Medical Policy: 02.01.01 

Original Effective Date: April 1995 

Reviewed: February 2020 

Revised: February 2020 

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

Allergic or hypersensitivity disorders can manifest themselves as generalized systemic reactions as well as localized reactions in any organ system of the body. Numerous agents, e.g., pollen, mold, dust mites, animal dander, insect stings, foods or drugs, may precipitate allergic or hypersensitive reactions. For details on coverage of allergy testing services, see Policy 02.01.02, Allergy Testing. For information on oral immunotherapy tablets see drug policy Oral Immunotherapy Policies: 05.01.110 Oralair, 05.01.111 Ragwitek, and 05.02.31 Odactra.

 

The management of an allergic patient should include a comprehensive history, physical examination and should include confirming the cause of allergies. Once the agent is identified, treatment is provided by avoidance, medication or immunotherapy.

 

Immunotherapy involves regular injections of offending allergens which are not readily avoidable. The treatment is provided over a period of months to years, with a goal of reducing symptoms. Allergy shots work like a vaccine. Your body responds to injected amounts of a particular allergen, given in gradually increasing doses, by developing immunity or tolerance to the allergen.

 

Allergoids: Allergoids are allergenic proteins that are treated with formaldehyde to produce larger molecules with decreased ability to react with IgE antibodies. Allergoids are licensed and manufactured for general distribution in Europe, but are not available in the United States.

 

There are two phases:

  • Build-up phase. This involves receiving injections with increasing amounts of the allergens about one to two times per week. The length of this phase depends upon how often the injections are received, but generally ranges from three to six months.
  • Maintenance phase. This begins once the effective dose is reached. The effective maintenance dose depends on your level of allergen sensitivity and your response to the build-up phase. During the maintenance phase, there will be longer periods of time between treatments, ranging from two to four weeks.

 

It would be the expectation that immunotherapy is based on symptom history and the results of allergy testing. The immunotherapy should be individualized to the needs of the patient. The immunotherapy dosages are expected to be personalized to the individual patient.

 

Immunotherapy should be discontinued in the maintenance phase when any of the following symptoms, or, signs of improvement is not experienced and all other reasonable factors have been ruled out:

  • A noticeable decrease of symptoms; or
  • An increase in tolerance to the offending allergen; or
  • A reduction in medication usage.

 

Rush immunotherapy would be provided over only a few visits. The exact mechanism of action is not known but may involve an increase in allergen specific IgG antibodies, a decrease in IgE synthesis and alteration in T-lymphocyte activity.

 

Allergen-specific immunotherapy involves administering well-characterized allergen extracts, the potencies of which are measured and compared with a reference standard. An initial induction or build-up phase progressively increases the allergen dose; this is followed by multiple years of maintenance injections at the highest dose. Allergen-specific immunotherapy has been used to treat a variety of conditions including insect allergy, allergic rhinitis, and asthma. Subcutaneous injection of allergen-specific immunotherapy is the standard approach.

 

Intralymphatic Immunotherapy (ILIT)

Intralymphatic immunotherapy is a new process of administering immunotherapy that is thought to increase the safety and convenience of prolonged immunotherapy. Allergen extract is injected into a lymph node under ultrasound guidance. Therapy is reported to be completed after 3 injections given on a monthly basis. This method of immunotherapy is currently being studied in clinical trials. The reason that ILIT appears to be effective in some studies but did not show efficacy in others might be related to the different outcome parameters. The parameters that signify efficacy are not straightforward.

 

Epicutaneous Immunotherapy (EPIT)

Our mechanism of action aims to target specific epidermal dendritic cells, called Langerhans cells. Pre-clinical research has shown that these cells capture antigens and migrate to the lymph node in order to activate the immune system without passage of the antigen into the bloodstream. The Viaskin® patch contains allergen protein in its original antigenic state, which allows the skin to be continuously exposed to the allergen over time. It is being studied in management of food allergies.

