Omalizumab (Xolair^®) is a monoclonal antibody that interferes with allergic response by binding to immuno-globulin E (IgE).  The drug received FDA approval in 2003 and is indicated for individuals 12 years of age and above with moderate to severe persistent asthma, who have shown reactivity to an allergen and whose symptoms are inadequately controlled with inhaled corticosteroids.

Medically Necessary:

Omalizumab (Xolair^®) is considered medically necessary for individuals with moderate to severe persistent asthma* who meet all of the following criteria:

• 12 years of age or older; and
• Symptoms are inadequately controlled with combination controller therapy (medium to high doses of inhaled corticosteroids plus long acting beta2-agonists or leukotriene modifiers), or cannot tolerate the medications; and
• Shows a positive skin test or in vitro reactivity to a perennial aeroallergen; and
• A forced expiratory volume in one second (FEV₁) less than 80% predicted; and
• A serum Immunoglobulin E (IgE) level equal to or greater than 30 IU/ml.

*As defined by the National Heart, Lung, and Blood Institute (2007 criteria for determining asthma severity should be applied to the situation before treatment or adequate control and severity should be assigned to the most severe category in which any feature occurs.):  (See Background section for further information.)

Severe persistent asthma:

• Symptoms throughout the day; OR
• Extremely limited normal activity; OR
• Nocturnal symptoms are frequent (often 7 times/week); OR
• FEV₁ or Peak Expiratory Flow (PEF) less than 60% predicted; OR
• Daily use of inhaled, short-acting, beta2-agonist for symptom control (can be several times/day); OR
• FEV₁ FVC (forced vital capacity) is reduced greater than 5% (see normal ranges below); OR
• Exacerbations requiring oral systemic corticosteroid use greater than or equal to 2 per year.

Moderate persistent asthma:

• Daily symptoms; OR
• Daily use of inhaled, short-acting, beta2-agonist; OR
• Somewhat limited activity; OR
• Nocturnal symptoms occur greater than 1 time a week but not nightly; OR
• FEV₁ or PEF is greater than 60% and less than 80% predicted; OR
• FEV₁^/FVC (forced vital capacity) is reduced 5% (see normal ranges below); OR
• Exacerbations requiring oral systemic corticosteroid use greater than or equal to 2 per year.

According to this NHLBI document, the following constitute the normal ranges by age for FEV₁^/FVC:

• 8-19 years of age – 85%;
• 20-39 years of age – 80%;
• 40-59 years of age – 75%;
• 60-80 years of age – 70%.

Investigational and Not Medically Necessary:

Omalizumab (Xolair^®) is considered investigational and not medically necessary for individuals who do not meet the criteria set forth above.

In June of 2003, the FDA approved Xolair^® omalizumab (Genentech, Inc., South San Francisco, CA jointly marketed with Novartis Pharmaceutical Corp., East Hanover, NJ), which is a monoclonal anti-IgE antibody.  This drug forms complexes with free IgE antibodies, thus preventing interactions between free IgE and cells containing substances, such as histamines, that lead to allergic symptoms.  Xolair^® is approved by the FDA for moderate to severe persistent asthmatics (age greater than or equal to 12 years old) who have a demonstrated sensitivity to a perennial aeroallergen, (e.g., dust mites, molds, animal dander, and cockroaches) and who have significant symptoms, despite inhaled corticosteroid treatment. 

The FDA approval was based, in part, on the results of three randomized, double blind, placebo-controlled multi-center trials, where the number of asthma exacerbations was the principal outcome.  The trials enrolled subjects 12 to 76 years old, with moderate to severe persistent asthma, (as defined by the National Heart Lung and Blood Institute [NHLBI]), a positive skin test reaction to a perennial aeroallergen and a total IgE level greater than 30 IU/ml.  The number of exacerbations was reduced in those receiving omalizumab, compared to the placebo group.  However, individuals whose FEV₁ was greater than 80% predicted at enrollment did not experience a reduction in exacerbations.

In 2007, the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma was issued with:

• A new focus on monitoring asthma control as the goal for asthma therapy and distinguishing between classifying asthma severity and monitoring asthma control.
• A new focus on impairment and risk as the two key domains of severity and control, and multiple measures for assessment.

