Allergy Immunotherapy

Italicized font – represents CMS national NCD language/wording copied directly from CMS Manuals or CMS Transmittals. Contractors are prohibited from changing national NCD language/wording.

Title XVIII of the Social Security Act, Section 1833 (e) prohibits Medicare payment for any claim which lacks the necessary information to process the claim.

Title XVIII of the Social Security Act, Section 1862 (a) (1) (A) allows coverage and payment of those items or services that are considered to be medically reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member.

Title XVIII of the Social Security Act, Section 1862 (a) (1) (D) excludes investigational or experimental from Medicare coverage.

42 CFR Section 410.68 – Antigens: Scope and Conditions. This section describes that Medicare Part B pays for (a) antigens that are furnished as services incident to a physician’s professional services; or (b) a supply of antigen sufficient for not more than 12 months that is. It describes who prepares, administers, and supervises.

CMS Pub 100-02 Medicare Benefit Policy Manual, Chapter 15 – Covered Medical and Other Health Services, Sections
20.2 – Physician Expense for Allergy Treatment,
50.4.4.1 – Antigens,
60.2 – Services of Nonphysician Personnel Furnished Incident to Physician’s Services
80.1 – Clinical Laboratory Services, and
80.6 – Requirements for Ordering and Following Orders for Diagnostic Tests.
Chapter 16 – General Exclusions From Coverage, Section
90 – Routine Services and Appliances, B. Antigens.

CMS Pub 100-03 Medicare National Coverage Determinations (NCD) Manual, Chapter 1 – Coverage Determinations, Part 2, Sections
110.9 – Antigens Prepared for Sublingual Administration
110.11 – Food Allergy Testing and Treatment

CMS Pub 100-04 Medicare Claims Processing Manual, Chapter 12 – Physicians/Nonphysician Practitioners, Section
200 - Allergy Testing and Immunotherapy, and
Chapter 16 – Laboratory Services, Section
40.7 – Billing for Noncovered Clinical Laboratory Tests.

The management of the allergy following a diagnosis can be a complex process depending upon the number of allergens causing an immunological response and the severity of the associated symptoms. There are three courses of treatments for allergy, which may be used individually, or in a combination with one another:

1. Avoidance and environmental control - the goal of this treatment is to minimize exposure to allergy triggers.
2. Pharmacotherapy - this treatment can include one or more types of oral antihistamines, oral steroids, nasal sprays including corticosteroids, eye drops, leukotriene modifiers, and/or nasal sinus rinse with saline. Many take these medications without identifying the allergens that are causing the symptoms. This is an on-going therapy and the long-term health effects are unknown.
3. Immunotherapy - this treatment involves injection of a patient with an allergen solution in an effort to develop an immune system tolerance. It treats the cause of the disease rather than managing the symptoms.

The management plan must be individualized, with careful consideration given to the patient’s preference, disease severity, and response (or lack of response) to previous treatment.

Overview:
Allergy Immunotherapy (AIT) is defined as the repeated administration of specific allergens to patients with IgE-mediated conditions, for the purpose of providing protection against the allergic symptoms and inflammatory reactions associated with natural exposure to these allergens. Immunotherapy (hyposensitization) may extend over a period of years, usually on an increasing dosage scale. This is followed by a build-up of tolerance to the antigen (as evidenced by the markedly higher doses that can be administered) and a decline in the symptoms and medication requirements of the patient. Indications for immunotherapy are determined by diagnostic testing appropriate to the individual needs of each patient and his/her clinical history of allergic diseases. It is an effective treatment for allergic asthma and rhinitis/conjunctivitis, as well as stinging insect hypersensitivity. In addition to reducing symptoms, AIT can change the course of allergic disease and induce allergen-specific immune tolerance. It appears to have duration of efficacy of up to 12 years and can prevent the development of asthma and new allergen sensitivities.

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 of exposure or expectation of exposure would not be considered clinically relevant, and therefore, is non-covered.

Allergen immunotherapy should be differentiated from the process of desensitization, which usually applies to the rapid progressive administration of an allergenic substance to render effector cells less reactive. This is commonly referred to as “Rush” or “Cluster” immunotherapy.

