MEDICAL POLICY

POLICY
RELATED POLICIES
POLICY GUIDELINES
DESCRIPTION
SCOPE
BENEFIT APPLICATION
RATIONALE
REFERENCES
CODING
APPENDIX
HISTORY

Omalizumab (Xolair®)

Number 5.01.513

Effective Date June 9, 2015

Revision Date(s) 06/09/15; 05/12/15; 05/12/14; 02/10/14; 03/11/13; 02/14/12; 02/08/11; 12/08/09; 10/14/08; 11/13/07; 10/10/06; 10/11/05; 09/14/04; 01/01/04; 08/12/03

Replaces N/A

Policy

Omalizumab (Xolair®) may be considered medically necessary for the following FDA-approved indications:

Severe Persistent Asthma

Adults and adolescents (12 years of age and above) with severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen, and who also meet the following criteria:

  • An allergy, immunology or pulmonary specialist has evaluated the patient and all of the following are documented in the medical record:
  • Severe allergic asthma (FEV1 40-80% predicted), AND
  • Total serum IgE 30-700 IU/ml AND
  • Daily use of inhaled corticosteroid (ICS) and long-acting beta agonist is required AND
  • Positive skin test or RAST (when skin test is not appropriate) to a perennial aeroallergen (i.e., dust mite, cockroach, dog, cat or molds).
  • Omalizumab dose should be less than or equal to 750mg every four weeks, based on serum IgE and body weight according to the manufacturer’s dosing table.
  • The initial approval is for a 6 month trial period.
  • Subsequent approvals require chart notes that show efficacy in any of the following parameters:
  • Decrease in requirement for oral steroids, exacerbation frequency, ER and urgent care visits, hospitalizations.
  • Decrease in frequency and severity of asthma symptoms.
  • Increase in quality of life measures and ability to perform activities of daily living.

Severe Chronic Idiopathic Urticaria

Adults and adolescents (12 years of age and above) with moderate to severe chronic idiopathic urticaria who remain symptomatic despite treatment with first line agents, when the following criteria are met:

  • An allergist, immunologist or dermatologist has evaluated the member and documented the following in the medical record:
  • No evidence of another cause of the urticarial reaction.
  • At least 3 months of symptoms including chronic urticaria, itching, hives or angioedema.
  • Failure to respond to at least any two of the following therapeutic regimens (unless contraindicated):
  1. Two or more H1 antihistamines in high doses (2-3 times normal dosing).
  2. One H1 inhibitor used in combination with any one or more of the following: an H2 antihistamine, oral corticosteroids, or Leukotriene modifiers.
  • The initial trial of therapy is for 12 weeks, and subsequent approval requires documentation of improved symptoms (second approval for 12 months).
  • Usual dosing is 150- 300 mg every four weeks.
  • Patients need to continue a low dose of H1 antihistamines.
  • Some patients may be able to adjust dose or interval (i.e., to 6 weeks) once they have been stable for four months or longer.

Omaluzimab has not been FDA approved for use in children under the age of 12, although is approved for children beginning at age 6 in the European Union. There has been one study suggesting efficacy in children younger than age 12. Use for individuals less than age 12 years may be covered on an individual basis depending on the individual member needs when there is severe persistent asthma, not-responsive to all standard therapies, with informed consent by the responsible adult on behalf of the child.

Omaluzimab is considered investigational for all other uses including , but not limited to the following:

  • Allergic rhinitis,
  • Atopic dermatitis,
  • Other IgE-mediated allergic conditions not listed in this document,
  • Peanut and other food allergies, and
  • Latex allergy.
  • Bullous pemphigoid
  • Eosinophilic gastrointestinal disorders

Related Policies

2.01.500

Allergy Testing

Policy Guidelines

 

Drug Class

Drug Names

Inhaled corticosteroids

Asmanex® (mometasone furoate), Flovent® HFA (fluticasone propionate), QVAR® (beclomethasone dipropionate HFA)

