CurrentBlue Cross Blue Shield - IowaPolicy N/A

Allergy Immunotherapy

Defines medical necessity, investigational indications, and criteria for subcutaneous allergy immunotherapy (SCIT), rapid drug/insect-sting/aspirin desensitization, and alternative/unproven immunotherapy methods for members of Blue Cross Blue Shield - Iowa (Wellmark). Affects clinicians providing allergy immunotherapy and prior authorization/coverage reviewers.

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyAllergy Immunotherapy

Policy CodePolicy N/A

Change TypeAnnual review — no material changes

Effective DateOriginal Effective Date: April 1995

Next Review DateN/A

Key ActionVerify member benefits and include documentation confirming IgE‑mediated allergy and prior trial of avoidance/pharmacotherapy when requesting coverage.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

severalMedically necessary indications

multipleInvestigational treatments

3095144 annual limit

356PEPITES participants

20+CPT/HCPCS entries

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria and Medical Necessity

Allergy Immunotherapy (Subcutaneous) - Initial criteria

Covered when ALL of the following are met

SCIT medical necessity general criteria: The individual has severe, seasonal, or perennial IgE-dependent symptoms of allergic rhinoconjunctivitis or asthma after natural exposure to the allergen

From policy: Allergy Immunotherapy (Subcutaneous)

Diagnostic confirmation: There is skin test and/or serological evidence of IgE-mediated antibody to a potent extract of the allergen (corresponding to the allergen planned for immunotherapy)

Documented IgE-mediated allergy required

Failure of or contraindication to standard therapy: Avoidance or pharmacologic therapy cannot control allergic symptoms or the member has unacceptable side effects with pharmacologic therapy; a trial of two or more medications should have been attempted if not contraindicated

Stepwise care expectation and prior medication trial described in background

Allergy Immunotherapy (Subcutaneous) - Other covered indications

Also considered medically necessary when ANY of the following apply

Life-threatening insect sting allergy: The individual has a life-threatening IgE-mediated allergy to insect stings (venom) for which venom immunotherapy is planned

Hymenoptera venom listed as covered indication

Allergens not manageable by avoidance/medication: Hypersensitivity to allergens that cannot be managed by medication or avoidance

Additional covered scenario per policy

Rapid Desensitization - Covered indications

Rapid desensitization covered when ANY of the following are met

Drug desensitization indication: Allergy to a particular drug that cannot be treated effectively with alternative medications and continued administration of the implicated drug is clinically necessary; desensitization protocol will be used to permit uninterrupted therapy

Drug desensitization used when no effective alternative exists

Venom hypersensitivity indication: Insect sting (Hymenoptera) hypersensitivity for which rapid (rush/cluster) or conventional venom immunotherapy is indicated to reduce future systemic reactions

VIT (conventional or rush) considered effective for moderate-to-severe systemic reactions

Seasonal timing indication: Individuals with moderate-to-severe allergic rhinitis who need treatment during or immediately before the season of the affecting allergy (require rapid protection)

Rush/cluster protocols used to reach therapeutic dose quickly

Aspirin Desensitization - Covered indications

Aspirin desensitization considered medically necessary when ANY of the following apply

Chronic rhinosinusitis with nasal polyposis refractory to topical glucocorticoids, leukotriene-modifying agents, and other therapies

AERD-related indication in policy

Cardiovascular indication: Stable cardiovascular disease or cardiovascular risk factors requiring aspirin antiplatelet therapy when aspirin avoidance is not possible

Desensitization to permit cardioprotective aspirin use

Chronic inflammatory conditions: Need for NSAIDs to treat chronic inflammatory conditions (e.g., arthritis) when avoidance is not possible

Allows continuation of necessary NSAID therapy

Antiphospholipid syndrome in pregnancy: Antiphospholipid syndromes during pregnancy requiring aspirin therapy

Initial therapy eligibility

Covered when ALL of the following are met

Allergen exposure and test concordance: The triggering allergen is not readily avoidable and the documented allergy corresponds to the allergen planned for immunotherapy

From BACKGROUND: correspondence of documented allergy to planned immunotherapy

IgE-mediated confirmation: Allergy is IgE-mediated as documented by appropriate skin testing or RAST (serological testing)

Required diagnostic confirmation

Inadequate control with standard therapy: Symptoms are not easily controlled with medication and allergen avoidance despite trials of appropriate therapies (two or more medications if not contraindicated) within the past year

Stepwise care expectation and prior medication trial

Patient cooperation and follow-up:

Administration schedules and risks

Coverage considerations for administration schedules

Conventional build-up and maintenance: Conventional build-up with injections administered 1–3 times per week until maintenance achieved, followed by maintenance injections at intervals typically every 3–4 weeks (can be increased up to 4 weeks for inhalant allergens and up to 8 weeks for venom)1-3 injections/week; maintenance intervals up to 4-8 weeks

