Response to Comments: Allergen Immunotherapy (AIT) with Subcutaneous Immunotherapy DL36408

The Advocacy Council of the American College of Allergy, Asthma and Immunology (“ACAAI”), together with its sponsoring organization—the ACAAI, appreciate the opportunity to submit comments on Wisconsin Physicians Service Insurance Corporation’s (“WPS”) proposed local coverage determination (“LCD”) DL36408—Allergen Immunotherapy (“AIT”) with Subcutaneous Immunotherapy (“SCIT”). The Advocacy Council and the ACAAI represent the interests of more than 6,000 allergists-immunologists and health care professionals who provide care in diverse clinical settings, from solo and small-group practices to large academic medical centers. Our members routinely deliver patient-specific allergen immunotherapy as part of evidence-based allergy and asthma management.

We appreciate WPS’ efforts to update the LCD governing allergy immunotherapy. However, we strongly urge WPS to adopt documentation and claims processing standards that are consistent with guidelines developed by medical societies representing the field of allergy. Excessive audits and improper pre-payment denials of claims for allergen immunotherapy services (CPT codes 95165, 95115, and 95117) continue to pose a persistent and significant challenge for allergy practices. These inappropriate claims processing practices create substantial financial burdens, particularly for small and independently owned practices that often lack the administrative resources to engage in lengthy appeals, pursue the provider dispute resolution process, or compile extensive documentation. This financial strain not only threatens the stability of individual practices but also jeopardizes patient access to medically necessary allergen immunotherapy. Accordingly, we urge WPS to align its documentation and claims review standards with the evidence-based, consensus-driven guidance issued by ACAAI, the American Academy of Allergy, Asthma, and Immunology (“AAAAI”), and the American Academy of Otolaryngic Allergy (“AAOA”).

Documentation for Allergen Immunotherapy Services

On November 5, 2024, ACAAI, AAAAI, and AAOA jointly released guidance to inform payors about the appropriate documentation requirements for claims related to CPT codes 95165, 95115, and 95117.1 This guidance outlines the types of documentation that should be requested during claims review, as well as those that should not be required. Below is a summary of our recommendations regarding reasonable and unreasonable documentation requests for these CPT codes. We believe that payors should limit documentation requirements to the reasonable list provided and refrain from requesting additional materials that are not essential for adjudicating claims. The list of unreasonable requests is included for illustrative purposes only and is not intended to be exhaustive. Rather, it highlights the kinds of unnecessary documentation demands that create undue administrative burden for providers.

CPT Code 95165

“Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy; single or multiple antigens (specify number of doses)”
Based on the collective expertise and experience in the field of allergy medicine, ACAAI, AAAAI, and AAOA, strongly recommend that payors limit their documentation requests to the following documents to determine the medical necessity of CPT code 95165.

Reasonable Requests for Documentation

1. The identity of the physician who established the treatment plan.

2. The identity of the patient and a short description of the clinical indications for allergen immunotherapy.

3. A brief description of the treatment plan and the date on which it was formulated.

4. A description of the response to allergy immunotherapy and the need for continued allergen immunotherapy at routine visits.

5. A signed and dated order for allergen extract listing the allergy extract ingredients (i.e., antigens), concentrations (Allergy Unit, Bioequivalent Allergy Unit, and weight to volume), volumes of extract, and diluent (cubic centimeters or milliliters) should be available to document the contents of both the initial and refill allergy extracts vial.

6. The initials of the allergen extract compounding healthcare professional.

Unreasonable Requests for Documentation

A demand for the following documentation when a claim is submitted under CPT code 95165 is unnecessary and unduly burdensome on allergy practices.

1. A requirement that allergy extracts billed under CPT 95165 be based on a volume of 1 ml. or some other insurer-specific maximum. Depending on the condition of the patient and the composition of the appropriate allergen, the patient may receive injections of different volumes and require additional extract vials. In addition, there are limits to the number of allergens that can be compounded in a vial. Annual dose limits should allow these variations.

2. Adhering to medically unlikely edits (“MUEs”) limits or insurer-specific unit maxima. it is often the standard of care to provide allergen extracts that are not 1 ml.