Long Acting Bronchodilators

Foradil® Aerolizer (formoterol fumarate), Severent® Diskus (salmeterol xinafoate)

H1 Antihistamines

Bromopheniamine, chlorophenriamine ( Chlor-Trimeton), clemastine (Tavist), cyproheptadine ( periactin), debrompheniramine, dexochlorpheniramine, diphenhydramine (Benadryl), hydroxyzine (Vistaril), cetirizine (Zyrtec), desoloratidine (Clarinex), fexofenadine (Allegra), loratidine (Claritin)

H2 Antihistamines

ranitidine, famotidine, nizatidine, cimetidine

Combination Long-acting Bronchodilator and Corticosteriod

Advair® (fluticasone/salmeterol), Symbicort® (budesonide/fomoterol fumarate)

Oral Corticosteroids

methylprednisolone, prednisone, prednisolone

Leukotriene Modifiers

Singulair® (montelukast sodium), Accolate® (zafirlukast)

Other anti-inflammatory medications

Cyclosporine, dapsone, methotrexate, sulfasalazine, corticosteroids

H1 and H2 Antihistamines (Only dosing for adults and children > or = 12 years is included in the following table [according to the current Xolair labeling]).

Drug Class

Drug Name

Standard Drug Dosage

H1

Brompheniramine (J-Tan PD®: 1mg/mL (30mL); Respa-BR®: 11 mg ER tablet)

Adult dosing varies depending on product type/combination.

Some combination products contain 2mg per 5 mL of the brompheniramine Maleate component, with standard dosing for adults and children 12 years and older of 10mL every 4 hours (i.e. 4mg of brompheniramine component every 4 hours).

H1

Chlorpheniramine (Chlor-Trimeton® + multiple other brand names)

Adult Immediate Release:

4mg every 4 to 6 hours; NTE 24mg/24 hours.

Adult Extended Release:

12mg every 12 hours; NTE 24mg/24 hours.

Children Immediate/Extended Release:

> or = 12 years: see adult dosing above.

H1

Clemastine (Tavist®; Dayhist®)

Adult: 1.34mg (1mg base*) twice daily to 2.68mg three times daily; NTE 8.04mg/day (6mg base).

OTC labeling: 1.34mg (1mg base*) twice daily; NTE 2mg base/24 hours.

Children > or = 12: see adult dosing above.

H1

Cyproheptadine (Periactin®)

Adult: 4 to 20mg daily divided every 8 hours (NTE: 0.5mg/kg/day). Some patients may require up to 32mg daily for optimal symptom management.

Children 7 to 14 years: 4mg every 8 to 12 hours (NTE: 16mg daily).

Children > or = 15 years: start with 4mg every 8 hours; range 12 to 16mg/day. S ome patients may require up to 32mg; Max daily dose: 0.5mg/kg/day.

H1

Dexchlorpheniramine (Polaramine®)

Adult: 2mg every 4 to 6 hours.

Children > or = 12 years: see adult dosing above.

H1

Diphenhydramine (Benadryl®)

Adult Oral: 25 to 50mg ever 4 to 8 hours, max: 300mg daily.

Adult IM/IV: 10 to 50mg per dose; single doses up to 100mg may be used; NTE: 400mg daily.

Children > or = 12 years: see adult dosing above.

H1

Hydroxyzine (Vistaril®)

Adult: 25mg three to four times daily.

Children > or = 6 years: 50 to 100mg daily in divided doses.

H1

Cetirizine (Zyrtec®)

Adult: 5 to 10mg once daily; Max: 10mg daily.

Children > or = 6 years to adults: 5 to 10 mg/day as a single dose or divided into 2 doses.

H1

Desloratadine (Clarinex®)

Adult: 5mg once daily.

Children > or = 12 years: see adult dosing above.

H1

Fexofenadine (Allegra®)

Adult: 60mg twice daily OR 180mg once daily.

