Anti-IgE monoclonal antibody (omalizumab) in the treatment of atopic asthma and allergic respiratory diseases.
Since the discovery of immunoglobulin E (IgE) antibodies thirty-six years ago, our understanding of the mechanisms of allergy has improved to such an extent that we can now better differentiate allergy from non-allergic hypersensitivity, and allergic/atopic from intrinsic/non-atopic bronchial asthma. IgE antibodies are crucial immune mediators of airway inflammation in allergic atopic asthma and IgE-mediated hypersensitivity reactions are the likely mechanisms of allergen-induced airway obstruction. In addition, IgE may cause chronic airway inflammation in asthma through effector cells activated via high-affinity (Fcepsilon RI) or low-affinity (Fcepsilon RII) IgE receptors. Therapeutic anti-IgE antibodies able to reduce free IgE levels and to block the binding of IgE to Fcepsilon RI without cross-linking IgE and triggering degranulation of IgE-sensitised cells have been developed. This non-anaphylactogenic anti-IgE monoclonal antibody (rhuMAb-E25; omalizumab) binds IgE at the same site as these antibodies bind Fcepsilon RI and Fcepsilon RII. As a consequence, omalizumab inhibits IgE effector functions by blocking IgE binding to high-affinity receptors on IgE effector cells and does not cause mast cell or basophil activation because it cannot bind to IgE on cell surfaces where the Fcepsilon R1 receptor already masks the anti-IgE epitope. Studies in patients with atopic asthma demonstrated that omalizumab decreases serum IgE levels and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen. In several clinical controlled trials omalizumab resulted to be able to reduce asthma-related symptoms, to decrease corticosteroid use and to improve quality of life of asthmatic patients. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases (allergic rhinitis, allergic conjunctivitis, atopic dermatitis and food allergies), a favourable side-effect profile and a twice-monthly dosing frequency.
D'Amato
Gennaro
G
Division of Respiratory and Allergic Diseases, Department of Chest Diseases, High Speciality Hospital A Cardarelli, Naples, Italy. gdamato@qubisoft.it
Liccardi
Gennaro
G
Noschese
Paolo
P
Salzillo
Antonello
A
D'Amato
Maria
M
Cazzola
Mario
M
D018926:Anti-Allergic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D002986:Clinical Trials as Topic; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology*; D000069444:Omalizumab
D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069444:Omalizumab; D007073:Immunoglobulin E