3. Compounding logs for each dilution and lot numbers.

4. Results of allergy skin testing.

CPT Codes 95115 and 95117
CPT Code 95115 “Professional services for allergen immunotherapy not including provision of allergenic extracts; single injection”
CPT Code 95117 “Professional services for allergen immunotherapy not including provision of allergenic extracts; 2 or more injections”

The following documentation is appropriate to request to determine whether services described by CPT codes 95115 and 95117 are medically necessary.
Reasonable Requests for Documentation
1. The date of the injection, the patient’s name, and the patient’s birth date.

2. The dose administered, specifying volume, dilution, and number of injections.

3. The site(s) of the injection (e.g., right arm).

4. The initials or signature of the person administering the injection.

Unreasonable Requests

To require the following documentation for every claim submitted under these two codes imposes an entirely unnecessary and time-consuming burden on small practices.
1. Date of vial expiration/” best use by”.

2. Full planned dosing schedule.

3. Specification of subcutaneous administration. Anthem recognizes that all injections are subcutaneous.2

4. Signature of ordering healthcare professional. It is quite burdensome to obtain the signature of the ordering professional every time that a claim is submitted.

5. Credentials of the person administering the injection.

6. A history of previous injections.

Therefore, we respectfully urge WPS to issue additional guidance to its claims reviewers, instructing them to limit documentation requests to only what is necessary to adjudicate individual claims, consistent with the standards outlined in our joint guidance. ACAAI believes that the information/documentation requested during reviews of individual claims for payment should be limited unless there is evidence of fraud that warrants additional scrutiny. We welcome the opportunity to meet with WPS’ clinical team to discuss the proper evaluation of allergen immunotherapy services. For a more detailed explanation of our recommendations, please refer to the enclosed guidance document.

Thank you for your comment.

1. The documentation is only required upon claims review. This documentation is not required for normal claims that follow the billing and coding article. However, consistent with 42 CFR 424.5(a)(6), the following applies: Sufficient information. The provider, supplier, or beneficiary, as appropriate, must furnish sufficient information to the intermediary or carrier to determine whether payment is due and the amount of payment. Thus, the documentation requirements will be maintained per the Code of Federal Regulations.

2. See previous comments regarding dosing requirements from IOMs cited in the billing and coding article. According to the LCD, the following are the only recommended documentation requirements:
   • Patient information, including name, patient number, birth date, telephone number, and picture (if available), to reduce the risk of an extract being given to the wrong patient.
   • Preparation information, including name of person preparing and date of preparation.
   • AIT extract content, including (for each allergen) common name or genus and species, extract manufacturer, concentration of manufacturer's extract, volume of manufacturer's extract added, the type of diluent (if any), volume of diluent added, lot number, and expiration date of each individual component.

However, individual MACs may request additional documentation beyond what is recommended in the LCD to determine the medical necessity of the procedure.

3. The build-up phase or the payment for the initiation of SCIT versus the maintenance of SCIT with code CPT 95165 is not differentiated from coverage and payment and is similarly provided as a reasonable and necessary service. The MACs will clarify this in the billing and coding article.

On behalf of Nebraska physicians, I am adding my written comments to my oral comments that were recorded at the last meeting if the CAC on June 26, 2025. The information below is taken from Allergen Immunotherapy: A practice parameter third update (1) which has been approved by both AAAAI and ACAAI:

Immunity has been defined as protection against certain diseases. The initial immunotherapeutic interventions, which included the use of preventive vaccines and xenogeneic antisera by Jenner, Pasteur, Koch, and von Behring, were effective for disease prevention. These initial efforts in immune modulation served as a model for later developments in allergen immunotherapy. From its empiric emergence in the early 1900s, when grass pollen inoculation was proposed as therapy for hay fever, allergen immunotherapy has progressed in both theory and practice from the passive immunologic approach to the active immunologic procedures pioneered by Noon (2) and Freeman (3), (4). Advances in allergen immunotherapy have depended on the improved understanding of IgE-mediated immunologic mechanisms, the characterization of specific antigens and allergens, and the standardization of allergen extracts. Proof of the efficacy of allergen immunotherapy has accumulated rapidly during the past 30 years. Numerous well-designed controlled studies demonstrate that allergen immunotherapy is efficacious in the treatment of allergic rhinitis, allergic conjunctivitis, allergic asthma, and stinging insect hypersensitivity. Randomized controlled studies showed that allergen immunotherapy prevents the development of asthma in subjects with allergic rhinitis.(5-7) Allergen immunotherapy is effective when appropriate doses of allergens are administered. Effective subcutaneous allergen immunotherapy appears to correlate with administration of an optimal maintenance dose in the range of 5 to 20 mg of major allergen for inhalant allergens (9-14). It should be differentiated from unproved methods, such as neutralization-provocation therapy (15) and low-dose subcutaneous regimens based on the Rinkel technique,(16,17) which have been found to be ineffective in double-blind, placebo-controlled trials. The selection of allergens for immunotherapy is based on clinical history, the presence of specific IgE antibodies, and allergen exposure.