Children > or = 12 years: see adult dosing above.

H1

Loratadine (Claritin®)

10mg once daily or 5mg twice daily.

Children > or = 6 years: see adult dosing above.

H2

Ranitidine (Zantac®)

**Dosing for adults and children > or = 12 years depends on the indication and may vary. Dosing for common indications is as follows:

Adult: 150mg twice daily or 300mg once before bedtime

Children > or= 12 years in the setting of heartburn prophylaxis: 75mg per day; Max 150mg/24 hours. Treatment (vs. maintenance) dosage can go up to adult dosage.

H2

Famotidine (Pepcid®)

**Dosing for adults and children > or = 12 years depends on the indication and may vary. Dosing for common indications is as follows:

Adult: 20mg twice daily or 20 to 40mg once before bedtime.

Children > or = 12 years: see adult dosing above.

H2

Nizatidine (Axid®)

**Dosing for adults and children > or = 12 years depends on the indication and may vary. Dosing for common indications is as follows:

Adult: 150mg twice daily or 300mg once before bedtime.

Children > or = 12 years: see adult dosing above.

H2

Cimetidine (Tagamet®)

**Dosing for adults and children > or = 12 years depends on the indication and may vary. Dosing for common indications is as follows:

Adult: 400mg twice daily or 400 to 800mg once before bedtime.

Children > or = 12 years: see adult dosing above.

*Note: dosage differs depending on clemastine base versus clemastine fumarate formulation.

**Note: dosage differs depending on indication, and if therapy is used for prophylaxis versus active treatment vs. maintenance. Please double check dosages provided in this table based on the case-specific information.

Sources:

  1. UpToDate: http://www-uptodate-com.offcampus.lib.washington.edu/contents/chlorpheniramine-drug-information?source=search_result&search=chlorpheniramine+adult&selectedTitle=1%7E62
  2. Cleveland Clinic: http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/allergy/urticaria-and-angioedema/Default.htm

Description

Omalizumab is a recombinant, humanized construct of murine antibody MaE11 directed against human Immunoglobulin E (IgE). The critical amino acids responsible for the binding of the murine monoclonals to IgE were engrafted onto a human Immunoglobulin GR1R (IgGR1R) subclass framework to yield a humanized antibody with the properties of the selected murine monoclonal. The antibody has a molecular weight of approximately 149 kilo-daltons and is produced by a Chinese hamster ovary cell suspension culture in a nutrient medium containing the antibiotic gentamicin.

Omalizumab inhibits the binding of IgE to the high-affinity IgE receptor (FcRI) on the surface of mast cells and basophils. Reduction in surface-bound IgE on FcRI-bearing cells limits the degree of release of mediators of the allergic response. Treatment with omalizumab also reduces the number of FcRI receptors on basophils in atopic patients.

Maintenance Therapy of Asthma

Asthma is a chronic airway disorder that affects an estimated 17 million Americans. About 10 million of these have allergic asthma, mediated by a cascade in which IgE is bound to high-affinity FcRI receptors on the surface of basophils and mast cells, and is cross-linked by an allergen that results in the degranulation of these effector cells and the release of inflammatory mediators, such as histamine and leukotrienes. These mediators then produce the symptoms of asthma, as well as other related conditions such as allergic rhinitis, atopic dermatitis and anaphylaxis. The severity of the response varies from trivially annoying to immediately life-threatening. As their common mechanism would predict, these diseases share overlapping populations.

Treatment with anti-inflammatory drugs such as inhaled corticosteroids can reverse some of these processes; however, successful response often requires weeks to achieve and sometimes a complete reversal is not achieved, even with optimal combinations of steroids, long-acting beta agonists and other agents. A smaller percentage of patients may have persistent airflow limitations for which no current therapy has been found to be effective (steroid-resistant asthma). The paradigm of asthma has been expanded from bronchospasm and airway inflammation to include airway remodeling in some patients. The concept that asthma may be a continuum of these processes that can lead to moderate and severe persistent disease is of critical importance to understanding this disease’s pathogenesis and pathophysiology.

