Future Use of Biologicals in Allergy and Asthma - Con
Klaus F. Rabe
Department of Pulmonology
Leiden University Medical Center
Klaus F. Rabe
Department of Pulmonology, Leiden University Medical Center, The Netherlands
Asthma as a chronic condition is highly prevalent, frequently associated with allergies, and for the most part can be treated adequately, following guidelines, with existing therapies including bronchodilators and/or inhaled corticosteroids, sometimes in combination with leukotriene receptor antagonists or theophylline. Disease modification can be afforded by immunotherapy in selected patients and has undoubted efficacy in patients with respiratory allergies. Novel drugs and the use of biologicals for these conditions are being developed and are targeting the more severe population of asthmatics, and if there was a future role it should be reserved for this indication.
The definition of severe asthma is based on clinical parameters of which the management is directly influenced by risk factors and determinants that individually influence the course of the disease. The estimate for the prevalence of severe asthma lies between 5% and 10% of the population with asthma, and by now a number of risk factors have been identified. Tobacco smoking, female gender, and obesity are some of the determinants that have been described although the precise contribution is not always certain. There is good evidence that severe asthma can be described by various phenotypes and for clinical practice it seems advisable to differentiate individuals that have a more rapid decline in lung function from those that present with frequent exacerbations. For those patients with frequent exacerbations, respiratory viruses seem to play an important role as well as allergen exposure and occupational sensitizers. Furthermore, trigger factors such as nonsteroidal anti-inflammatory drugs are important for a subset of individuals with severe asthma. Patients with a rapid decline in lung function appear to have a different risk factor profile with persistent (eosinophilic) inflammation, persistence of inflammation of the upper airways, and structural changes of the lungs. The common abnormality lies in a poor corticosteroid response which is likely to be multi-factorial and is still insufficiently understood.
Nevertheless, the management of severe asthma relies also on the use of inhaled corticosteroids and bronchodilators, and a limited number of studies have addressed the use of high doses of corticosteroids above those routinely recommended. Leukotriene receptor antagonists are included in several guidelines although their benefit is questionable for this indication. Alternative immunosuppressive therapies have been disappointing so far and there is an urgent need for alternative pharmacological developments. The data available on the use of anti-TNF therapies for severe asthma has been disappointing; anti IL-5 strategies are not tested for this indication; only the monoclonal antibody omalizumab has demonstrated efficacy in this patient group.
Given the complexity of the disease, the role of non-pharmacological strategies, including education and instructions in medication use, need to be stressed. Severe asthma is, undoubtedly, frequently associated with a range of co-morbid conditions and the management strategies need to include pharmacological and non-pharmacological approaches. The role of so-called biologicals is at best very limited, with the exception of anti-IgE for highly selected patients. Finally, clinical trials in the future should be performed in pathologically well phenotyped patients to test the efficacy of novel biological interventions; At present, most of the evidence is lacking.