 

Oral mucosal immunotherapy (OMIT)

Allovate’s approach to allergy immunotherapy is built around the Allerdent® allergy therapeutic platform. The proprietary Allerdent® toothpaste base is designed to incorporate and stabilize immunotherapeutic agents used to treat allergies. The Allerdent® toothpaste base is available without active pharmaceutical agents. It can be customized by physicians.

 

Guidelines Task Force: American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy Asthma & Immunology.

Immunotherapy is effective for the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma, and stinging insect hypersensitivity. Clinical trials do not support the use of subcutaneous immunotherapy for food hypersensitivity. Oral immunotherapy and SLIT (sublingual immunotherapy) for food hypersensitivity/food allergies are considered investigational. Immunotherapy is not currently approved by the Food and Drug Administration for use to treat food allergy.

 

The European Academy of Allergy and Clinical Immunology (EAACI)

The risk of adverse reactions, including anaphylaxis. EAACI guidelines do not recommend food immunotherapy for routine clinical use. The conclusions of the position statement: Immunotherapy is effective in reducing symptoms of allergic asthma and rhinitis and potentially modifies the underlying course of disease. Studies on AIT in the treatment of AD and food allergy could broaden the indications. However, AIT remains underused because of a lack of awareness, limited access to specialist care, the reimbursement policy, long duration, and concerns regarding safety and effectiveness. The major barrier for the further development of immunotherapy, especially for the new technologies, is the capacity to perform 1 or more phase 3 confirmatory double-blind, placebo-controlled trials per allergen source.

 

Medicare Billing Guidelines for Immunotherapy (95165, 95170)

In establishing the practice expense component for mixing a multidose vial of antigens, we observed that the most common practice was to prepare a 10 cc vial; we also observed that the most common use was to remove aliquots with a volume of 1 cc. Our PE computations were based on those facts. Therefore, a physician’s removing 10 1cc aliquot doses captures the entire PE component for the service.

 

This does not mean that the physician must remove 1 cc aliquot doses from a multidose vial. It means that the practice expenses payable for the preparation of a 10cc vial remain the same irrespective of the size or number of aliquots removed from the vial. Therefore, a physician may not bill this vial preparation code for more than 10 doses per vial; paying more than 10 doses per multidose vial would significantly overpay the practice expense component attributable to this service.

 

Prior Approval:

Not applicable

 

Policy:

See Associated Policies: 02.01.02 for Allergy Testing. For information on oral immunotherapy tablets see Oral Immunotherapy Policies: 05.01.110 Oralair, 05.01.111 Ragwitek and 05.02.31 Odactra

 

Allergy immunotherapy is only recommended and considered medically necessary for:

  • allergic rhinitis not due to food allergy
  • allergic conjunctivitis, not due to food allergy
  • allergic asthma, not due to food allergy
  • stinging insect hypersensitivity (current state). 

 

Allergy immunotherapy is considered investigational for all other indications, including but not limited to:

  • Angioedema
  • Atopic dermatitis
  • Chronic urticaria
  • Food allergies
  • Intrinsic (non-allergic) asthma
  • Migraine headaches
  • Poison ivy/poison oak
  • Treatment of behavior health disorders
  • Treatments for electromagnetic sensitivity syndrome/disorder
  • Non-allergic rhinitis 

 

Intralymphatic and Epicutaneous Immunotherapy are considered investigational.

 

Allergy therapy with Rapid Desensitization (also known as Rush or Cluster Desensitization process), in which the person would get an increased dosage over only a few days instead of over months or years, may be considered medically necessary only for patients with the following:

  • Insect sting hypersensitivity
  • IgE antibodies to a particular drug that is essential for a condition that cannot be treated effectively with alternative medications 

 

Rapid Desensitization for any other condition, including but not limited to food allergies and inhalant allergies is considered investigational.

 

Sublingual drop immunotherapy is considered investigational for all indications.

 

Oral mucosal immunotherapy compounds (eg toothpaste/Allerdent) is considered investigational.

 

Allergen-proof supplies, such as mattresses, pillows, and casings, etc., are considered personal convenience items and are not covered.

 

Per unit reimbursement for allergy immunotherapy is based on the number of dosages prepared and intended for administration. When billing, providers should report the number of units representing the number of 1cc doses being prepared. A maximum of 10 doses per vial is allowed.

