Omalizumab
Introduction
Omalizumab, known commercially as XOLAIR, is an IgG monoclonal antibody drug used to
treat moderate to severe asthma, chronic urticaria, and nasal polyps (1, 2). Omalizumab targets
and binds to IgE antibodies to reduce allergy symptoms (1). XOLAIR is produced by Genentech
in cooperation with Novartis Pharmaceuticals Corporation (2). Omalizumab was first approved
by the Food and Drug Administration (FDA) for usage in treating asthma in 2003, chronic
urticaria in 2014, and nasal polyps in 2020 (1, 3).
Disease Pathology and the Role of IgE
Severe Asthma
Asthma is an airway inflammatory disease with symptoms of cough, shortness of breath, mucous
production, and chest tightness (4). Allergic Type 2 -high asthma is characterized by a type 2
cytokine release that gathers eosinophils in the lungs, creating mucous overproduction, and
leading to a high synthesis of IgE (4). IgE bind to FcRI on mast cells and basophils which
triggers the allergic cascade (4). This causes the release of histamines, proteases, lipid
mediators, and T helper 2 associated cytokines (4). These all are proinflammatory
signals which lead to the symptoms presented by severe asthma patients.
IgE continues to play a role outside of just basophils and mast cells. The smooth
muscles of the airways contain IgE receptors and contract when bound, leading to even
more closed airways (4). Also, Dendritic Cells have FcRI which bind to IgE and
facilitate antigen presentation to helper T cells leading to even more IgE production (4).
Chronic Urticaria
Chronic urticaria is characterized by hives present for most of the day for 6 weeks or
more (5). IgE binds to basophils which initiates the complement system leading to the
release of C5a, which activates the inflammatory response as well as mast cell and
basophil activation (5).
Nasal Polyps
Nasal polyps are benign growths in the sinus due to mucosal inflammation (6). The role
of IgE is not fully understood in the development of nasal polyps, but the usage of
omalizumab has shown decreased symptoms linking the antibody and disease (7).
Dosage
Dosage of Omalizumab is dependent upon the disease as well as the patients initial IgE levels
and weight (1). Counterintuitively, adjustments are not needed based on changes in serum IgE
levels and patient weight through the course of treatment (1). For a patient who has asthma, the
typical dosage is 75mg to 375mg per treatment, once every two or four weeks (1). A suitable
candidate with asthma must be six years of age or older and test positive to a perennial
aeroallergen skin or in vitro reactivity test (1). A patient experiencing urticaria should receive
150mg to 300mg once every four weeks (1). Omalizumab is approved for patients with chronic
urticaria 12 years or older, but no other types of urticaria (1). Finally, a patient with nasal polyps
can receive anywhere from 75mg to 600mg every two to four weeks (1). The patient must be at
least18 years old and have not had a response to nasal corticosteroids (1).
Mechanism of Action
IgE plays a role in binding to mast cells, basophils, and eosinophils and triggering an
allergy cascade (4). Omalizumab is an IgG monoclonal antibody (8). It is designed to bind to
the C3 locus of IgE and prevent its interaction with FcRI (8). By preventing IgE from
binding to FcRI, Omalizumab inhibits the initiation of this cascade and prevents the
overexcited allergy pathway from detrimental effects.
In severe asthma, this would appear as a decrease in histamines, proteases, lipid
mediators, and T helper 2 associated cytokines (4). It would also reduce the smooth
muscle constriction cause by IgE binding to smooth muscle IgE receptors and a
decrease in the production of IgE by antigen presenting dendritic cells activated by IgE
(4).
The exact mechanisms of action in chronic urticaria and nasal polyps are not well
known, however theories point to similar mechanisms of reducing mast cell and
basophil activation (1). The inhibition of the complement pathway by binding to IgE may
also play a role in reducing symptoms of chronic urticaria (5).
Side effects
Some severe side effects have been associated with Omalizumab, including
anaphylaxis and parasitic infection (1). The rates of anaphylaxis because of
Omalizumab are statistically low (0.09%, 35/39,510) (1). Even so, it is recommended
that patients receive two hours surveillance after the first three injections of Omalizumab
(1). Another side effect of Omalizumab is an increase in the potential for parasitic. IgE is
known to target parasites (1). By decreasing the level of circulating and binding capable
IgE, Omalizumab reduces the patients overall parasitic defenses (1). One study found a
slight decrease in hosts’ defenses against helminths in omalizumab patients: 50%
infection of omalizumab treatment group compared to 41% of placebo group (9).
References
1. Kumar, C., & Zito, P. M. (2023). Omalizumab. In StatPearls [Internet]. StatPearls
Publishing.
2. Genentech, Inc. & Novartis Pharmaceuticals Corporation. (n.d.). What is XOLAIR?.
Xolair.
https://www.xolair.com/#:~:text=What%20is%20XOLAIR%3F,asthma%20medicines%2
0called%20inhaled%20corticosteroids.
3. Genentech. (2020, December 1). *Genentech announces FDA approval of Xolair
prefilled syringe for self-injection across all approved U.S. indications*.
https://www.gene.com/media/press-releases/14887/2020-12-01/genentech-announcesfda-approval-of-xola
4. Hammad, H., & Lambrecht, B. N. (2021). The basic immunology of
asthma. Cell, 184(6), 1469-1485.
5. Kaplan, A. P. (2004). Chronic urticaria: pathogenesis and treatment. Journal of Allergy
and Clinical Immunology, 114(3), 465-474.
6. Georgy, M. S., & Peters, A. T. (2012, May). Nasal polyps. In Allergy and asthma
proceedings (Vol. 33, No. 3, p. 22). OceanSide Publications.
7. Bachert, C., Maurer, M., Palomares, O., & Busse, W. W. (2021). What is the contribution
of IgE to nasal polyposis?. Journal of Allergy and Clinical Immunology, 147(6), 19972008.
8. Easthope, S., & Jarvis, B. (2001). Omalizumab. Drugs, 61, 253-260.
9. Cruz, A. A., Lima, F., Sarinho, E., Ayre, G., Martin, C., Fox, H., & Cooper, P. J. (2007).
Safety of anti‐immunoglobulin E therapy with omalizumab in allergic patients at risk of
geohelminth infection. Clinical & Experimental Allergy, 37(2), 197-207.
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