Asthma therapies targeting Il-13

This month’s clinical review article by Ingram and Kraft (J Allergy Clin Immunol 2012;130: 829-842) presents exhaustive and timely coverage of a complex issue in asthma treatment, namely, the interface of IL-13 pathophysiology, asthma phenotypes, and IL-13 targeted therapies. The authors take the discussion to foundations of IL-4/IL-13 signaling in asthma before delving into the clinical and investigative implications associated with IL-13 dominance in atopic asthma. The review comprehensively covers current knowledge on the clinical and genetic heterogeneity of asthma, emerging phenotypes and subtypes, biomarker diagnostics, and systemic and targeted therapy responses in well-characterized asthma phenotypes.


Review highlights include:

• Cluster analysis of clinical asthma phenotypes by several research groups, including the consistent finding of eosinophilic, high TH2 cytokine profile asthma and non-eosinophilic, low TH2 cytokine profile asthma.

• Evidence confirming therapeutic efficacy of systemic and targeted therapies in eosinophilic, high TH2 asthma.

• Reports of the successful use of biomarkers in characterizing response to therapy, including recent research involving omalizumab, mepolizumab, and lebrikizumab for patients with severe and/or uncontrolled asthma characterized using clinical and biomarker indices.

• Specific evidence for applying FENO, induced sputum, IgE, and periostin to treatment decision making.

Ingram and Kraft note that traditional and targeted therapies are effective only for eosinophilic, TH2 high asthma patients, leaving a gap in our knowledge about how to effectively manage the low TH2 profile patients. They also remark that TH2 inflammation in asthma patients may be more effectively assessed through the use of combinations of inflammatory and molecular markers, rather than relying on observations of single biomarkers. They conclude by commenting that application of the molecular features of asthma phenotypes, in combination with clinical evidence, is being used to predict response to intervention. They follow by pointing out that the current knowledge base has defined a gap in managing asthma that does not present with a TH2 dominant signature.