Duration of therapy generally 3–5 years; progress reviewed regularly

Accelerated protocols (cluster/rush): Accelerated (cluster or rush) schedules may be used to reach maintenance dose more rapidly but are associated with a higher risk of systemic reactions and should be administered under experienced supervision

Cluster: multiple injections per visit; rush achieves maintenance more quickly but higher systemic reaction risk

Risk mitigation: Choose protocol based on clinical need, patient risk factors, and center capability; if systemic reactions occur, reduce dose or discontinue immunotherapy

Rapid desensitization

Drug and aspirin desensitization

Drug desensitization general: Drug desensitization may be utilized when a patient has IgE-mediated hypersensitivity to a needed medication and no effective alternative exists; protocols involve rapid administration of incremental doses to induce temporary tolerance and can be performed via oral, IV, intraperitoneal or subcutaneous routes

Desensitization allows uninterrupted administration of the implicated drug

Aspirin desensitization general: Aspirin desensitization is used for aspirin-sensitive individuals (including AERD) who require aspirin/aspirin-like NSAIDs for cardioprotection, pain relief, or control of nasal polyp regrowth; procedure performed in controlled setting with graded dosing over several days and requires continued daily aspirin to maintain tolerance

Gaps >48 hours may lead to loss of tolerance; target daily aspirin doses vary (eg, 325 mg typical; 81 mg for antiplatelet)

Safety and monitoring: Desensitization (drug or aspirin) should be done with appropriate monitoring in settings experienced with rapid protocols due to risk of systemic reactions

Rush protocols carry higher systemic reaction risk

SCIT initial therapy criteria

Covered when ALL of the following are met

IgE-mediated allergy documented: IgE-mediated allergy is documented by skin testing or RAST that correlates with the clinical history and planned allergen extract

Diagnostic confirmation required

Symptoms not controlled: Symptoms are not easily controlled with medication and avoidance is inadequate

Standard care comparator; immunotherapy indicated when standard care insufficient

Allergen exposure not avoidable: Triggering allergens are not readily avoidable in the patient's environment

Consideration relevant for selecting immunotherapy

Patient adherence likely: Patient is likely to cooperate with long-term treatment and follow-up

Rush/cluster immunotherapy and drug desensitization criteria

Covered when ALL of the following are met

Clinical necessity for accelerated protocol: There is a clinical need for rapid attainment of protection (e.g., imminent allergy season, high risk of subsequent stings, or urgent requirement for tolerated medication) and alternatives are ineffective or not available

Rush/cluster indicated when rapid protection required

IgE-mediated hypersensitivity documented: IgE-mediated hypersensitivity to the target allergen or drug is documented and corresponds to the planned accelerated protocol

Testing/documentation required

Appropriate setting and monitoring: Accelerated (rush/cluster) immunotherapy or drug desensitization will be performed in an experienced setting with appropriate monitoring due to increased systemic reaction risk

Safety and center capability considerations

Venom immunotherapy (VIT) criteria

Covered when ALL of the following are met for venom hypersensitivity

Physician-confirmed systemic sting reaction to insect venom (bees, wasps, hornets, fire ants) with moderate-to-severe systemic features

VIT indicated for individuals with moderate-to-severe systemic reactions

Appropriate VIT protocol selected: Clinician plans venom immunotherapy (conventional, cluster, rush or ultra-rush) appropriate to patient risk and need for rapid protection

Protocol choice based on clinical need and center capability; rush may be used when rapid protection required

Expectation of benefit and monitoring: Plan includes monitoring and follow-up; VIT is expected to reduce frequency/severity of future systemic reactions and improve quality of life despite limited high-quality trial data

Benefit supported by systematic review though primary studies vary in quality

Covered therapies (VIT, aspirin desensitization, SCIT/cluster)

Covered when ALL of the following are met:

Venom immunotherapy (VIT): Individual has moderate-to-severe systemic reaction(s) to insect venom (Hymenoptera) and clinician plans VIT (conventional or accelerated) to reduce risk of future systemic reactions

Established treatment option though evidence quality limited

Aspirin desensitization for AERD: Patient has aspirin-exacerbated respiratory disease or aspirin hypersensitivity and requires aspirin/aspirin-type NSAID therapy for cardioprotection, pain relief, or control of nasal polyp regrowth; desensitization protocol is used to achieve temporary tolerance and a planned daily aspirin dose

Continued daily aspirin required to maintain tolerance; target doses vary

SCIT/cluster for allergic rhinitis: Individuals with moderate-to-severe allergic rhinitis not controlled with allergen avoidance and/or pharmacotherapy may be offered SCIT; cluster protocols may be used to reduce accumulation phase duration and achieve similar short-term efficacy

Cluster may reduce build-up time >60% vs conventional in cited study

Trial eligibility and responder definitions

Trial-based eligibility and responder criteria (examples from included EPIT trials)

