Purpose Current asthma management relies on inhaled corticosteroids, but some asthma is not well controlled with inhaled steroids alone or in combination with long-acting bronchodilators or leukotriene pathway inhibitors. The field of biologic therapy has grown dramatically in the past two decades, with current availability of three molecules, with two distinct, and highly selective approaches to interfering with the allergic and eosinophilic airway inflammation common to most asthma. This review summarizes current and future options for incorporating biologic therapy into the overall management of asthma. Recent Findings Two new biologic agents have recently come on the US market, supported by well-controlled, randomized clinical trials. These trials have provided insight into the types of patients who are most likely to benefit from these novel agents. Summary In asthma patients with frequent exacerbations, the addition of a biologic agent targeting the IL-5 pathway, or IgE, can significantly reduce exacerbations and improve asthma control. The clinical predictors of utility of specific agents overlap with one another, highlighting the importance of clinical judgment in the overall management of this complex disorder.

Although patients with ACOS or overlap symptoms may be an exception, overall there appears to be more evidence supporting that asthma and COPD are distinct processes. Targeting eosinophils with anti-IL-5 therapy appears to be an exciting pathway in the properly selected patient with asthma and recent data also supports its use in COPD.

Purpose of review Asthma is a chronic, inflammatory disorder of the airways caused by a complex interplay of various biologic mechanisms. Several monoclonal antibody therapies targeting interleukin (IL)-4/IL-13 and IL-5 cytokine pathways have been developed for the treatment of severe eosinophilic asthma. As individuals can display biomarkers and clinical features characteristic of several asthma phenotypes, selection of anoptimal biologic can be difficult. Recent findings Dupilumab, a monoclonal antibody that binds to the α subunit of the IL-4 receptor (IL-4Rα) and has been approved for the treatment of adults with severe atopic dermatitis, has been shown in recent phase 3 trials to also have significant clinical benefits in the asthmatic population irrespective of baseline eosinophil counts. Summary As monoclonal antibodies targeting either IL-4 or IL-13 cytokines individually have failed to demonstrate significant clinical benefits, biologics that target cytokine receptors may be more efficacious compared to those that target cytokines. Furthermore, inhibition of the IL-4/IL-13 signaling cascades may disrupt a broader Th2 inflammatory response compared to a more selective impairment of eosinophil proliferation and activity via blockage of the IL-5 pathway. Future research with independently funded, head-to-head trials of approved biologics is needed to elucidate a favorable therapeutic option.

This JAMA Insights Clinical Update reviews recent evidence favoring use of inhaled corticosteroids (ICS)in all patients with asthma, regardless of frequency, and summarizes the SMART (single maintenance and reliever therapy) treatment approach, which uses an inhaler combining ICS and formoterol for control and relief of symptoms, and differences between SMART and symptom-driven therapy.

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