The physician prescribing immunotherapy should be trained and experienced in prescribing and administering immunotherapy. The prescribing physician must select the appropriate allergen extracts based on that particular patient’s clinical history and allergen exposure history and the results of tests for specific IgE antibodies. The quality of the allergen extracts available is an important consideration. When preparing mixtures of allergen extracts, the prescribing physician must take into account the cross-reactivity of allergen extracts and the potential for allergen degradation caused by proteolytic enzymes. The prescribing physician must specify the starting immunotherapy dose, the target maintenance dose, and the immunotherapy schedule. In general, the starting immunotherapy dose is 1,000- to 10,000-fold less than the maintenance dose. For highly sensitive patients, the starting dose might be lower. The maintenance dose is generally 500 to 2000 allergy units (AU; eg,for dust mite) or 1000 to 4000 bioequivalent allergy units (BAU; eg, for grass or cat) for standardized allergen extracts. For nonstandardized extracts, a suggested maintenance dose is 3000 to 5000 protein nitrogen units (PNU) or 0.5 mL of a 1:100 or 1:200 wt/vol dilution of manufacturer’s extract. If the major allergen concentration of the extract is known, a range between 5 and 20 mg of major allergen is the recommended maintenance dose for inhalant allergens and 100 mg for Hymenoptera venom. Immunotherapy treatment can be divided into 2 periods, which are commonly referred to as the build-up and maintenance phases. The immunotherapy build-up schedule (also called updosing, induction, or the dose-increase phase) entails administration of gradually increasing doses during a period of approximately 8 to 28 weeks. 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. The maintenance dose (or effective therapeutic dose) is the dose that provides therapeutic efficacy without significant adverse local or systemic reactions. The effective therapeutic dose might not be the initially calculated projected effective dose. The maintenance goal (or projected effective dose) is the allergen dose projected to provide therapeutic efficacy. Not all patients will tolerate the projected effective dose, and some patients experience therapeutic efficacy at lower doses. The maintenance phase begins when the effective therapeutic dose is reached. Once the maintenance dose is reached, the intervals between allergy injections are increased. The dose generally is the same with each injection, although modifications can be made based on several variables (ie, new vials, persistent local reactions causing discomfort, or systemic reactions). The intervals between maintenance immunotherapy injections generally range from 4 to 8 weeks for venom and every 2 to 4 weeks for inhalant allergens but can be advanced as tolerated if clinical efficacy is maintained. Since the injections contain to which allergen that patients are sensitive, injections of allergen immunotherapy extract can cause local or systemic reactions. Most serious systemic reactions develop within 30 minutes after the immunotherapy injection. However, immunotherapy-induced systemic reactions can occur after 30 minutes. Patients should be counseled on the possibility of immediate and delayed systemic reactions during risk communication; an action plan for such an event should be discussed. In the event of a delayed systemic reaction, the patient should be counseled on appropriate treatment based on his or her symptoms.

