Medical Policy

Subject: Allergen Immunotherapy Medical Policy #: 44.0 Original Effective Date: 05/26/2021 Status: New Last Review Date: N/A

Disclaimer

Refer to the member’s specific benefit plan and Schedule of Benefits to determine coverage. This may not be a benefit on all plans or the plan may have broader or more limited benefits than those listed in this Medical Policy.

Description

Allergen Immunotherapy is defined as the repeated administration of specific allergens to patients with IgE-mediated conditions for the purpose of providing protection against allergic symptoms and inflammatory reactions associated with natural exposure to these allergens. Allergen immunotherapy should be considered for patients who have demonstrable evidence of specific IgE antibodies to clinically relevant allergens. The decision to begin allergen immunotherapy might depend on a number of factors, including but not limited to patient's preference/acceptability, adherence, medication requirements, response to avoidance, and the adverse effects of medications. The presence of IgE antibodies alone does not infer the need for immunotherapy. For example the presence of IgE antibodies to an allergen not locally found, with no history or exposure or expectation of exposure, would not be considered to be clinically relevant. In order for immunotherapy to be considered reasonable and necessary there must be: 1. Clinical relevance 2. Trial of avoidance or unavoidable exposure to allergy triggers identified in allergy testing 3. Adherence to medical regimens which is clearly documented in the medical record 4. Stable pharmacotherapy for certain conditions, such as asthma Medical documentation should demonstrate the decision to begin immunotherapy. Without clear cut reasoning documented, these services will be denied. In 2010, a Joint Task Force on Practice Parameters for Allergen Immunology issued guidelines. The Task Force included American Academy of Allergy, Asthma and Immunology (AAAAI), the American College of Allergy, Asthma and Immunology (ACAAI), and the Joint Council of Allergy, Asthma and Immunology. As these guidelines were peer reviewed, incorporated, and invited reviewers, they are felt to be the state of the art in allergen immunotherapy. The indications set out in this LCD often will reflect the principals set out in the Practice Parameters when Medicare guidelines allow.

Coverage Determination

Prior Authorization is not required. Logon to Pres Online to submit a request: https://ds.phs.org/preslogin/index.jsp Please note treatment will not be reimbursed after a 2-year period when there is no apparent clinical benefit. Coverage is for Medicare, Medicaid and Commercial. PHP follows LCD Allergen Immunotherapy (L36240) and the related article LCA (A56538). This policy imposes frequency limitations. Covered Indications Conditions for which immunotherapy is effective include: 1. Allergic rhinitis, 2. Allergic conjunctivitis, 3. Allergic asthma and 4. Stinging insect hypersensitivity. Note: Atopic dermatitis secondary to aeroallergen has been reported to be influenced by immunotherapy. (These rare issues will be reviewed through the appeals process with documentation review.) Immunotherapy has two phases. A build-up phase and a maintenance phase. Not every Presbyterian health plan contains the same benefits. Please refer to the member’s specific benefit plan and Schedule of Benefits to determine coverage [MPMPPC051001].