According to this NAEPP document, (sponsored by the National Heart, Lung, and Blood Institute [NHLBI] of the National Institutes of Health [NIH]), the level of asthma severity is determined by assessment of both impairment and risk.  The degree of functional impairment domain is to be assessed by the affected individual or his/her caregiver by recalling symptoms (see lists below) within the previous 2–4 weeks and spirometry. Severity should be assigned to the most severe category in which any feature occurs.  The NAEPP document notes that, "At present, there are inadequate data to correspond frequencies of exacerbations with different levels of asthma severity. In general, more frequent and intense exacerbations, (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate greater underlying disease severity.  For treatment purposes, patients who had > 2 exacerbations requiring oral systemic corticosteroids in the past year may be considered the same as patients who have persistent asthma, even in the absence of impairment levels consistent with persistent asthma" (NAEPP, 2007).

Based on symptoms, the classification of asthma severity for severe persistent and moderate persistent asthma for individuals 12 years of age and older who are not currently taking long-term control medications is based on the presence of some of the following features:

Severe persistent asthma:

• Symptoms throughout the day; OR
• Extremely limited normal activity; OR
• Nocturnal symptoms are frequent (often 7 times/week); OR
• FEV₁ or PEF less than 60% predicted; OR
• Daily use of inhaled, short-acting, beta₂-agonist for symptom control (can be several times/day); OR
• FEV₁^/FVC (forced vital capacity) is reduced greater than 5% (see normal ranges below); OR
• Exacerbations requiring oral systemic corticosteroid use greater than or equal to 2 per year. 

Moderate persistent asthma:

• Daily symptoms; OR
• Daily use of inhaled, short-acting, beta₂-agonist; OR
• Somewhat limited activity; OR
• Nocturnal symptoms occur greater than 1 time a week but not nightly; OR
• FEV₁ or PEF is greater than 60% and less than 80% predicted; OR
• FEV₁^/FVC (forced vital capacity) is reduced 5% (see normal ranges below); OR
• Exacerbations requiring oral systemic corticosteroid use greater than or equal to 2 per year. 

According to this NHLBI document, the following constitute the normal ranges by age for FEV₁^/FVC:

• 8-19 years of age – 85%;
• 20-39 years of age – 80%;
• 40-59 years of age – 75%;
• 60-80 years of age – 70%.

These criteria for determining asthma severity are to be applied to the situation before treatment is initiated and before adequate control is achieved. The 2007 NAEPP Asthma guidelines recommend that Xolair may be considered as adjunctive therapy in Step 5 or 6 care of individuals with allergies and severe persistent asthma that is inadequately controlled with the combination of high-dose inhaled corticosteroids and long-acting beta₂-agonists (Level of Evidence: B NHLBI [NAEPP] Guidelines for the Diagnosis and Management of Asthma, 2007). 
Note: Please see the Definitions section for an explanation of Step 5 and 6 asthma care and also definitions of the NHLBI Levels of Evidence.

In 2009, the Global Initiative for Asthma^® (GINA) Global Strategy for Asthma Management and Prevention Report was updated.  This is a collaborative initiative of the NHLBI with the World Health Organization (WHO) which originally convened a workshop in 1993 and continues to present a comprehensive plan toward the management of asthma through the world wide dissemination of information on asthma care.  The 2009 update to the GINA Report revised its former classifications of asthma based on published evidence and consensus recommendations.  The clinical characteristics of asthma, (which is described as, "A working scheme based on current opinion and has not been formally validated"), are now classified according to "Controlled, partly controlled and uncontrolled asthma" on the basis of the intensity of treatment required to achieve good asthma control.  It is noted by the GINA collaborators that this updated classification system correlates well with the NAEPP guidelines (GINA, 2010).

In 2010, the GINA document was updated with the following information:

Consensus Recommendation --

For allergic patients with an elevated IgE not controlled on high dose inhaled glucocortico-steroids and a long acting B₂ -agonist and who continue to have exacerbations, a trial of omalizumab can be considered.  This recommendation is based on a modest response rate for the main endpoint, exacerbations and its high cost.

