New age of personalized medicine for biologic therapy in asthma

Asthma is a common chronic disease with various phenotypes and therapeutic responses.

Unlike other diseases, current anti-inflammatory treatment with corticosteroids does not include any reference to biological measures which may vary among different asthma phenotypes. Morbidity from uncontrolled asthma is high. There is need for specific targeted treatment approaches such as biologic medications.



Human chromosomes (grey) capped by telomeres (white). Image source: Wikipedia, public domain.

In half of asthmatics, chronic airway inflammation may be driven by T helper (Th)-2 cells, which release pro-inflammatory cytokines, such as interleukin (IL)-4, IL-5 and IL-13, contributing to eosinophil inflammation and IgE production.

Initial studies of cytokine-targeted biologic therapy on non-phenotyped asthma patients were ineffective.

This literature review by Sally Wenzel et al. included 32 studies (1958–2013).

Approaches to personalized medicine with expression profiling studies, genetic analysis and clinical biomarkers of Th2 inflammation have allowed identification of asthma phenotypes including a Th2 “high” phenotype.

Studies targeting IgE, IL-5, IL-13 and the IL4 receptor alpha chain have shown some efficacy in phenotyped patients. For those without evidence of Th2 inflammation, no specific therapies have been identified.

Identification of Type-2 cytokine “high” asthma in numerous studies has predicted the clinical response to the Th2 associated therapies. It is not yet clear whether all Type 2 high asthma will respond similarly to IL-4, 5 and 13 approaches. "Sub-phenotyping" of phenotypes may be needed to find the patients who would respond to a specific therapy.

References:

Biologic therapy in asthma: entering the new age of personalized medicine. Journal of Asthma, Posted online on May 13, 2014. (doi:10.3109/02770903.2014.910221)
http://informahealthcare.com/doi/abs/10.3109/02770903.2014.910221