Therapeutic monoclonal antibodies in allergy: current landscape and future directions

Abstract

Monoclonal antibodies have significantly revolutionized the therapeutic options available to allergists over the past two decades, encompassing four principal categories: anti-type E immunoglobulin (IgE) monoclonal antibodies (e.g., omalizumab), anti-interleukin (IL) 5/IL-5R monoclonal antibodies (e.g., mepolizumab, benralizumab), anti-IL-4R monoclonal antibodies (e.g., dupilumab), and anti-alarmin monoclonal antibodies (e.g., tezepelumab). The selection of an appropriate monoclonal antibody is guided by several factors, including disease severity, associated allergic and/or eosinophilic comorbidities, glucocorticoid dependence, and the presence of a type 2 allergic pattern characterized by specific IgE, eosinophils, and in asthma higher levels of fractional exhaled nitric oxide. In accordance with the selected criteria utilized to define therapeutic response, super-responders vary across studies, diseases, and biologics to constitute approximately 25 to 50 % of patients. Conversely, in up to 40 % of cases, switching therapies may be warranted due to inadequate or ineffective treatment response, glucocorticoid dependence, adverse effects, non-compliance, or, rarely, the development of antidrug antibodies. Discontinuation of antiallergic monoclonal antibodies carries a risk of therapeutic failure. However, this risk can be mitigated in selected and well-controlled patients or through gradual tapering strategies such as extending injection intervals or reducing dosages. Omalizumab, an anti-IgE monoclonal antibody, can be administered either as monotherapy in cases of food allergy, not as a curative intervention but to reduce the risk of allergic reactions, or in combination with allergen immunotherapy to attenuate initial allergic reactions, to accelerate desensitization, and to facilitate the consumption of allergenic foods in cases involving tropho-allergens. Emerging research continues to explore new targets, provide improvements in monoclonal antibody characteristics, as well as the development of biosimilars and multispecific monoclonal antibodies.