 

Allergy immunotherapy, including insect immunotherapy, is limited to 120 units annually (this would equate to 12 pure allergen vial preparations that are then diluted and used for therapy) for the first year of therapy during escalation, and 90 units (which equates to 9 pure allergen vials) for yearly maintenance therapy thereafter.

 

There would not be a medical necessity to receive allergy immunotherapy through injections for grass allergies if oral immunotherapy tablets are also being utilized. 

Home Immunotherapy/Self Infusion

According to guidelines from the American Academy of Asthma, Allergy and Immunotherapy: allergen immunotherapy should be administered in a medical facility with trained staff and medical equipment capable of recognizing and treating anaphylaxis.

 

The administration of, and the provision of allergy serum for home immunotherapy (sometimes referred to as low dose immunotherapy) is considered a safety concern and not supported in guidelines, therefore it will be considered investigational.

 

Chemically modified allergen extracts (allergoids) are considered investigational. Currently allergoids are not approved for use in the United States.

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.

  • 95115 Professional services for allergen immunotherapy not including provision of allergenic extracts; single injection
  • 95117 Professional services for allergen immunotherapy not including provision of allergenic extracts; 2 or more injections
  • 95144 Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy, single dose vial(s) (specify number of vials)
  • 95145 Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy (specify number of doses); single stinging insect venom
  • 95146 Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy (specify number of doses); 2 single stinging insect venoms
  • 95147 Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy (specify number of doses); 3 single stinging insect venoms
  • 95148 Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy (specify number of doses); 4 single stinging insect venoms
  • 95149 Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy (specify number of doses); 5 single stinging insect venoms
  • 95165 Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy; single or multiple antigens (specify number of doses)
  • 95170 Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy; whole body extract of biting insect or other arthropod
  • 95180 Rapid desensitization procedure, each hour (eg, insulin, penicillin, equine serum)
  • 95199 Unlisted allergy/clinical immunologic service or procedure ( e.g., sublingual immunotherapy)
  • J7999 Compounded drug, not otherwise classified

 

Selected References:

  • Munoz-Lopez F. Editorial; New administration route in immunotherapy. Allergologia et Immunopathologia 2000; 28(6):295-297.
  • Lockey RR, Bousquet J, Malling HJ. WHO position paper on oral (Sublingual) immunotherapy. Annals of Allergy, Asthma and Immunology 1999; vol. 8:423-424.
  • Seidenfeld, J, et al. Sublingual Immunotherapy for Adults. TEC Assessment Program Vol. 18, No. 4 June 2003
  • American Academy of Allergy, Asthma and Immunology. American College of Allergy, Asthma and Immunology.   Allergen immunotherapy: a practice parameter.  Ann Allergy Asthma Immunol. 2003 Jan; 90(1 Suppl 1): 1-40
  • Barrett S, Index of Questionable Treatments Nambudripad's Allergy Elimination Technique (NAET); Accessed on the web 12/20/05.
  • Cox L; Linnemann D, et al.  Sublingual immunotherapy: a comprehensive review.  J Allergy Clin Immunol 2006 May;117(5):1021-35.
  • Varshney P, Jones SM, Scurlock AM et al. A randomized controlled study of peanut oral immunotherapy: clinical desensitization and modulation of the allergic response. J Allergy CLin Immunol. 2011 Mar; 127(3):654-60.
  • Jones SM, Pons L, Roberts JL et al. Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol. 2009 Aug; 124(2):292-300, 300.el-97. Epub 2009 Jul 3.
  • Shripak JM, Nash SD, Rowley H et al. A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow's milk allergy. J Allergy Clin Immunol. 2008 Dec; 122(6):1154-60. Epub 2008 Oct 25.
  • Zapatero L, Alonso E, Fuentes V et al. Oral desensitization in children with cow's milk allergy. J Investig Allergol Clin Immunol. 2008; 18(5):389-96.
  • De Bot CM, 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.
  • Calderon MA, Penagos M, Sheikh A et al. Sublingual immunotherapy for treating allergic conjunctivitis. Cochrane Database Syst Rev 2011; (7):CD007685.
  • Radulovic S, Wilson D, Calderon M et al. Systematic reviews of sublingual immunotherapy (SLIT). Allergy 2011; 66(6):740-52.
  • 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.
  • 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. 
  • Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M, 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 2013;131:1288-96.
  • MK-3641 (SCH 0693413): Ragweed Allergy Immunotherapy tablet page 102 fda advisory committee meeting background package. January 28, 2014. p1-105.
  • Stallergenes S.A. Oralair® (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass mixed pollens allergen extract) tablet for sublingual use package insert, April 2014. FDA. Briefing document: Grastek, Allergenic Products Advisory Committee (APAC) meeting December 12, 2013.
  • Lin SY, Erekosima N, Kim JM et al. Sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma: a systematic review. JAMA : the journal of the American Medical Association 2013; 309(12):1278-88.
  • 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.
  • Stallergenes S.A. Oralair® (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue Grass mixed pollens allergen extract) tablet for sublingual use package insert, April 2014.
  • Merck & Co., Inc. Grastek® (Timothy grass pollen allergen extract) tablet for sublingual use prescribing information, April 2014.
  • American Academy of allergy Asthma and Immunology, CMS and Medically Unlikely Units.
  • Martínez-Gómez JM, Johansen P, Erdmann I, Senti G, Crameri R, Kündig TM. Intralymphatic injections as a new administration route for allergen-specific immunotherapy. Int Arch Allergy Immunol. 2009;150:59–65.
  • Senti G, Johansen P, Kündig TM. Intralymphatic immunotherapy. Curr Opin Allergy Clin Immunol. 2009;9:537–543.
  • Patterson A, Bonny A, IIShiels W, Erwin E, Shiels W. Three-injection intralymphatic immunotherapy in adolescents and young adults with grass pollen rhinoconjunctivitis. Annals Of Allergy, Asthma & Immunology [serial online]. February 2016;116(2):168-170. Available from: CINAHL Complete, Ipswich, MA.
  • Hylander T, Latif L, Petersson-Westin U, Cardell LO. Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis. J Allergy Clin Immunol 2013;131: 412-20.
  • Medicare Claims Processing Manual, Chapter 12- Physicians/Non-physician practitioners. Revised 3883, 10/13/17. database/lcd_attachments/34597_9/L34597_ALRG001_BCG.pdf
  • DBV Technologies, Epicutaneous Immunotherapy (EPIT®), Viaskin Technologies.
  • Roberts G, Pfaar O, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: allergic rhinoconjunctivitis. Allergy. Apr 2018;73(4):765-798. PMID 28940458
  • Allovate Therapeutics, LLC. Product insert.
  • Reisacher WR, et al. Oral mucosal immunotherapy for allergic rhinitis: A pilot study. Allergy Rhinol (Providence). 2016 Spring; 7(1): e21-e28.
  • Carnes, J.,, Gallego, M.,  et al. Allergoids for Allergy Treatment, Recent Patents on Inflammation & Allergy Drug Discovery (2018) 12: 110. 
  • Kopp M, V, Bovermann X, Klimek L: Accelerated Dose Escalation with Three Injections of an Aluminum Hydroxide-Adsorbed Allergoid Preparation of Six Grasses Is Safe for Patients with Moderate to Severe Allergic Rhinitis. Int Arch Allergy Immunol 2020;181:94-102. doi: 10.1159/000503684

 

Policy History:

  • February 2020 - Annual Review, Policy Revised
  • February 2019 - Annual Review, Policy Revised
  • February 2018 - Annual Review, Policy Revised
  • February 2017 - Annual Review, Policy Revised
  • April 2016 - Annual Review, Policy Revised
  • January 2016 - Interim Review, PolicyRevised
  • May 2015 - Annual Review, PolicyRevised
  • May 2014 - Annual Review, PolicyRevised
  • July 2013 - Annual Review, PolicyRevised
  • September 2012 - Annual Review, PolicyRevised
  • September 2011 - Annual Review, PolicyRevised

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.