Future Use of Biologicals in Allergy and Asthma - Pro
Andrew Wardlaw, United Kingdom
Institute for Lung Health
University of Leicester
Professor Andrew Wardlaw
Institute for Lung Health, University of Leicester, United Kingdom
Asthma is a disease characterised by variable airflow obstruction, bronchial hyperresponsivness(AHR) and airway inflammation which is usually but not always eosinophilic. However within this definition there is a considerable heterogeneity in the clinical presentation, physiology and pathology of the disease. This relates to heterogeneity in response to treatment. In order to take full advantage of the new biological therapeutic agents that are becoming available to treat asthma and related diseases we need to understand this phenotypic complexity and relate it to pathogenesis and treatment response.
Asthma (and indeed most airway diseases) can be seen as a syndrome caused by external agents such as smoking, allergens or infection leading to an inflammatory process in the airways which in turn leads to a number of pathophysiological abnormalities. Each of these abnormalities has its own specific aetiological pathway and can be defined by a distinct immunological process. These abnormalities include the classical airway dysfunction phenotype caused by an abnormality in airway smooth muscle function and pathologically associated with infiltration of the airway smooth muscle with mast cells, a severe exacerbation (SE) phenotype characterised by eosinophilic airway inflammation, a cough phenotype, a bronchiectasis phenotype, and a fixed airflow obstruction phenotype. Patients usually express one or more of these phenotypes which are often dissociated. Any one form of treatment is going to be more effective at treating one of these abnormalities than another. For example bronchodilators effectively treat the airway dysfunction phenotype and steroids the SE phenotype. Biological therapies are very specifically targeted at one immune pathway and therefore generally speaking will only treat one pathophysiological phenotype. Using these agents to treat the totality of ‘asthma’ without any bias towards the phenotype being treated will result in a failure to recognise their benefit. In addition, as they are so expensive, it is important to target patients where they will have the maximum impact. Three antibody based therapies illustrate this point. Anti-IgE (omalizumab) is only effective in patients with atopic asthma whose disease is driven by IgE mediated allergic reactions. Anti-TNF alpha approaches appear to be most effective in treating the airway dysfunction phenotype and anti-IL-5 (mepolizumab) appears to be mainly effective at treating SE, the phenotype most closely associated with eosinophilic inflammation. When targeted at appropriate patients these agents can be both clinically and cost-effective.