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1. The build-up phase includes the initiation and subsequent rise of applicable antigen concentrations. (Meaning, the phase when the dose and concentration of allergen immunotherapy extract are increased)4. Documentation of this phase should include the initial concentration, any changes/delay of progress and the reasoning for such delays, and the target concentration. Immunotherapy build-up schedule: Injections usually occur 1-3 times per week and can take anywhere from 8-28 weeks to achieve a maintenance dose. The immunotherapy build-up schedule (also called updosing, induction, or the dose increase phase) entails administration of gradually increasing doses can take anywhere from 8-28 weeks to achieve a maintenance dose. In conventional schedules a single dose increase is given on each visit, and the visit frequency can vary from 1 to 3 times a week. Accelerated schedules, such as rush or cluster immunotherapy, entail administration of several injections at increasing doses on a single visit. Accelerated schedules offer the advantage of achieving the therapeutic dose earlier but might be associated with increased risk of a systemic reaction in some patients.4 Various techniques such as cluster immunotherapy and rush immunotherapy are also included in the build-up phase and should be documented as such in the medical records. These techniques are noted to have more frequent injections in the build-up phase. • 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 nonconsecutive 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).4 • Rush immunotherapy is an accelerated immunotherapy buildup schedule that entails administering incremental doses of allergen at intervals varying between 15 and 60 minutes over 1 to 3 days until the target therapeutic dose is achieved.4 Note: Since it should be rare that injections would be administered less frequently than the dosing intervals above, providers should expect denials when reporting these services less frequently. These less frequent services will need to be reviewed through the appeals process with documentation as to why the frequency was not met, i.e. hospitalizations, illness, acute asthma events which would preclude the continuation of the build-up phase. 2. The maintenance phase occurs when the effective therapeutic dose is reached. This dose is defined as the dose that provides therapeutic efficacy without significant adverse local or systemic reactions. This dose may not be the initial target concentration but documentation should clearly show why the target concentration is not being used. All references to the therapeutic effective dose should be referenced to the maintenance concentrate and should be noted as a volume-to- volume dilution (e.g., 1:100 vol/vol dilution of maintenance concentrate). Maintenance dose concentrations: Although all treatment regimens have to be individualized for a given patient, acceptable maintenance dose concentrations are generally as follows: • For standard allergen extracts: o 500 to 2,000 allergy units (AU; e.g. for dust mite): or o 1,000-4,000 bioequivalent allergy units (BAU, e.g. for grass or cat). • For non-standardized extracts: o a suggested maintenance dose is 3,000-5,000 protein nitrogen units (PNU) or 0.5ml of a 1:100 or 1:200 wt/vol dilution of manufacturer's extract; o non-standard extracts are noted to be estimates and will need to be individualized. • For major known allergen concentration of the extract: o a range between 5 and 20 micrograms of major allergen is the recommended dose for inhalant allergens and 100 micrograms for Hymenoptra venon. Documentation of extraction: Documentation of the extracts being used should include concentrations, even if an estimate is used for non-standard extracts. Significant sub-therapeutic dosing in a maintenance manner will be considered not reasonable and necessary. Table IX and X in the Guidelines outline probable effective dose ranges. Sub-therapeutic dosing would be considered to be below these levels. Maintenance Dose Interval: The frequency of maintenance dosing can be variable depending on the extract used. During the first year, frequency may vary from subsequent years. The Task Force notes for some antigens, the maintenance dose could be every 4-8 weeks. However, the frequency should be at least every two weeks for this dosing. Follow-up Care and Duration of Treatment • Follow-up Care: During maintenance therapy, follow up visits to assess progress or lack of progress should be done at least every 6-12 months. This documentation must be available upon request. o to assess efficacy; o to implement and reinforce its safe administration and to monitor adverse reactions; o to assess the patient’s compliance with treatment; o to determine whether immunotherapy can be discontinued; and Not every Presbyterian health plan contains the same benefits. Please refer to the member’s specific benefit plan and Schedule of Benefits to determine coverage [MPMPPC051001].

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o to determine whether adjustments in the immunotherapy o dosing schedule or allergen content are necessary.4 • Length of Maintenance Therapy: The duration of all forms of immunotherapy must be individualized. A presumption of failure can be made when, after 12-24 months of therapy, a person does not experience: 1. a noticeable decrease of symptoms, 2. an increase in tolerance to the offending allergen, and 3. a reduction in medication usage. • Duration of treatment: For many patients, the recommended duration of allergen immunotherapy is 3-5 years. However, the duration of immunotherapy should be individualized based on the clinical response, disease severity, immunotherapy reaction, patient preference and certain antigens in the therapy. Allergen Supply: Please refer to the CMS IOM Publication 100-02, Medicare Benefit Policy Manual, Chapter 15, section 50.4.4.1 for information on the supply of antigen use in immunotherapy. Billing for Antigens When billing for antigens, if the beneficiary’s doses are adjusted for any reason and they receive more or less doses than initially planned providers are not to make any adjustment to the number of units billed. The number of units planned at the time of the preparation of the antigen is what is to be reported. Provider Qualifications

Providers of Immunotherapy: The physician prescribing immunotherapy should be trained and experienced in prescribing and administering immunotherapy. PHP expects practitioners’ documented training to be commensurate with the degree to which his or her practice is related to allergy testing and immunotherapy. The preparation of allergen extract should have direct supervision of any employee. Please refer to the CMS IOM Publication 100-04, Medicare Claims Processing Manual, Chapter 15, Section 60.1 Direct Personal Supervision.

Hence, if an auxiliary staff member, such as a registered nurse or technician, prepares the antigens, the physician must provide direct supervision of the services for the employee to bill an antigen therapy service incident-to the physician based on Medicare incident-to-rules. A qualified non-physician practitioner (NPP) must meet incident-to guidelines for services to qualify as incident-to. Generally, the NPP must be a full-time, part-time or leased employee of the physician or physician group practice. (In limited cases, the NPP may be an independent contractor of the physician or physician group practice.) The NPP must provide such services under the direct supervision of the physician. The supervising physician should be documented in the medical record. Additionally, the physician must have examined the patient and determined a plan of treatment and a dosage regimen.

