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Omalizumab

A monoclonal antibody designed to bind to circulating immunoglobulin E (IgE) , preventing IgE from binding to high and low affinity receptors on mast cells and basophils.

Humanized monoclonal antibody that targets the IgE Fc region

Trade name Xolair

Administered by subcutaneous injection.

Half-life 26 days

A humanized antibody approved for patients as young as 6; years and older with moderate to severe allergic asthma.

Iit is approved  for chronic, spontaneous urticaria and chronic rhinosinusitis with nasal polyps in adolescents and adults.

A recombinant DNA-derived humanized IgG1k monoclonal antibody.

it increases the threshold of reactivity to foods, when given alone, and when, given with oral immunotherapy, can reduce the incidence and severity of adverse events, and decrease the time needed for those escalation.

Selectively binds to free human immunoglobulin E (IgE) in the blood and interstitial fluid and to membrane-bound form of IgE on the surface of B lymphocytes.

Does not bind to IgE that is already bound by the high affinity IgE receptor (FcεRI) on the surface of mast cells, basophils, and antigen-presenting dendritic cells

Mainly prescribed for patients with severe, persistent asthma, which cannot be controlled with high doses of corticosteroids.

IgE is commonly involved in type I hypersensitivity.

Type I hypersensitivity manifests in the most prevalent allergic diseases.

As high as 20 to 40% of the population are affected by allergy.

Allergy occurs more frequently in individuals with higher serum IgE levels but the correlation is only statistical and not absolute, so some allergic individuals have very low serum IgE levels and some people with very high IgE have no allergic problems.

Xolair is approved for treating patients 12 years and older with moderate to severe allergic asthma.

Its primary use is for patients mostly with severe, persistent allergic asthma, uncontrollable with oral or injectable corticosteroids.

The efficacy is greater among severe asthmatics than among those with moderately severe disease, with response rates 60-80% or higher..

30-40% of adult asthma cases are not related to allergy and are unresponsive to Xolair.

Patients that respond have reduced frequency of exacerbations, improved lung function, reduced hospitalizations, and improved quality of life.

Most responding patients can reduce or spare entirely the use of corticosteroids

Requires long-term administration and that remains a barrier to its use.

Subcutaneous injection every 2 to 4 weeks during treatment.

Has positive effects on patients with antihistamine-resistant chronic idiopathic angioedema.

In combination with allergen-based specific immunotherapy can reduce anaphylactic reactions when receiving allergen immunizations and of accelerating immunization schedule.

Efficacious and safe for treating various IgE-mediated allergic or non-allergic diseases.

Safe and well tolerated, and rarely causes major adverse effects.

The main adverse effect of omalizumab is anaphylaxis with a rate of occurrence of 1 to 2 patients per 1,000.

The allergic reaction toward omalizumab is probably due to the protein nature of the antibody.

The patients who use Xolair are highly allergic.

No association was between omalizumab treatment and risk of malignancy in trials.

Patients have immune responses to proteins in one or more of the hundreds environmental substances, which they take in by: inhalation, such as house dust mites, pollens, molds, pet animal dander, and other airborne allergens, and by ingestion, to include peanuts, tree nuts, shellfish, and other food allergens, and via the skin as with bee and fire ant stings, or latex gloves.

In sensitized individuals, the IgE molecules, both allergen-specific and allergen-nonspecific ones, bind to the high affinity IgE receptor (FcεRI) on the surface of mast cells and basophils triggering activation of those cells.

The allergenic proteins bind to the allergen-specific IgE bound by FcεRI on the surface of mast cells and basophils and trigger the activation of those inflammatory cells, which release mediators, such as histamine, leukotrienes, tryptase, inflammatory cytokines, and others, causing various allergic symptoms/diseases.

Inhibits the binding of IgE to FcεRI on mast cells and basophils by binding to an antigenic epitope on IgE that overlaps with the site to which FcεRI binds and prevents release of chemical mediators stored inside the cells.

The free IgE in patients is depleted by omalizumab, the FcεRI receptors on basophils, mast cells, and dendritic cells are gradually down-regulated making those cells much less sensitive to the stimulation by allergens.

Administered subcutaneously once every 2 or 4 weeks.

The dosing schedule, 2 vs 4 weeks, between injections and the amount in miligrams, for each injection, for a patient is determined according to the serum IgE level and the body weight of the patient.

Approved for patients with serum IgE in the range of 30 to about 700 IU/ml (international units per mililiter).

The drug be administered by a patient’s health care provider, due to a risk of anaphylaxis.

A glycosylated IgG monoclonal antibody produced by cells of an adapted Chinese hamster ovary cell line.

IgE is central to the pathobiology of allergic asthma.

Antigen-specific IGE involved with dust mites, dogs, cats, cockroaches from sensitized B lymphocytes binds to mass cells in the bronchial smooth muscle of asthmatics.

Mast cells can become primed to release mediators such as histamine, leukotrienes, and proteases immediately, and interleukin 4, 5, and 13 later in the early and late phases of the allergic inflammatory cascade when the offending antigen is encountered again and mast cell-bound IgE antibodies cross-link on the cell surface.

While approximately 60% of patients with asthma achieve control with inhaled corticosteroids, patients require blocking IgEà anti–allergy medications.

Majority of treated patients have sustained short-term benefits of significantly better asthma control at 16 weeks, but also have longer benefits for many years, including a reduced number of exacerbations and a higher quality of life.

It is a recommended as an add-on on drug to combine with inhaled corticosteroids and a long acting bronchodilator to treat moderate to severe persistent asthma before prednisone.

In children as young as  one year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut andother common food allergies including cashews, eggs, and milk (Wood RA).

 

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