General trial eligibility: IgE-mediated food allergy confirmed by double-blind, placebo-controlled food challenge (DBPCFC) or physician diagnosis with supportive testing (specific IgE, skin prick) and baseline eliciting dose thresholds; trials commonly excluded severe life‑threatening anaphylaxis and uncontrolled persistent asthma

Examples drawn from PEPITES/EPITOPE/PEOPLE/Viaskin trials

Responder definition — Viaskin Milk trial: Responder defined as ≥10‑fold increase in cumulative reactive dose reaching at least 144 mg or cumulative reactive dose ≥1444 mg at 12‑month DBPCFC10‑fold or ≥1444 mg

Petroni et al. 2024 trial definition

Responder definition — Viaskin Peanut trial: Responder criteria: if baseline eliciting dose >10 mg then post‑treatment ED >1000 mg; if baseline ED ≤10 mg then post‑treatment ED >300 mgED thresholds as specified

Unproven/Experimental Allergy Therapies

Not covered / considered unproven when the following apply

Unproven alternative therapies: Therapies lacking peer‑reviewed evidence or FDA approval are considered unproven and not established for coverage

Examples include: enzyme potentiated desensitization (EPD), helminth (Trichuris suis) therapy, homeopathic remedies, injection of food extracts, intranasal immunotherapy, low‑dose immunotherapy/LDA, peptide therapy, provocation‑neutralization therapy, rhinophototherapy, rotational/multiple food elimination diets

EPIT (peanut patch) — conditional/informational

Emerging therapy: Epicutaneous immunotherapy (EPIT) evidence summary

EPIT efficacy and safety findings: Phase 3 (PEPITES/EPITOPE) and extension (PEOPLE) data show modest responder rates and increased eliciting doses for some patients over time, frequent local patch‑site reactions, high adherence, and mixed attainment of prespecified trial success criteria; EPIT remains investigational/pending additional safety data for routine coverage decisions

Trial results show statistically significant responder differences but limitations and additional safety data needed

Evidence considerations for SLIT coverage

Summary of evidence-based considerations for coverage

Efficacy evidence for SLIT: Randomized trials for SLIT in food allergy are limited in number and size; evidence for peanut SLIT is more consistent versus placebo, whereas evidence for non‑peanut SLIT is limited or inconsistent

SLIT less effective than OIT for peanut in comparative studies; RCT quality variable

Long‑term outcomes and durability: Some long‑term studies report clinically significant desensitization with SLIT (eg, Kim 2023: 70.2% at 48 months) but sustained unresponsiveness may be lost within weeks to months after cessation

Durability variable; median time to loss ~22 weeks in Kim 2023

Safety profile: Adverse events with SLIT are commonly mild (oropharyngeal itching, lip swelling, local reactions); antihistamine use reported for a minority of doses and epinephrine use was not required in studied cohorts

Operative safety considerations for outpatient dosing

Guideline-based coverage and clinical criteria

Guideline-based recommendations (conditional/moderate or conditional/low certainty) included in the referenced statements

NSAID/aspirin management guidance: For suspected NSAID‑induced urticaria/angioedema or AERD, consider oral aspirin challenge to identify COX‑1 cross‑reactivity and use desensitization when the intention is to place a patient on daily therapeutic aspirin for cardioprotection, pain relief, or to control nasal polyp regrowth

Conditional recommendations from AAAAI/ACAAI guidance

Chemotherapeutic hypersensitivity guidance: For immediate reactions to chemotherapeutics where the implicated drug is the preferred therapy, consider drug desensitization; for nonimmediate or inconsistent reactions consider slowed infusion, graded dose escalation, and/or premedication

Conditional/Low certainty per guideline statements

Allergen immunotherapy indications and monitoring: Offer allergen immunotherapy (SCIT or SLIT tablets) through shared decision‑making to patients with moderate/severe allergic rhinitis not controlled with avoidance/pharmacotherapy; evaluate response regularly and generally reassess continuation after 3–5 years

Allergy immunotherapy (subcutaneous) and rapid desensitization are considered investigational when used for indications other than those explicitly listed as medically necessary in this policy. Examples of indications considered investigational include: angioedema, atopic dermatitis (except dust-mite associated cases specifically indicated elsewhere), chronic urticaria, food allergies, intrinsic (non-allergic) asthma, migraine headaches, nasal polyposis, and non-allergic vasomotor rhinitis

Allergen-proof supplies (for example, mattresses, pillows, casings) are considered non-covered as personal convenience items. Coverage is determined by the member's plan document and these items are excluded from benefit reimbursement under this policy.

A range of alternative allergy immunotherapy methods are identified as investigational/unproven and are not supported as standard therapy based on the available evidence. These include but are not limited to: allergoids, epicutaneous immunotherapy (EPIT), enzyme potentiated desensitization (EPD), intranasal immunotherapy, and sublingual immunotherapy (SLIT) for food allergies, as well as autogenous urine immunization, helminth therapy, injection of food extracts, low-dose immunotherapy, peptide therapy, provocation-neutralization, rhinophototherapy, and rotational/multiple food elimination diets.