Role in therapy –

Anti-IgE (omalizumab) is a treatment option limited to patients with elevated serum levels of IgE.  Its current indication is for patients with severe allergic asthma who are uncontrolled on inhaled glucocorticosteroids (ICS), although the dose of concurrent treatment has varied in different studies. Improved asthma control is reflected by fewer symptoms, less need for reliever medications and fewer exacerbations.  Further investigations will likely provide additional clarification of the role of anti-IgE in other clinical settings…Withdrawal of glucocorticosteroids facilitated by anti-IgE therapy has led to unmasking the presence of Churg Strauss syndrome in a small number of patients. Clinicians successful in initiating steroid withdrawal using anti-IgE should be aware of this side effect (Wechsler, 2009).

Additional comments include a statement about use in children between 6 and 12 years of age as follows:

"Anti-IgE (omalizumab) has proven efficacy in children aged 6 to 12 years with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma."  This statement is based on the findings of available studies of omalizumab (Milgrim, 2001; Lemanske, 2002), as well as another study of omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. This randomized, double-blind, placebo-controlled trial enrolled children age 6 to less than 12 years with perennial allergen sensitivity and history of exacerbations and asthma symptoms, despite at least medium-dose ICSs.  Subjects were randomized 2:1 to receive omalizumab or placebo over a period of 52 weeks (24-week fixed-steroid phase followed by a 28-week adjustable-steroid phase).  A total of 627 subjects (omalizumab, n = 421; placebo, n = 206) were randomized, with efficacy analyzed in 576 (omalizumab, n = 384; placebo, n = 192). Over the 24-week fixed-steroid phase, omalizumab reduced the rate of clinically significant asthma exacerbations (worsening symptoms requiring doubling of baseline ICS dose and/or systemic steroids) by 31% versus placebo (0.45 vs. 0.64; rate ratio, 0.69; P = .007).  Over a period of 52 weeks, the exacerbation rate was reduced by 43% versus placebo (P < .001).  Over a period of 52 weeks, omalizumab had an acceptable safety profile with no difference in overall incidence of adverse events compared with placebo.  The authors concluded that add-on omalizumab is effective and well tolerated as maintenance therapy in children (6 to less than 12 years) with moderate-to-severe persistent allergic (IgE-mediated) asthma whose symptoms are inadequately controlled despite medium to high doses of ICSs (Lanier, 2009).

The GINA update also made the following comment about predicting responders to omalizumab --

"A substantial number of children with difficult asthma will have higher IgE levels than the upper limit of IgE recommended for therapy (1,300 IU).  It is unknown if these patients will still benefit from omalizumab therapy.  There are no tests which can currently be recommended, in order to predict who will respond" (GINA, 2010).

Xolair^® is administered through subcutaneous injection in a physician's office.  The individual is then monitored for hypersensitivity reactions including the possibility of anaphylaxis.  Reported side effects of Xolair^® were similar to placebo in most instances, but most common adverse events reported during clinical trials included injection site reactions, viral infections, upper respiratory tract infections, sinusitis, headache, and pharyngitis.  During a one-year follow-up of over 6300 subjects, 0.5% of subjects receiving Xolair^® reported various malignancies, as compared to 0.2% of subjects in the control groups.

In February 2007, the FDA issued an 'Alert' regarding Xolair^® following receipt of reports of serious, life-threatening allergic reactions (anaphylaxis) after treatment with omalizumab (Xolair^®).  The FDA reported that usually these reactions occurred within two hours of receiving a Xolair^® subcutaneous injection.  However, these reports also included individuals who had delayed anaphylaxis, with onset two to 24 hours or even longer, after receiving Xolair^® treatment.  The FDA added that anaphylaxis may occur after any dose of Xolair^® (including the first dose), even if the individual had no allergic reaction to the first dose, and has also been reported in individuals beyond one year of regularly scheduled treatment (Xolair Package Labeling, July 2007).  Based on reports from approximately 39,500 subjects, anaphylaxis following Xolair^® treatment occurred in at least 0.1% of treated people.  Additional post-marketing results indicate the incidence to be 0.2% based on reports from use in 57,300 subjects (Xolair Package Labeling, July 2007).  The FDA advised that Xolair-treated subjects should be observed by health care professionals for at least two hours after Xolair^® is given.  Individuals taking Xolair should also be informed of the signs and symptoms of anaphylaxis and instructed to seek immediate medical care should symptoms occur. Xolair is contraindicated for use and should be discontinued in those individuals who have experienced a severe hypersensitivity reaction.  The 'Alert' noted that this information reflected the FDA's preliminary analysis of data concerning this drug.  The FDA is considering, but has not reached, a final conclusion about this information and intends to update the public when additional information or analyses become available (FDA: as of February 21, 2007).

