GSK presented data at European Respiratory Society Congress that show blood eosinophil levels may help inform COPD treatment decisions

LONDON, 10-9-2014 — /EuropaWire/ — GSK today presented data at the European Respiratory Society (ERS) Congress that show blood eosinophil levels may help predict those patients with COPD who will have a greater reduction in exacerbation rates when receiving an inhaled corticosteroid (ICS) containing regimen, and could potentially be used in the future, if supported by further studies, to help physicians tailor their treatment decisions.

A number of scientific studies have suggested that eosinophils (a type of white blood cell), although primarily associated with asthma, may also influence and be associated with an increased risk of exacerbations among patients with COPD. To explore whether measuring and stratifying patients by blood eosinophil levels could help identify those patients who are likely to derive the most benefit from a particular treatment, GSK undertook a post-hoc analysis of data from almost 8,000 patients to explore whether there was a differential response to treatment based on eosinophil levels measured at study start.

Data were analysed from studies undertaken as part of the development of Relvar® Ellipta® (fluticasone furoate/vilanterol or FF/VI), an inhaled corticosteroid/long-acting beta2 agonist combination (ICS/LABA) and its individual components, and also Anoro® Ellipta® (umeclidinium/vilanterol or UMEC/VI), a long-acting muscarinic antagonist/long-acting beta2 agonist (LAMA/LABA) and its individual components.

The findings from each study were as follows:

1. Blood eosinophil count as a biomarker of ICS effectiveness in reducing exacerbation rates in COPD (Pascoe S, Locantore N, Dransfield MT, Pavord ID) – P2817
Post-hoc analysis of data from two randomised, double-blind, placebo-controlled 1-year trials comparing exacerbation rates in patients with moderate to severe COPD, showed that in the subgroup with an eosinophil level ≥2%, exacerbation rates were reduced by 29% (p<0.001) in those treated with FF/VI all doses (50/25mcg, 100/25mcg and 200/25mcg) compared to VI (25mcg) alone. In patients with an eosinophil level of <2% a decrease of 10% (p=0.283) was observed between those receiving FF/VI and those receiving VI.

Results from this analysis suggest that baseline eosinophil levels might predict improvement in exacerbation rates in patients taking FF/VI compared to VI alone and that the magnitude of improvement is likely to be greatest in those with the highest levels of eosinophils.

2. Is blood eosinophil count a predictor of response to bronchodilators in COPD?(Iqbal A, Barnes NC, Brooks J) P2819
Post-hoc analysis of data from four 6-month studies of UMEC/VI (62.5/25mcg and 125/25mcg) and VI (25mcg) found that response to treatment with UMEC, VI or UMEC/VI, evaluated by bronchodilator response, health-related quality of life or dyspnoea, were similar when stratified by blood eosinophil levels ≥2% or <2% at baseline.

Results from this analysis suggested that blood eosinophils levels are not predictive of a bronchodilator response.

Neil Barnes, Global Franchise Medical Head, Respiratory, GSK said: “COPD is a heterogeneous disease and enhancing our understanding of how individual patients respond to different treatments is critical to allow treatment to be tailored to their specific needs, with the ultimate aim of improving outcomes.

“These data, and those from other studies, are very valuable and support our belief that these circulating white blood cells could play an important role in guiding effective COPD management. We believe it is important that further work, including prospective studies, is undertaken to generate more evidence about the promising role of blood eosinophil levels as an indicator of response to an ICS-containing regimen.”

Further analysis of existing data and also prospective studies are needed to substantiate these findings and provide further scientific data regarding the role of the eosinophil in COPD, as well as help inform the most appropriate use of our medicines. GSK is committed to working with the scientific community and exploring this further, including prospective eosinophil data collection from the large-scale phase III Closed Triple study of FF/UMEC/VI, known as IMPACT.

About COPD
Chronic obstructive pulmonary disease (COPD) is a disease of the lungs that includes chronic bronchitis, emphysema or both. COPD is characterised by obstruction to airflow that interferes with normal breathing.

Long-term exposure to lung irritants that damage the lungs and the airways are usually the cause of COPD. Cigarette smoke, breathing in second-hand smoke, air pollution, chemical fumes or dust from the environment or workplace can all contribute to COPD.iv Most people who have COPD are at least 40 years old when symptoms begin.

About eosinophils
Eosinophils are a type of white blood cell thought to play a role in the development of allergic airway inflammation.