Current clinical trial data and guideline reviews indicate insufficient evidence to support routine use of subcutaneous immunotherapy (SCIT) or other allergen immunotherapy (AIT) for food allergy and several other conditions. Professional society guidance and systematic reviews report a paucity of studies demonstrating benefit for food hypersensitivity, migraine headaches, vasomotor rhinitis, intrinsic (non-allergic) asthma, angioedema, atopic dermatitis (except certain dust-mite associated cases), and chronic urticaria; therefore these uses are not supported as standard indications.

Numerous alternative or complementary allergy treatments are described in the literature but lack sufficient peer-reviewed evidence of safety and effectiveness and are therefore considered unproven. These include homeopathic remedies, autogenous urine immunization, helminth (Trichuris suis) therapy, low-dose/ultra-low dose immunotherapies, detoxification approaches, and multiple other non‑FDA-approved techniques. Such therapies should be considered experimental and are not covered under standard AIT policy.

Clinical trials of immunotherapy and EPIT commonly exclude individuals at highest risk for severe outcomes; for example, many studies exclude patients with a history of severe life‑threatening anaphylaxis to the study allergen and those with uncontrolled persistent asthma. These trial eligibility restrictions limit the generalizability of efficacy and safety results to such high‑risk populations and should be considered when assessing potential coverage.

Multiple alternative allergy immunotherapy methods are explicitly described as unproven or not FDA‑approved and thus excluded from coverage as established therapies. Examples called out in the evidence review include epicutaneous immunotherapy (EPIT) pending additional safety data, enzyme potentiated desensitization (EPD), helminth therapy, homeopathy, intranasal immunotherapy, low‑dose immunotherapy, peptide therapy, provocation‑neutralization, rhinophototherapy, and rotational or multiple food elimination diets.

The randomized trial evidence for sublingual immunotherapy (SLIT) in food allergies is limited and often rated as low quality. While some RCTs show efficacy for peanut SLIT compared with placebo, evidence for SLIT in non‑peanut food allergies is inconsistent or lacking. Given the low quantity and quality of RCT data for non‑peanut foods, SLIT for those indications may be considered not medically necessary or excluded from coverage unless higher‑quality, food‑specific evidence is provided.

Clinical trials and guideline reviews do not support the routine use of SCIT for food hypersensitivity and do not recommend allergen immunotherapy for chronic urticaria or angioedema. Practice parameters and evidence summaries indicate insufficient high‑quality data to endorse SCIT for these indications, and such uses are therefore not recommended as standard care.

When no specific CPT code exists for a reported allergy immunotherapy service (for example, some forms of sublingual immunotherapy), providers should report the procedure using 95199 (unlisted allergy/clinical immunologic service or procedure) as appropriate.

Coding, Units, and Frequency Limits

Covered CPT Codes (frequency limits listed)CPTCovered

95115	Allergy immunotherapy, extract preparation
95117	Allergy immunotherapy, extract preparation (additional)
95120	Allergen immunotherapy code
95125	Allergen immunotherapy code
95130	Allergen immunotherapy code
95131	Allergen immunotherapy code
95132	Allergen immunotherapy code
95133	Allergen immunotherapy code
95134	Allergen immunotherapy code
95144	Allergen immunotherapy, administration - CPT description per table

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Covered CPT Codes (excerpt)CPTCovered

0604U	Allergy and immunology (chronic recurrent angioedema), 4 bradykinin peptides, liquid chromatography and tandem mass spectrometry (LC-MS/MS), whole blood, quantitative.
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.
95120	Professional services for allergen immunotherapy in the office or institution of the prescribing physician or other qualified health care professional, including provision of allergenic extract; single injection.
95125	Professional services for allergen immunotherapy in the office or institution of the prescribing physician or other qualified health care professional, including provision of allergenic extract; 2 or more injections.
95130	Professional services for allergen immunotherapy in the office or institution of the prescribing physician or other qualified health care professional, including provision of allergenic extract; single stinging insect venom.
95131	Professional services for allergen immunotherapy in the office or institution of the prescribing physician or other qualified health care professional, including provision of allergenic extract; 2 stinging insect venoms.
95132	Professional services for allergen immunotherapy in the office or institution of the prescribing physician or other qualified health care professional, including provision of allergenic extract; 3 stinging insect venoms.
95133	Professional services for allergen immunotherapy in the office or institution of the prescribing physician or other qualified health care professional, including provision of allergenic extract; 4 stinging insect venoms.
95134	Professional services for allergen immunotherapy in the office or institution of the prescribing physician or other qualified health care professional, including provision of allergenic extract; 5 stinging insect venoms.

