Latest Review Date: March 2024

Category: Medical                              

POLICY:

Effective for dates of service on and after May 16, 2024:

Allergy Immunotherapy

Allergy immunotherapy may be considered medically necessary for individuals with demonstrated hypersensitivity that cannot be managed by medications or avoidance when delivered based on ALL of the following guidelines:

• Maximum of 180 units for the first year of therapy during escalation, and
• Maximum of 120 units for yearly maintenance therapy thereafter, and
• Per unit reimbursement for allergy immunotherapy is based on the number of dosages prepared and intended for administration.

The following treatments for allergies are considered  investigational:

• Provocative and neutralization therapy for food allergies, using oral, intradermal and subcutaneous routes
• Urine auto-injections
• Repository emulsion therapy
• Tolerance Induction Program™ (TIP)

As of August 1, 2014, Sublingual Immunotherapy (SLIT), including FDA approved tablets (Oralair®, Grastek® and Ragwitek®), is considered a prescription benefit and coverage is dependent on member's formulary and benefit plan design.

Non-FDA approved SLIT therapy which is typically prepared and billed by an allergist is considered non-covered under the medical benefit.

Aspirin Desensitization

Aspirin (ASA) desensitization may be considered medically necessary in individuals with aspirin-exacerbated respiratory disease (AERD) when one of the following criteria is met:

• Asthma or rhinosinusitis which is suboptimally controlled with inhaled corticosteroids and leukotriene-modifying drugs; OR
• Individuals who have required multiple polypectomies for nasal polyp control; OR
• Individuals who require anti-platelet therapy with cyclo-oxygenase-Y inhibitors.

The testing must be done in a hospital or physician’s office with direct supervision by an eligible provider.  The desensitization procedure should be followed by daily aspirin therapy.

Effective for dates of service prior to May 16, 2024:

Allergy Immunotherapy

Allergy immunotherapy may be considered medically necessary for individuals with demonstrated hypersensitivity that cannot be managed by medications or avoidance when delivered based on ALL of the following guidelines:

• Maximum of 180 units for the first year of therapy during escalation, and
• Maximum of 120 units for yearly maintenance therapy thereafter, and
• Per unit reimbursement for allergy immunotherapy is based on the number of dosages prepared and intended for administration.

The following treatments for allergies are considered  investigational:

• Provocative and neutralization therapy for food allergies, using intradermal and subcutaneous routes
• Urine auto-injections
• Repository emulsion therapy

As of August 1, 2014, Sublingual Immunotherapy (SLIT), including FDA approved tablets (Oralair®, Grastek® and Ragwitek®), is considered a prescription benefit and coverage is dependent on member's formulary and benefit plan design.

Non-FDA approved SLIT therapy which is typically prepared and billed by an allergist is considered non-covered under the medical benefit.

Aspirin Desensitization

Aspirin (ASA) desensitization may be considered medically necessary in individuals with aspirin-exacerbated respiratory disease (AERD) when one of the following criteria is met:

• Asthma or rhinosinusitis which is suboptimally controlled with inhaled corticosteroids and leukotriene-modifying drugs; OR
• Individuals who have required multiple polypectomies for nasal polyp control; OR
• Individuals who require anti-platelet therapy with cyclo-oxygenase-Y inhibitors.

The testing must be done in a hospital or physician’s office with direct supervision by an eligible provider.  The desensitization procedure should be followed by daily aspirin therapy.

DESCRIPTION OF PROCEDURE OR SERVICE:

Allergy immunotherapy (a.k.a., desensitization, allergy injection therapy, or "allergy shots"), is an effective treatment for allergic rhinitis, allergic asthma, atopic dermatitis and Hymenoptera sensitivity. Immunotherapy is indicated in patients whose triggering allergens have been determined by appropriate skin or in vitro testing. The goal is to reduce the allergy patient's sensitivity when exposed to the offending allergen in the future. Treatment begins with low doses to prevent severe reactions. Gradually the doses are increased and are given once or twice a week until the body becomes tolerant of the allergen. After the maintenance dose is achieved, the interval between injections may range between two and six weeks. Immunotherapy may be administered continuously for several years.

