Asthma continues to impose a major health burden worldwide. Asthma control in Europe remains poor – a 2014 survey found that 45% of 8,000 participants had uncontrolled asthma1 and many patients suffer from largely preventable symptoms and exacerbations, which may result in hospital admission and even death.1 Patients with severe asthma have very poor quality of life, experience considerable difficulty in everyday activities, and are often unable to work. The severity of the problem was illustrated in a number of industry presentations at the 27th European Respiratory Society Congress, which was held on 9–13 September 2017 in Milan, Italy.
GlaxoSmithKline and Innoviva presented the first findings from the innovative Salford Lung Study, which is investigating fluticasone furoate and vilanterol, a new inhaled corticosteroid (ICS) and long-acting β2-agonist (LABA) combination developed for once-daily administration via a dry powder inhaler in patients with asthma.2 This open-label, randomised controlled trial (RCT) is the world’s first digitally enhanced RCT to include a broad and inclusive population of patients in an everyday clinical practice setting and included many people who would normally be excluded from participation in RCTs, including those with other chronic diseases. The study was conducted at 74 general practice clinics in Salford and South Manchester, UK, and included 4,233 patients aged 18 years or older with a general practitioner's diagnosis of symptomatic asthma and on maintenance inhaler therapy. At baseline, 72% of patients had uncontrolled asthma with an Asthma Control Test (ACT) total score of 5 to 19. Patients were randomly assigned to treatment either with an inhaled combination of fluticasone furoate (100 or 200 μg) and vilanterol (25 μg) or usual care, which included ICS administered as monotherapy or as ICS/LABA combinations. Throughout the duration of the study, doctors were allowed to modify or switch treatment at any point as in normal clinical practice, with the exception of a switch from usual care to fluticasone furoate/vilanterol.
At 24 weeks, significantly more patients in the treatment group reported an improvement in their asthma control (measured by ACT) compared with patients who continued to take their usual care medicines (71% versus 56%, p<0.0001). Patients in the fluticasone furoate/vilanterol group also had significantly higher quality of life scores and a reduced impact of their ability to work and participate in activity. The treatment was well tolerated and there was there was no difference in other serious adverse events between the groups.
In a late-breaking abstract, AstraZeneca presented results from the PATHWAY phase IIb study, which is investigating the efficacy and safety of tezepelumab as an add-on therapy in patients with severe, uncontrolled asthma.3 Tezepelumab is a novel monoclonal antibody that targets anti-thymic stromal lymphopoietin, an upstream regulator of multiple inflammatory pathways in asthma. Patients receiving tezepelumab 70 mg or 210 mg every four weeks or 280 mg every two weeks experienced annual asthma exacerbation rate reductions of 61%, 71% and 66%, respectively (p<0.001 compared with placebo in all). Tezepelumab also demonstrated improvements in lung function at all doses and in asthma control at the two higher doses (p<0.05 compared with placebo in all). Adverse event rates were similar between treatment and control arms. AstraZeneca also presented the latest findings of the WINDWARD clinical trial program, which is designed to evaluate the efficacy and safety of a regular, subcutaneous administration of benralizumab (fixed 30 mg dose) for up to 56 weeks in exacerbation-prone asthma patients aged 12 years and older. A pooled analysis of the SIROCCO and CALMIA studies found that patients with high blood eosinophil thresholds and a history of more frequent exacerbations had an enhanced response to benralizumab. These findings will help guide future therapeutic decisions.4
Highlights of Teva’s eight presentations on reslizumab, a humanized interleukin-5 antagonist monoclonal antibody for the treatment of severe eosinophilic asthma, included post-hoc pooled analyses from two 52-week trials.5 Reslizumab has demonstrated reductions in clinical asthma exacerbations as well as improving lung function, asthma control and quality of life.
Finally, Mundipharma presented new data from the Assessment of fluticasone propionate/formoterol In Real life Maintenance treatment (AffIRM) study, the largest study to date of the flutiform k-haler, a novel, breath-triggered inhaler, with 2,539 patients enrolled.5 More than two thirds of participants had switched from another ICS/LABA to flutiform. At 12 months, the proportion of patients with well-controlled asthma increased from 29.4% at baseline to 67.4% and the mean total ACT score increased from 16.3 to 20.4. Patients receiving flutiform also reported improvements from baseline in Asthma Quality of Life scores, adherence and physician/patient satisfaction.
While the control of asthma remains suboptimal, these new therapeutic advances reflect the changing treatment landscape of asthma. New ICS/LABA combinations, novel biologic therapies and more effective drug-delivery devices have demonstrated promising efficacy and safety, and offer hope to millions of asthma patients.
References1. Price D, Fletcher M, van der Molen T, Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey, NPJ Prim Care Respir Med, 2014;24:14009.