The major risk of allergen immunotherapy is anaphylaxis. An assessment of the patient’s current health status should be made before administration of the allergy immunotherapy injection to determine whether there were any health changes that might require modifying or withholding the patient’s immunotherapy treatment. Poorly controlled asthma has been identified as a risk factor for a severe immunotherapy-induced reaction. Allergen immunotherapy should, therefore, be administered under the supervision of an appropriately trained physician who can recognize early symptoms and signs of anaphylaxis and administer emergency medications where necessary. In addition, immunotherapy should be administered only in facilities equipped to treat anaphylaxis. It would be rare to see the patient receive allergy immunotherapy in the home by a properly trained individual due to the risk of anaphylaxis and death.

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 the patient’s clinical history, allergen exposure history, and the test results 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 consider 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.

Immunotherapy should be administered in a setting that permits the prompt recognition and management of adverse reactions. The preferred location for such administration is the prescribing physician’s office. However, patients can receive immunotherapy injections at another health care facility if the physician and staff at that location are trained and equipped to recognize and manage immunotherapy reactions, particularly anaphylaxis. Patients should wait at the physician’s office/medical clinic for at least 30 minutes after the immunotherapy injection(s) so that reactions can be recognized and treated promptly if they occur.

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. The immunotherapy dose and schedule, as well as the benefits and risks of continuing immunotherapy, should be evaluated by the prescribing physician after any immunotherapy-induced systemic reaction.

Immunotherapy has two phases: A build-up phase and a maintenance phase.

The build-up phase (also called updosing, induction, or the dose-increase phase) includes the initiation and subsequent rise of applicable antigen concentrations. The starting dose of an allergenic extract and the progression of the dose must be individualized for each patient. Documentation of this phase should include the initial concentration, any changes/delay of progress and the reasoning for such delays, and the target concentration.

Injections usually occur 1-3 times per week and can take anywhere from 8-28 weeks to achieve a maintenance dose. Since it should be rare that injections would be administered less frequent than the dosing intervals above, providers should expect denials when reporting these services less frequently. 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. Accelerated schedules 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 systemic reaction in some patients.

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 (eg.1:100 vol/vol dilution of maintenance concentrate). Although all treatment regimens must be individualized for a given patient, acceptable maintenance dose concentrations are generally as the following:

1. For standard allergen extracts: 500 to 2000 allergy units (AU; e.g. for dust mite): or
   1000-4000 bioequivalent allergy units (BAU; e.g. for grass or cat).
2. For non-standardized extracts: a suggested maintenance dose is 3000-5000 protein nitrogen units (PNU) or 0.5ml of a 1:100 or 1:200 wt/vol dilution of manufacturer's extract.
3. For major known allergen concentration of the extract: a range between 5 and 20 micrograms of major allergen is the recommended maintenance dose for inhalant allergens and 100 micrograms for Hymenoptra venom.

Documentation of the extracts being used should include concentrations. The maintenance concentrate should be formulated to deliver a full projected therapeutic dose of each of its constituent components. However, some patients might not tolerate the targeted therapeutic dose because of local reactions, systemic reactions, or both, and their maintenance dose would be lower to the highest tolerated effective therapeutic dose. The maintenance dose of immunotherapy for a particular patient must be individualized. Significant subtherapeutic dosing in a maintenance manner will be considered not reasonable and not necessary.

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.

Treatment will not be reimbursed after a 2-year period when there is no apparent clinical benefit as noted above.

The American Academy of Allergy, Asthma, and Immunology (AAAAI), the American College of Allergy, Asthma, and Immunology (ACAAI), and Joint Council of Allergy, Asthma, and Immunology for Allergen Immunotherapy issued guidelines in 2011 regarding immunotherapy frequency and duration:

1. Cluster immunotherapy is an accelerated build-up schedule that entails administering several injections at increasing dose (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 4-8 weeks).
2. Rush immunotherapy is an accelerated immunotherapy buildup schedule that entails administrating incremental doses of the rapid administration of incremental doses of allergens at intervals varying between 15 and 60 minutes over 1 to 3 days until the target schedules for inhalant allergens can be associated with a greater risk of systemic reactions, particularly in high risk patients, and premedication primarily with antihistamines and corticosteroids appears to reduce the risk associated with rush immunotherapy. When maintenance dose is achieved, intervals between injections can be progressively increased as tolerated to 4 – 6 weeks.
3. Venom immunotherapy (VIT) injections generally are given at weekly intervals. The maintenance dose and clinical protection can routinely be achieved with 8 weekly treatments, and even 2-day rush schedules can be used in most patients without an increased risk of systemic reactions. VIT intervals between maintenance dose injections can increase to 4 weeks the first year of VIT and eventually to every 6 – 8 weeks during subsequent years.
4. 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.
5. The patient’s response to immunotherapy should be evaluated on a regular basis. A decision about continuation of effective immunotherapy should generally be made after the initial period of 3 to 5 years of treatment. Some patients might experience sustained clinical remission of their allergic disease after discontinuing immunotherapy, but others might relapse. The severity of disease, benefits sustained from treatment, and convenience of treatment are all factors that should be considered in determining whether to continue or stop immunotherapy for any individual patient. Currently, there are inadequate diagnostic tools available to identify which patients will experience a sustained clinical remission after discontinuing inhalant immunotherapy. Therefore, the duration of treatment should be determined by the physician and patient after considering the benefits and risks associated with discontinuing or continuing inhalant immunotherapy.
6. Although there are no specific tests to distinguish which patients will relapse after discontinuing VIT, there are clinical features that are associated with a higher chance of relapse, notably a history of a very severe reaction to a sting, an increased baseline serum tryptase level, a systemic reaction during VIT (to a sting or a venom injection), honeybee venom allergy, and treatment duration of less than 5 years.

Allergen Supply:
Payment may be made for a reasonable supply of antigens that have been prepared for a particular patient when certain criteria are met. See: CMS Pub 100-02 Medicare Benefit Policy Manual, Chapter 15 - Covered Medical and Other Health Services, Section - 50.4.4.1 - Antigens (Rev. 186, Issued: 04-16-14, Effective: 01-01 01, Implementation: 05-12-14)

Providers of Immunotherapy:
The physician prescribing immunotherapy should be trained and experienced in prescribing and administering immunotherapy. For those providers without formal training moving into an allergy type practice, ongoing yearly training specifically for allergy testing and treatment should be evident in CMEs. If any Medicare entity requests documentation of training, formal training, or ongoing CME updates, this information must be made available.

Antigens need to be prepared by a physician who is a doctor of medicine or osteopathy who has examined the patient and has determined a plan of treatment and a dosage regimen. (CMS Pub 100-02 Medicare Benefit Policy Manual, Chapter 15, Section 50.4.4.1)

WPS GHA would continue to expect compliance with CMS Pub 100-02 Medicare Benefit Policy Manual, Chapter 15 – Covered Medical and Other Health Services Sections, Section 60.2 – Services of Nonphysician Personnel Furnished Incident to Physician’s Services.

Indications:
Indications for immunotherapy are determined by appropriate diagnostic procedures coordinated with clinical judgment and knowledge of the natural history of allergic diseases. The following indications are considered medically reasonable and necessary for allergy immunotherapy:

1. Controlled studies have shown that allergen immunotherapy is effective for patients with:

a. Allergic rhinitis,
b. Allergic conjunctivitis,
c. Allergic asthma, and
d. Stinging insect hypersensitivity.

Allergen-induced asthma is an indication for immunotherapy along the guidelines for allergic rhinitis when there is a poor response to environmental control or pharmacologic treatment. Allergen immunotherapy in asthmatic patients should not be initiated unless the patient’s asthma is stable. Patients with severe or uncontrolled asthma are at increased risk for systemic reactions to immunotherapy injections.

2. The necessity of allergen immunotherapy depends on the:

a. Degree to which symptoms can be reduced by medications,
b. Ability of the patient to tolerate possible side effects of the medication,
c. Amount, type, and cost of the medications required to control symptoms,
d. Significant exposure to an allergen in which there is a significant level of sensitivity, and the pattern of symptoms conform to the pattern of exposure, and
e. Whether conservative therapies (including avoidance) have failed to control the symptoms, or avoidance of the relevant antigen (e.g., dust mites, pollen, and mold) is impractical.

3. Animal dander sensitivity (epidermal) may respond to immunotherapy. While removal of the offending allergen is recommended, this is often not possible or there may be occupational or other sources of exposure. Antihistamines are used first before immunotherapy, but a trial of immunotherapy may be warranted if the antihistamines do not relieve symptoms. 