On July 16, 2009 the FDA issued an "Early Communication about an Ongoing Safety Review of Omalizumab (marketed as Xolair)" which is excerpted as follows:

The FDA is evaluating interim safety findings from an ongoing study of Xolair (omalizumab) that suggests an increased number of cardiovascular and cerebrovascular adverse events in a group of patients using Xolair compared to a group of patients not given the drug (control group)… The ongoing study, titled Evaluating the Clinical Effectiveness and Long-Term Safety in Patients with Moderate to Severe Asthma (EXCELS), is an observational study of approximately 5,000 Xolair treated patients and a control group of approximately 2,500 non-Xolair treated patients.  The primary objective of the EXCELS study is to assess the long-term safety profile of Xolair in patients followed for 5 years. Study patients are 12 years of age and older with moderate to severe persistent asthma and who have a positive skin test or blood test for an aeroallergen. The interim data, submitted by the manufacturer of Xolair (Genentech), suggests a disproportionate increase in ischemic heart disease, arrhythmias, cardiomyopathy and cardiac failure, pulmonary hypertension, cerebrovascular disorders, and embolic, thrombotic and thrombophlebitic events in patients treated with Xolair, compared to the control group of patients not given the drug. The FDA has not made any conclusions regarding these data. The Agency is working with Genentech to obtain further information and will continue to review the strengths and limitations of these interim results. For example, since EXCELS is an observational study, there could be differences in underlying risk factors for cardiovascular and cerebrovascular events between the two study groups. The Agency will communicate any new findings when its analysis of the interim safety data is complete. The EXCELS study is ongoing and final results are not expected until 2012…The FDA is not recommending any changes to the prescribing information for Xolair and is not advising patients to stop taking Xolair at this time.  Until the evaluation of the EXCELS study is completed, healthcare providers and patients should be aware of the risks and benefits described in the prescribing information, as well as the new information from the ongoing EXCELS study that may suggest a risk of cardiovascular and cerebrovascular adverse events (FDA, 2009). 

Updated information regarding this study was not posted on the FDA web site as of June, 2011.

In 2009, the FDA convened a meeting of the Pulmonary-Allergy Drugs Advisory Committee of the Center for Drugs Evaluation and Research to review the safety and efficacy of omalizumab for the treatment of asthma in children 6-11 years of age with moderate to severe persistent asthma whose symptoms are inadequately controlled with inhaled corticosteroids.  The following summarizes the findings reviewed by this advisory committee:

Efficacy Findings:

1. Statistically-significant benefit in primary end- point rate of exacerbations (protocol-defined);
2. No consistent effect on supporting secondary end-points:
   Steroid-sparing effect, diminished use of rescue medications, rate of medical encounters, asthma symptoms,
3. Clinical relevance unclear as rate of exacerbations low:
   No exacerbations: 64 % Xolair vs. 58% Placebo,
   Number needed to treat: 2.34 (1.30, 11.26) Patient-Years.

Safety Findings:

1. Short-term data demonstrates Xolair is well tolerated in children 6 to 12 years old;
2. Two cases each of anaphylaxis and malignancy, not related to omalizumab;
3. Asthma Safety Database (n = 926; 624 exposed during placebo-controlled trials):
   1 year exposure (n= 292),
   6 month exposure (n= 583).

Note: The number treated may not be sufficient to detect anaphylaxis or malignancy if rates are in children.

The FDA Advisory Committee summarized its review determination as follows and added this information to the July 2010 updated Prescription Information for omalizumab:

Considering the risk of anaphylaxis and malignancy seen in Xolair-treated patients greater than or equal to 12 years old and the modest efficacy of Xolair in the pivotal pediatric study, the risk-benefit assessment does not support the use of Xolair in patients 6 to < 12 years of age. Although patients treated with Xolair in these two studies did not develop anaphylaxis or malignancy, the studies are not adequate to address these concerns because patients with a history of anaphylaxis or malignancy were excluded, and the duration of exposure and sample size were not large enough to exclude these risks in patients 6 to < 12 years of age. Furthermore, there is no reason to expect that younger pediatric patients would not be at risk of anaphylaxis and malignancy seen in adult and adolescent patients with Xolair (FDA, 2010).