Supervision/preparation and related codesCPT | HCPCSCovered

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).
95146	Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy (specify number of doses); single stinging insect venom.
95147	Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy (specify number of doses); 2 single stinging insect venoms.
95148	Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy (specify number of doses); 3 single stinging insect venoms.
95149	Professional services for the supervision of preparation and provision of antigens for allergen immunotherapy (specify number of doses); 4 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 biting insect or other arthropod.
95180	Rapid desensitization procedure, each hour (e.g., insulin, penicillin, equine serum).
95199	Unlisted allergy/clinical immunologic service or procedure (e.g., sublingual immunotherapy).

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Per-calendar-year Unit Limits — Key CPT Codes

95115Max Units = 1 per calendar year

95117Max Units = 1 per calendar year

95144Max Units = 30 per calendar year

95145-95149Combined Max Units = 120 units (all codes combined) per calendar year

95165Max Units = 180 per calendar year

95170Max Units = 10 per calendar year

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization
Prior Approval
Prior approval is not applicable for allergy immunotherapy under this policy. However, certain therapies and administration types require documentation to support medical necessity and may be subject to prior authorization processes if applicable under a member's benefit plan.
Verify member benefits and contract terms prior to initiating therapy — benefits may vary by contract.
When evaluation and management is billed the same day as immunotherapy by the same physician, a separately identifiable service must be documented.

Billing Rule
Per-unit reimbursement and frequency limits
Per-unit reimbursement and calendar-year frequency limits apply to allergy immunotherapy CPT codes and are enforced when medical necessity criteria are met. Providers must document the number of dosages prepared/intended for administration.

Background and Evidence Summary

Background: Allergy immunotherapy (subcutaneous; SCIT) involves the repeated administration of specific allergen extracts to individuals with IgE‑mediated conditions to reduce allergic symptoms and inflammatory responses on natural exposure. It is indicated when the allergen is not readily avoidable, the allergy is documented as IgE‑mediated by skin or serologic testing, and symptoms are not adequately controlled with avoidance and pharmacologic therapy. Rapid desensitization protocols accelerate dose escalation (rush/cluster) or enable temporary tolerance for necessary drugs and are used when alternatives are ineffective or rapid protection is required.

Evidence and investigational treatments summary: The policy and evidence review identify numerous alternative or complementary allergy treatments that lack sufficient peer‑reviewed evidence or FDA approval (for example, allergoids, EPIT pending safety data, EPD, helminth therapy, intranasal immunotherapy, homeopathy, injection of food extracts, low‑dose immunotherapy, peptide therapy, and various dietary elimination approaches). These methods are considered investigational or experimental and are not established as standard allergen immunotherapy options.

Trial eligibility and responder definitions: Trials of epicutaneous immunotherapy and other food‑allergen interventions commonly required confirmatory diagnostic testing (for example, double‑blind, placebo‑controlled food challenge or physician diagnosis with supportive specific IgE/skin prick testing) and specified baseline eliciting dose thresholds. Many trials excluded subjects with a history of severe life‑threatening anaphylaxis to the study allergen and those with uncontrolled persistent asthma, which limits generalizability to these high‑risk groups.

Evidence considerations for SLIT coverage: Randomized trials and systematic reviews show few, generally small studies of SLIT for food allergies. SLIT demonstrates more consistent efficacy for peanut allergy than for other foods, but overall trial quality is limited and SLIT is generally less effective than oral immunotherapy (OIT) where compared. Long‑term open‑label studies report clinically significant desensitization for some patients, but durability of response and sustained unresponsiveness after cessation vary across studies and adverse events (even if generally mild) are common.

Definitions and Terminology

Allergy immunotherapy — Definition

DefinitionAllergy immunotherapy: repeated administration of specific allergens to individuals with IgE-mediated conditions to provide protection against allergic symptoms and inflammatory reactions associated with natural exposure.

PurposeIntended to reduce symptoms when allergens are not readily avoidable and when pharmacologic therapy/avoidance are inadequate.

Routes and extractsPrincipal and most effective route is subcutaneous injection; standardized extracts should be used.

Rapid desensitization — Definition

DefinitionRapid desensitization: accelerated protocols (rush/cluster) that permit patients with IgE-mediated drug hypersensitivity or urgent allergen exposure to reach therapeutic doses quickly and receive necessary therapy when alternatives are ineffective.

Purpose

Policy Revision History

2026-02Policy revisedLatest

Annual review and policy revision completed; policy updated in February 2026.

2025-02Policy renewed/annual review

Annual review and policy renewal completed in February 2025.

2024-02Policy revised/annual review

Policy Summary

PayerBlue Cross Blue Shield - Iowa

PolicyAllergy Immunotherapy

Policy CodePolicy N/A

Change TypeAnnual review — no material changes

Effective DateOriginal Effective Date: April 1995

Next Review DateN/A

Key ActionVerify member benefits and include documentation confirming IgE‑mediated allergy and prior trial of avoidance/pharmacotherapy when requesting coverage.

