When to Use Xolair (Omalizumab) in Asthma?

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at NSU

A 50-year-old African American female (AAF) is referred to the allergy and immunology (A/I) clinic for severe persistent asthma and allergic rhinitis. She was seen at the clinic 3 years ago and was considered for omalizumab (Xolair) therapy at that time but never received insurance approval. She is currently managed with fluticasone/salmeterol (Advair) 500/50 BID, Combivent 4 times daily, montelukast (Singulair), fexofenadine (Allegra), and as needed albuterol/Xopenex. Her condition has declined over the past 2 years when she has experienced an increased frequency and severity of asthma exacerbations and hospitalizations, most recently requiring intubation for 4 days several months ago. She has done moderately well since this admission, not requiring oral corticosteriods or other hospitalizations. She currently reports needing her rescue inhaler 1-2 times/week, no nocturnal symptoms, mild exercise limitations due to her asthma, and currently feels that her asthma is not well controlled.

She had recently replaced all carpeting with tile floors. She continues to smoke cigarettes but is down to a reported 1-2 cigarettes/day. Her previous cat was removed from the home after skin testing 4 years ago revealed that she was sensitized but still has two dogs, which stay outside at all times. Previous skin test results from 4 years ago revealed positive reactions to multiple perennial and seasonal allergens and her most recent IgE was 634 (done 3 months ago).

Past medical history (PMH)

Asthma, hypertension (HTN), diabetes type 2 (DM2).

Medications

Albuterol, Duoneb, fexofenadine (Allergra), momethasone nose spray (Nasonex), Hyzaar, fluticasone/salmeterol (Advair), metformin (Glucophage), montelukast (Singulair), Combivent, Calcium-D, amlodipine (Norvasc), atorvastatin (Lipitor), Glipizide, Fosamax.

Physical examination

Stable vital signs (VSS), in non-apparent distress (NAD).
HEENT: conjunctiva non-injected, external ears normal, canals clear. TM's normal. Nose: moderate turbinate hypertrophy bilaterally with mild erythema of the mucosa noted. Lips, tongue normal. Oropharynx clear, no erythema.
CVS: Clear S1S2.
Chest: good aeration bilaterally with scattered end expiratory wheezes noted throughout all lung fields; no increased work of breathing noted on exam.
Extremities: no cyanosis, clubbing or edema (c/c/e).
Skin: no rashes or lesions.

Laboratory tests

PFT (spirometry): moderate obstruction with mild improvement post bronchodilator. "LLN" is the lower limit of normal for each value.

Figure 1. PFT (click to enlarge the image).

Skin testing results:
Allergen
1. Control: E = 0
2. Cat: E = 3+
3. Dog: E = 2+
4. Cockroach Mix: E = 0
5. Mite Df: E = 1+
6. Mite Dp: E = 0
7. Alternaria tenuis: E = 0
8. Aspergillus fumigatus: E = 0
9. Cladosporium: E = 0
10. Maple Mix: E = 0
11. Elm, American: E = 0
12. Hickory, Shagbark: E = 0
13. Oak, Black: E = 0
14. Ryegrass, Perennial: E = 4+
15. Timothy: E = 4+
16. Marsh Elder, Burweed: E = 4+
17. Ragweed, Short: E = 3+
18. Histamine: E = 3+

IgE = 634

What is the most likely diagnosis?

This patient has a severe persistent asthma with multiple recent hospitalizations and worsening asthma control despite appropriate use of high-dose inhaled corticosteroids, long acting beta agonists, and antileukotriene therapy. She currently has severe refractory asthma.

She continues to smoke which is a risk factor in addition to asthma for accelerated loss of lung function and disease progression, and she has manifested the potential for potentially life threatening exacerbations of asthma (recent intubation).

Is she a candidate for Xolair (omalizumab)?

Xolair (omalizumab) is a recombinant, DNA-derived, humanized IgG monoclonal antibody that binds selectively to human IgE on surface of mast cells and basophils.

She meets the requirements for initiating Xolair, including:
- severe refractory asthma
- IgE levels between 30-700
- evidence of sensitization to at least one perennial aeroallergen.

What are the risks and benefits of using Xolair (omalizumab)?

The benefits of Xolair include improved asthma control with decreased frequency and severity of exacerbations and may also lead to improved lung function over time.

Risks associated with Xolair include local and systemic reactions with each injection as well as an increased risk of malignancy compared with placebo. A causal relationship between omalizumab therapy and malignancy is unlikely [J Allergy Clin Immunol. 2012].

Injections must be given in a physician's office with a 2-hour observation period after the first injection and 30 minutes with each subsequent injections. Patients are also given an EpiPen to have on hand for 24 hours after each injection.

