Code Description CPT

95199 Unlisted allergy/clinical immunologic service or procedure

Sublingual Immunotherapy as a Technique of Allergen- Specific Therapy

Treating allergies often involves giving the person small doses of what they are allergic to. This tends to increase a person’s immunity, or tolerance, to the substance. These substances are often given by injections (shots). But a newer method is to put the substance in drops and give them under the tongue. This is called sublingual (which means under the tongue) immunotherapy. This treatment is also sometimes called allergy drops. This policy explains when sublingual immunotherapy is medically necessary.

Policy Coverage Criteria

Sublingual Immunotherapy Medical Necessity

* Oralair®
* Grastek®
* Ragwitek®

Sublingual immunotherapy using Oralair®, Grastek®, or Ragwitek® may be considered medically necessary, when used according to U. S. Food and Drug Administration labeling, for the treatment of pollen-induced allergic rhinitis when the following conditions are met:

* Patient has a history of rhinitis or rhinoconjunctivitis symptoms related to grass or short ragweed pollen exposure

* Patient has a documented positive pollen-specific skin test or pollen-specific immunoglobulin E test.

o Allergy must be confirmed by positive skin test or in vitro testing for pollen-specific immunoglobulin E antibodies to the species contained in the product or, for Grastek®, Timothy grass pollen extract, to cross-reactive species.

* Patient’s symptoms are not adequately controlled by appropriate pharmacotherapy (see Related Information). Sublingual immunotherapy as a technique of allergy immunotherapy is considered investigational for all other uses.

Use of Oralair®, Grastek®, and Ragwitek®


Contraindications include severe, unstable or uncontrolled asthma; history of any severe reactions (local or systemic) to sublingual or other immunotherapy; or a history of eosinophilic esophagitis.

Administration and Dose

* Prescribing information includes a black box warning for severe allergic reactions including anaphylaxis and severe laryngopharyngeal edema. Patients must be prescribed an epinephrine auto-injector and be trained on how to use it.

* Oralair® is approved by the Food and Drug Administration (FDA) for patients 10 to 65 years of age. Grastek® has been FDA-approved for patients 5 to 65 years of age. Ragwitek® has been FDA-approved for patients 18 to 65 years of age.

* Treatment should begin 12 weeks (16 weeks for Oralair®) before the expected onset of the allergy-inducing pollen season. Each product is dosed once daily and continued throughout the pollen season (precoseasonal dosing).

* The first dose is administered under the supervision of a physician experienced in diagnosing and treating severe allergic reactions. Subsequent doses may be taken at home.

* For Oralair®, dose titration is required in patients 10 to 17 years of age. Titration can be completed over 3 days at home, 100 IR [index of reactivity] on day 1, 2 times 100 IR on day 2, and 3 times 100 IR on day 3. In patients between 18 and 65 years, no dose titration is needed; treatment is initiated at the maintenance dose of 300 IR.

* Grastek® and Ragwitek® both are initiated at the maintenance dose (2800 bioequivalent allergy unit and 12 Amb a 1 unit, respectively). Pharmacotherapy of Pollen-Induced Allergic Rhinitis

There is general agreement from clinical practice guidelines on the pharmacologic treatment of pollen-induced allergic rhinitis or rhinoconjunctivitis:

* Treatment should be individualized based on symptom severity and duration, comorbidities, patient age, preference (eg, route of administration, tolerance for adverse effects), and previous treatment history

* Measures to increase treatment adherence (eg, shared decision making, consideration of the patient’s school or work schedule, use of a medication calendar or check-off list) are encouraged

* Goals of treatment are symptom reduction and improvements in functional capacity and quality of life

* A “step-up” (if treatment is inadequate) or “step-down” (if symptom relief is achieved with other interventions, eg, avoidance) approach to treatment is recommended

* Allergen avoidance is the first step of treatment but may be unrealistic for some patients Six medication classes are used to treat allergic rhinitis:
1. H1-antihistamines (oral and intranasal)
2. Corticosteroids (oral [short-course for severe disease] and intranasal)
3. Leukotriene receptor antagonists (oral)
4. Sympathomimetic decongestants (oral and intranasal)
5. Chromones (intranasal)
6. Anticholinergic, ipratropium bromide (intranasal)

o Treatment should be symptom-specific, eg, oral antihistamines may be less effective for prominent congestion than other treatments; prominent rhinorrhea may respond to intranasal ipratropium; rhinitis-only symptoms may be treated with local (intranasal) rather than systemic (oral) therapy
o For mild or intermittent symptoms, oral or nasal antihistamine may be considered firstline treatment
o Newer generation (selective) oral antihistamines generally are recommended over older (nonselective) antihistamines. Patients with insomnia and pregnant women may prefer older antihistamines because of their sedating effects and longer safety history, respectively
o Intranasal corticosteroids may be effective for more severe or persistent symptoms
o Combination treatment (eg, oral antihistamine plus intranasal corticosteroid, intranasal antihistamine and corticosteroid, antihistamine [oral or intranasal] plus sympathomimetic [oral or short-course (=5 days to avoid rebound congestion) intranasal]) may be effective for symptoms nonresponsive to single medications
o Oral sympathomimetics may cause insomnia; their use is limited in patients with certain comorbidities (eg, diabetes mellitus, unstable hypertension)
o Oral leukotriene receptor antagonists may reduce asthma exacerbations in patients with comorbid asthma

Consideration of Age

The ages stated in this policy for which Grastek®, Ragwitek®, and Oralair®, are considered medically necessary is based on the ages approved in the FDA labeling.

Benefit Application

Sublingual immunotherapy may be offered by specialized clinics.

Evidence Review Background

Sublingual immunotherapy (SLIT) is a potential alternative to subcutaneous immunotherapy (SCIT) for providing allergen-specific therapy. SLIT is proposed as a more convenient alternative delivery route for treating a variety of allergic disorders.

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 immunotherapy is the standard of care. Due to the inconvenience of multiple injections, particularly in children, alternative delivery routes have been investigated; of these, sublingual immunotherapy is the most prominent. Sublingual immunotherapy targets absorption to the sublingual and buccal mucosa. Allergen preparations used for sublingual immunotherapy are held under the tongue for one to several minutes and then swallowed or spit out.