SourceLink

On This Page

Specific high-risk obstetric indication

Poorly controlled asthma in an aspirin-sensitive individual when aspirin therapy is required and avoidance is not possible

AERD context noted in policy

Patient is likely to cooperate with the program and adhere to long-term treatment and follow-up

Adherence required for 3-5 years of maintenance typically

Operational note: monitor for systemic reactions during build-up and maintenance

Adherence and ability to complete build-up/maintenance important

Greenhawt et al. 2023 (EPITOPE) responder definition

Practice parameter recommendations regarding duration, build‑up frequency, and maintenance intervals

Administration frequency and scheduling: Conventional build‑up frequency generally 1–3 injections/week; cluster and rush accelerate attainment of maintenance; maintenance intervals can often be increased up to 4 weeks for inhalant allergens and up to 8 weeks for venom1-3 injections/week; maintenance intervals up to 4-8 weeks

Operational guidance from Joint Task Force practice parameters

Ineffective or not recommended uses: SCIT is not supported for food hypersensitivity and allergen immunotherapy is not recommended for chronic urticaria/angioedema per guideline updates

Guideline‑based exclusions to inform coverage decisions

Aspirin Desensitization — Typical Target Doses

Typical target dose325 mg daily is the typical target dose for aspirin desensitization

Antiplatelet target81 mg daily may be used when the goal is antiplatelet effect (final dose of desensitization)

Higher doses for nasal polypsHigher doses (example: 650 mg twice daily) may be required for management of nasal polyps and airway inflammation

Maintenance requirementContinued daily aspirin required to maintain tolerance; gaps >48 hours may lead to loss of tolerance

Place of Service

Place of Service (examples)Outpatient / Physician's Office indicated for certain allergen immunotherapy services (e.g., supervision/preparation codes).

Coding contextPlace of service guidance appears alongside CPT/HCPCS code descriptions for immunotherapy services.

Service setting implicationMost supervised preparation and administration CPT codes are reported in outpatient/office settings as described in the code table.

95115 — Max Units = 1 per calendar year
95117 — Max Units = 1 per calendar year
95144 — Max Units = 30 per calendar year
95145–95149 (combined) — Max Units = 120 per calendar year
95165 — Max Units = 180 per calendar year
95170 — Max Units = 10 per calendar year

Prior Authorization
Authorization requirements for SCIT, rush/cluster, and desensitization
Authorization or documentation to support medical necessity should confirm IgE‑mediated allergy and inability to control symptoms with avoidance or pharmacotherapy when requesting SCIT, rush/cluster protocols, or rapid drug desensitization. For desensitization protocols (eg, drug or aspirin desensitization) document indication, prior attempts or lack of alternatives, and monitoring plans.
Document positive skin testing or serum specific IgE (RAST) to the relevant allergen.
Document trial of systemic medications and/or allergen avoidance and reasons for failure or unacceptable side effects.
For rush or cluster protocols, include rationale for accelerated build-up (eg, need for rapid protection) and plan for monitoring and management of systemic reactions.
For rapid drug desensitization, document drug hypersensitivity reaction details, prior alternative therapies considered, and that the implicated drug is the preferred therapy.
For aspirin desensitization (AERD), document indication (eg, requirement for aspirin for cardioprotection or nasal polyp control), dosing goals, and plan for ongoing daily dosing and monitoring.

Prior Authorization
Prior authorization for EPIT — diagnostic and treatment documentation
Epicutaneous immunotherapy (EPIT) — including investigational patches used in trials — requires documentation of diagnosis and trial-based efficacy/safety data when considered. Prior authorization requests should include confirmatory diagnostic testing and a detailed treatment plan (dose, administration schedule, monitoring) and cite relevant clinical trial criteria if treatment follows a trial protocol.
Document physician-diagnosed food allergy and confirmatory testing (preferably DBPCFC when available, or positive skin/IgE supporting history).
Specify the EPIT product/dose, planned duration, first-application supervision plan, and home-application instructions.
Include prior trial results or rationale when EPIT is being continued under an open-label extension or considered off-trial.
Provide safety monitoring plan for local and systemic reactions and plan for management of adverse events, including use of epinephrine.
Include documentation of baseline eliciting dose and intended outcome measures (eg, target eliciting dose at specified timepoints).

Denial Risk
Prior authorization for non‑FDA or unproven allergy therapies
Non‑FDA‑approved or unproven allergy therapies (eg, enzyme potentiated desensitization [EPD], helminth therapy, homeopathy, intranasal immunotherapy as described without established evidence) are considered experimental or unproven. Prior authorization is not appropriate unless robust peer-reviewed evidence supports clinical benefit; requests should include high-quality clinical evidence and rationale.
EPD (Epidyme) is not FDA‑approved and lacks high-quality clinical trials — importation is banned; documentatory evidence will not generally establish coverage.
Epicutaneous immunotherapy outside approved indications or without sufficient safety data remains investigational — include clinical trial data if available.
Providers should document why standard, evidence-based therapies are not appropriate or have failed before pursuing unproven options.

