Omalizumab : other indications and unanswered questions.
ABSTRACT Omalizumab, a recombinant humanized monoclonal antibody against immunoglobulin (Ig)E, represents a unique therapeutic approach for the treatment of allergic diseases. This agent acts as a neutralizing antibody by binding IgE at the same site as the high-affinity receptor. Subsequently, IgE is prevented from sensitizing cells bearing high-affinity receptors. Inhibition of the biological effects of IgE targets an early phase of the allergic cascade before the generation of allergic symptoms. Currently, omalizumab has been approved for the treatment of persistent allergic asthma in patients who are poorly controlled with inhaled corticosteroids. However, other allergic disorders may be amenable to treatment with omalizumab because of its ability to inhibit effector functions of IgE. Studies of omalizumab in the treatment of allergic rhinitis comprise the greater part of the literature pertaining to the use of this agent for clinical indications other than asthma. This article summarizes clinical trials of omalizumab in allergic rhinitis and examines the evidence regarding the effects of omalizumab on the pathophysiological mechanisms underlying allergic rhinitis. Additionally, we consider the role of this novel therapeutic agent in combination with specific allergen immunotherapy and discuss other potential indications for omalizumab in IgE-mediated disorders, including food allergy, latex allergy, atopic dermatitis, and chronic urticaria.
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ABSTRACT: Atopic diseases and asthma are increasing at a remarkable rate on a global scale. It is now well recognized that asthma is a chronic inflammatory disease of the airways. The inflammatory process in many patients is driven by an immunoglobulin E (IgE)-dependent process. Mast cell activation and release of mediators, in response to allergen and IgE, results in a cascade response, culminating in B lymphocyte, T lymphocyte, eosinophil, fibroblast, smooth muscle cell and endothelial activation. This complex cellular interaction, release of cytokines, chemokines and growth factors and inflammatory remodeling of the airways leads to chronic asthma. A subset of patients develops severe airway disease which can be extremely morbid and even fatal. While many treatments are available for asthma, it is still a chronic and incurable disease, characterized by exacerbation, hospitalizations and associated adverse effects of medications. Omalizumab is a new option for chronic asthma that acts by binding to and inhibiting the effects of IgE, thereby interfering with one aspect of the asthma cascade reviewed earlier. This is a humanized monoclonal antibody against IgE that has been shown to have many beneficial effects in asthma. Use of omalizumab may be influenced by the cost of the medication and some reported adverse effects including the rare possibility of anaphylaxis. When used in selected cases and carefully, omalizumab provides a very important tool in disease management. It has been shown to have additional effects in urticaria, angioedema, latex allergy and food allergy, but the data is limited and the indications far from clear. In addition to decreasing exacerbations, it has a steroid sparing role and hence may decrease adverse effects in some patients on high-dose glucocorticoids. Studies have shown improvement in quality of life measures in asthma following the administration of omalizumab, but the effects on pulmonary function are surprisingly small, suggesting a disconnect between pulmonary function, exacerbations and quality of life. Anaphylaxis may occur rarely with this agent and appropriate precautions have been recommended by the Food and Drug Administration (FDA). As currently practiced and as suggested by the new asthma guidelines, this biological agent is indicated in moderate or severe persistent allergic asthma (steps 5 and 6).Clinical and Molecular Allergy 02/2008; 6:4. · 1.39 Impact Factor
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ABSTRACT: Chronic urticaria is a cutaneous condition in which recurrent pruritic wheals (hives) manifest on the body and typically last for longer than 6 weeks. Chronic urticaria, including physically induced urticarias, such as cold, solar exposure or delayed pressure urticaria, is estimated to occur in approximately 25% of urticaria patients. Of these patients, 75% present with idiopathic disease, which is essentially an exclusionary diagnosis when no contributing factors can be determined that cause the cutaneous reaction. Chronic urticaria symptoms can have a profound effect on a patient's quality of life (QoL); therefore, treatment should address both physical symptom relief and improvements in QoL. This review will discuss the benefits and limitations of several treatment options available to relieve urticarial symptoms, including H1- and H2-receptor antagonists, doxepin, antileukotriene therapy and corticosteroids. Other experimental therapies, such as immunomodulatory agents, plasmapheresis treatment, i.v. immunoglobulins, and omalizumab will also be discussed.Southern medical journal 03/2008; 101(2):186-92. · 0.92 Impact Factor
Article: Treatment of chronic urticaria.[show abstract] [hide abstract]
ABSTRACT: Urticaria is a disorder characterized by rapid onset of localized swelling of the skin or mucosa, called wheals or urtica. According to frequency and duration, urticaria can be divided into acute and chronic type. Chronic urticaria is any type of urticaria occurring every day or twice per week, lasting longer than 6 weeks. Chronic urticaria is a common disorder and estimated prevalence is 1% of the population. Also, it is not rare in childhood. The pathogenesis of chronic urticaria has not yet been completely understood. Chronic urticaria is a heterogeneous group of disorders, and according to the etiology and cause, several groups of chronic urticaria are distinguished, i.e. autoimmune, pseudoallergic, infection-related, physical urticaria, vasculitis urticaria and idiopathic urticaria. Treatment and management of chronic urticaria can be non-pharmacological and pharmacological, and sometimes it is not possible to control the disease with antihistamines only, which are considered to be the mainstay of treatment. In severe cases of chronic urticaria, especially if autoimmunity has been proven, several authors describe different modules of immunomodulation: cyclosporine, cyclophosphamide, mycophenolate-mofetil, omalizumab, plasmapheresis, systemic corticosteroids, and immunoglobulin therapy. This article primarily addresses the treatment of chronic idiopathic and autoimmune urticaria.Acta dermatovenerologica Croatica: ADC / Hrvatsko dermatolosko drustvo 12/2009; 17(4):305-22. · 0.48 Impact Factor