PURPOSE OF REVIEW: Severe asthma is a heterogeneous disease that can be 
classified into phenotypes and endotypes based upon clinical or biological 
characteristics. Interleukin (IL)-4 and IL-13 play a key role in type 2 (T2) 
asthma. This article reviews the signaling pathway of IL-4 and IL-13 and 
highlights its targeted therapy in severe asthma.
RECENT FINDINGS: Several clinical trials of biologics targeting the IL-4/IL-13 
pathway have recently been completed. In patients with severe, uncontrolled 
asthma, targeting IL-13 alone with biologics including lebrikizumab and 
tralokinumab has not shown consistent reduction in asthma exacerbations. 
Simultaneous targeting of both IL-4 and IL-13 by blocking IL-4 receptor α using 
dupilumab has yielded more consistent results in reducing asthma exacerbations 
and improving lung function, especially in patients with increased blood 
eosinophils. Other biomarkers of T2 inflammation such as exhaled nitric oxide 
and serum periostin may also predict response to biologics targeting the 
IL-4/IL-13 pathway.
SUMMARY: No biologic targeting the IL-4/IL-13 pathway is currently available for 
treatment of asthma, but emerging data suggest that biologics targeting IL-4 and 
IL-13 together may benefit patients with T2 high asthma. Additional data are 
needed about long-term efficacy and safety prior to incorporating these drugs 
into routine clinical practice.