Chris Compton

Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach. This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements. Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2.99% versus 1.05%; p=0.004) despite treatment with higher doses of inhaled and/or oral corticosteroids. Consistent with other severe asthma cohorts, U-BIOPRED is characterised by poor symptom control, increased comorbidity and airway inflammation, despite high levels of treatment. It is well suited to identify asthma phenotypes using the array of “omic” datasets that are at the core of this systems medicine approach. Severe asthma results in more airway inflammation, worse symptoms and lower lung function, despite increased therapy http://ow.ly/QznR3

The Innovative Medicines Initiative (IMI): a new opportunity for scientific collaboration between academia and industry at the European level

The introduction of truly new drug treatments is dwindling to a troublesome extent in all fields of medicine, at the same time as the costs for drug development are skyrocketing. New strategies are urgently required as old schemes for drug development are failing. The largest European public–private partnership in biomedical research, the Innovative Medicines Initiative (IMI), is therefore launched. IMI is a unique pan-European research and development (R&D) initiative with the strategic focus of strengthening the competitiveness of European Union (EU)-based biopharmaceutical industry by, amongst other activities, supporting research that aims at a faster discovery and development of safer and more effective medicines for patients. The founding organisations of this new legal entity are the European Federation of Pharmaceutical Industries and Associations (EFPIA) 1 and the European Commission (EC). The partnership is a \#8364;2 billion joint venture, which will be set up to run over the next 10 yrs. The funding system is balanced 1:1; the EC will contribute funding and the industry will contribute in kind, for instance by providing access to specialised expertise and platform approaches. Public consortia made up of universities, hospitals, regulatory authorities, small- and medium-sized biopharmaceutical and healthcare companies (or SMEs) and patient organisations will, on a competitive basis, be able to apply for funding; if this is approved, it will be matched by equal in-kind resources from the EFPIA members. The overarching objectives of IMI have been outlined in a Strategic Research Agenda (SRA) of IMI 2, which was developed over the past 3 yrs by the Research Directorate of the EC and EFPIA via numerous consultations that included stakeholders, such as academic scientists, regulatory authorities and patient groups. The legal act on IMI was adopted by the Council in December 2007 and was published in the Official Journal of the European Union in February 2008 …

Preventing clinically important deterioration with single-inhaler triple therapy in COPD

Clinically important deterioration (CID) is a novel composite end-point (lung function, health status, exacerbations) for assessing disease stability in patients with chronic obstructive pulmonary disease (COPD). We prospectively analysed CID in the FULFIL study. FULFIL (ClinicalTrials.gov NCT02345161; randomised, double-blind, double-dummy, multicentre study) compared 24 weeks of once daily, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 µg with twice daily budesonide/formoterol (BUD/FOR) 400/12 μg in patients aged ≥40 years with symptomatic advanced COPD (Global Initiative for Chronic Obstructive Lung Disease group D). A subset of patients received study treatment for up to 52 weeks. Time to first CID event was assessed over 24 and 52 weeks using two approaches for the health status component: St Georges Respiratory Questionnaire and COPD assessment test. FF/UMEC/VI significantly reduced the risk of a first CID event by 47–52% versus BUD/FOR in the 24- and 52-week populations using both CID definitions (p<0.001). The median time to first CID event was ≥169 days and ≤31 days with FF/UMEC/VI and BUD/FOR, respectively. Only stable patients with no CID at 24 weeks demonstrated sustained clinically important improvements in lung function and health status at 52 weeks versus those who had experienced CID. Once daily, single-inhaler FF/UMEC/VI significantly reduced the risk of CID versus twice daily BUD/FOR with a five-fold longer period without deterioration. Fluticasone furoate/umeclidinium/vilanterol improves disease stability in COPD compared with budesonide/formoterol http://ow.ly/TaNY30loBa8

Demographic and Clinical Characteristics of COPD Patients at Different Blood Eosinophil Levels in the UK Clinical Practice Research Datalink

ABSTRACT Blood eosinophil count may be a useful biomarker for predicting response to inhaled corticosteroids and exacerbation risk in chronic obstructive pulmonary disease (COPD) patients. The optimal cut point for categorizing blood eosinophil counts in these contexts remains unclear. We aimed to determine the distribution of blood eosinophil count in COPD patients and matched non-COPD controls, and to describe demographic and clinical characteristics at different cut points. We identified COPD patients within the UK Clinical Practice Research Database aged ≥40 years with a FEV1/FVC <0.7, and ≥1 blood eosinophil count recorded during stable disease between January 1, 2010 and December 31, 2012. COPD patients were matched on age, sex, and smoking status to non-COPD controls. Using all blood eosinophil counts recorded during a 12-month period, COPD patients were categorized as “always above,” “fluctuating above and below,” and “never above” cut points of 100, 150, and 300 cells/μL. The geometric mean blood eosinophil count was statistically significantly higher in COPD patients versus matched controls (196.6 cells/µL vs. 182.1 cells/µL; mean difference 8%, 95% CI: 6.8, 9.2), and in COPD patients with versus without a history of asthma (205.0 cells/µL vs. 192.2 cells/µL; mean difference 6.7%, 95%, CI: 4.9, 8.5). About half of COPD patients had all blood eosinophil counts above 150 cells/μL; this persistent higher eosinophil phenotype was associated with being male, higher body mass index, and history of asthma. In conclusion, COPD patients demonstrated higher blood eosinophil count than non-COPD controls, although there was substantial overlap in the distributions. COPD patients with a history of asthma had significantly higher blood eosinophil count versus those without.

