MEDICAL POLICY

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

Omalizumab (Xolair®)

Number 5.01.513

Effective Date February 24, 2014

Revision Date(s) 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

When symptoms are inadequately controlled with inhaled corticosteroids and long-acting beta-agonists, and Policy Guidelines are met, omalizumab (Xolair®) may be considered medically necessary for the following FDA-approved indication:

  • 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.

When symptoms are inadequately controlled with inhaled corticosteroids, and Policy Guidelines are met, omalizumab may be considered medically necessary for the off-label indications for which clinical trials have demonstrated safety and efficacy:

  • Children with severe persistent asthma who have a positive skin test or in vitro reactivity to a perennial aeroallergen.
  • Antihistamine-refractory chronic idiopathic urticaria.

Use in other IgE-mediated disorders is considered investigational. These off-label uses include:

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

Related Policies

2.01.500

Allergy Testing

Policy Guidelines

Severe Persistent Allergic Asthma

Initial evaluation and prescription of omalizumab should be performed by a specialist (allergy/pulmonology), and should include the following:

  • Appropriate pulmonary function measures (e.g., peak flow FEV).
  • Documented elevated IgE levels (Required for proper dosing).
  • Appropriate skin testing and other alternatives such as allergen shots evaluated as treatment options.
  • Documented full patient compliance with previous therapies, including appropriate techniques for using inhalers or other devices so that the patient received the full dose of medication.

Patients must meet ALL of the following initial screening criteria:

  • Severe allergic asthma (FEV1 40-80% predicted), AND
  • Total serum IgE 30-700 IU/ml (Measurement is required for correct dosing according to the manufacturer’s instructions.), 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.

When there has been inadequate response or adverse reaction to a trial (full doses per guidelines with verified patient compliance) of combination-inhaled corticosteroid and long-acting beta agonist therapy, the initial approval for omalizumab should be for a 6 month trial period.

Approval of continuation of therapy beyond the initial trial period will be based on progress notes demonstrating any of the following:

  • 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.

Use in patients with concomitant allergic disorders:

  • Omalizumab should not be approved for the treatment of other allergic disorders (allergic rhinitis, food allergies, etc.) in patients with asthma unless evaluation of the asthma demonstrates that they meet the above criteria.
  • Specifically, patients who have mild to moderate asthma that is well controlled on inhaled corticosteroids, with or without an inhaled long-acting beta agonist, should not be approved, even if the concomitant rhinitis or other allergic symptoms are poorly controlled.
  • may be used in patients aged 12 years and older with antihistamine-refractory chronic idiopathic urticaria:
  • Fixed doses of 300mg and 600mg have been shown to be effective, in combination with an H1-antihistamine.

Anaphylaxis, presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue, has been reported to occur after administration of Xolair. Anaphylaxis has occurred as early as after the first dose of Xolair, but also has occurred beyond 1 year after beginning regularly administered treatment. Because of the risk of anaphylaxis, patients should be closely observed for an appropriate period of time after Xolair administration, and health care providers administering Xolair should be prepared to manage anaphylaxis that can be life-threatening. Patients should also be informed of the signs and symptoms of anaphylaxis and instructed to seek immediate medical care should symptoms occur (see Warnings and Precautions sections of package insert. Therefore, omalizumab should be administered in a clinic setting where the patient can be observed for symptoms of anaphylaxis for an appropriate period of time after the injection.

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:

  • Health Group (an Express Scripts company) – Call 1-877-244-2995
  • 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 Benefit Advisory is recommended 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 3, 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.

2013 Update

A literature search from January 2013 to December 2013 did not identify any new studies that would prompt reconsideration of the policy statement.

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 March 8, 2013.
  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 March 8, 2013.
  29. American Academy of Allergy Asthma & Immunology. Right drug at right time for moderate to severe allergic asthmatics. www.aaaai.org Last accessed March 8, 2013.
  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.

Coding

Codes

Number

Description

ICD-9 Diagnosis

493.00-493.92

Asthma (range)

HCPCS

J2357

Injection, omalizumab (Xolair) – 5 mg

 

J3590

Unclassified biologics

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.


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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