Rush immunotherapy (allergy shots) is a treatment that includes a fast increase in concentration and allergen extract doses. It was started to reduce hospital visits and the required hospital stay.  This treatment delivers doses varying between 15 to 60 minutes over 1-3 days until the target therapeutic dose is achieved. Very sensitive individuals may experience various degrees of systemic reaction during this procedure.  Therefore, physicians who use this method frequently pre-medicate individuals with both antihistamines and corticosteroids to minimize the risk of a systemic reaction. These forms of immunotherapy allow for faster advancement to maintenance.

The Joint Council of Allergy, Asthma and Immunology state that rush immunotherapy and cluster immunotherapy are forms of allergen immunotherapy in which incremental doses of allergen are administered at varying intervals, until the optimal effective dose is achieved. Cluster immunotherapy is an accelerated build-up schedule that entails administering several injections at increasing doses (generally 2-3 per visit) sequentially in a single day of treatment on non-consecutive days. The maintenance dose is generally achieved more rapidly than with a conventional (single injection per visit) build-up schedule (generally within 4-8 weeks).

Provocative and Neutralization Therapy

This procedure is purported to diagnose allergy to foods, chemicals, inhalant allergens, and endogenous hormones. Varying concentrations of test extracts of these substances are given to the patient by intracutaneous or subcutaneous injection or sublingually. The patient records all subjective sensations for 10 minutes afterward, and any reported sensation is taken as a positive test result for allergy. In the event of a positive test result, other doses of the same substance are given until the sensation has disappeared, at which point the action is said to be “neutralized.” Some proponents recommend measuring increase in the size of the injected wheal in the intracutaneous provocation procedure, but the primary indication of a positive result is the provocation and neutralization of symptoms.

Oral Immunotherapy (OIT) is an allergen-specific approach to the treatment of food allergy.  Doctors prescribe and supervise a regimen of allergenic food, gradually increasing the dosage each day. This type of therapy will desensitize the food to the point where accidental ingestion of the allergenic food in a social setting would not cause anaphylaxis, and possibly intentionally eaten food can be added safely to a regular diet.

KEY POINTS:

The most recent literature review for this policy was performed March 27, 2024. 

Summary of Evidence

For provocative and neutralization therapy for food allergies, urine auto-injections, and repository emulsion therapy, the evidence includes studies, and randomized controlled trials. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Oral immunotherapy for food is a major focus of investigation in the treatment of food allergy. However, studies have yet to demonstrate the ability to cure food allergy (and induce true tolerance). Furthermore, allergic reactions to OIT are common and occur at higher rates in patients on OIT than those avoiding the food. Many unanswered questions remain, and additional long-term follow-up data are needed to help determine in which patients the benefits may outweigh the risks.

Practice Guidelines and Position Statements

In 2013, the American Academy of Allergy, Asthma and Immunology and the European Academy of Allergy and Clinical Immunology published a consensus report on allergy immunotherapy. The report summarized the literature and current practices in the U.S. and Europe; it did not include clinical recommendations. The authors concluded, “AIT (allergy immunotherapy) is effective in reducing symptoms of allergic asthma and rhinitis, as well as venom-induced anaphylaxis. In addition, AIT modifies the underlying course of disease. However, AIT remains a niche treatment secondary to symptomatic drugs because of its cost, long duration of treatment and concerns regarding safety and effectiveness…”

In 2011, a joint task force of 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 issued updated practice parameters for allergen immunotherapy. The document stated that RCTs of SLIT for individuals with allergic rhinitis and asthma have demonstrated significant improvement in symptoms. The authors note that there are no FDA approved extract formulations for a non-injection route of immunotherapy.

U.S Preventive Services Task Force Recommendations

Not applicable.

KEY WORDS:

Allergy immunotherapy, IgE antibodies, allergen, antigen, immunotherapy, Rush immunotherapy, Rush schedules, sublingual immunotherapy, SLIT, acetylsalicylic acid (ASA), aspirin, asthma, desensitization, aspirin desensitization treatment, asthma-exacerbated respiratory disease (AERD), Allervision, cluster immunotherapy, Tolerance Induction Program, TIP, food allergy, oral immunotherapy, OIT

APPROVED BY GOVERNING BODIES:

Not applicable.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits.  Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: Special benefit consideration may apply. Refer to member's benefit plan.