The immunotherapy dose and schedule, as well as the benefits and risks of continuing immunotherapy, should be evaluated after any immunotherapy-induced systemic reaction. For some patients, the immunotherapy maintenance dose might need to be reduced and then increased again over time to the maintenance dose. The dose is the actual amount of allergen administered in the injection. If the starting dose is too diluted, an unnecessarily large number of injections will be needed, resulting in a delay in achieving a therapeutically effective dose. On the other hand, if the starting dose is too concentrated, the patient might be at increased risk of having a systemic reaction. When choosing the starting dose, most allergists/immunologists start at a dilution of the maintenance concentrate that is appropriate based on the sensitivity of the patient to the allergens in the extract, which, in turn, is based on the history and skin test reactivity. The volume and concentration can vary such that the same delivered dose can be given by changing the volume and concentration (ie, 0.05 mL of a 1:1 vol/vol allergen would equal 0.5 mL of a 1:10 vol/vol allergen). The starting dose for build-up is usually a 1,000-fold or 10,000-fold dilution of the maintenance concentrate, although a lower starting dose might be advisable for highly sensitive patients. There are 2 phases of allergen immunotherapy administration: the initial build-up phase, when the dose and concentration of allergen immunotherapy extract are increased, and the maintenance phase, when the patient receives an effective 3 therapeutic dose over a period of time. Common starting dilutions from the maintenance concentrate are 1:10,000 (vol/vol) or 1:1,000 (vol/vol), although more diluted concentrations frequently are used for patients who are highly sensitive, as indicated by history or skin test reactions. Allergen immunotherapy extracts used during the build-up phase usually consist of three or four 10-fold dilutions of the maintenance concentrate. The volume generally is increased at a rate that depends on several factors, including (1) the patient’s sensitivity to the extract, (2) the history of prior reactions, and (3) the concentration being delivered (with smaller percentage increments being given at higher concentrations). In the case of venom immunotherapy, the aim is to achieve a uniform maintenance dose of 100 mg of each venom; to this end, patients might be expected to tolerate relatively large local reactions that might not be considered acceptable with inhalant immunotherapy. The dose of allergen immunotherapy extract should be appropriately reduced after a systemic reaction if immunotherapy is continued. It is customary to either reduce the dose if a systemic reaction has occurred or consider discontinuation of immunotherapy, especially if the reaction has been severe. Although there are no evidence-based guidelines on dose adjustment after a systemic reaction, many allergists/immunologists reduce the dose to one that was previously tolerated or an even lower dose if the reaction was severe. Once the patient tolerates a reduced dose, a cautious increase into the maintenance dose. Patients receiving maintenance immunotherapy should have follow-up visits at least every 6 to 12 months. Periodic visits should include a reassessment of symptoms and medication use, the medical history since the previous visit, and an evaluation of the clinical response to immunotherapy. The immunotherapy schedule and dose, reaction history, and patient compliance should also be evaluated. The physician can at this time make adjustments to the immunotherapy schedule or dose, as clinically indicated.

Recommend:

1. Since the dose of allergen immunotherapy could be changing throughout the time of treatment (due to patient’s sensitivity, or intervals between injections) is why the use of one mL of extract cannot be the definition of a dose of allergen immunotherapy. Using the CPT definition for 95165 is more appropriate. A dose is based on the volume and concentration given and varies during the buildup phase and may even vary during the maintenance phase.
2. Limiting the amount of mL made per day and per year should not be limited because of patient safety issues since the vials need to be diluted for new vials when starting the build-up stage, large local site or systemic reactions.

Thank you for your comment. We recognize the benefits of allergen immunotherapy and the work required to administer immunotherapy and the preparation of antigens. MACs follow the guidelines provided in the IOM by CMS and are limited to those requirements.

The build-up phase or the payment for the initiation of SCIT versus the maintenance of SCIT with code CPT 95165 is not differentiated from coverage and payment and is similarly provided as a reasonable and necessary service. The MACs will clarify this in the billing and coding article.

These are the written comments to support my oral testimony at the recent CAC meeting.

The original 1 cc "dose" by Medicare for CPT 95165 never made sense to begin with.

A "dose" of immunotherapy is based on a dilution, a volume, and the various extracts contained in the vial. The other variable is the frequency of the dose, which can vary from several times per week to every 4-8 weeks, depending on the type of immunotherapy being discussed.

Four Medicare administrators (Palmetto, Noridian, National Government Services, and Novitas have endorsed changes to this code as proposed by the American College of Allergy, Asthma and Immunology (ACAAI) and the American Academy of Allergy, Asthma and Immunology (AAAAI).

These entities collectively cover 40 states. Subcutaneous allergen immunotherapy (SCIT) has been demonstrated to be equivalent to taking an inhaled corticosteroid for asthma control. Furthermore, SCIT has been shown to reduce the chance of a child who is genetically predisposed to developing asthma by 25-50%. SCIT helps patients control their allergies and asthma, thereby saving money for the healthcare system.

I would strongly encourage Dr Vlahakis and her executive team to adopt the suggested changes to DL 36408 as suggested by the ACAAI and the AAAAI.

