|Year : 2016 | Volume
| Issue : 2 | Page : 121-123
Viva Voce on omalizumab
Kiran Godse1, Resham Vasani2
1 Department of Dermatology, Dr. D Y Patil Medical University, Navi Mumbai, Maharashtra, India
2 Department of Dermatology, K J Somaiya Medical College, Mumbai, Maharashtra, India
|Date of Web Publication||20-Dec-2016|
C-1, 22, Karmakshetra, Near Shanmukhananda Hall, Sion, Mumbai - 400 037, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Godse K, Vasani R. Viva Voce on omalizumab. Indian J Drugs Dermatol 2016;2:121-3
| WHAT IS OMALIZUMAB?|| |
Omalizumab is a recombinant, humanized, monoclonal antibody against human immunoglobulin E (IgE). It is derived from a murine monoclonal antibody, which was humanized to produce omalizumab.
It was approved by the United States Food and Drug Administration on March 21, 2014, for the use in chronic spontaneous urticaria (CSU). It is also approved by the Drug Controller General of India for indication of urticaria in November 2014.
| WHAT IS MECHANISM OF ACTION OF OMALIZUMAB?|| |
To understand the mechanism of action of omalizumab, we need to first understand the role of IgE in the pathogenesis of allergic conditions including urticaria. When an environmental allergen first enters the body, it is taken up by the antigen presenting cells and it is processed and presented to the T- and B-lymphocytes. This is followed by B-lymphocyte activation and production of allergen-specific IgE. This IgE is then secreted by plasma cells and is available to bind to IgE receptors on various cells.
IgE binds to the high-affinity (FcεR1) and low-affinity (FcεRII) receptors on various cells of the immune system. On subsequent antigenic exposure, cross-linking of the antigen occurs by multiple FcεR1-bound IgE molecules on the surface of basophils and mast cells. This causes activation of mast cells and histamine release, producing wheals and other symptoms of urticaria.
To now elucidate the mechanism of action of omalizumab in CSU,
• Omalizumab inhibits the binding of IgE to the high-affinity FcεR1 by binding to the free IgE with a much higher affinity. Omalizumab does not bind to receptor-bound IgE, nor does it bind to FcεR1 receptors. This allows omalizumab to neutralize IgE-mediated responses without causing basophil degranulation or cross-linking with basophil-bound IgE
• It promotes FcεR1 downregulation on basophils because of direct correlation between serum IgE and the number of FcεR1 receptors expressed on basophils. The reduced-free IgE levels ultimately cause dissociation of IgE from basophils with subsequent receptor downregulation 
• Recent therapies have also demonstrated that therapy with omalizumab is associated with lowering of interleukin-31 (IL-31) levels in mast cells in those who were successfully treated. However, role of IL-31 in the pathogenesis of CSU is not known. 
| WHAT ARE INDICATIONS OF OMALIZUMAB IN DERMATOLOGY?|| |
As per the 2013 update of the European Academy of Allergology and Clinical Immunology (EACCI), Global Allergy and Asthma European Network (GA 2 LEN), European Dermatology Forum and World Allergy Organization guideline for the management of urticaria, omalizumab has strong recommendation/high level of evidence as the third-line therapy in the management of urticaria. Omalizumab should be used as add-on to the second-line therapy, i.e., 4-fold updosing of modern second-generation antihistamines in the management of urticaria.
• Atopic dermatitis
• Bullous mastocytosis
• Systemic mastocytosis
• Bullous urticaria.
| WHAT ARE THE CONTRAINDICATIONS TO THE USE OF OMALIZUMAB?|| |
Known hypersensitivity to omalizumab is an absolute contraindication.
| WHEN DOES ONE CONSIDER OMALIZUMAB AS AN OPTION IN TREATMENT OF URTICARIA?|| |
As per the EACCI guidelines, omalizumab is placed as the third-line therapy. As per the position statement on use of omalizumab in the treatment of chronic urticaria, the Indian consensus recommends omalizumab as the fourth-line therapy. 
| CAN IT BE GIVEN CONCOMITANTLY WITH STEROIDS/NONSTEROIDAL IMMUNOSUPPRESSANTS? (CONSIDERING THE FACT THAT PATIENTS OF CHRONIC AUTOIMMUNE URTICARIA HAVE A HIGHER LIKELIHOOD OF BEING ON THEM)|| |
Yes, it can be used with steroids and then one start tapering steroids. Usually, there is no problem since omalizumab is not an immunosuppressant unlike other biologics.
| HOW TO COUNSEL A PATIENT OF URTICARIA BEFORE STARTING OMALIZUMAB?|| |
The patient needs to be counseled that after increasing the dose of antihistamine four folds, this is the best option in the treatment of CSU.
| WHAT IS THE DOSE AND METHOD OF ADMINISTRATION OF OMALIZUMAB IN CHRONIC SPONTANEOUS URTICARIA?|| |
Omalizumab is available as a lyophilized, sterile powder in a single-use 5 ml vial, 150 mg. Dosage of more than 150 mg should be divided into two or more injection sites.