CURRENT CODING:

CPT codes:  

REFERENCES:

1. American Academy of Allergy Asthma Immunology, American College of Allergy Asthma Immunology, Joint Council of Allergy Asthma Immunology. Allergen immunotherapy: a practice parameter third update. 2011. Available online at: www.guideline.gov.

2. Bahceciler NN, Galip N. Comparing subcutaneous and sublingual immunotherapy: what do we know? Curr Opin Allergy Clin Immunol 2012; 12(6):640-7.

3. Berges-Gimeno MP, et al. Long-term treatment with aspirin desensitization in asthmatic patients with aspirin-exacerbated respiratory disease. Journal of Allergy and Immunology, January 2003, Vol. 111, No. 1.

4. Bernstein IL, Li JT, Bernstein DI, et al.  Allergy diagnostic testing: an updated practice parameter. Annals of Allergy, Asthma and Immunology, March 2008, Vol, 100.

5. Bikhazi NB. Contemporary management of nasal polyps. Otolaryngologic Clinics of North America, April 2004, Vol. 37, No. 2.

6. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Sublingual immunotherapy for allergies. TEC Assessments 2003; Volume 18, Tab 4.

7. Burks AW, Calderon MA, Casale T et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol, May 2013; 131(5):1288-96.

8. Calamita Z, Saconato H, Pela AB and Atallah AN. Efficacy of sublingual immunotherapy in asthma: Systematic review of randomized-clinical trials using the Cochrane Collaboration method. Allergy, October 2006; 61(10): 1162-1172.

9. Calderon MA, Penagos M, Sheikh A et al. Sublingual immunotherapy for treating allergic conjunctivitis. Cochrane Database Syst Rev 2011; (7):CD007685.

10. Compalati E, Penagos M, Tarantini F et al. Specific immunotherapy for respiratory allergy: state of the art according to current meta-analyses. Ann Allergy Asthma Immunol 2009; 102(1-Jan):22-8.

11. Covar RA, et al. Medications as asthma triggers. Immunology and Allergy Clinics of North America, February 2005, Vol. 25, No. 1.

12. Cox L, et al. Allergen immunotherapy: A practice parameter third update. Journal of Allergy and Clinical Immunology 2011; 127(1):S1-S55.

13. Cox LS, Linnemann DL, Nolte H, et al. Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol, May 2006; 117(5): 1021-1035.

14. De Bot C. M., Moed H, Berger MY et al. Sublingual immunotherapy in children with allergic rhinitis: quality of systematic reviews. Pediatr Allergy Immunol 2011; 22(6):548-58.

15. Di Bona D, Plaia A, Scafidi V et al. Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis. J Allergy Clin Immunol 2010; 126(3) 558-66.

16. Dretzke J, Meadows A, Novielli N et al. Subcutaneous and sublingual immunotherapy for seasonal allergic rhinitis: A systematic review and indirect comparison. J Allergy Clin Immunol. May 2013; 131(5):1361-6.

17. Durham SR, Yang WH, et al. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol, April 2006; 117(4): 802-809.

18. Dykewicz MS, Fineman S, Skoner DP. Joint Task Force summary statements on Diagnosis and Management of Rhinitis. Ann Allergy Asthma Immunol. 1998 Nov;81(5 Pt 2):474-477.

19. Eifan AO, Akkoc T, Yildiz A et al. Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial. Clin Exp Allergy 2010; 40(6):922-32.

20. Feuille E, Nowak-Wegrzyn A. Allergen-Specific Immunotherapies for Food Allergy. Allergy Asthma Immunol Res 2018; 10:189.
21. Food Allergy Institute. Tolerance Induction Program (TIP)™Guide. 2024. foodallergyinstitute.com/resources/tip-program-guide/.
22. Food Allergy Resource Alliance. Are There Any Treatment Options? 2022. www.foodallergyresourcealliance.com/treatment-options.

23. Fritzsching, B., Contoli, M., Porsbjerg, C., Buchs, S., Larsen, J. R., Elliott, L., Rodriguez, M. R., & Freemantle, N. (2021). Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study. The Lancet regional health. Europe, 13, 100275. 

