|Year : 2018 | Volume
| Issue : 1 | Page : 1-2
Omalizumab in the treatment of chronic urticaria
Department of Dermatology, DY Patil University School of Medicine, Navi Mumbai, Maharashtra, India
|Date of Web Publication||10-Jul-2018|
Prof. Kiran Godse
Shree Skin Centre and Pathology Laboratory, 21/22, L Market, Sector 8, Nerul West, Navi Mumbai - 400 706, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Godse K. Omalizumab in the treatment of chronic urticaria. Indian J Drugs Dermatol 2018;4:1-2
Omalizumab (OMA) has been approved by the Drug Controller General of India (DCGI) in 2013 for the treatment of urticaria. OMA, a humanized monoclonal antibody against the constant region of the immunoglobulin E (IgE) molecule, was launched almost two decades ago for the treatment of severe allergic asthma.
Chronic spontaneous urticaria (CSU) affects 1% of the world population and also their quality of life. Most of the patients suffering from chronic urticaria have no etiologic diagnosis or are considered as idiopathic. They continue to take oral antihistamines for symptomatic relief of troublesome wheals over a long duration of time. However, about 50% of these patients are refractory to H1-antihistamines because of varied reasons, including tachyphylaxis. Apart from antihistamines, there has been no good drug to nullify the effects of histamine or drugs that would directly decrease levels of free IgE which mediates Type-I hypersensitivity or IgE-mediated hypersensitivity reactions such as urticaria. OMA was developed as a humanized monoclonal anti-IgE antibody that binds with free IgE antibodies and reduces the circulating levels of free IgE. It does not bind to FcεRI receptors or receptor-bound IgE. OMA has been reported to work in solar urticaria, cold urticaria, and dermographism.
| Omalizumab in Chronic Urticaria: Dosages and Indications|| |
The first-line therapy of CSU is nonsedating antihistamine, while the second-line therapy has now been revised to updosing of the same. OMA is a third-line therapy if updosing of antihistamines has failed to control urticaria. OMA dose can be adjusted with increasing interval between doses or by decreasing dose, thus saving cost.
The recommended dose of OMA is 300 mg, 4 weekly in the management of CSU refractory to standard of care with H1-antihistamines in adults and adolescents ≥12 years of age. There have been reports of low-dose OMA with variable success rates. One-third of the patients may respond to 150 mg dose and a few may need >300 mg dose in real-life setting. In my experience, a fewer number of patients may need combination of cyclosporine and OMA for the control of urticaria.
In some patients, when OMA therapy was discontinued in patients of CSU due to various reasons and when it was restarted after some time, it was observed by Metz et al. that such retreatment with OMA was successful. This adds to the evidence that OMA can be restarted offering same efficacy. This could be because of less chances of neutralizing anti-OMA antibodies.
| Omalizumab and Serum Immunoglobulin E Levels|| |
OMA binds to the constant region of the IgE molecule, inhibiting it from binding to its receptor, FcεRI. As a result, total IgE levels in the peripheral blood rise, but free IgE is reduced to very low levels. There has been a good correlation between baseline levels of serum IgE and response to OMA. This is predictable as OMA is an anti-IgE monoclonal antibody. Two studies found that low baseline IgE (<43 UI/mL) was associated with a poor response, while the complete responders had the highest serum baseline IgE values.,
| Fast and Slow Responders|| |
Patients with CSU respond differently to OMA. Among people with CSU, the clinical presentation might be indistinguishable, but the response to OMA can be fast (<1 week) or slower (1 week–3 months) or even very slow (12–24 weeks).
Basophil histamine release assay and in vivo autologous serum skin test correlate with slow responders, due to higher levels of autoantibodies. Autoreactive urticaria shows slow response to OMA. Angiotensin-converting enzyme inhibitors given along with OMA could interfere with its effect and efficacy. OMA fast responders are generally autologous serum skin test negative, those with higher baseline IgE levels and low d-dimer levels.
| Omalizumab and Cure of Urticaria|| |
When a biological like OMA was introduced for chronic urticaria, it was looked upon with great hope, especially for patients suffering for trouble chronic urticaria. It needs to be remembered that like other biologicals, OMA cannot cure disease as it will only deplete allergen-specific serum IgE available for binding to FcεRI receptors on the mast cells releasing histamine responsible for urticarial reaction. OMA can reduce disease severity in patients who are taking antihistamines for a very long period of time or those who are not responding to even higher dosages of antihistamines. For such patients, OMA therapy offers better quality of life. However, each injection effect can last up to maximum 6–12 weeks and not more. Symptoms of urticaria come back rapidly in those who discontinue treatment, and it is dependent on initial urticarial activity score and early treatment response.
OMA does not lose its effectiveness over time. There are no reports of antidrug antibodies demonstrated so far.
| Safety Profile of Omalizumab|| |
OMA has recently been assigned pregnancy category B risk status by the Food and Drug Administration. Although not approved, OMA is considered a safe and effective therapy for those pregnant females not responding to antihistamines.
Side effect profile of OMA is good with only a few reports of hair loss, angioedema, and late-onset anaphylaxis. OMA is advised to be taken in the hospital setting and keep patient under observation for 2–4 h. As this a humanized monoclonal antibodies, allergenicity or chances of formation of antibodies against the OMA molecule is less. It contains only 5% of nonhuman (murine) amino acid residues. OMA has good safety profile in clinical studies and in postmarketing studies. In a large Phase-III studies by Maurer et al. and Kaplan et al., there were little differences in side effects between placebo and OMA group. In my clinical practice, I have not observed any significant side effects with OMA therapy.,
In the coming years, it is expected that more data will be published about use of omalizumab in the treatment of chronic urticaria.
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Consensus statement for the diagnosis and treatment of urticaria: A 2017 update. Indian J Dermatol 2018;63:2-15.
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