Pediatric usage of Omalizumab: A promising one

Abstract

Allergic and related diseases have a substantial epidemiological impact on the pediatric population. Small molecule-based medicines have been traditionally used to manage the diseases. Omalizumab is the first monoclonal antibody-based medicine used in children's allergy and shows great promises. It binds to free IgE and prevents it from binding to IgE receptors, thus interrupting the IgE-dependent allergic inflammatory cascade. Vast amounts of data demonstrate its effectiveness and well tolerance by patients, including the children. However, the drug was only approved to use in allergic asthma and chronic spontaneous urticaria (CSU), though other applications were explored in clinical trials. In this review, we summarized current pediatric applications of omalizumab in allergic diseases, focusing on its usages beyond asthma and CSU, including allergic rhinitis, allergic bronchopulmonary aspergillosis, vernal keratoconjunctivitis, food allergy and atopic dermatitis. In addition, we highlighted the unmet needs and controversial issues of anti-IgE therapy.

Keywords: Allergy treatment; IgE; Omalizumab; Pediatrics.

Fig. 1

Overview of roles played by IgE in allergic diseases. IgE plays an important role in allergic responses. (Left) Exposures to allergens can result in the binding of IgE to DC and promoting Th2 cell differentiation. Th2 cells release a range of pro-inflammatory mediators such as IL-4 and IL-13, that promote B cell transfer into plasma cells and secrete IgE. In addition, Th2 cell activation further contributes to infiltration and activation of eosinophils, basophils, neutrophils, macrophages and so on. (Right) Upon binding with IgE, mast cells and basophils rapidly release inflammatory mediators, leading to smooth muscle contraction, extracellular matrix accumulation, vasodilation coma mucosal gland secretion, and increasing in vascular permeability and sensory nerve endings. Smooth muscle contraction, activation of eosinophils, vasodilation coma mucosal gland secretion, and increasing in vascular permeability contribute to airway allergic disease. Activation of eosinophils, vasodilation coma mucosal gland secretion, increasing in vascular permeability and sensory nerve endings contribute to disease associated with skin and mucous membranes. And all these factors contribute to food allergy. ABPA, allergic bronchopulmonary aspergillosis; AD, atopic dermatitis; AR, allergic rhinitis; CSU, chronic spontaneous urticaria; DC, dendritic cell; FcεRI, high affinity receptor; FcεRII, low affinity receptor; IL, interleukin; Th, T helpercell; Treg, regulatory T cell; VKC, vernal keratoconjunctivitis

Fig. 2

Mechanism of action of omalizumab in treatment of pediatric allergic and related diseases. Omalizumab is very effective in treating pediatric allergic diseases. By binding IgE it can block various allergic responses, including decreasing mast cell activation and sensitivity, reducing eosinophil infiltration and activation, leading to a down regulation of inflammatory mediators release. Furthermore, omalizumab improves smooth muscle contraction and proliferation, decreases vasodilation and vascular permeability, reduces mucosal gland secretion and so on. DC, dendritic cell; IFN, interferon; IL, interleukin; PAF, platelet activating factor; Th, T helper cell; Treg, regulatory T cell