24. Greenhawt M, et al. Sublingual immunotherapy: a focused allergen immunotherapy practice parameter updaate. Annuals of Allergy, Asthma, & Immunology. 2017:118:276-282.

25. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.

26. Joint Task Force on Practice Parameters, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunology. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol 2007; 120(3 Suppl):S25-85.

27. Keles S, Karokov-Aydiner E, Ozen A et al. A novel approach in allergen-specific immunotherapy: combination of sublingual and subcutaneous routes. J Allergy Clin Immunol 2011; 128(4):808-15.

28. Lee JH, Choi JH, Jeong KB, Lee SJ, Lee MK, Lee WY, Yong SJ, Kim SH. Safety and Utility of Rush Immunotherapy with Aqueous Allergen Extracts for Treatment of Respiratory Allergies. J Korean Med Sci. 2021 Jan 18;36(3):e18.

29. Li JT, Lockey RF, et al. Allergen immunotherapy: a practice parameter. Annals of Allergy, Asthma, & Immunology. January 2003, Vol. 90.

30. Lin SY, Erekosima N, Kim JM et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. JAMA 2013; 309(12):1278-88.

31. Lin SY, Erekosima N, Suarez-Cuervo C et al. Allergen-specific immunotherapy for the treatment of allergic rhinoconjunctivitis and/or asthma: comparative effectiveness review No. 111. (Prepared by the Johns Hopkins University Evidence-based Practice Center under Contract No. 290-2007-10061-I.) AHRQ Publication No. 13-EHC061-EF. 2013. Available online at: www.effectivehealthcare.ahrq.gov/reports/final.cfm.

32. Macy E, Bernstein JA, Castells MC, et al. Aspirin challenge and desensitization for aspirin-exacerbated respiratory disease: a practice paper. Annals of Allergy, Asthma and Immunology, February 2007, Vol. 98, pp. 172-174.

33. Mauro M, Russello M, et al. Comparison of efficacy, safety and immunologic effects of subcutaneous and sublingual immunotherapy in birch pollinosis: A randomized study. Allerg Immunol 2007; 39(4): 119-122.

34. Penagos M, Passalacqua G, Compalati E, et al. Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age. Chest, March 2008; 133(3): 599-609.

35. Pipet A, Botturi K, Pinot D et al. Allergen-specific immunotherapy in allergic rhinitis and asthma: mechanisms and proof of efficacy. Respir Med 2009; 103(6):800-12.

36. Radulovic S, Wilson D, Calderon M et al. Systematic reviews of sublingual immunotherapy (SLIT). Allergy 2011; 66(6):740-52.

37. Shaker M, Lobb A, Jenkins P, et al. An economic analysis of aspirin desensitization in aspirin-exacerbated respiratory disease. J Allergy Clin Immunol. January 2008Vol. 121, No. 1, pp. 81-86.

38. Sieber J, Shah-Hosseini K, Mosges R. Specific immunotherapy for allergic rhinitis to grass and tree pollens in daily medical practice- symptom load with sublingual immunotherapy compared to subcutaneous immunotherapy. Ann Med 2011; 43(6):418-24.

39. Slavin RG, et al. The diagnosis and management of sinusitis: a practice parameter update. Journal of Allergy and Clinical Immunology. December 2005, Vol. 116, No. 6 (Suppl).

40. Stevenson DD, et al. Aspirin desensitization treatment of aspirin-sensitive patients with rhinosinusitis-asthma: long-term outcomes. Journal of Allergy and Clinical Immunology. October 1996, Vol. 98, No. 4.

41. Stevenson DD. Aspirin and NSAID sensitivity. Immunology and Allergy Clinics of North America, August 2004, Vol. 24, No. 3.

42. Szczeklik A, Stevenson DD, et al. Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. Journal of Allergy and Clinical Immunology. 2003 May;111(5):913-921.
43. Vickery BP, Burks AW. Immunotherapy in the treatment of food allergy: focus on oral tolerance. Curr Opin Allergy Clin Immunol 2009; 9:364.

44. Wise SK, Schlosser RJ. Evidence-based practice: sublingual immunotherapy for allergic rhinitis. Otolaryngol Clin North Am 2012; 45(5):1045-54.