Although primarily associated with asthma, eosinophilic airway inflammation is present in some patients with COPD and has been shown to occur during exacerbations of COPD. A blood eosinophil count of ≥2% has been suggested to identify a group of patients who show a greater response to corticosteroid treatment in COPD.v

Please note that all doses listed above are specified as the pre-dispensed dose as reported in the abstracts, which are equivalent to the delivered dose (emitted from the inhaler). The approved dose within the European SmPC for Relvar Ellipta, Anoro and Incruse are all stated as the delivered dose.

About Relvar® Ellipta® (fluticasone furoate/vilanterol)
Relvar Ellipta is a once-daily dual combination treatment comprising fluticasone furoate, an inhaled corticosteroid and vilanterol, a long-acting beta2-agonist, in a single inhaler, the Ellipta®. For the EU Summary of Product Characteristics for Relvar Ellipta, please visit http://ec.europa.eu/health/documents/community-register/index_en.htm.

About Anoro® Ellipta® (umeclidinium/vilanterol)
Anoro Ellipta is a once-daily combination treatment comprising two bronchodilators: umeclidinium, a long-acting muscarinic antagonist, and vilanterol, a long-acting beta2 agonist, in a single inhaler, the Ellipta®. For the EU Summary of Product Characteristics for Anoro, please visit: http://ec.europa.eu/health/documents/community-register/index_en.htm.

Important safety information for Relvar Ellipta in Europe
FF/VI is contraindicated in patients with hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients.

FF/VI should not be used to treat acute asthma symptoms or an acute exacerbation in COPD, for which a short-acting bronchodilator is required. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control and patients should be reviewed by a physician.
Patients should not stop therapy with FF/VI in asthma or COPD, without physician supervision since symptoms may recur after discontinuation.

Asthma-related adverse events and exacerbations may occur during treatment with FF/VI. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of treatment with FF/VI.

Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a short-acting inhaled bronchodilator. FF/VI should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.

Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and extrasystoles may be seen with sympathomimetic medicinal products including FF/VI. Therefore FF/VI should be used with caution in patients with severe cardiovascular disease.

For patients with moderate to severe hepatic impairment, the 92/22 mcg dose should be used and patients should be monitored for systemic corticosteroid-related adverse reactions. FF/VI 184/22 mcg is not indicated for patients with COPD. There is no additional benefit of the 184/22 mcg dose compared to the 92/22 mcg dose and there is a potential increased risk of pneumonia and systemic corticosteroid-related adverse reactions.

Pneumonia is a recognised risk with ICS/LABA treatments in COPD. An increase in the incidence of pneumonia has been observed in subjects with COPD receiving FF/VI compared with VI alone. There was also an increased incidence of pneumonias resulting in hospitalisation and 8 fatal pneumonias, 7 of which occurred on the 184/22 mcg dose, which is not licensed in COPD.

The incidence of pneumonia in patients with asthma was common at the higher dose. The incidence of pneumonia in patients with asthma taking FF/VI 184/22 mcg was numerically higher compared with those receiving FF/VI 92/22 mcg or placebo.

Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations. Risk factors for pneumonia in patients with COPD receiving FF/VIinclude current smokers, patients with a history of prior pneumonia, patients with a body mass index <25 kg/m2 and patients with a (forced expiratory volume) FEV1<50% predicted. These factors should be considered when FF/VI is prescribed and treatment should be re-evaluated if pneumonia occurs.

Hyperglycaemia: There have been reports of increases in blood glucose levels in diabetic patients and this should be considered when prescribing to patients with a history of diabetes mellitus.

Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

FF/VI should be administered with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated infections.

Data from large asthma and COPD clinical trials were used to determine the frequency of adverse reactions associated with FF/VI.

Very common adverse reactions (occurring in >1/10 patients) with FF/VI were headache and nasopharyngitis. Common adverse reactions (occurring in >1/100 to <1/10 patients) were pneumonia, upper respiratory tract infection, bronchitis, influenza, candidiasis of mouth and throat, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, fractures and pyrexia. Extrasystoles were observed as an uncommon adverse reaction (occurring in >1/1,000 to <1/100 patients). With the exception of pneumonia and fractures, the safety profile was similar in patients with asthma and COPD. During clinical studies, pneumonia and fractures were more frequently observed in patients with COPD.
Important Safety Information for Anoro
The following Important Safety Information is based on a summary of the Summary of Product Characteristics for Anoro. Please consult the full Summary of Product Characteristics for all the safety information for Anoro.

UMEC/VI is contraindicated in patients with hypersensitivity to either umeclidinium, vilanterol, or any of the excipients.

UMEC/VI should not be used in patients with asthma since it has not been studied in this patient population. Administration of UMEC/VI may produce paradoxical bronchospasm that may be life-threatening. UMEC/VI is not indicated for the treatment of acute episodes of bronchospasm.