 4.   Aeroallergen immunotherapy is indicated for patients with allergic rhinitis due to:

a.   Seasonal pollinosis caused by trees, grasses, and weeds.
b. The treatment of mold-induced rhinitis.
c. Perennials such as cat and dog dander, dust mite and cockroach. 

5. Standardized dust mite extracts appear effective for immunotherapy. Other environmental allergens (e.g., kapok, jute, feathers, and unstandardized house dust extracts) are of questionable value in immunotherapy, however, and generally should not be used.

6. Venom immunotherapy is indicated for patients who have a severe systemic anaphylactic reaction after an insect sting and a positive skin test or other documented IgE sensitivity to specific insect venom.

7. Patients with delayed systemic reactions, with symptoms of anaphylaxis or serum sickness and with a positive skin test or presence of venom specific IgE by in vitro testing are also recommended for treatment.

 8.  Rapid desensitization is indicated in cases of allergy to insulin, penicillin and horse serum, as well as sulfonamides, cephalosporins and other commonly used drugs (e.g. aspirin). Rush desensitization can also be used in select patients with stinging insect allergies. In patients with a positive history of reaction and with documented skin test reactivity, every effort should be made to avoid the use of these substances. When circumstances require the use of one of these substances, the patient will have to be desensitized. Desensitization may need to be repeated if future circumstances require an additional course of the offending allergen. Full-dose therapy should be initiated immediately after reactions (treated and controlled), requiring strict physician monitoring in a setting with continuous monitoring of vital signs and cardio-respiratory status. In most cases, this can be performed in a physician’s office if a physician trained to treat anaphylaxis is physically present for the entire duration. In cases where the initial reaction was severe, desensitization should be performed in the ambulatory care department of a hospital.

Limitations:
The following allergy immunotherapy services are considered investigational and experimental, therefore, are not medically necessary. The effectiveness also has not been established; therefore, these indications will not be covered;

1. Angioedema. 
2. Food hypersensitivity/allergy. 
3. Intrinsic (non-allergic) asthma. 
4. Migraine headaches. 
5. Non-allergic vasomotor rhinitis.

The following allergy immunotherapy services are considered investigational and experimental, and are therefore not medically necessary. The effectiveness also has not been established; therefore, these indications will not be covered:

1. Therapy with allergoids or adjuvants. 
2. Therapy via other administration:
   
   1. Oral or sublingual food immunotherapy*,
   2. Epicutaneous immunotherapy,
   3. Intralymphatic immunotherapy,
   4. Intranasal immunotherapy, or
   5. Sublingual immunotherapy. 
3. Desensitization with commercially available extracts of poison ivy, poison oak, or poison sumac. 
4. Desensitization for hymenoptera sensitivity using whole body extracts, with the exception of fire ant extracts**. 
5. Desensitization with bacterial vaccine (BAC: bacterial, antigen complex, streptococcus vaccine, staphylo-strepto vaccine, serobacterin, staphylococcus phage lysate). 
6. Food allergenic extracts immunotherapy. 
7. Intracutaneous desensitization (Rinkel Injection Therapy, RIT). 
8. Intracutaneous titration. 
9. Neutralization therapy (intradermal and subcutaneous). 
10. Repository emulsion therapy. 
11. Sublingual desensitization***. 
12. Sublingual provocative therapy***. 
13. Urine auto-injection (autogenous urine immunotherapy). 
14. Allergen immunotherapy for the management of skin and mucous membrane diseases such as atopic dermatitis, chronic urticaria, and Candida vulvovaginitis. 
15. Postmortem examination for IgE antibodies to identify allergens responsible for lethal anaphylaxis (postmortem work is not-covered by Medicare).

Patients who are mentally or physically unable to communicate clearly with the allergist and those with a history of noncompliance are not good candidates for allergy immunotherapy. If a patient cannot communicate clearly with the physician; it will be difficult for the patient to report signs and symptoms, especially early symptoms, suggestive of systemic reactions.

*Several clinical trials with oral and sublingual immunotherapy demonstrate an increased tolerance to oral food challenge in subjects with food hypersensitivity while receiving therapy. Oral and sublingual food immunotherapy is investigational. At present, the only treatment for food hypersensitivity is avoidance.