45. Yepes-Nuñez J, et al. Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms. J Allergy Clin Immunol. 2023 Jan;15(1):147-158.

46. Yukselen A, Kendirli SG, Yilmaz MEoo-ys et al. Int Arch Allergy Immunol 2011; 157(3-Jan):288-98.

47. Zacharek MA, et al. The office management of recalcitrant rhinosinusitis. Otolaryngologic Clinics of North America, April 2004, Vol. 37, No. 2.

POLICY HISTORY:

Medical Policy Group, November 2002 (1)

Medical Policy Administration Committee, July 2003

Available for comment August 13-September 27, 2003

Medical Policy Group, May 2005 (1)

Medical Policy Administration Committee, May 2005

Available for comment May 21-July 4, 2005

Medical Policy Administration Committee, July 2005

Available for comment July 20-September 2, 2005

Medical Policy Group, February 2006 (1)

Medical Policy Administration Committee, February 2006

Available for comment February 10-March 27, 2006

Medical Policy Group, August 2006 (2)

Medical Policy Administration Committee, August 2006

Available for comment August 30-October 13, 2006

Medical Policy Group, August 2008 (1)

Medical Policy Group, September 2008 (3)

Medical Policy Administration Committee, October 2008

Available for comment October 4-November 17, 2008

Medical Policy Group, (1): Updated Key Points

Medical Policy Group, March 2011 (1): Updated Key Points and References

Medical Policy Group, March 2012 (1): Updated Key Points, Key Words and References related to MPP update

Medical Policy Group, December 2012 (3): 2013 Coding Update – Verbiage change to Codes 95120, 95125, and 95130 through 95134

Medical Policy Panel, May 2013

Medical Policy Group, September 2013 (1): Update to Key Points and References with no change in policy statement related to SLIT; removed criteria prior to 2008 related to aspirin desensitization with no change in policy statement

Medical Policy Group, November 2013 (2): Statement regarding direct physician supervision changed to supervision by an eligible provider

Medical Policy Group, August 2014 (1): Policy statement updated to remove SLIT testing from medical policy and place statement that SLIT testing is now a pharmacy benefit.

Medical Policy Administration Committee, August 2014

Available for comment July 29 through September 11, 2014

Medical Policy Group, September 2014 (5):  Updated Key Points by removing the statement that SLIT therapy is considered investigational under the summary section of the SLIT therapy.

Medical Policy Panel, April 2015

Medical Policy Group, June 2015 (3):  No updates needed at this time to ASA-desensitization information – no change in related policy statements; pharmacy now managing SLIT testing benefit.

Medical Policy Group. October 2016 (6): Updates to policy statement, added statement “Maximum of 180 units for the first year of therapy during escalation, and maximum of 120 units for yearly maintenance therapy thereafter, and Per unit reimbursement for allergy immunotherapy is based on the number of dosages prepared and intended for administration”, removed SLIT from policy(Pharmacy policy).

Medical Policy Administration Committee, October 2016

Available for comment October 19 through December 2, 2016

Medical Policy Group, March 2017 (6): Updated description to include cluster therapy. Added cluster immunotherapy to Key Words. No change to policy statement.

Medical Policy Group, April 2018 (6): Updated verbiage for SLIT therapy.

Medical Policy Group, November 2020 (5): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy. Update to Key Points. No change in Policy Statement.

Medical Policy Group, January 2022 (5): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy. Updates to Key Points, and References. No change to Policy Statement. 

Medical Policy Group, January 2023 (5): Reviewed by consensus. No new published peer-reviewed literature available that would alter the coverage statement in this policy. Minor update to Key Points, and References. No change to Policy Statement.

Medical Policy Group, February 2024 (9): Reviewed by consensus. No new published peer-reviewed literature is available that would alter the coverage statement in this policy update. Updates to Key Points, Benefit Application and References. No change to policy intent.

Medical Policy Group, March 2024 (9): Updates to Description, Key Points, Key Words and References. Policy statement updated to include oral provocative and neutralization therapy and tolerance induction program for food allergies as investigational.

Available for comment April 1, 2024 through May 15, 2024.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.