P275 Comparing clinically relevant improvement with umeclidinium/vilanterol and tiotropium/olodaterol in symptomatic copd: a randomised non-inferiority crossover trial

Introduction and Objectives Here we report the Results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg and tiotropium/olodaterol (TIO/OLO) 5/5 mcg in patients with chronic obstructive pulmonary disease (COPD). Methods This randomised, 2-period crossover study (204990, NCT02799784) included inhaled corticosteroid-free patients with COPD, a modified Medical Research Council dyspnoea score ≥2, forced expiratory volume in 1 s (FEV1)/forced vital capacity ratio of <0.70 and post-salbutamol FEV150%–70% predicted. Patients were randomised to UMEC/VI (62.5/25 mcg once daily) via an ELLIPTA dry powder inhaler followed by TIO/OLO 5/5 mcg (2 puffs once daily) via a RESPIMAT inhaler (each for 8 weeks with an interim 3 week washout period), or vice versa. The primary endpoint was change from baseline (CFB) in trough FEV1 at Week 8 with a non-inferiority (NI) margin of –50 mL in the per protocol (PP) population. Additional outcomes included inspiratory capacity (IC), rescue medication use and ease of inhaler use (assessed using a six-point questionnaire). Adverse events (AEs) were also assessed. Results 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat (ITT) population and 227 in the PP population. The primary endpoint of CFB in trough FEV1 at Week 8 confirmed NI of UMEC/VI vs TIO/OLO (175 mL vs 122 mL; least squares mean difference 53 mL [95% confidence interval: 26, 80]; p<0.001; PP population) and demonstrated superiority in the ITT population (Table). Patients receiving UMEC/VI were significantly more likely to achieve clinically meaningful improvements (≥100 mL) in trough FEV1 at Weeks 4 and 8 vs TIO/OLO, and showed significant improvements at Weeks 4 and 8 in IC and rescue medication use (Table). The ELLIPTA inhaler was rated higher than RESPIMAT in all ease-of-use questionnaire items (p≤0.001). The incidence of on-treatment AEs was similar in both groups (UMEC/VI, n=59 [25%]; TIO/OLO, n=71 [31%]). Conclusions In this first, direct, once-daily LAMA/LABA comparison, a greater likelihood of improvements in lung function was demonstrated with UMEC/VI vs TIO/OLO. The ELLIPTA inhaler was preferred to RESPIMAT. Both LAMA/LABAs were well tolerated. Funding GSK (204990 [NCT02799784]) Please refer to page A261 for declarations of interest in relation to abstract P275. Abstract P275 Table 1 Summary of changes from baseline in lung function endpoints and rescue medication use, and trough FEV1 responder analysis (ITT population) N UMEC/VI N TIO/OLO Difference/OR (95%  CI) UMEC/VI vs TIO/OLO Trough FEV1, mL Week 4 231 189 (13) 224 141 (13) +48 (25, 71)* Week 8 225 180 (13) 224 128 (13) +52 (28, 77)* Trough FEV1 responders,† n (%) Week 4 234 162 (69) 227 116 (51) OR: 2.09 (1.39, 3.14)* Week 8 234 154 (66) 229 109 (48) OR: 2.05 (1.34, 3.14)* IC, mL Week 4 223 164 (17) 215 112 (18) +52 (16, 88)** Week 8 212 169 (17) 212 122 (17) +47 (14, 81)** Rescue medication use (Weeks 1–8), puffs/day 222 −0.94 (0.08) 217 −0.68 (0.08) −0.25 (-0.37,–0.14)* All data are presented as LS mean (SE) change from baseline, unless otherwise stated; *p<0.001; **p<0.01; † Defined as a change from baseline in trough FEV1 of ≥100 mL CI, confidence interval; FEV1, forced expiratory volume in 1 s; IC, inspiratory capacity; ITT, intent-to-treat; LS, least squares; OR, odds ratio; SE, standard error; TIO/OLO, tiotropium/olodaterol 5/5 mcg; UMEC/VI, umeclidinium/vilanterol 62.5/25 mcg