At the present time, there is insufficient evidence to demonstrate the safety and effectiveness of Xolair^® for off-label uses (Bez, 2004; Kanu, 2008; Pinto, 2010; Ricci, 2009; Zirbes, 2008).

Asthma is a respiratory disorder characterized by increased responsiveness of the trachea and bronchi to various stimuli, resulting in the narrowing of the airways, along with mucous secretion.  This airway hyper-responsiveness is reversible either spontaneously or through therapy.  The symptom triad includes wheezing, cough, and dyspnea, which can vary widely in severity and duration, although a typical attack does not last for more than several hours.  Attacks can be triggered by a number of factors, including allergic triggers, smoke and pollution, cold air, colds and other respiratory infections, exercise, and strong emotions. 

Asthma is a major chronic health problem, affecting a total of about 17 million Americans.  Approximately 1.5 million emergency room visits and 500,000 hospitalizations occur annually in the United States, as a result of asthma exacerbations, including 5,000 deaths.  Treatment for acute exacerbations usually includes an inhaled beta-receptor agonist, such as albuterol and, when necessary, bursts of corticosteroid therapy.  For chronic control, inhaled corticosteroids, leukotriene inhibitors, long-acting beta-agonists, theophylline, and, in treatment-resistant cases, oral corticosteroids may be utilized.

Anaphylaxis:  A very severe allergic or immunologic response that leads to the constriction of the bronchial tree in the lungs, dilation of capillaries and eventually shock.

Asthma:  Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role: in particular, mast cells, eosinophils, neutrophils (especially in sudden onset, fatal exacerbations, occupational asthma, and patients who smoke), T lymphocytes, macrophages, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of coughing (particularly at night or early in the morning), wheezing, breathlessness, and chest tightness. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment (NAEPP, 2007).

Churg-Strauss syndrome (also known as allergic granulomatosis and allergic angiitis):  A disorder marked by blood vessel inflammation. This inflammation can restrict blood flow to vital organs and tissues, sometimes permanently damaging them. It involves mainly the blood vessels of the lungs, beginning as a severe type of asthma, gastrointestinal system, and peripheral nerves, but also affects the heart, skin and kidneys. It is a rare disease that is non-inheritable and non-transmissible.

Dyspnea:  Shortness of breath, which is also described as subjective difficulty or distress in breathing.

FEV₁ (forced expiratory volume in 1 second):  A measure of airway obstruction determined using spirometry. Individual FEV₁ values are compared to predicted values based on age, height, sex and race.

PEF (peak expiratory flow): PEF is often described as a percent of personal best measurement.  Personal best PEF is the highest PEF value attained after 2 to 3 weeks of testing when asthma is in good control.

Pulmonary function tests (PFTs):  A battery of respiratory tests that include spirometry and other tests to determine lung functional parameters, such as lung capacity and forced expiratory volume in one second (FEV₁).

Step 5 Care, long-term control medications: (According to the updated National Asthma Education and Prevention Program [NAEPP] Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma from the National Heart Lung and Blood Institute, 2007):

• High-dose inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) is the preferred treatment (Evidence B);
• Omalizumab may be considered at this step for patients who have sensitivity to relevant perennial allergens (e.g., dust mites, cockroach, cat, or dog) (Evidence B);
• Clinicians who administer omalizumab are advised to be prepared and equipped for the identification and treatment of anaphylaxis that may occur, to observe patients for an appropriate period of time following each omalizumab injection (the optimal length of the observation is not established), and to educate patients about the risks of anaphylaxis and how to recognize and treat it if it occurs (e.g., using prescription auto injectors for emergency self-treatment, and seeking immediate medical care) (see "FDA Warning/Regulatory Alert" field);
• Consultation with an asthma specialist is recommended for patients who require this step of therapy (Evidence D).

Step 6 Care, long-term control medications: (NHLBI, 2007)

• Add oral corticosteroids to step 5 therapy. Patients who are not controlled on step 5 therapy may require regular oral corticosteroids to achieve well-controlled asthma.