Since the asthma patient population is heterogeneous, successful maintenance treatment requires an individualized regimen. Current guidelines suggest that patients with chronic persistent asthma be started on an inhaled corticosteroid. For patients with moderate to severe symptoms, a long-acting inhaled beta agonist (salmeterol or formoterol) is generally initiated at the same time as the corticosteroid. Patients with mild symptoms should receive a beta agonist if they fail to achieve full response with a corticosteroid. Other agents such as leukotriene modifiers and theophylline may be added. Omalizumab now offers an additional therapeutic option for patients who have not achieved control with these strategies.

Scope

Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer services representative to determine whether there are any benefit limitations applicable to this service or supply. This medical policy does not apply to Medicare Advantage.

Benefit Application

Xolair® is an injectable drug that must be administered in a health care provider’s office. We have contracted with two specialty pharmacies to supply the drug to a provider’s office if needed. Their contact numbers are:

  • Accredo Health Group (an Express Scripts company) – Call 1-877-244-2995
  • Walgreens Specialty Pharmacy – Call 1-877-223-6447

These specialty pharmacies will deliver the drug to the health care provider’s office and bill Premera directly.

A Pre-service Review is advised for Xolair®.

Rationale

In two well-designed pivotal trials over 1000 patients age 12 and above with moderate to severe chronic steroid-resistant asthma, omalizumab reduced the overall frequency of asthma exacerbations by 40-50%. Hospitalizations and emergency visits for asthma exacerbation were also reduced. Reduction in protocol defined exacerbations was observed in approximately 15% of the subjects (NNT = 6); the majority of patients therefore did not benefit according to the primary endpoint; however reduction in asthma symptom scores and improvement in quality of life scores were observed in the overall population.

After subcutaneous (SC) administration, omalizumab has an average absolute bioavailability of 62%. Following a single SC dose in adult and adolescent patients with asthma, omalizumab reached peak serum concentrations after an average of 7-8 days. Following multiple doses, areas under the serum concentration-time curve from Day 0 to Day 14 at steady state were up to 6-fold of those after the first dose. In vitro, Omalizumab forms complexes with IgE. Precipitating complexes are not observed. Clearance involves IgG clearance processes as well as hepatic clearance of the omalizumab:IgE complexes. Intact IgG is also excreted in bile. In asthma patients elimination half-life averaged 26 days, with apparent clearance averaging 2.4 ± 1.1 mL/kg/day. Doubling body weight approximately doubled apparent clearance.

Free IgE decrease was greater than 96% using recommended doses. Serum total IgE levels increased due to the formation of omalizumab:IgE complexes, which have a slower elimination rate. The increase in total IgE and decrease in free IgE were reversible, with no observed rebound in IgE levels after drug washout. Total IgE levels did not return to pre-treatment levels for up to one year after discontinuation.

Subsequently published studies continue to affirm the hypothesis that omalizumab is an appropriate last-line agent in patients who are inadequately controlled, despite best standard therapy with inhaled corticosteroids in combination with other controllers. The bulk of the evidence suggests that many of these patients will achieve significant benefit when omalizumab is added to their existing treatment.

A published cost-effectiveness analysis concluded that:

“…from a pharmacoeconomic standpoint, omalizumab would be better used in allergic asthmatic patients with poorly controlled symptoms despite maximal therapy, given the high cost and modest efficacy of this agent. It could be cost saving if given to nonsmoking patients who are hospitalized 5 or more times or 20 days or longer per year despite maximal asthma therapy.”

2007 Update

A September 2007 literature review update did not identify any published reports that would change the conclusions of our assessment of the policy statement above.