In the event of deterioration of COPD during treatment with UMEC/VI, a re-evaluation of the patient and of the COPD treatment regimen should be undertaken.

Cardiovascular effects, such as cardiac arrhythmias e.g. atrial fibrillation and tachycardia, may be seen after the administration of muscarinic receptor antagonists and sympathomimetics, including UMEC/VI. Patients with clinically significant uncontrolled cardiovascular disease were excluded from clinical studies. Therefore, UMEC/VI should be used with caution in patients with severe cardiovascular disease.

Consistent with its antimuscarinic activity, UMEC/VI should be used with caution in patients with urinary retention or with narrow-angle glaucoma.

Beta2-adrenergic agonists may produce significant hypokalaemia in some patients, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. No clinically relevant effects of hypokalaemia were observed in clinical studies with UMEC/VI at the recommended therapeutic dose of 55mcg/22mcg. Caution should be exercised when UMEC/VI is used with other medicinal products that also have the potential to cause hypokalaemia.

Beta2-adrenergic agonists may produce transient hyperglycemia in some patients. No clinically relevant effects on plasma glucose were observed in clinical studies with UMEC/VI at the recommended therapeutic dose of 55mcg/22mcg. Upon initiation of treatment with UMEC/VI, plasma glucose should be monitored more closely in diabetic patients.

UMEC/VI should be used with caution in patients with convulsive disorders or thyrotoxicosis and in patients who are unusually responsive to beta2-adrenergic agonists.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take UMEC/VI.

The most frequently reported adverse reaction with UMEC/VI was nasopharyngitis (9%). Other common adverse reactions (reported with a frequency of ≥1/100 to <1/10) include: urinary tract infection, sinusitis, pharyngitis, upper respiratory tract infection, headache, cough, oropharyngeal pain, constipation and dry mouth.

Important Safety Information for Incruse
The following Important Safety Information is based on the Highlights section of the Prescribing Information for Incruse (UMEC). Please consult the full Prescribing Information for all the labeled safety information for Incruse.

UMEC is contraindicated in patients with severe hypersensitivity to milk proteins or who have demonstrated hypersensitivity to either umeclidinium, or any of the other ingredients.

UMEC should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD, or as rescue therapy for the treatment of acute episodes of bronchospasm, which should be treated with an inhaled, short-acting beta2-agonist.

As with other inhaled medicines, Incruse Ellipta can produce paradoxical bronchospasm, which may be life-threatening.

Incruse Ellipta should be used with caution in patients with narrow-angle glaucoma. Instruct patients to contact a physician immediately should any signs or symptoms of narrow-angle glaucoma occur.
Incruse Ellipta should be used with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder neck obstruction. Instruct patients to contact a physician immediately should any signs or symptoms of urinary retention occur.

The most common adverse reactions (incidence ≥2% and more common than placebo) with UMEC (and placebo) were nasopharyngitis, 8% (7%); upper respiratory tract infection, 5% (4%); cough, 3% (2%); and arthralgia, 2% (1%). Other adverse reactions with Incruse Ellipta observed with an incidence less than 1% but more common than placebo included atrial fibrillation.

Avoid co-administration of UMEC with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects such as worsening of narrow-angle glaucoma, and worsening of urinary retention.

RELVAR®, ANORO®, INCRUSE® and ELLIPTA® are trademarks of the GlaxoSmithKline group of companies.

GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.

References

[1] Bafadhel M, McKenna S, Terry S, Mistry V, Pancholi M, Venge P, Lomas DA, Barer MR, Johnston SL, Pavord ID, et al . Blood eosinophils to direct corticosteroid treatment of exacerbations of COPD: a randomized placebo controlled trial. Am J Respir Crit Care Med 2012;186:48–55

[1] Pascoe S, Locantore N, Dransfield MT, Pavord ID.  Blood eosinophil count as a biomarker of ICS effectiveness in reducing exacerbation rates in COPD.  ERS 2014

[1] Iqbal A, Barnes NC, Brooks J.  Is blood eosinophil count a predictor of response to bronchodilators in COPD? (ANORO).  ERS 2014

[1] Saha S, Brightling CE. Eosinophilic airway inflammation in COPD. Int J Chron Obstruct Pulmon Dis 2006;1:39–47 [PMC free article] [PubMed]

[1] Bafadhel M, McKenna S, Terry S, Mistry V, Reid C, Haldar P, McCormick M, Haldar K, Kebadze T, Duvoix A, et al. Acute exacerbations of COPD: identification of biological clusters and their biomarkers. Am J Respir Crit Care Med 2011;184:662–671 [PubMed]