Prior Authorization
Prior authorization recommended for SLIT
Prior authorization is recommended for sublingual immunotherapy (SLIT) requests when used for food allergies or off‑label indications. Requests should include confirmatory diagnostic information, detailed SLIT protocol, and prior therapy history demonstrating inadequate response to alternatives.
Document diagnosis of food allergy and supporting testing (DBPCFC preferred when available, or positive IgE/skin test and consistent history).
Provide the specific allergen targeted, SLIT dosing regimen (build‑up and maintenance doses), dates of therapy, and monitoring plan.
Document prior trials of avoidance/pharmacotherapy and rationale for SLIT over other options (eg, oral immunotherapy), including discussion of comparative efficacy and risks.
For pediatric SLIT, include age-specific considerations and any trial evidence supporting use in the age group.

Documentation Required
Eligibility triggers
Eligibility for allergen immunotherapy requires documentation that the allergy is IgE-mediated, the triggering allergen is not readily avoidable, and symptoms are not adequately controlled with first-line measures (avoidance and pharmacotherapy).
Confirm IgE-mediated sensitization by skin testing or serum specific IgE.
Document that avoidance strategies were attempted or are not feasible.
Document trials of pharmacologic therapy (eg, antihistamines, intranasal steroids, leukotriene antagonists, bronchodilators) and response; two or more medications in the past year are commonly expected unless contraindicated.
Indicate severity, duration, and frequency of episodes and patient's ability/willingness to comply with a multi-year treatment program.

Step Therapy
Use of standard care without allergen‑specific immunotherapy
Standard care (avoidance and pharmacotherapy) is the usual comparator. Providers should document prior use of first‑line measures and reasons for escalation to immunotherapy; failure to document prior attempts at avoidance and medication trials may affect coverage decisions.
List prior medications tried, durations, and outcomes; document any intolerances or contraindications to pharmacotherapy.
Describe environmental control measures attempted and outcomes, and why exposure cannot be sufficiently avoided.
Note that immunotherapy may be considered through shared decision-making when symptoms remain uncontrolled despite these measures.

Denial Risk
Evidence insufficiency for non‑peanut allergies
Evidence for SLIT and other immunotherapy modalities varies by allergen. For non‑peanut food allergies the evidence base is limited and inconsistent; this insufficiency should be documented in prior authorization requests for non‑peanut indications and may limit coverage.
Trials for non‑peanut food allergies are small and of low quality — provide available RCT data if requesting coverage.
For peanut allergy, stronger trial data exist for some modalities (SLIT, EPIT) but comparative effectiveness versus oral immunotherapy differs; document why chosen therapy is clinically appropriate.
If evidence is insufficient, outline alternative evidence-based therapies attempted and clinical rationale for the request.

Note
None specified in this section
No additional payer-specific prior authorization rules are stated in this section beyond the documentation and eligibility requirements summarized above; follow the member's benefit plan for any plan-level prior authorization procedures.
When no payer prior authorization is specified, verify contract terms and internal utilization management rules.
Submit complete documentation to facilitate any review and avoid delays.

Documentation Required
Required documentation
Medical records must fully support medical necessity for services. Required documentation includes history, physical exam, diagnostic testing results, treatment plan and dosage regimen, sequence of injections, and coding details.
Medical history, examination, and diagnostic testing (including allergy testing) on which treatment is based.
Plan of treatment with detailed dosage regimen, injection schedule, and sequence so responses are clear and chronological.
Documentation to support use of billing codes (eg, number of venoms, number of vials) and any separately identifiable E/M services provided the same day.
Use appropriate CPT, HCPCS, Revenue, and ICD diagnosis codes on claims.

Documentation Required
Required clinical documentation
Clinical documentation should confirm diagnosis, correlate history with positive allergy testing, describe severity, prior therapy trials, and document treatment response and monitoring.
Confirm IgE-mediated allergy by skin testing or serum specific IgE (RAST) and correlate with clinical history.
Describe diagnosis severity, duration, and prior failure of allergen avoidance/pharmacotherapy.
Document treatment response over time (eg, symptom improvement, medication reduction), adverse events, and rationale for continuation or discontinuation after 3–5 years as applicable.
For venom immunotherapy, document number of venoms treated and dosing details.

Guideline-based coverage and clinical criteria: Recommendations from AAAAI/ACAAI and the Joint Task Force support offering allergen immunotherapy (SCIT or SLIT tablets where appropriate) to patients with moderate‑to‑severe allergic rhinitis or controlled asthma with coexisting allergic rhinitis who have not achieved control with avoidance and pharmacotherapy. Guidelines emphasize shared decision‑making, regular evaluation of response (typically after 3–5 years to determine continuation), and acknowledge that accelerated schedules (cluster/rush) can achieve maintenance doses faster but may carry higher systemic reaction risk and should be used with experienced supervision.

