Biologic Therapy's Potential for Treating Patients with Refractory Asthma

One of the difficulties in treating patients with asthma is the heterogeneity and complexity of the disease. Asthma responds differently to specific medications and treatment regimens based on subtypes, but those subtypes are often difficult to identify.

A new article from 11 leading asthma and immunology researchers from Canada and the US aimed to clarify and address these concerns in relation to new discoveries about the role of targeted biologic therapies in connection with refractory asthma.

Lead author Rohit K. Katial, MD (photo), of the Department of Medicine and Division of Allergy and Clinical Immunology at National Jewish Health, in Denver Colorado, said the paper was inspired by a panel discussion held at the Cohen Family Asthma Institute at National Jewish Health on emerging biologics "to discuss and debate the characteristics of severe asthma, asthma phenotypes in treatment selection, the role of T helper cells type 2 (Th2) pathways in severe asthma" and the safety and efficacy of focused biologic therapies.

Many types of asthma can be difficult to treat, according to Katial, but severe refractory asthma is one of the most difficult. Patients with refractory asthma have "poor asthma control despite taking high doses of inhaled corticosteroids (ICSs) with our without additional controller medications." Katial and colleagues saw biologic therapies as the most promising option for treatment of patients with refractory asthma.

One of the difficulties clinicians face when treating severe refractory asthma is that there are several different endotypes of the disease, which are difficult to diagnose. Katial wrote that "individuals with severe asthma can be phenotypically similar yet have heterogeneous responses to systemic corticosteroids" and that comorbidities can often further obscure identification of endotypes. Katial and colleagues suggested that biomarker analysis may be the method of identifying these phenotypes, and constructing a focused treatment for individual patients with severe refractory asthma based on that identification.

According to Katial and colleagues, one of the difficulties of treating severe refractory asthma is that refractory asthma often carries a "challenging" tangle of phenotypic manifestations from inflammation, excessive mucus production, airway remodeling, and immunological cell responses. Distinct phenotypes of refractory asthma also carry "distinct physiological and clinical characteristics." Examining those characteristics in connection to biomarker identification can help clinicians predict patient response, and treat patients accordingly.

Katial and colleagues were especially interested in the roles biomarkers make in predicting patient response in the case of type 2-high asthma (eosinophilic asthma). Type-2 high asthma is not often controlled by ICS usage, but does benefit from targeted anti-IL and anti-IgE therapies such as mepolizumab, omalizumab, librikizumab, and others. Without identifying biomarkers for specific phenotypes, it is difficult for clinicians to determine which of these biologic therapies might best benefit an individual patient.

Omalizumab is of particular interest to those working with patients with severe refractory asthma, because it seems to work across many of the Type-2 high phenotypes. Each of these medications decreases the risk of asthma exacerbations and reduces blood eosinophil levels, but predicting the efficacy of these treatments is dependent on the identification of biomarkers.

With the introduction of new biologic therapies, Katial and colleagues see the potential for effective treatments of different asthma endotypes and phenotypes, but advise that "clinicians will need to consider each biologic's target and mechanism of action to determine the ideal treatment option for the individual patient." Identifying phenotypes will become crucial to determining that treatment and to "assess whether patients are candidates for novel therapies."

"Changing Paradigms in the Treatment of Severe Asthma: The Role of Biologic Therapies" appears in the March-April 2017 issue of The Journal of Allergy and Clinical Immunology: In Practice.

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