Limitations

Treatment will not be reimbursed after a 2-year period when there is not apparent clinical benefit as noted above. Allergen immunotherapy is not indicated and is considered investigational for: 1. Food hypersensitivity 2. Urticaria and angioedema 3. Therapy with allergoids or adjuvants 4. Therapy Via Other administration: ◦Oral or sublingual food immunotherapy a. Epicutaneous immunotherapy b. Intralymphatic immunotherapy c. Intranasal immunotherapy d. Sublingual Immunotherapy 5. Desensitization with commercially available extracts of poison ivy, poison oak, or poison sumac, 6. Desensitization for hymenoptera sensitivity using whole body extracts, with the exception of fire ant extracts 7. Desensitization with bacterial vaccine (BAC: bacterial, antigen complex, streptococcus vaccine, staphylo- streptovaccine, serobacterin, staphylococcus phage lysate) 8. Food allergenic extract immunotherapy 9. Intracutaneous desensitization (Rinkel Injection Therapy, RIT) 10. Intracutaneous titration

Not every Presbyterian health plan contains the same benefits. Please refer to the member’s specific benefit plan and Schedule of Benefits to determine coverage [MPMPPC051001].

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11. Neutralization therapy (intradermal and subcutaneous) 12. Repository emulsion therapy 13. Sublingual desensitization 14. Sublingual provocative therapy 15. Urine autoinjection (autogenous, urine immunotherapy) 16. Allergen immunotherapy for the management of skin and mucous membrane disease such as atopic dermatitis (rare exceptions as noted above reviewed in the appeals process), urticarial, and Candida vulvovaginitis 17. Intranasal immunotherapy 18. Postmortem examination for IgE antibodies to identify allergens responsible for lethal anaphylaxis (post mortem work is not covered by Medicare) Coding

The coding listed in this medical policy is for reference only. Covered and non-covered codes are within this list.

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

ICD-10 CODE For covered ICD-10 codes, please see LCA Allergy Testing (A56538).

• For the following CPT codes: 95115, 95117, 95144, 95145, 95146, 95147, 95148, 95149, 95165, and 95199 see the ICD-10 code listing under Group 1 • For the following CPT code: 95170 see the ICD-10 code listing under Group 2: • For the following CPT codes: 95180 see the ICD-10 code listing under Group 3.

Reviewed by / Approval Signatures

Clinical Quality & Utilization Mgmt. Committee: Norman White MD Medical Director: David Yu MD Date Approved: 05/26/2021

Not every Presbyterian health plan contains the same benefits. Please refer to the member’s specific benefit plan and Schedule of Benefits to determine coverage [MPMPPC051001].

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References

1. CMS, Local Coverage Determination, Novitas Solutions, LCD Allergen Immunotherapy L36240, Revision history date: 11/14/2019, R6, Related article LCA (A56538), Revision history date: 10/01/2020, R3 2. CMS Internet-Only Manuals (IOMs), Publication 100-02, Medicare Benefit Policy Manual, Chapter 15, Section 20.2 Physician Expense for Allergy Treatment 3. CMS Internet-Only Manuals (IOMs), Publication 100-04, Medicare Claims Processing Manual, Chapter 12, Section 200 Allergy Testing and Immunotherapy 4. 2021 American Academy of Allergy, Asthma & Immunology, Joint Task Force, Allergen immunotherapy: A practice parameter third update, January 2011, Volume 127, numnber1. [Cited 04/25/2021]

Publication History

05/26/2021 New policy. Reviewed by PHP Medical Policy Committee on 05/12/2021. The committee agreed to follow LCD Allergen Immunotherapy L36240 and the related article LCA (A56538) for all LOB. This policy developed to impose immunotherapy guideline such as schedule, frequency limitations and duration and/or length of treatment. The CPT codes listed in the policy will not require PA. ICD-10 codes will be configured using LCA Allergen Immunotherapy (A56538) for CPT codes 95115, 95117, 95144, 95145, 95146, 95147, 95148, 95149, 95165, 95199, 95170, and 95180. Look into configuring no payment after a 2-year period for all LOB, when there is no apparent clinical benefit.

This Medical Policy is intended to represent clinical guidelines describing medical appropriateness and is developed to assist Presbyterian Health Plan and Presbyterian Insurance Company, Inc. (Presbyterian) Health Services staff and Presbyterian medical directors in determination of coverage. The Medical Policy is not a treatment guide and should not be used as such. For those instances where a member does not meet the criteria described in these guidelines, additional information supporting medical necessity is welcome and may be utilized by the medical director in reviewing the case. Please note that all Presbyterian Medical Policies are available online at: Click here for Medical Policies

Web links: At any time during your visit to this policy and find the source material web links has been updated, retired or superseded, PHP is not responsible for the continued viability of websites listed in this policy.

When PHP follows a particular guideline such as LCDs, NCDs, MCG, NCCN etc., for the purposes of determining coverage; it is expected providers maintain or have access to appropriate documentation when requested to support coverage. See the References section to view the source materials used to develop this resource document.

Not every Presbyterian health plan contains the same benefits. Please refer to the member’s specific benefit plan and Schedule of Benefits to determine coverage [MPMPPC051001].

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