Innovative Drugs for Allergies

Allergic disorders are caused by immune responses to normally harmless environmental antigens. These allergens typically induce the production of type 2 T helper cell (TH2) cytokines, such as interleukin (IL)-4, IL-5 and IL-13 that promote class switch recombination to immunoglobulin E (IgE) in antigen-activated B cells and the functional activation of mast cells, basophils and eosinophils. The classical therapeutic interventions for the management of allergic diseases include corticosteroids, antihistamines targeting the histamine H1 receptor and other symptomatic medications, with variable clinical success. In recent years, a variety of pathobiological mechanisms implicated in the heterogeneous allergic phenotypes and endotypes have been exposed, driving the development of optimized small molecule drug candidates and novel targeted biologics. In the indented new era of personalized or precision medicine, numerous monoclonal antibody (mAb) products that are targeted at a specific determinant – usually a cytokine or a cytokine receptor – are at various stages of preclinical and clinical evaluation for their efficacy in managing allergic inflammation. Despite the plethora of emerging targeted options, only a few medications have been approved for human use to date. The anti-IgE mAb omalizumab is the first biologic that has been approved since 2003 for the treatment of patients with moderate to severe persistent asthma, and more recently for the management of chronic spontaneous urticaria. Subsequently, the anti-IL-5 humanised mAbs mepolizumab and reslizumab received market authorization as add-on maintenance therapies for patients with severe eosinophilic asthma that is not adequately controlled with inhaled corticosteroids. The latest addition to the armamentarium of approved medications for allergic disorders is dupilumab, a human mAb that inhibits IL-4 and IL-13 signaling by targeting the IL-4Rα subunit of the IL-4 receptor. Dupilumab received its first global approval in 2017 for the treatment of moderate to severe atopic dermatitis . Certainly, the complexity of asthma, atopic dermatitis and other related pathologies comprises heterogeneous, yet elusive, phenotypes and endotypes. In spite of the frequently disappointing outcomes of translational research, the emerging scientific evidence on the cellular and molecular mechanisms underlying the inflammatory responses, and the constantly expanding fields of immunopharmacology and bioengineering are promising indications for the expected successful development of better therapeutic approaches for allergic diseases in the future.