**Immunotherapy with whole-body extracts of biting insects or other arthropod is covered only for fire ant extracts.

***Sublingual immunotherapy (SLIT) involves the use of FDA approved allergenic extracts administered orally. In early 2014, the FDA approved oral administration of 3 allergenic extracts, two for grasses and one for ragweed. These extracts are not approved by the FDA for anyone over the age of 65 years. Medicare does not cover sublingual immunotherapy. Effective October 31, 1988, sublingual intracutaneous and subcutaneous provocative and neutralization testing and neutralization therapy for food allergies are excluded from Medicare coverage because available evidence does not show that these tests and therapies are effective. (CMS Pub 100-03 Medicare National Coverage Determinations Manual, Chapter 1- Coverage Determinations, Part 2, Section 110.11 – Food Allergy Testing and Treatment).

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Documentation Requirements
Adequate documentation is essential for high-quality patient care and to demonstrate the reasonableness and medical necessity of the treatment. Documentation must support the criteria for coverage as described in the Coverage Indications, Limitations, and/or Medical Necessity section of this LCD. There should be a permanent record of the allergy test and its interpretation including the test methodology and measurement (in mm) of reaction size of both wheal and erythema response in vivo testing. For the in vitro testing, the quantitative result(s) (in kIU/L) for specific IgE must be documented. If vitro testing is used, the medical necessity must be documented. All patient reaction(s) or complications should be recorded. The report should address or answer any specific clinical questions. If there are factors that prevent answering the clinical questions specific for this patient, this should be explained in the documentation. An official interpretation (final report) of the testing and plan for treatment, should be included in the patient’s medical record. Retention of the allergy test(s) and treatment plan should be consistent both with clinical need and with relevant legal and local health care facility requirements.

The medical record must document the elements of the medical and immunologic history including but not limited to correlation of symptoms; occurrence of symptoms; exposure profile; documentation of allergic sensitization by accepted means and where attempts at avoidance have proven unsuccessful (or the impracticality of avoidance exists); and a copy of the sensitivity results; along with the physical examination. Testing results and treatment need to justify the diagnosis and code on each claim form. The clinical condition that is claimed to justify this treatment must be clearly documented in the record. Note: A payable diagnosis alone does not support medical necessity of ANY service. The interpretation of the test results and how the results of the test was used in the patient’s plan of care for treatment and the management of the patient’s medical condition (s) must be documented. The treating physician must clearly document the medical necessity to initiate allergen immunotherapy and the continued need thereof. This plan of care needs to include the dosage regimen. Progress notes that document physician management during the course of the allergic disease, anticipated length of treatment, and explanation of any deviations from normal treatment frequency should be included. The record should be prepared so that the data regarding injection and responses can be appreciated in a logical and sequential sense. Documentation must support the use of the CPT code (e.g., number of venoms, number of vials) being billed.

When the documentation does not meet the criteria for the service rendered or the documentation does not establish the medical necessity for the services, such services will be denied as not reasonable and necessary under Section 1862(a)(1) of the Social Security Act.

All documentation must be maintained in the patient’s medical record and made available to Medicare upon request.

If the provider of the service is other than the ordering/referring physician, the provider of the service must maintain hard copy documentation of test results and interpretation, along with copies of the ordering/referring physician’s order for the testing. The physician must state the clinical indication/medical necessity for the test in his/her order.

When an evaluation and management service is billed on the same day as allergen immunotherapy (by the same physician), a separately identifiable service must be documented in the medical record.

When claims are submitted for rapid desensitization to environmental allergens, documentation of the medical necessity for this form of immunotherapy must be maintained in the medical record.

It is rare to see a patient receiving immunotherapy in home by properly trained person (who could be the patient) due to risk of anaphylaxis and death. The physician making the immunotherapy can bill for that service but not the administration of the immunotherapy as the patient is performing the service themselves. The record should clearly state why it is being done by the patient in the home and that they were educated in the recognition and treatment of allergic reactions and anaphylaxis related to administration of immunotherapy.

Utilization Guidelines
It is expected that these services would be performed at frequencies as indicated by current medical literature and/or standards of practice. When services are performed in excess of established parameters, they may be subject to review for medical necessity.

A reasonable supply of antigens is considered to be not more than a 12-month supply of antigens that has been prepared for a particular patient at any one time. (CMS Pub 100-02 Medicare Benefit Policy Manual, Chapter 15- Covered Medical and Other Health Services, 50.4.4.1 – Antigens)

Preventive and/or screening services unless covered in Statute are not covered by Medicare.

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