The Expert Panel Report 3 (EPT-3) from the National Heart Lung and Blood Institute contains updated definitions of asthma. (27)

2008 Update

The American Academy of Allergy Asthma & Immunology supports the FDA labeling of Xolair and states: “Xolair is indicated for the moderate to severe persistent asthmatic patient who is 12 and older, has a positive skin test or in-vitro reaction to a perennial aeroallergen, and does not have control of their symtpoms with inhaled corticosteroids. Clinical studies have shown that serum-free IgE levels were reduced by 96% within one hour after using the proper dosing requirements (total serum IgE level and body weight.)

A PubMed literature search through September 2008 did not reveal any published studies which would prompt a reconsideration of the policy statement. The policy was recommended for approval without changes by the P & T Committee (September 2008).

2009 Update

A PubMed literature search through October 2009 did not reveal any published studies which would prompt a reconsideration of the policy statement. The policy was recommended for approval without changes by the P & T Committee in November 2009.

2011 Update

A literature search from Jan 2008 to Jan 2011 did not identify any studies that would prompt reconsideration of the policy statement. A 2011 published review of MEDLINE search spanning from September 2008 to August 2010 revealed investigations and case reports of omalizumab as an add-on agent to standard therapy. The policy statements remain unchanged. The policy was recommended for approval without changes by the P & T Committee in November 2010.

2012 Update

A literature search from Jan 2011 to Dec 2011 did not identify any studies that would prompt reconsideration of the policy statement. Hanania, et al., reported results of an 850 patient RCT evaluating the impact of omalizumab as add on therapy in patients with severe asthma treated with high dose inhaled corticosteroid (ICS) plus long-acting beta agonist (LABA), with or without other controllers. Patients were followed for 48 weeks. Asthma exacerbations were significantly reduced in the omalizumab arm (RRR=0.75, p=0.006). Patients on omalizumab also reported improved quality of life (AQLQ) scores, reduced albuterol use and decreased mean asthma symptom score. In Feb 2011, a disturbing report from the ongoing EXCELS prospective cohort study, suggested that they might be seeing an imbalance of arterial thrombotic events; however, the finding was not statistically significant at the time of report. As of this update, no further information on this report is available.

2013 Update

A Phase III, multicenter, double-blind RCT evaluated the efficacy and safety of omalizumab in patients with moderate-to-severe chronic idiopathic urticaria refractory to H1-antihistamine therapy. 323 patients were randomized to receive 3 subcutaneous injections at 4 week intervals, of omalizumab 75 mg, 150 mg, or 300 mg or placebo, followed by a 16-week observation period. The primary endpoint was change weekly itch-severity score (ISS, ranging from 0 to 21, with higher scores indicating more severe itching). Baseline weekly ISS was ~14 in all groups. At week 12, the mean (±SD) change from baseline in weekly ISS was −5.1±5.6 in the placebo group, −5.9±6.5 in the 75-mg group (P = 0.46), −8.1±6.4 in the 150-mg group (P = 0.001), and −9.8±6.0 in the 300-mg group (P<0.001). Adverse events were similar across groups. Serious AE were infrequent but higher in the 300-mg group (6%). A literature search from Jan 2012 to Dec 2012 did not identify other studies that would prompt reconsideration of the policy statement.

2014 (April) Update

A literature search conducted from 1/1/2013 through 2/28/2014 found no new evidence that would change this policy. An updated Cochrane meta-analysis published in January 2014 confirmed a reduction in both the frequency of asthma exacerbations and hospitalizations in patients treated with omalizumab versus placebo. Patients dependent on systemic corticosteroids were able to reduce or eliminate the requirement for systemic steroids. The authors identified a need for double-dummy trials and more studies in pediatric patients. Given the drug’s high cost it would be valuable to identify biomarkers predictive of response.

2014 (May) Update

In November 2013 two additional Phase II clinical trials were presented at the European Academy of Dermatology and Venerology combined with the study reported above (40). The three studies included close to 1,000 patients between the ages of 12 and 75 years, who were severely affected by chronic idiopathic/spontaneous urticaria despite treatment with high doses of H1- antihistamines. The results were consistent across the studies with 80-90% response rate of symptomatic improvement (decreased itching, wheals, and increased days without angioedema). The response was does dependent, with most response to the highest dose tested (400 mg q 4 weeks). Patients were able to decrease the daily dose of H1 antihistamines.

