Asthma omalizumab

Omalizumab (Xolair) is the first biological drug approved for the treatment of asthma. Omalizumab is a recombinant humanized monoclonal antibody targeted against IgE. IgE bound to omalizumab cannot bind to IgE receptors on mast cells and basophils, thereby preventing the allergic reaction at a very early step in the process. 

USE IN ASTHMA Omalizumab is indicated for adults and adolescents >12 years of age with allergies and moderate-to-severe persistent asthma. In this population, omalizumab has proven to be effective in reducing the dependency on inhaled and oral corticosteroids and in decreasing the frequency of asthma exacerbations. OmaMzumab is not an acute bronchodUator and should not be used as a rescue medication or as a treatment of status asthmaticus. 

Persson GB, Chung KF, Bousquet J. Kerstjens HA, Fox H, Thirlwell J, Cioppa GD Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy 2004 34 632-638. 

Omalizumab is a recombinant humanized monoclonal anti-IgE antibody that inhibits binding of IgE to receptors on mast cells and basophils, resulting in the inhibition of mediator release and attenuation of the early- and late-phase allergic response. It may be a treatment option for moderate to severe persistent asthmatics 12 years of age or older whose asthma is not controlled by inhaled corticosteroids and who have a positive skin test or in vitro reactivity to perennial allergens.37 Omalizumab significantly decreases inhaled corticosteroid use, number and length of exacerbations, and increases asthma-related quality of life.37... 

Clinical trials have indicated that omalizumab, a recombinant humanized monoclonal IgE antibody approved for use in moderate to severe persistent asthma in patients with reactivity to a perennial allergen, is effective in the treatment of SAR.25-27 Omalizumab inhibits the binding of IgE to mast cell and basophil receptors, resulting in a reduction of allergic mediator release.25 Additionally, serum free IgE levels are decreased.2 27 In SAR patients, omalizumab improves quality of life and nasal symptoms and reduces antihistamine needs. The most effective dose in SAR appears to be omalizumab 300 mg administered subcutaneously every 3 to 4 weeks depending on baseline IgE levels.26,27... 

The most common adverse effect with omalizumab is injection-site reaction, reported in 45% of patients in clinical trials. Other adverse effects include viral and upper respiratory tract infections, sinusitis, headache, and pharyngitis. Rare cases of malignant neoplasms and anaphylaxis were reported during clinical trials of omalizumab in asthma. Patients should be monitored for at least 2 hours following the injection so that anaphylaxis and/or injection-site reactions may be managed.25... 

Omalizumab (Xolair) is an anti-IgE antibody approved for the treatment of allergic asthma not well controlled by oral or inhaled corticosteroids. The dosage is determined by the patient s baseline total serum IgE (international units/mL) and body weight (kg). Doses range from 150 to 375 mg given subcutaneously at either 2- or 4-week intervals. 

Q53 Before initiating treatment with omalizumab, body weight and immunoglobulin E concentration need to be determined. Omalizumab is a monoclonal antibody administered by subcutaneous injection for the prophylaxis of allergic asthma. 

Omalizumab is a monoclonal antibody that binds to immunoglobulin E. It is used as additional therapy in asthma patients who have a proven IgE-mediated sensitivity to inhaled allergens and who are presenting with severe, persistent, uncontrolled asthma. It is administered by subcutaneous injection and the dose is calculated based on the immunoglobulin E concentration and body weight. 

Winchester D, Jacob A, Murphy T, Tonnel A, Tillie-Leblond 1. Omalizumab for asthma. N Engl J Med 2006 355 1281-2. 

Immediate improvement in asthma symptoms may not be apparent after beginning omalizumab therapy... 

Treatment with omalizumab, the monoclonal humanized anti-IgE antibody, is reserved for patients with chronic severe asthma inadequately controlled by high-dose inhaled corticosteroid plus long-acting B-agonist combination treatment (eg, fluticasone 500 meg plus salmeterol 50 meg inhaled twice daily). This treatment reduces lymphocytic, eosinophilic bronchial inflammation and effectively reduces the frequency and severity of exacerbations. It is reserved for patients with demonstrated IgE-mediated sensitivity (by positive skin test or radioallergosorbent test [RAST] to common allergens) and an IgE level within a range that can be reduced sufficiently by twice-weekly subcutaneous injections. 

Omalizumab Humanized IgE antibody reduces circulating IgE Reduces frequency of asthma exacerbations Severe asthma inadequately controlled by above agents Parenteral duration 2-4 d Toxicity Injection site reactions (anaphylaxis extremely rare)... 

Omalizumab is an anti-IgE recombinant humanized monoclonal antibody that is approved for the treatment of allergic asthma in adult and adolescent patients whose symptoms are refractory to inhaled corticosteroids (see Chapter 20). The antibody blocks the binding of IgE to the high-affinity Fes receptor on basophils and mast cells, which suppresses IgE-mediated release of type I allergy mediators such as histamine and leukotrienes. Total serum IgE levels may remain elevated in patients for up to 1 year after administration of this antibody. 

Immunosuppressive therapy is utilized in chronic severe asthma, where cyclosporine is often effective and sirolimus is another alternative. Omalizumab (anti-IgE antibody) has recently been approved for the treatment of severe asthma (see previous section). Tacrolimus is currently under clinical investigation for the management of autoimmune chronic active hepatitis and of multiple sclerosis, where IFN-3 has a definitive role. 

Studies of omalizumab in asthmatic volunteers showed that its administration over 10 weeks lowered plasma IgE to undetectable levels and significantly reduced the magnitude of both the early and the late bronchospastic responses to antigen challenge. Clinical trials have shown repeated intravenous or subcutaneous injection of anti-IgE MAb to lessen asthma severity and reduce the corticosteroid requirement in patients with moderate to severe disease, especially those with a clear environmental antigen precipitating factor, and to improve nasal and conjunctival symptoms in patients with perennial or seasonal allergic rhinitis. 

Omalizumab Xolair Asthma (positive skin test or in-vitro reactivity to a perennial aeroallergen) 2003 (not by EMEA)C)... 

Xolair Omalizumab Humanized IgGi IgE Asthma sc 150-375 mg B iweekly-monthly... 

Xolair omalizumab (2003) Anti-IgE (mAb-IgGl) Asthma Cynomolgus monkey (F, EFD)... 

Omalizumab Xolair Genentech Anti-IgE IgGl kappa Asthma 2003... 

Anon (2006) Omalizumab for severe asthma Drug and Therapeutics Bulletin 44 86-88. 

Strunk RC and Bloomberg GR (2006) Omalizumab for asthma. New England Journal of Medicine 354 2689-2695. 

Anti-IgE monoclonal antibody (omalizumab) is of benefit in highly selected patients. It is given fortnightly or monthly as a subcutaneous injection. It is licensed for use by doctors experienced in severe persistent asthma. Published evidence in severe allergic asthma is poor. Trials so far have been relatively short term. 

Omalizumab should only be used if the asthma is IgE-mediated. It has been reported that patients requiring daily prednisolone to control their asthma are unlikely to respond. This lady is already on high dose oral corticosteroids, and long-acting inhaled beta2-agonists, but with no details of her IgE level, and this needs to be checked before a decision is made. 

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