Recommended dose and best response are seen with 300 mg subcutaneous injection once in 4 weeks. Some patients may respond to 150 mg once in 4 weeks and can be tried as per the discretion of treating dermatologist. Because the solution is slightly viscous, the injection may take 5-10 s to administer.
| WHAT ARE THE AVAILABLE PREPARATIONS OF OMALIZUMAB IN INDIA? ARE ANY BIOSIMILARS AVAILABLE?|| |
Xolair ® by Novartis Pharmaceuticals TM costs 7500 INR for 150 mg injection. There are no biosimilars available till date.
| WHAT INVESTIGATIONS SHOULD BE DONE BEFORE STARTING?|| |
Complete blood count, random blood sugar, urine routine, and microscopy should be done before starting omalizumab. There is no need to screen for tuberculosis as is done for other biologicals.
| IS HOSPITALIZATION MANDATORY? CAN IT BE ADMINISTERED IN A DAY CARE SETTING?|| |
Hospitalization is not mandatory; patient can be observed for 2-4 h postinjection.
| ARE PRETREATMENT MEDICATIONS NECESSARY? HOW LONG SHOULD THE PATIENT BE MONITORED POSTINJECTION? WHAT ARE THE POSSIBLE IMMEDIATE ADVERSE REACTIONS AND HOW TO HANDLE THEM?|| |
The frequency of anaphylaxis attributable to omalizumab was estimated to be at least 0.2%. An observation period of 2 h for the first three injections and 30 min for the subsequent injections has been recommended in all patients receiving omalizumab.
| HOW COMMON ARE LOCAL REACTIONS POSTINJECTION OF OMALIZUMAB? WHAT ARE THE LOCAL REACTIONS THAT CAN HAPPEN?|| |
Severe injection site reactions have been reported in 12% of the omalizumab-treated patients. The types of injection site reactions include swelling, erythema, pain, bruising, itching, bleeding, and urticaria. Ice compresses may be applied at the site of injection to minimize complications.
| WHAT IS THE DURATION OF TREATMENT IN CHRONIC SPONTANEOUS URTICARIA?|| |
Biologics will not cure disease as it is true with other biologicals. Omalizumab gives long remission and better quality of life to the patient.
| IS THERE A NEED TO MONITOR THE PATIENT ON OMALIZUMAB?|| |
In view of rare reports of thrombocytopenia, monitoring of platelet counts at baseline and during therapy may be advisable. All reports of thrombocytopenia have been transient and reversible. Currently, there are no such guidelines available.
| ARE THERE ANY DRUG INTERACTIONS THAT ONE NEEDS TO KEEP IN MIND WHILE ADMINISTERING OMALIZUMAB?|| |
No formal drug interaction studies have been performed and no reports about possible interactions exist.
| WHAT HAS BEEN YOUR PERSONAL EXPERIENCE WITH THE USE OF OMALIZUMAB?|| |
This works significantly well in patients of urticaria as it provides immediate relief to bothersome symptoms of urticaria. This also works in patients of physical urticaria.
| IS ANY DOSE ADJUSTMENT REQUIRED AS PER THE WEIGHT OF THE PATIENT?|| |
No. Various studies have observed no correlation between the type of urticaria, autoimmune status, gender, presence of concomitant disease, serum level of IgE, body weight, age of the patients, or dosing protocol used and the response to omalizumab treatment. ,
| DOES OMALIZUMAB WORK IN PHYSICAL URTICARIA?|| |
Yes. It is an off-label indication.
| ANY DOSE ADJUSTMENTS FOR REQUIRED FOR PATIENTS WITH A HEPATIC OR A RENAL COMPROMISE?|| |
No special adjustments in dosages needed.
| CAN OMALIZUMAB BE ADMINISTERED TO A PREGNANT PATIENT?|| |
No studies are available in this regard, but omalizumab is a pregnancy category B drug and should be administered only if benefits overweigh risks.
| CAN OMALIZUMAB BE ADMINISTERED IN THE PEDIATRIC AGE GROUP?|| |
No studies are available in this regard with respect to its use in urticaria. It is approved in children 12 years and older.
| DOES OMALIZUMAB LEAD TO THE PRODUCTION OF ANTI OMALIZUMAB ANTIBODIES AS SEEN WITH OTHER BIOLOGICAL CAUSING DECREASE IN THE EFFICACY?|| |
Studies have reported that omalizumab does not lead to measurable anti-omalizumab antibodies as seen with other biologicals, and hence, retreatment with omalizumab can be effective and safe in patients with chronic urticaria who have previously benefitted from this treatment.
| HOW EFFECTIVE IS OMALIZUMAB IN ATOPIC DERMATITIS IN YOUR EXPERIENCE? WHAT ARE DOSAGE REGIMENS IN THIS CONDITION?|| |
Higher doses are needed in atopic dermatitis in the range of 300 mg twice a week. The response is variable.
| CAN OMALIZUMAB BE USEFUL IN URTICARIAL VASCULITIS?|| |
There are a few reports available in the literature where it has been found to be effective.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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Successful omalizumab treatment in chronic spontaneous urticaria is associated with lowering of serum IL-31 levels. J Eur Acad Dermatol Venereol 2016;30:454-5.
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