate 250 mcg (SFC 250) in Japanese patients with chronic obstructive pulmonary disease (COPD).<h4>Patients and methods</h4>Patients were treated in a randomized, double-blind, parallel group, placebo-controlled trial with SFC 250 twice daily (n=26) or placebo (n=26) for 12 weeks. At the st ...[more]

PMID: 25945045

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Project description:BACKGROUND: In Europe, administration of an inhaled corticosteroid (ICS) combined with a long-acting ?2 agonist is approved in chronic obstructive pulmonary disease (COPD) patients with a pre-bronchodilator FEV1 < 60% predicted normal, a history of repeated exacerbations, and who have significant symptoms despite regular bronchodilator therapy. Minimal data are available on the use of the fluticasone propionate/salmeterol xinafoate combination (FSC) in the real-life COPD setting and prescription compliance with the licensed specifications. METHODS: A French observational study was performed to describe the COPD population prescribed with FSC, prescription modalities, and the coherence of prescription practices with the market authorized population. Data were collected for patients initiating FSC treatment (500 ?g fluticasone propionate, 50 ?g salmeterol, dry powder inhaler) prescribed by a general practitioner (GP) or a pulmonologist, using physician and patient questionnaires. RESULTS: A total of 710 patients were included, 352 by GPs and 358 by pulmonologists. Mean age was over 60 years, and 70% of patients were male. More than half were retired, and overweight or obese. Approximately half were current smokers and one-third had cardiovascular comorbidities. According to both physician evaluation and GOLD 2006 classification, the majority of patients (>75%) had moderate to very severe COPD. Strict compliance by prescribing physicians with the market-approved population for dry powder inhaler SFC in COPD was low, notably in ICS-naïve patients; all three conditions were fulfilled in less than a quarter of patients with prior ICS and less than 7% of ICS-naïve patients. CONCLUSIONS: Prescription of dry powder inhaler SFC by GPs and pulmonologists has very low conformity with the three conditions defining the licensed COPD population. Prescription practices need to be improved and systematic FEV1 evaluation for COPD diagnosis and treatment management should be emphasized.

Project description:The efficacy of inhaled salmeterol plus fluticasone propionate (SFC) in patients with severe or very severe COPD is well documented. However, there are only limited data about the influence of GOLD severity staging on the effectiveness of SFC, particularly in patients with milder disease.TORCH was a 3-year, double-blind, placebo-controlled trial of 6112 patients with moderate/severe COPD with pre-bronchodilator FEV1 < 60% predicted (mean age 65 years, 76% male, mean 44% predicted FEV1, 43% current smokers). To understand the relative efficacy of SFC and its components by GOLD stages, we conducted a post-hoc analysis of the TORCH dataset using baseline post-bronchodilator FEV1 to segment patients into three groups: moderate COPD (GOLD stage II and above: >or= 50%; n = 2156), severe COPD (GOLD stage III: 30% to < 50%; n = 3019) and very severe COPD (GOLD stage IV: < 30%; n = 937).Compared with placebo, SFC improved post-bronchodilator FEV1: 101 ml (95% confidence interval [CI]: 71, 132) in GOLD stage II, 82 ml (95% CI: 60, 104) in GOLD stage III and 96 ml (95% CI: 54, 138) in GOLD stage IV patients, and reduced the rate of exacerbations: 31% (95% CI: 19, 40) in GOLD stage II, 26% (95% CI: 17, 34) in GOLD stage III and 14% (95% CI: -4, 29) in GOLD stage IV. SFC improved health status to a greater extent than other treatments regardless of baseline GOLD stage. Similarly, SFC reduced the risk of death by 33% (hazard ratio [HR] 0.67; 95% CI: 0.45, 0.98) for GOLD stage II, 5% (HR 0.95; 95% CI: 0.73, 1.24) for GOLD stage III, and 30% (HR 0.70; 95% CI: 0.47, 1.05) for GOLD stage IV. The rates of adverse events were similar across treatment arms and increased with disease severity. Overall, there was a higher incidence of pneumonia in the fluticasone propionate and SFC arms, compared with other treatments in all GOLD stages.In the TORCH study, SFC reduced moderate-to-severe exacerbations and improved health status and FEV1 across GOLD stages. Treatment with SFC may be associated with reduced mortality compared with placebo in patients with GOLD stage II disease. The effects were similar to those reported for the study as a whole. Thus, SFC is an effective treatment option for patients with GOLD stage II COPD.Clinicaltrial.gov registration NCT00268216; Study number: SCO30003.

Project description:BACKGROUND:Easyhaler® dry powder inhaler (DPI) containing salmeterol and fluticasone propionate was developed for the treatment of asthma and chronic obstructive pulmonary disease. Three different Salmeterol/fluticasone Easyhaler test products (Orion Pharma, Finland) were compared against the reference product Seretide® Diskus® DPI (GlaxoSmithKline, United Kingdom) to study whether any of the test products are bioequivalent with the reference. METHODS:Open and randomized pharmacokinetic four-period crossover study on 65 healthy volunteers was performed in a single center to compare the lung deposition and total systemic exposure of salmeterol and fluticasone propionate after administration of single doses (two inhalations of 50/500??g/inhalation strength) in fasting conditions. Blood samples were drawn before dosing and at frequent time points between 2 minutes and 34 hours after dosing for determination of drug concentrations. The primary variables for total systemic exposure and lung deposition of fluticasone propionate were maximum concentration of the concentration-time curve (Cmax) and area under the concentration-time curve from time zero to the last sample with quantifiable concentration (AUCt). For salmeterol, the primary variables for total systemic exposure were Cmax and AUCt and for lung deposition Cmax and AUC up to 30 minutes after study treatment administration (AUC30min). RESULTS:One of the Easyhaler test products met all the criteria for bioequivalence with the reference. The 96.7% confidence intervals (CIs) for the test/reference ratios of fluticasone propionate Cmax and AUCt were 0.9901-1.1336 and 0.9448-1.0542, respectively. Ninety percent CIs for salmeterol Cmax, AUC30min, and AUCt ratios were 1.0567-1.2012, 1.0989-1.2255, and 1.0769-1.1829, respectively. Median salmeterol time to maximum concentration (tmax) was 4.0 minutes. Median fluticasone propionate tmax was from 1.5 to 2.0 hours. Terminal elimination half-life was 11 hours for salmeterol and 9-10 hours for fluticasone propionate. CONCLUSIONS:Salmeterol/fluticasone Easyhaler was shown to be bioequivalent with the reference product.