Adverse reactions from Xolair include:

1. Injection-site reaction, which has been reported in 45% of patients receiving Xolair, compared with 43% of patients exposed to control vehicle.

2. Anaphylaxis, which occurred within 2 hours of the first or subsequent administration in three of more than 4000 patients. These events included urticaria and throat and/or tongue edema. For this reason, she was informed that she would be required to wait two hours after initial dose of Xolair, then 30 minutes after each subsequent administration of this medication.

3. Malignancies were observed in 20 of 4127 (0.5%) of Omalizumab-treated patients, as compared with 5 of 2236 (0.2%) controls. A causal relationship between these malignant neoplasms and Omalizumab is unclear, since they were of various types and 60% of patients developed malignancy within 6 months of Xolair exposure. Efforts to further understand a possible relationship between Xolair and malignancy are continuing during post-marketing surveillance of Xolair. A causal relationship between omalizumab therapy and malignancy is unlikely [J Allergy Clin Immunol. 2012].

What happened?

The risks, benefits, and adverse events of Xolair were discussed with the patient, she expressed full understanding and agreed to proceed with treatment. Our office began to obtaining the necessary insurance approval.

Continued use of all current asthma medications was recommended and she was advised to stop smoking. Allergen avoidance measures were reviewed with the patient.

She was given a prescription for an EpiPen and was asked to have this filled by her first Xolair injection. Proper storage and use will be reviewed at that time.

What did we learn from this case?

Asthma is the most common chronic respiratory disease, affecting up to 10% of adults and 30% of children (JACI, 2011).

Xolair (omalizumab) is a subcutaneously administered monoclonal anti-IgE antibody that reduces free IgE concentrations and promotes downregulation of IgE receptors on basophils. It can be useful as an add-on therapy to inhaled corticosteroids in patients with severe asthma. Omalizumab reduced mean asthma exacerbations (ie, asthma attacks) per patient by 33%-75% during the stable-steroid phase and 33%-50% during the steroid-reduction phase.

Initial Xolair dose is dependent on serum IgE level and body weight. Serum IgE levels increase after start of therapy because of omalizumab-IgE complex formation and may remain high up to 1 year after stopping therapy; therefore, IgE levels should not be routinely checked. Patients may have false-negative skin prick test and RAST results.

On July 16, 2009, the U.S. Food and Drug Administration announced that it was conducting a safety review of omalizumab looking for a possible association between patients who use it and an increased risk of heart attack, abnormal heart rhythm, heart failure, and stroke.

Final diagnosis

Severe asthma with allergic rhinitis, sensitization to multiple perennial and seasonal aeroallergens and elevated IgE level make this patient a candidate to receive Xolair.



Severe asthma - differential diagnosis and management (click to enlarge the image).

References

Omalizumab: A Monoclonal Anti-IgE Antibody. Paul P. Belliveau, PharmD, MedGenMed Pulmonary Medicine, 01/27/2005.
FDA Orders Black Box Anaphylaxis Warning for Omalizumab (Xolair). Peggy Peck, MedPage Today, February 21, 2007.
Asthma. eMedicine, June 26, 2006.
Hypersensitivity Reactions, Immediate. eMedicine, Dec 13, 2004.
Omalizumab for Asthma. R. Strunk, G. Bloomberg. NEJM, June 22, 2006.
FDA Approves Omalizumab (Xolair), a Recombinant Anti-IgE Antibody, to Treat Moderate to Severe Allergic Asthma. T. Casale, AAAAI, 2003.
Delayed allergic reactions to omalizumab: Are patients reporting all cases? JACI, 03/2008.
Severe Asthma in Adults. Wenzel S. American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 149-160, (2005).
American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. Cox L, Platts-Mills TA, Finegold I, Schwartz LB, Simons FE, Wallace DV. J Allergy Clin Immunol. 2007 Dec;120(6):1373-7. Epub 2007 Nov 9.

Oral corticosteroids were withdrawn in 74% of severe asthma patients treated with omalizumab - Current Medical Research and Opinion, 2010.

Images

Mechanisms of action of omalizumab. JACI, 02/2008.
Delayed allergic reactions to omalizumab: Are patients reporting all cases? JACI, 03/2008.

Related reading

FDA is reviewing possible heart risks with asthma drug Xolair (omalizumab). AllergyNotes, 07/2009.

Response to omalizumab after 16 weeks is a predictor of continuing persistent response to omalizumab in asthmatics. Allergy 2011.

Omalizumab for Asthma. NEJM blog, 2011.

Randomized Trial of Omalizumab (Anti-IgE) for Asthma in Inner-City Children. NEJM, 2011.
"Super-omalizumab" new monoclonal XmAb7195 has 5-fold higher affinity for IgE, 400-fold higher affinity for FcγRIIb. JACI, 2012.

Published: 06/28/2007
Updated: 01/16/2012