PURPOSE OF REVIEW: A small proportion of patients with asthma have severe 
disease characterized by persistent airflow obstruction, airway 
hyperresponsiveness and eosinophilic airway inflammation. This review focuses on 
the clinical efficacy of inhibiting T helper 2-cytokine-mediated inflammatory 
responses using monoclonal antibodies directed against immunoglobulin E (IgE), 
interleukin (IL)-5, and IL-4/IL-13 in patients with severe refractory asthma.
RECENT FINDINGS: The heterogeneity of airway inflammation in severe asthma has 
led to the recognition of multiple pathophysiologically distinct severe asthma 
endotypes. Biomarkers are being developed and evaluated to identify these 
endotypes and to guide the use of specific biologics in the appropriate patients 
who remain uncontrolled on high doses of inhaled corticosteroids and long-acting 
bronchodilators or oral corticosteroids. Examples include the efficacy of 
omalizumab in patients with severe refractory atopic asthma characterized by 
raised serum total IgE, mepolizumab, reslizumab, and benralizumab in patients 
with recurrent eosinophilic exacerbations characterized by blood and sputum 
eosinophilia despite high doses of corticosteroids, and lebrikizumab, 
pitrakinra, dupilumab, and tralokinumab that target the IL-4/IL-13 signalling 
pathways in patients with eosinophilic asthma or raised serum periostin.
SUMMARY: In severe refractory asthma, both an understanding of the underlying 
pathophysiologic mechanisms driving airway inflammation and the identification 
of appropriate biomarkers in individual patients are critical in guiding the use 
of biologics and monoclonal antibodies that target the specific pathological 
processes.