Project description:BACKGROUND:Mometasone furoate/formoterol (MF/F) is a novel combination therapy for treatment of persistent asthma. This noninferiority trial compared the effects of MF/F and fluticasone propionate/salmeterol (FP/S) combination therapies on pulmonary function and onset of action in subjects with persistent asthma. METHODS:Following a 2- to 4-week run-in period with MF administered via a metered-dose inhaler (MDI) 200 ?g (delivered as 2 inhalations of MF-MDI 100 ?g) twice daily (BID), subjects (aged ?12 y) were randomized to MF/F-MDI 200/10 ?g BID (delivered as 2 inhalations of MF/F-MDI 100/5 ?g) or FP/S administered via a dry powder inhaler (DPI) 250/50 ?g (delivered as 1 inhalation) BID for 12 weeks. The primary assessment was change from baseline to week 12 in area under the curve for forced expiratory volume in 1 second measured serially for 0-12 hours postdose (FEV1 AUC0-12 h). Secondary assessments included onset of action (change from baseline in FEV1 at 5 minutes postdose on day 1) and patient-reported outcomes. RESULTS:722 subjects were randomized to MF/F-MDI (n = 371) or FP/S-DPI (n = 351). Mean FEV1 AUC0-12 h change from baseline at week 12 for MF/F-MDI and FP/S-DPI was 3.43 and 3.24 L × h, respectively (95% CI, -0.40 to 0.76). MF/F-MDI was associated with a 200-mL mean increase from baseline in FEV1 at 5 minutes postdose on day 1, which was significantly larger than the 90-mL increase for FP/S-DPI (P < 0.001). The overall incidence of adverse events during the 12-week treatment period that were considered related to study therapy was similar in both groups (MF/F-MDI, 7.8% [n = 29]; FP/S-DPI, 8.3% [n = 29]). CONCLUSIONS:The results of this 12-week study indicated that MF/F improves pulmonary function and asthma control similar to FP/S with a superior onset of action compared with FP/S. Both drugs were safe, improved asthma control, and demonstrated similar results for other secondary study endpoints. TRIAL REGISTRATION:ClinicalTrials.gov: NCT00424008.

Project description:Inhaled corticosteroid/long-acting ?2-agonist combinations (ICS/LABA) have emerged as first line therapies for chronic obstructive pulmonary disease (COPD) patients with exacerbation history. No randomized clinical trial has compared exacerbation rates among COPD patients receiving budesonide/formoterol combination (BFC) and fluticasone/salmeterol combination (FSC) to date, and only limited comparative data are available. This study compared the real-world effectiveness of approved BFC and FSC treatments among matched cohorts of COPD patients in a large US managed care setting.COPD patients (?40 years) naive to ICS/LABA who initiated BFC or FSC treatments between 03/01/2009-03/31/2012 were identified in a geographically diverse US managed care database and followed for 12 months; index date was defined as first prescription fill date. Patients with a cancer diagnosis or chronic (?180 days) oral corticosteroid (OCS) use within 12 months prior to index were excluded. Patients were matched 1-to-1 on demographic and pre-initiation clinical characteristics using propensity scores from a random forest model. The primary efficacy outcome was COPD exacerbation rate, and secondary efficacy outcomes included exacerbation rates by event type and healthcare resource utilization. Pneumonia objectives included rates of any diagnosis of pneumonia and pneumonia-related healthcare resource utilization.Matching of the identified 3,788 BFC and 6,439 FSC patients resulted in 3,697 patients in each group. Matched patients were well balanced on age (mean=64 years), gender (BFC: 52% female; FSC: 54%), prior COPD-related medication use, healthcare utilization, and comorbid conditions. During follow-up, no significant difference was seen between BFC and FSC patients for number of COPD-related exacerbations overall (rate ratio [RR]=1.02, 95% CI=[0.96,1.09], p=0.56) or by event type: COPD-related hospitalizations (RR=0.96), COPD-related ED visits (RR=1.11), and COPD-related office/outpatient visits with OCS and/or antibiotic use (RR=1.01). The proportion of patients diagnosed with pneumonia during the post-index period was similar for patients in each group (BFC?=17.3%, FSC?=19.0%, odds ratio=0.92 [0.81,1.04], p=0.19), and no difference was detected for pneumonia-related healthcare utilization by place of service.This study demonstrated no difference in COPD-related exacerbations or pneumonia events between BFC and FSC treatment groups for patients new to ICS/LABA treatment in a real-world setting.ClinicalTrials.gov identifier NCT01921127 .

Dataset Information

Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease.

Publications

Anti-inflammatory effects of salmeterol/fluticasone propionate 50/250 mcg combination therapy in Japanese patients with chronic obstructive pulmonary disease.

Similar Datasets

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