On March 21, 2014, the FDA approved Xolair® (omaluzimab) for use in the treatment of chronic idiopathic urticarial for people age 12 and older who have failed first line treatment with H1 antihistamine therapy.

2015 Update

A literature search conducted from 1/1/2013 through 2/28/2014 found no new evidence that would change this policy.

References

  1. Presta LG, Lahr SJ, Shields RL, et al. Humanization of an antibody directed against IgE. J Immunol 1993 Sep 1; 151(5):2623-32.
  2. Nayak AS. A common pathway: asthma and allergic rhinitis. Allergy Asthma Proc 2002 Nov-Dec; 23(6):359-65.
  3. National Asthma Education and Prevention Program. Guidelines for the Diagnosis and Management of Asthma: Expert Panel Report 2. Bethesda, MD: National Institutes of Health; 1997. NIH publication 97-4051.
  4. National Asthma Education and Prevention Program. Guidelines for the Diagnosis and Management of Asthma—Update on Selected Topics 2002. Bethesda, MD: National Institutes of Health; 2002. NIH publication 02-5075.
  5. Prescribing information for Xolair. Genentech, Inc., South San Francisco, CA. Last accessed April 28, 2014.
  6. 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 Feb; 111(2):278-84.
  7. 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 Jan; 111(1):87-90.
  8. Buhl R, Hanf G, Solèr M, et al. The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma. Eur Respir J 2002 Nov; 20(5):1088-94.
  9. Buhl R, Solèr M, Matz J et al. Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma. Eur Respir J 2002 Jul; 20(1):73-8.
  10. Solèr M, Matz J, Townley R et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J 2001; Aug; 18(2):254-61.
  11. Lemanske RF Jr, Nayak A, McAlary M et al. Omalizumab improves asthma-related quality of life in children with allergic asthma. Pediatrics 2002 Nov; 110(5):e55.
  12. Noga O, Hanf G, Kunkel G. Immunological and clinical changes in allergic asthmatics following treatment with omalizumab. Int Arch Allergy Immunol 2003 May; 131(1):46-52.
  13. Plewako H, Arvidsson M, Petruson K et al. The effect of omalizumab on nasal allergic inflammation. J Allergy Clin Immunol 2002 Jul; 110(1):68-71.
  14. Kuehr J, Brauburger J, Zielen S et al. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol 2002 Feb; 109(2):274-80.
  15. Casale TB, Condemi J, LaForce C et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA 2001 Dec 19; 286(23):2956-67.
  16. 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 Aug; 108(2):184-90.
  17. Milgrom H, Berger W, Nayak A et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics 2001 Aug; 108(2):E36.
  18. Buhl R. Omalizumab (Xolair) improves quality of life in adult patients with allergic asthma: a review. Respir Med 2003 Feb; 97(2):123-9.
  19. Milgrom H. Is there a role for treatment of asthma with omalizumab? Arch Dis Child 2003 Jan; 88(1):71-4.
  20. Premera Pharmacy and Therapeutics Committee reviewed and recommended for approval on September 26, 2006.
  21. Vignola AM, Humbert M, Bousquet J et al. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR. Allergy 2004;59(7):709-717.
  22. Ayres JG, Higgins B, Chilvers ER et al. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergic asthma. Allergy 2004;59(7):701-708.
