As part of our ongoing seminar series, the Centre of Excellence in Severe Asthma hosted Prof. Liam Heaney, for a webinar on “Stratified Medicine in Severe Asthma” on 09 April, 2016.
Presentation Summary:
Clinical assessment of difficult-to-treat and severe asthma is complex. A range of disease mechanisms cause disease in different patients. Stratified medicine is an approach to improve diagnosis and treatment for individual patients. The aim is to provide a personalised approach. This approach targets the specific processes causing disease in each person.
The goal of stratified medicine is to direct the right treatment, to the right patient, at the right dose. This approach is different from current asthma guidelines. Traditional guidelines use a step-wise approach to asthma. This approach centres on escalation of steroid doses to control asthma symptoms.
Biomarkers provide information about biological processes. Biomarkers have been proposed to inform stratified medicine. Biomarkers may be useful to identify poor adherence, predict response to therapy and to inform the selection of targeted treatment options for individual patients.
Key Points:
- Stratified medicine aims to optimise diagnosis and treatment of individual patients
- Goal is to target treatment to the patients that will benefit most, while limiting negative side effects
- Biomarkers are accessible molecules that can provide information about pathological or physiological processes
- Biomarkers inform diagnosis, define disease severity and identify specific disease mechanisms (endotypes)
- Biomarkers predict response to treatment, confirm treatment efficacy and confirm treatment thresholds to limit inappropriate escalation
- Biomarkers provide prognostic information to reduce exacerbation risk and limit lung function decline
- The current guidelines approach to asthma management is “one size fits all”, with increased medication doses recommended to establish symptom control
- Severe asthma is defined as asthma that remains uncontrolled, despite treatable factors being addressed and maximal inhaled therapy being taken regularly
- Different patients have different responses to inhaled corticosteroids (e.g. changes in lung function)
- Early work demonstrated that treatment with the corticosteroid prednisolone only improved symptoms in patients with elevated sputum eosinophils
- Gene expression studies identify gene signatures that subdivide the asthma population, indicating different disease processes at work in different patients (e.g. TH2 gene signature)
- An increased TH2 gene signature predicts improvements in lung function in response to steroid treatment
- A large subgroup of patients with mild-to-moderate asthma have persistently low eosinophil numbers and may not respond to steroid treatment
- New biomarkers have been proposed that are easily assessed, including serum periostin, FeNO and peripheral blood eosinophils (alone or in composite)
- High levels of Type-2 inflammation is associated with increased likelihood of an asthma attack
- Stratification in severe asthma identifies populations that are non-adherent to therapy, relatively resistant to steroid treatment and individuals that are non-responsive to steroids
- A significant portion of the severe asthma population is not adherent to prescribed steroid treatment (e.g. 35-60% in UK studies, based on prescription records)
- Non-adherence is associated with increased disease exacerbation, lower lung function and increased eosinophil levels
- Exhaled nitric oxide (FeNO) measurement is a useful approach to identify unintentional non-adherence or when prescription records are not available
- Reduced FeNO levels following directly observed inhaled steroid therapy is predictive of treatment non-adherence
- Elevated FeNO, blood eosinophils and periostin may be useful biomarkers to predict response to omalizumab (anti-IgE) monoclonal antibody therapy
- High periostin levels are associated with improved lung function following lebrikizumab (anti-IL-13) monoclonal antibody therapy in clinical trials
- Biomarkers may be useful to guide reductions in steroid dose in the patient population with truly steroid-resistant disease
- A management approach where steroid dosing was guided by sputum eosinophil levels reduced severe exacerbations and corticosteroid dose
- A composite biomarker score based on FeNO, blood eosinophil and periostin levels stratifies exacerbation risk, independent of symptoms and lung function
- The mechanisms causing non-eosinophilic asthma are less clear
- Many new targeted therapies are currently being assessed in clinical trials and biomarkers will be required for each to identify suitable patient populations
About Prof. Liam Heaney:
Prof. Heaney is a Clinical Professor at Queen’s University Belfast and a member of the British Thoracic Society and the European Respiratory Society. He founded and coordinates the British Thoracic Society UK Severe Asthma Network, the British Thoracic Society National Difficult Asthma Registry and the National Institute of Health and Clinical Excellence (NICE) UK Thermoplasty Registry. He is also Academic Lead for the Medical Research Council UK Refractory Stratification Programme (RASP-UK), which aims to further understand how biomarkers can be used in severe asthma management.
Prof. Heaney has participated in clinical trials in severe asthma and co-authored over 100 research publications in the clinical assessment and management of severe asthma.
Prof. Heaney’s major research areas are the clinical assessment in difficult-to-treat asthma and mechanisms involved in severe disease, including the identification and management of poor adherence to therapy and development of novel biomarkers and translational therapeutics in severe disease.
