Targeting the interleukin-4 and interleukin-13 pathways in severe asthma: current knowledge and future needs

Area of Science:

• Immunology
• Pulmonology
• Pharmacology

Background:

• Severe asthma is a complex condition with distinct phenotypes and endotypes.
• Interleukin-4 (IL-4) and Interleukin-13 (IL-13) are key cytokines in type 2 (T2) asthma.
• Understanding the IL-4/IL-13 signaling pathway is crucial for developing targeted therapies.

Purpose of the Study:

• To review the IL-4 and IL-13 signaling pathway in severe asthma.
• To highlight targeted therapeutic strategies for severe asthma.
• To evaluate recent clinical trial data on biologics targeting the IL-4/IL-13 pathway.

Main Methods:

• Review of recent clinical trials involving biologics targeting the IL-4/IL-13 pathway.
• Analysis of treatment outcomes, including asthma exacerbations and lung function.
• Evaluation of biomarkers predictive of treatment response.

Main Results:

• Monotherapy targeting IL-13 (lebrikizumab, tralokinumab) showed inconsistent results in reducing exacerbations.
• Dual blockade of IL-4 and IL-13 via IL-4 receptor α (dupilumab) demonstrated consistent benefits in reducing exacerbations and improving lung function.
• Increased blood eosinophils and biomarkers like exhaled nitric oxide and serum periostin may predict response.

Conclusions:

• Biologics targeting both IL-4 and IL-13 together show potential for treating T2 high severe asthma.
• No IL-4/IL-13 pathway-targeted biologic is currently approved for asthma treatment.
• Further data on long-term efficacy and safety are required before clinical adoption.