  23. Walker S, Monteil M, Phelan K et al. Anti-IgE for chronic asthma in adults and children. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003559.
  24. Humbert M, Beasley R, Ayres J et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy 2005;60:309–316.
  25. Bousquet , Cabrera P, Berkman N et al. The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy 2005:60:302–308.
  26. Oba Y and Salzman GA. Cost-effectiveness analysis of omalizumab in adults and adolescents with moderate-to-severe allergic asthma. J Allergy Clin Immunol 2004;114:265-9.
  27. National Heart Lung and Blood Institute. Clinical Practice Guidelines: Guidelines for the Diagnosis and Management of Asthma (EPR-3). Last updated 2007. Last accessed March 8, 2013.
  28. National Institute for Health and Clinical Excellence (NICE). Omalizumab for severe persistent allergic asthma. Technology Appraisal Guidance No. 133. London, UK. November 2007. Last accessed April 28, 2014.
  29. American Academy of Allergy Asthma & Immunology. Right drug at right time for moderate to severe allergic asthmatics. www.aaaai.org Last accessed April 28, 2014.
  30. Reviewed by P & T Committee in September 2008.
  31. Reviewed by P & T Committee in November 2009.
  32. Li JT, Oppenheimer J, Bernstein IL, Nicklas RA. Attaining optimal asthma control: A practice Parameter.  7 October 2005. Accessed via the Practice Guidelines section of the American Academy of Allergy Asthma & Immunology.
  33. Morjaria JB, Proiti M, Polosa R. Stratified medicine in selecting biologics for the treatment of severe asthma. Current Opinion in Allergy and Clinical Immunology 2011, 11:58–63.
  34. Hanania NA, Alpan O, Hamilos DL, et al. Omalizumab in severe allergic asthma inadequately controlled with standard therapy. Ann Intern Med. 2011;154:573-582.
  35. Drug Safety Update. Omalizumab: potential risk of arterial thrombotic events. 2011;4(7):A4.
  36. Reviewed by P & T Committee in November 2010; January 2012; March 2013.
  37. Saini S, Rosén KE, Hsieh HJ, et al., A randomized, placebo-controlled, dose-ranging study of single-dose omalizumab in patients with H1-antihistamine-refractory chronic idiopathic urticaria.JACI 2011;128:567-573.
  38. Maurer M, Rosén KE, Hsieh H, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. NEJM, epublished February 24, 2013.
  39. Normansell R, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev 2014 Jan 13;1:CD003559.
  40. Norman G, Faria R, Paton F, et al. Omalizumab for the treatment of severe persistent allergic asthma: a systematic review and economic evaluation. Health Technol Assess 2013;17(52):1-342.
  41. Maurer M. Phase III randomized, double-blind, placebo-controlled study evaluating efficacy and safety of omalizumab in H1-antihistamine-refractory chronic idiopathic/spontaneous urticaria. European Academy of Dermatology and Venereology (EADV) annual meeting 2013. Oral Presentation. 5 October 2013, 11:30 a.m.
  42. Long A, Rahmaoui A, Rothman KJ, et al. Incidence of malignancy in patients with moderate-to-severe asthma treated with or without omalizumab. J Allergy Clin Immunol. 2014 Sep;134(3):560-567.

