An evaluation of comparative treatment effects with high and low dose fluticasone propionate/formoterol combination in asthma.

Abstract Background Despite extensive use of inhaled corticosteroid/long-acting β2-agonist combinations in asthma, limited data evaluating dose–response for this combination class are available. The benefits of dose escalation and nature of patient subgroups likely to benefit are thus ill-defined. Method In this randomised, double-blind, 8-week study the effects of two dose levels (100/10 and 500/20 μg b.i.d.) of a fixed combination of fluticasone/formoterol (flutiform®) were compared in 309 patients. Treatment effects upon spirometric and symptom-based endpoints were examined in the overall population and in two subgroups defined a priori by % predicted FEV1 at baseline (≥40–≤60% ["severe" airways obstruction] and >60–≤80% ["moderate" airways obstruction]). Results No dose–response was evident for spirometric outcomes (FEV1, FEV1 AUC0–12, PEFR) either overall or in either subgroup. At variance with the spirometric data, statistically significant dose-dependent differences were seen for nocturnal outcomes and consistent numerical differences were found across multiple symptom-based outcomes (symptom scores, sleep scores, rescue medication use, asthma control days, AQLQ scores, exacerbations); greater effects were noted with the higher dose of fluticasone/formoterol. Between-group differences for the overall population were driven by treatment effect differences in the "severe" subgroup. Conclusion In this exploratory comparison a high dose of fluticasone/formoterol in asthmatic patients appears to provide additional improvement in symptom-based rather than spirometric outcomes. Additional benefits from high versus low dose treatment are most likely in patients with severe airway obstruction, although the doses at which ceiling effects are attained may vary between individuals. Trial registration ClinicalTrials.gov identifier: NCT00734318 ; EudraCT number: 2007-001633-34

A review of the and valved holding chamber (VHC) literature with a focus on the AeroChamber Plus Flow-Vu Anti-static VHC

Valved holding chambers (VHCs) reduce the need for inhalation-actuation coordination with pressurized metered dose inhalers (pMDIs), reduce oropharyngeal drug deposition and may improve lung deposition and clinical outcomes compared to pMDIs used alone. While VHCs are thus widely advocated for use in vulnerable patient groups within clinical and regulatory guidelines, there is less consensus as to whether the performance differences between different VHCs have clinical implications. This review evaluates the VHC literature, in particular the data pertaining to large- versus small-volume chambers, aerosol performance with a VHC adjunct versus a pMDI alone, charge dissipative/conducting versus non-conducting VHCs, and facemasks, to ascertain whether potentially meaningful differences between VHCs exist. Inconsistencies in the literature are examined and explained, and relationships between in vitro and in vivo data are discussed. A particular focus of this review is the AeroChamber Plus ® Flow-Vu ® Anti-static VHC, the most recent iteration of the AeroChamber VHC family

The EFFECT trial: Evaluating exacerbations, biomarkers, and safety outcomes with two dose levels of fluticasone propionate/formoterol in COPD

Abstract Inhaled corticosteroid/long-acting β2-agonist combination therapy is recommended in chronic obstructive pulmonary disease (COPD) patients at high risk of exacerbations. The EFFECT (Efficacy of Fluticasone propionate/FormotErol in COPD Treatment) trial is a Phase III, 52-week, randomized, double-blind study to evaluate the efficacy and safety of two doses of fluticasone propionate/formoterol compared to formoterol monotherapy in COPD patients with FEV1 ≥50% predicted and a history of exacerbations. The primary endpoint is the annualized rate of moderate and severe exacerbations. Secondary endpoints include pre-dose FEV1, EXACT-PRO (EXAcerbations of Chronic pulmonary disease Tool - Patient-Reported Outcome)-defined exacerbations, St George's Respiratory Questionnaire for COPD, COPD Assessment Test, and EXACT-Respiratory Symptoms total score. Lung-specific biomarkers (surfactant protein D and CC chemokine ligand-18) will be measured in a subset of patients to explore their relationship to other clinical indices in COPD and their predictive utility. Pneumonia will be diagnosed per criteria defined by the British Thoracic Society community acquired pneumonia guideline, primarily by radiological confirmation and, additionally, using clinical criteria when a chest radiograph cannot be obtained. Serial measurements of serum potassium, vital signs and electrocardiograms, 24-hour Holter monitoring, and 24-hour urinary cortisol measurement will be performed in a subset of patients in addition to conventional safety assessments

Supplementary Material, Supplementary_data – Efficacy and safety of fluticasone propionate/formoterol fumarate in pediatric asthma patients: a randomized controlled trial

<p>Supplementary Material, Supplementary_data for Efficacy and safety of fluticasone propionate/formoterol fumarate in pediatric asthma patients: a randomized controlled trial by Anna Płoszczuk, Miroslava Bosheva, Kay Spooner, Tammy McIver and Sanjeeva Dissanayake in Therapeutic Advances in Respiratory Disease</p

Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations.

BACKGROUND A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/long acting β2-agonist (ICS/LABA) combinations. METHODS The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs. RESULTS The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N = 16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the two fluticasone/formoterol trials (single-inhaler fluticasone/salmeterol [2.9%]; separate inhaler budesonide, beclometasone, or flunisolide plus formoterol [3.4%]). In Lasserson's review the pooled incidence of OCS exacerbations for single-inhaler combinations was 9.5% (95% CI: 8.4, 10.6%; n/N = 239/2516) for fluticasone/salmeterol, and 10.6% (95% CI: 9.3, 11.8%; n/N = 257/2433) for budesonide/formoterol. In Ducharme's and Chauhan's meta-analyses (primarily incorporating separate inhaler combinations [fluticasone, budesonide, beclometasone, or flunisolide plus salmeterol or formoterol]), the pooled incidences of OCS exacerbations were 16.0% (95% CI: 14.2, 17.8%, n/N = 258/1615) and 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643), respectively. CONCLUSIONS The incidence of exacerbations in two fixed-dose fluticasone/formoterol studies was low and less than in the majority of comparable published studies involving other ICS/LABA combinations. This difference could not be readily explained by differences in features of the respective studies and may be related to the favorable pharmacological/mechanistic characteristics of the constituent components fluticasone and formoterol compared to other drugs in their respective classes