Thank you for your comment. We recognize the benefits of allergen immunotherapy, and the work required to administer immunotherapy and the preparation of antigens. MACs follow the guidelines provided in the IOM by CMS and are limited to those requirements.

The build-up phase or the payment for the initiation of SCIT versus the maintenance of SCIT with code CPT 95165 is not differentiated from coverage and payment and is similarly provided as a reasonable and necessary service. The MACs will clarify this in the billing and coding article.

On behalf of the American Academy of Dermatology Association (AADA) and the Dermatologic Medicare Contractor Advisory Committee (DermCAC), thank you for the opportunity to comment on the Proposed LCD, DL36408 Allergen Immunotherapy (AIT) with Subcutaneous Immunotherapy (SCIT).
The AADA is the leading society in dermatological care, representing more than 17,500 dermatologists nationwide. The AADA is committed to excellence in the medical and surgical treatment of skin disease; advocating for high standards in clinical practice, education, and research in dermatology and dermatopathology; and driving continuous improvement in patient care and outcomes while reducing the burden of skin disease. The DermCAC is a national coalition of dermatologist representatives selected by their state dermatology societies and represents the board-certified dermatologists in your carrier region. The DermCAC advocates for policies that prioritize patient well-being.

The AADA and DermCAC support the proposed inclusion of atopic dermatitis (AD) due to dust mite sensitization as a covered indication for SCIT as an adjunctive treatment option for select patients with confirmed sensitization and a consistent clinical history. The AAD’s guidelines recommend assessing clinical history to determine potential allergen triggers, follow by targeted testing to confirm sensitization in appropriate cases.¹ This patient-specific approach aligns with the policy’s intent to limit coverage to those with a demonstrable allergic component contributing to their disease.

While SCIT is not routinely recommended for the general AD population, there is recent evidence supporting its use in select patients with confirmed house dust mite (HDM) sensitization and a clearly defined allergic trigger. Multiple prospective studies—including randomized controlled trials—have reported improvements in AD severity, pruritus, and reduced use of topical corticosteroids in HDM-sensitized patients who received SCIT.3,4 Although the current body of evidence is based on a limited number of small studies with varied methodologies, these findings suggest that SCIT may offer clinical benefit as an adjunct to standard AD management in appropriately selected patients.

The AADA and DermCAC appreciate the opportunity to provide feedback on the proposed LCD on allergen immunotherapy with subcutaneous immunotherapy. Thank you for your consideration of these comments. On behalf of dermatologists in the WPS region and nationwide, the AADA and DermCAC remain committed to ensuring patients have access to high-quality, medically necessary dermatologic care. We value continued collaboration with Medicare administrative contractors on all policies impacting the specialty.

Thank you for your comment. According to the article that was cited, the recommendations for allergen immunotherapy are conditional recommendations and suggestions from the AAAAI/ACAAI. From the article, the conclusion was that the AIT would be most beneficial in patients who had other allergic conditions requiring SCIT: “The panel inferred that most well-informed patients would value the moderate certainty for net benefit with AIT for moderate and severe atopic dermatitis especially if the patient had other allergic diseases that would respond to AIT”. Furthermore, the benefits of SCIT were correlated predominantly with patients who tested positive for house dust mites. The most benefit was achieved with patients who failed prior medical therapy, were continued on topical medications and who had moderate to severe AD due to dust mites. Therefore, coverage will be expanded to include patients who have failed medical therapy and have IgE-related immunity to house dust mites. Finally, in all of the studies cited in this article, the patients were also treated with topical therapy and other treatments which would infer a lesser impact from SCIT. The anticipated variability in values and preferences, particularly with age and allergic comorbidities, contributed to a conditional recommendation or suggestion. Based upon the moderate degree of evidence for SCIT for patients with AD due to house dust mites, coverage will be included as reasonable and necessary for these groups of patients who have moderate to severe AD due to dust mites.

Due to the risk of severe allergic reactions that may occur during pregnancy, it is not reasonable and necessary to initiate SCIT during the course of pregnancy. There are only a limited number of studies to support the initiation and continuation of SCIT during pregnancy and therefore this service is not considered reasonable and necessary. (Oykhman P, Kim HL, Ellis AK. Allergen immunotherapy in pregnancy. Allergy Asthma Clin Immunol. 2015;11:31.)