Asthma is a common heterogeneous disease with a complex pathophysiology. Current
therapies based on inhaled
corticosteroids and longacting β2 agonists are effective in controlling
asthma in most, but not all patients, with a few patients falling into the severe
asthma category. Severe
asthma is characterised by poor
asthma control, recurrent exacerbations, and
chronic airflow obstruction despite adequate and, in many cases, high-dose treatments. There is strong evidence supporting the role for
interleukins derived from T-helper-2 (Th2) cells and innate lymphoid cells, such as
interleukins 4, 5, and 13, as underlying the eosinophilic and allergic inflammatory processes in nearly half of these patients. An
anti-IgE antibody,
omalizumab, which binds to circulating
IgE, a product of B cells from the actions of
interleukin 4 and
interleukin 13, is used as treatment for severe allergic
asthma. Studies examining
cytokine blockers such as anti-interleukin-5, anti-interleukin-4Rα, and anti-interleukin-13
monoclonal antibodies in patients with severe
asthma with recurrent exacerbations and high blood eosinophil counts despite use of inhaled
corticosteroids have reported improved outcomes in terms of exacerbations,
asthma control, and forced expiratory volume in 1 s. The US Food and Drug Administration's recommendation to use an anti-interleukin-5 antibody for the treatment of severe eosinophilic
asthma suggests that there will be a therapeutic place for these anti-Th2 agents.
Biomarkers should be used to identify the right patients for such targeted approaches. More guidance will be needed as to which patients should receive each of these classes of selective antibody-based treatments. Currently, there is no treatment that targets the
cytokines driving
asthma associated with non-eosinophilic
inflammation and low Th2 expression.