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Utility of Biologics in Inflammatory Diseases

Three review articles examine the possible uses of biologic agents in treating pediatric asthma, controlling the atopic march, and treating monogenic systemic autoinflammatory diseases in children.

Addressing the treatment of asthma, authors note that “although biologics have been available for the management in adults and adolescents for nearly 20 years, research on the efficacy and safety of biologics in children and adolescents has lagged.” Most children with asthma have a type 2 inflammatory phenotype, and since that is the target of currently approved biologics, possible uses are reasonable: “Three biologics, omalizumab, mepolizumab, and duplilumab, are Food and Drug Administration–approved for children as young as 6 years, whereas benralizumab and tezepelumab are approved for adolescents older than 12 years. All these agents reduce the rates of severe asthma exacerbations, whereas their effects on pulmonary function vary across agents. Safety profiles are reassuring, although additional long-term safety data in children are still needed. The choice of a biologic agent follows a careful assessment of other factors that contribute to uncontrolled asthma and includes biomarkers of blood eosinophils, fractional exhaled nitric oxide, allergic sensitization, and IgE levels. This review focuses on the underlying pathophysiology of childhood asthma, an approach to phenotyping patients, and the efficacy, safety, and use of biologics in children and adolescents with severe asthma.”

“The atopic march was described more than 20 years ago on the basis of initial observations, and it is now seen in prospective studies,” according to the authors of the second article. “The concept has evolved and is now considered to be the progression of atopic dermatitis to other atopic conditions, including asthma, allergic rhinitis, food allergy, and eosinophilic esophagitis in a nonlinear fashion. The progression can include some or all of the aforementioned atopic conditions. The pathogenesis is part of the classic type 2 inflammatory process involving IL-4, IL-5, and IL-13 preceded by induction of the alarmins (thymic stromal lymphopoietin, IL-33, and IL-25), leading to production of IgE in a genetically predisposed individual. The development of new biologics that interact with T2 pathway represent possible ways to prevent or modify the atopic march.”

Both biologics and JAK inhibitors could play a role in interrupting the “aberrant activation” of inflammatory pathways, according to the authors of the third article. “Monogenic forms of [systemic autoinflammatory diseases (SAIDs)] typically manifest during childhood, and early treatment is essential to minimize morbidity and mortality. On the basis of the mechanism of disease and the dominant cytokine(s) that propagates inflammation, monogenic SAIDs can be grouped into major categories including inflammasomopathies/disorders of IL-1, interferonopathies, and disorders of nuclear factor-κB and/or aberrant TNF activity. This classification scheme has direct therapeutic relevance given the availability of biologic agents and small-molecule inhibitors that specifically target these pathways. Here, we review the experience of using biologics that target IL-1 and TNF as well as using Janus kinase inhibitors for the treatment of monogenic SAIDs in pediatric patients. We provide an evidence-based guide for the use of these medications and discuss their mechanism of action, safety profile, and strategies for therapeutic monitoring.”

Source: Journal of Allergy and Clinical Immunology