Coding

Codes

Number

Description

HCPCS

J2357

Injection, omalizumab (Xolair®) – 5 mg

Type of Service

Prescription Drug

 

Place of Service

Inpatient/
Physician’s Office

 

Appendix

Administration Every 4 Weeks

Xolair Doses (milligrams) Administered by Subcutaneous Injection Every 4 Weeks for Adults and Adolescents (12 years of age and older) with Asthma

Pre-treatment

Serum IgE (I/mL)

Body Weight (kg)

30 – 60

>60 – 70

>70 – 90

>90 – 150

>30 – 100

150

150

150

300

>100 – 200

300

300

300

N/A

>200 – 300

300

N/A

N/A

N/A

>300 – 400

N/A

N/A

N/A

N/A

>400 – 500

N/A

N/A

N/A

N/A

>500 – 600

N/A

N/A

N/A

N/A

Administration Every 2 Weeks

Xolair Doses (milligrams) Administered by Subcutaneous Injection Every 2 Weeks for Adults and Adolescents (12 years of age and older) with Asthma

Pre-treatment

Serum IgE (I/mL)

Body Weight (kg)

30 – 60

>60 – 70

>70 – 90

>90 – 150

>30 – 100

N/A

N/A

N/A

N/A

>100 – 200

N/A

N/A

N/A

225

>200 – 300

N/A

225

225

300

>300 – 400

225

225

300

N/A

>400 – 500

300

300

375

N/A

>500 – 600

300

375

N/A

N/A

>600 – 700

375

N/A

N/A

N/A

Dosing Adjustments

Total IgE levels are elevated during treatment and remain elevated for up to one year after the discontinuation of treatment. Therefore, re-testing of IgE levels during Xolair® treatment cannot be used as a guide for dose determination. Dose determination after treatment interruptions lasting less than 1 year should be based on serum IgE levels obtained at the initial dose determination. Total serum IgE levels may be re-tested for dose determination if treatment with Xolair® has been interrupted for one year or more.

Doses should be adjusted for significant changes in body weight. (See tables above.)

History

Date

Reason

08/12/03

Add to Prescription Drug Section. - New policy developed at time FDA approved the drug.

01/01/04

Replace Policy - HCPC code updates only.

09/01/04

Replace Policy - Policy renumbered from PR.5.01.113. No changes to dates.

09/14/04

Replace Policy - Scheduled review; policy statement unchanged. Reference section updated.

10/11/05

Replace Policy - Scheduled review, policy statement unchanged.

02/06/06

Codes updated - No other changes.

06/16/06

Update Scope and Disclaimer - No other changes.

10/10/06

Replace Policy - Policy updated with literature search; no change in policy statement. Reviewed by P&T committee on September 26, 2006.

11/13/07

Replace Policy - Policy updated with literature search. Policy statement includes changes in severity, “long-acting beta-agonists” as medically necessary; also includes “Peanut and other food allergies” and “Latex allergy” as investigational. References updated.

10/14/08

Replace Policy - Policy updated with literature search; no change to policy statement. References and codes added.

12/08/09

Replace Policy - Policy updated with literature search; no change to policy statement. References added. Reviewed by P&T committee on November 24, 2009.

02/08/11

Replace Policy - Policy updated with literature review; no change in policy statement. Reviewed by P&T in November 2010.

02/14/12

Replace policy. Policy updated with literature search. References added. Reviewed by P&T January 24, 2012.

10/11/12

Minor Update – Medco is now Express Scripts.

03/11/13

Replace policy. Policy updated with an additional medically necessary off-label indication: Antihistamine-refractory chronic idiopathic urticaria. Policy Guidelines section updated with dosing guidelines on the new indication. Supporting rationale added; reference 36 updated; references 37-38 added. Reviewed by P&T in March 2013.

02/24/14

Replace policy. Policy updated with literature review; no change in policy statement.

04/14/14

Interim update. Policy updated with literature; no change in policy statement. References 39 and 40 added.

05/12/14

Interim update. Policy section updated. The indication for severe persistent asthma rewritten; criteria moved from Policy Guidelines and is now listed within the Policy section. A notation was added that Xolair® is not FDA-approved for patients under age 12 in the US; however, cases may be approved on an individual member basis for those with severe persistent asthma with informed consent by a responsible adult on behalf of the child based upon approval for children age 6 and above in the EU. A new indication is added for treatment of severe chronic idiopathic urticaria for those aged 12 and above when the indicated criteria are met and documentation provided; this indication was approved by the FDA in March 2014. Reference 40 added. HCPCS code J3590 removed; there is a specific code for Xolair (J2357) which is listed in the policy.

05/22/15

Annual Review. Policy updated with literature review, policy statements unchanged.

06/09/15

Interim update. Table added to the Policy Guidelines section to provide dosage information for brand/generic names for H1 and H2 antihistamines and normal dosage ranges for H1 antihistamines. ICD-9 diagnosis codes removed; these were informational only.


Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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