Review of Biologics in Children With Severe Asthma

Stanley J. Szefler, MD

Disclosures

December 21, 2018

Editorial Collaboration

Medscape &

Shifts in Management

We have a unique opportunity to significantly reduce the worldwide burden of asthma in children and thus affect respiratory disease in adults.[1] This will require a paradigm shift that is directed at altering the natural history of asthma, reducing asthma exacerbations, and preventing long-term adverse outcomes of childhood asthma.[1]

For the past 50 years, we have seen paradigm shifts in asthma management about every 10 years (Figure).[1] With the latest update of the asthma guidelines in 2007, this paradigm shift focused on achieving asthma control defined within two domains: impairment and risk.[1] Impairment consists of day and night symptoms, rescue medication use, pulmonary function, and questionnaires to assess these measures over a short-term period.[1] Risk directs attention to the assessment of the potential for exacerbations, adverse responses to medications, and progression of the disease.[1]

Figure. A summary of the changes in asthma management that integrates the focus of disease activity and the corresponding medications developed to address this therapeutic target. This Figure was published in the Journal of Allergy and Clinical Immunology, Volume 142, Stanley J. Szefler, Asthma across the lifespan: Time for a paradigm shift, Pages 773-780, Copyright Elsevier (2018).[1]

Asthma treatment is organized into a step-care fashion to decrease impairment, minimize risk, and provide a decision path to achieve control.[1] As part of this decision path, it is important to follow spirometry over time to define trajectories of lung growth, measure asthma burden, use biomarkers to select and monitor therapy, carefully evaluate adherence to the current management plan, and address social determinants of health in making decisions to step up therapy.[1] In addition, as part of the current update to the asthma guidelines, six key questions are being addressed, including the intermittent use of inhaled corticosteroids (ICSs) and long-acting muscarinic antagonists, the safety and effectiveness of bronchial thermoplasty, the clinical utility of fraction of exhaled nitric oxide, the effectiveness of indoor allergen reduction, and the role of immunotherapy.[2]

Medications certainly play a role in asthma management. Several have been introduced in recent years, including tiotropium, a long-acting anticholinergic; mepolizumab and reslizumab, anti-interleukin (IL) 5 monoclonal antibodies; benralizumab, an antibody that is directed toward eosinophil receptors; and most recently dupilumab, a human monoclonal antibody to the alpha subunit of the IL4 receptor. This review briefly summarizes the information available for the approved biologics of omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab, in addition to a few new medications that are being evaluated.

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