Biologics in asthma – the next step towards personalized treatment

Published Online: March 2015

Asthma is a complex disease that has a large impact on quality of life. Current treatments are usually effective for individuals with mild to moderate disease; however, more severe asthma is often not fully controlled with currently available medication. The need for additional and different therapeutic approaches in those patients with severe disease has sparked research to identify molecules that contribute to asthma. Many of these molecules have been identified as potential targets for therapy. Monoclonal antibodies directed at these molecules have been developed and are currently being tested for their effectiveness in the treatment of asthma. However, responses to these medications are variable, raising the question of whether it is possible to predict the response to particular treatments based on an asthma patient’s individual characteristics of disease.

As the majority of asthma patients are also allergic, IgE, the antibody intimately involved in allergic responses, has been one target of therapy. Omalizumab is a monoclonal antibody directed against IgE, and acts to prevent its ability to function with multiple cell types. Omalizumab has been shown to be safe and effective for adults and children in the treatment of asthma, and is the only biologic agent currently approved for treatment of asthma in the United States, though only for patients 12 years of age or older. Interestingly, both allergic and non-allergic patients may benefit from this medication, leading many to believe that there are effects of omalizumab extending beyond just lowering IgE levels.  

Eosinophils are white blood cells that often contribute to inflammation and lead to loss of lung function in asthma. Several products have been developed to inhibit the production, function, and survival of eosinophils. These antibodies seem to work particularly well in individuals with high eosinophil counts prior to treatment and who have not responded to current treatment with inhaled corticosteroids. Collectively these products are well tolerated and are effective in reducing eosinophil numbers and preventing asthma exacerbations.

Finally, multiple antibodies have been developed in attempts to reduce cytokines (proteins used in cellular signaling) known to fuel allergic-type responses and inflammation. Studies with agents targeting only one cytokine have been met with frustration as many cytokines have overlapping effects. Therefore, the results of targeting only one cytokine have not been as effective as originally hoped. However, these studies have provided insight into mechanisms of allergic and asthmatic disease. Antibodies blocking the effect of more than one cytokine have shown promise, but further research as to their use in asthma is needed.

In summary, there remains a need for treatment options in patients with asthma who do not respond to standard therapies. Biological agents may fill this void, and their further study is helping to determine which patients will receive the most benefit based on their individual characteristics. Furthermore, not only are these new treatments providing promise of improved asthma control, but they are also leading to new insights into the mechanisms of the disease.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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