Biologic therapy in asthma: entering the new age of personalized medicine.
OBJECTIVE
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 suggests a need for specific targeted treatment approaches such as biologic medications. 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. Earlier studies of cytokine-targeted biologic therapy on non-phenotyped asthma patients were generally not clinically effective.


METHODS
Literature published from 1958-2013 was identified through PubMed using the search terms which included asthma and therapy. A total of 32 studies were reviewed covering both pediatric and adult asthmatics and included double-blind randomized placebo-controlled trials testing efficacy of biologic agents to treat asthma.


RESULTS
More recent 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.


CONCLUSIONS
In recent years, the 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.
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh Asthma Institute at UPMC/University of Pittsburgh School of Medicine.
Merritt L
ML
Fajt
Sally E
SE
Wenzel
D000328:Adult; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D001691:Biological Therapy; D002648:Child; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007378:Interleukins / Q000037:antagonists & inhibitors*; D057285:Precision Medicine; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D007378:Interleukins; D007073:Immunoglobulin E
Asthma; IL-13; IL-5; T helper (Th)-2 cells; biologic therapy; eosinophils; interleukin (IL)-4