Levels of Evidence:  The system used to describe the levels of evidence within the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (from the National Heart Lung and Blood Institute) is as follows:

Evidence Category A: Randomized controlled trials (RCTs), rich body of data
Evidence is from end points of well-designed RCTs that provide a consistent pattern of findings in the population for which the recommendation is made.  Category A requires substantial numbers of studies involving substantial numbers of participants.

Evidence Category B: RCTs, limited body of data
Evidence is from end points of intervention studies that include only a limited number of patients, post hoc or subgroup analysis of RCTs, or meta-analysis of RCTs.  In general, category B pertains when few randomized trials exist, they are small in size, they were undertaken in a population that differs from the target population of the recommendation, or the results are somewhat inconsistent.

Evidence Category C: Nonrandomized trials and observational studies
Evidence is from outcomes of uncontrolled or nonrandomized trials or from observational studies.

Evidence Category D: Panel consensus judgment
This category is used only in cases where the provision of some guidance was deemed valuable, but the clinical literature addressing the subject was insufficient to justify placement in one of the other categories.  The panel consensus is based on clinical experience or knowledge that does not meet the criteria for categories A through C
(Jadad, 2000).

The following codes for treatments and procedures applicable to this document are included below for informational purposes.  Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy.  Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

 When services may be Medically Necessary, when criteria are met: 

When services are Investigational and Not Medically Necessary:
For the procedure and diagnosis codes listed above when criteria are not met, for all other diagnoses not listed; or when the code describes a procedure indicated in the Position Statement section as investigational and not medically necessary.

Future ICD-10 coding (effective 10/01/2013)
A draft of ICD-10 Coding related to this document, as it might look today, is available for reference and comments at: Appendix 1: Future ICD-10 coding

Peer Reviewed Publications:

1. Ankerst J, Nopp A, Johansson SG, et al.  Xolair is effective in allergics with a low serum IgE level.  Int Arch Allergy Immunol. 2010; 152(1):71-74.
2. Berger W, Gupta N, McAlary M, Fowler-Taylor A. Evaluation of long-term safety of the anti-IgE antibody, omalizumab, in children with allergic asthma. Ann Allergy Asthma Immunol. 2003; 91(2):182-188.
3. Bez C, Schubert R, Kopp M, et al.  Effect of anti-immunoglobulin E on nasal inflammation in patients with seasonal allergic rhinoconjunctivitis.  Clin Exp Allergy. 2004; 34(7):1079-1085.
4. Brownell J, Casale TB. Anti-IgE therapy. Immunol Allergy Clin North Am. 2004; 24(4):551-568.
5. Buhl R, Hanf G, Soler M, et al. The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma. Eur Respir J. 2002; 20(5):1088-1094.
6. Buhl R, Soler M, Matz J, et al. Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma. Eur Respir J. 2002; 20(1):73-78.
7. Busse, W.  Anti-immunoglobulin E (omalizumab) therapy in allergic asthma. Am J Respir Crit Care Med. 2001; 164(8 Pt 2):S12-S17.
8. Busse, W, Corren J, Lanier, BQ, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001; 108(2):184-190.
9. Busse WW, Morgan WJ, Gergen PJ, et al.  Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children.  N Engl J Med. 2011; 364(11):1005-1015.
10. Casale TB, Comdemi J, LaForce C, et al.  Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA. 2001; 286(23):2956-2967.
11. Chervinsky P, Casale T, Townley R, et al.  Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis.  Ann Allergy Asthma Immunol. 2003; 91(2):160-167.
12. Corren J, Casale T, Deniz Y, Ashby M. Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol. 2003; 111(1):87-90.
13. Finn A, Gross G, van Bavel J, et al. Omalizumab improves asthma-related quality of life in patients with severe allergic asthma. J Allergy Clin Immunol. 2003; 111(2):278-284.
14. Holgate S, et al. Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortality.  Curr Med Res Opin. 2001; 17(4):233-240.
15. Jadad AR, Moher M, Browman GP, et al. Systematic reviews and meta-analyses on treatment of asthma:  critical evaluation. BMJ. 2000; 320(7234):537-540.
16. Johansson SG, Nopp A, Oman H, et al.  The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair) treatment.  Allergy. 2009; 64(10):1472-1477.
17. Kanu A, Patel K.  Treatment of allergic bronchopulmonary aspergillosis (ABPA) in CF with anti-IgE antibody (omalizumab).  Pediatr Pulmonol. 2008; 43(12):1249-1251.
18. Kulus M, Hébert J, Garcia E, et al.  Omalizumab in children with inadequately controlled severe allergic (IgE-mediated) asthma.  Curr Med Res Opin. 2010; 26(6):1285-1293.
19. Lanier B, Bridges T, Kulus M, et al.  Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma. J Allergy Clin Immunol. 2009; 124:1210-1216.
20. Lanier BQ, Corren J, Lumry W, et al. Omalizumab is effective in the long-term control of severe allergic asthma. Ann Allergy Asthma Immunol. 2003; 91(2):154-159.
21. Lemanske RF Jr, Nayak A, McAlary M, et al. Omalizumab improves asthma-related quality of life in children with allergic asthma. Pediatrics. 2002; 110(5):E55-E59.
22. Milgrom H, Berger W, Nayak A, et al.  Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001; 108(2):E36-E45.
23. Negro RW, Guerriero M, Micheletto C, et al.  Changes in Total IgE Plasma Concentration Measured at the Third Month during Anti-IgE Treatment Predict Future Exacerbation Rates in Difficult-to-Treat Atopic Asthma: A Pilot Study.  J Asthma. 2011; 48(5):437-441.
24. Pinto JM, Mehta N, DiTineo M, et al.  A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis.  Rhinology. 2010; 48(3):318-324.
25. Poole JA, Matangkasombut P, Rosenwasser LJ. Targeting the IgE molecule in allergic and asthmatic diseases: review of the IgE molecule and clinical efficacy. J Allergy Clin Immunol. 2005; 115(3):S376-S385.
26. Ricci G, Dondi A, Patrizi A, Masi M. Systemic therapy of atopic dermatitis in children.  Drugs. 2009; 69(3):297-306.
27. Rolinck-Werninghaus C, Hamelmann E, Keil T, et al. The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children. Allergy. 2004; 59(9):973-979.
28. Soler M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid    requirement in allergic asthmatics. Eur Respir J. 2001; 18(2):254-261.
29. Strunk RC, Bloomberg GR. Omalizumab for asthma. N Engl J Med. 2006; 354(25):2689-2695.
30. Wagelie-Steffen AL, Kavanaugh AF, Wasserman SI. Biologic therapies for the treatment of asthma. Clin Chest Med. 2006; 27(1):133-147.
31. Wechsler ME, Wong DA, Miller MK, et al.  Churg-strauss syndrome in patients treated with omalizumab.  Chest. 2009; 136(2):507-518.
32. Zirbes JM, Milla CE.  Steroid-sparing effect of omalizumab for allergic bronchopulmonary aspergillosis and cystic fibrosis.  Pediatr Pulmonol. 2008; 43(6):607-610.

Government Agency, Medical Society, and Other Authoritative Publications:

1. Brottman GM.  Health Information Technologies and Asthma "HIT Asthma" Improving Asthma Care in an Integrated Safety Net Institution Through a Commercially Available Electronic Medical Record.  Hennepin County Medical Center.  Available at:  http://www.icsi.org/icsi_colloquium_-_2009_/using_health_information_technology.html.  Accessed on June 19, 2011.
2. Canadian Agency for Drugs and Technologies in Health (CADTH), formerly the Canadian Coordinating Office for Health Technology Assessment (CCOHTA). Omalizumab as Add-on Therapy to Inhaled Steroids for Asthma. Issues in Emerging Health Technologies Bulletin, Issue 58. June 2004. Ottawa, ON. Available at:  http://www.cadth.ca/media/pdf/282_omalizumab_cetap_e.pdf.  Accessed on June 19, 2011.
3. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA).  Bethesda, MD.  Update 2010. Available at:  http://www.ginasthma.org/guidelines-gina-report-global-strategy-for-asthma.html.  Accessed on June 19, 2011.
4. Lang DM, Portnoy JM, Schuller DE, et al. Attaining optimal asthma control: A practice parameter.  Developed by the Joint Task Force on Practice Parameters representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology.  J Allergy Clin Immunol. 2005; 116:S3-11.  Available at: http://www.allergyparameters.org/file_depot/0-10000000/30000-40000/30326/folder/73825/2005+Asthma+Control.pdf.  Accessed on June 20, 2011.
5. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. NIH Publication Number 08-5846. October 2007. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.pdf. or   Accessed on June 19, 2011.
6. National Institute for Health and Clinical Excellence (NICE). Omalizumab for severe persistent allergic asthma. Technology Appraisal Guidance No. 133. London, UK: NICE; November 2007.  Reviewed August 2010.  Available at:  http://www.nice.org.uk/nicemedia/live/11894/38392/38392.pdf.  Accessed on June 19, 2011.
7. National Institute for Health and Clinical Excellence (NICE). Omalizumab for the treatment of severe persistent allergic asthma in children aged 6 to 11 years.  Technology Appraisal Guidance No. 201.  London, UK:NICE; October 2010.  Available at:  http://www.nice.org.uk/nicemedia/live/13256/51345/51345.pdf.  Accessed on June 19, 2011.
8. Omalizumab (Xolair^®) In: DrugPoints System [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Available at: http://www.thomsonhc.com. Accessed on June 20, 2011.
9. Pelligrino R, Viegi G, Brusasco V, et al.  American Thoracic Society and European Respiratory Society Task Force.  Standardization of lung function testing. Eur Respir J. 2005; 26:948–968.
10. U.S. Food and Drug Administration (FDA).  Center for Drug Evaluation and Research. FDA Alert: Omalizumab (Xolair^®) Information. February, 2007.  Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm126456.htm.  Accessed on June 20, 2011.
11. U.S. Food and Drug Administration (FDA).  Early Communication about an Ongoing Safety Review of Omalizumab (marketed as Xolair). July 16, 2009.  Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm172218.htm.  Accessed on June 19, 2011.
12. U.S. Food and Drug Administration (FDA). Prescribing information.  Omalizumab (Xolair^®) BLA 103976/5102. July 2007. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/103976s5102lbl.pdf.  Accessed on June 20, 2011.
13. Walker S, Monteil M, Phelan K, et al. Anti-IgE for chronic asthma in adults and children.  Cochrane Database Syst Rev. 2006; (2):CD003559.  Available at:  http://www2.cochrane.org/reviews/en/ab003559.html.  Accessed on June 19, 2011.

1. National Institutes of Health, National Heart, Lung, and Blood Institute. Information for patients and the public about asthma. Available at: http://www.nhlbi.nih.gov/health/public/lung/index.htm#asthma. Accessed on June 19, 2011.
2. National Institutes of Health (NIH).  National Asthma Control Initiative (NACI).  Information available at:  http://www.nhlbi.nih.gov/health/prof/lung/asthma/naci/.  Accessed on June 19, 2011.
3. National Institutes of Health (NIH).  National Institute of Environmental Health Sciences.  Updated information on asthma control and prevention.  May 3 2010.  Available at:   http://www.niehs.nih.gov/news/releases/2010/asthma.cfm.  Accessed on June 19, 2011.
4. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. Publications and Information Products. Available at: http://www.cdc.gov/nchs/products.htm. Accessed on June 19, 2011.
5. U.S. Food and Drug Administration (FDA).  Additional labeling history.  Available at:  http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory. Accessed on June 20, 2011.
6. U.S. Food and Drug Administration (FDA). Meeting of the Pulmonary-Allergy Drugs Advisory Committee.  Center for Drugs Evaluation and Research.  Safety and efficacy of Omalizumab for treatment of asthma in patients 6-11 years of age with moderate to severe persistent asthma whose symptoms are inadequately controlled with inhaled corticosteroids.  November 18, 2009.  Available at:  http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/UCM194068.pdf.  Accessed on June 19, 2011.
7. Xolair^®, omalizumab for subcutaneous use [package insert]. South San Francisco, CA: Genentech, Inc.; July 2010. Available at: http://www.gene.com/gene/products/information/immunological/xolair/insert.jsp . Accessed on June 19, 2011.

Allergic Asthma
Omalizumab
Persistent Asthma
Xolair^® 

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.