Allows uninterrupted administration of a needed medication or faster protection against allergens when timing or lack of alternatives necessitates accelerated dosing.

RisksAssociated with higher risk of systemic reactions compared with conventional schedules and should be performed under experienced supervision.

Allergy immunotherapy — Concise definition

Concise definitionRepeated administration of specific allergens to individuals with IgE-mediated conditions to provide protection against allergic symptoms and inflammatory reactions upon natural exposure.

Also calledAlso referred to as desensitization, hyposensitization, allergy injection therapy, or 'allergy shots'.

Indication summaryUsed when allergens are not readily avoidable and symptoms are not controlled with medication/avoidance.

Build-up and Maintenance Phases

Build-up phaseInitial phase during which dose and concentration of allergen extract are progressively increased (intervals commonly 2–7 days; conventional schedules usually 1–3 injections/week).

Maintenance phaseAfter reaching an effective therapeutic dose, injections are given at intervals (typically every 3–4 weeks) to maintain benefit; intervals may be increased up to 4 weeks for inhalant allergens and up to 8 weeks for venom.

Typical durationMaintenance therapy generally recommended for 3–5 years with regular review of progress.

Rapid desensitization / Rush immunotherapy — Definition

DefinitionRush/cluster (rapid desensitization): accelerated protocols that reach target therapeutic doses over hours to days (rush) or via multiple injections per visit (cluster) to shorten the build-up period.

Use casesUsed to provide rapid protection for inhalant or venom allergens or when imminent therapy is needed.

SafetyAssociated with higher systemic reaction risk for inhalant allergens; venom rush may have lower increased risk in some reports; must be administered under experienced supervision.

SCIT — Definition

SCIT definitionSubcutaneous immunotherapy (SCIT): repeated administration of specific allergen extracts by injection to patients with IgE-mediated conditions to reduce allergic symptoms on natural exposure.

Route and extractsAdministered subcutaneously using standardized extracts; principal and most effective route per policy background.

IndicationsIndicated when allergens are not readily avoidable and symptoms are inadequately controlled by pharmacotherapy/avoidance.

Rush/Cluster Allergen Immunotherapy — Definition

DefinitionRush/cluster allergen immunotherapy: accelerated immunotherapy schedules in which multiple injections (cluster) or incremental doses over short intervals (rush) are used to reach maintenance dose more rapidly.

AdvantagesPermit faster attainment of maintenance dose and shorter accumulation phases (>60% reduction in some studies).

RisksAssociated with increased risk of systemic reactions for inhalant allergens; requires experienced supervision and monitoring.

Drug Desensitization — Definition

DefinitionDrug desensitization: procedures that alter the immune response to an implicated drug to induce temporary tolerance, allowing uninterrupted administration of a necessary medication when no effective alternative exists.

RoutesCan be performed orally, intravenously, intraperitoneally, or subcutaneously depending on drug and protocol.

Success ratesPublished series report high success rates (e.g., 93–98% in limited studies), though evidence quality varies.

Aspirin sensitivity / AERD — Definition

Aspirin sensitivity (AERD)Aspirin sensitivity: harmful respiratory or skin reactions to aspirin/NSAIDs; AERD includes chronic asthma and sinusitis with nasal polyps and manifests as respiratory symptoms triggered by aspirin/NSAIDs.

Prevalence in asthmaApproximately 1 in 10 adults with asthma and about 1 in 3 patients with asthma plus nasal polyps are sensitive to aspirin/NSAIDs (AERD).

Clinical relevanceAERD patients may undergo aspirin desensitization to enable aspirin therapy for cardioprotection, pain relief, or control of nasal polyp regrowth.

Venom Immunotherapy (VIT) — Definition

DefinitionVenom immunotherapy (VIT): allergen immunotherapy using Hymenoptera venom extracts (e.g., bees, wasps, hornets, fire ants) intended to prevent systemic reactions to subsequent stings.

IndicationOffered to individuals with physician-confirmed systemic sting reactions and moderate-to-severe systemic reactions to venom.

ProtocolsCan be given by conventional or rush protocols depending on clinical need and center capability.

Responder (EPIT trials) — Definition

Responder (EPIT trials)Participant who meets prespecified increases in eliciting dose on DBPCFC (examples: 10-fold increase to at least 144 mg or cumulative reactive dose thresholds for milk; peanut trial thresholds vary by baseline ED).

ExamplesViaskin Milk responder: >=10-fold increase reaching at least 144 mg or cumulative reactive dose >=1444 mg at 12 months; Viaskin Peanut responder criteria vary by baseline ED (post-treatment ED >1000 mg or >300 mg thresholds).

Use in trialsResponder definitions used as primary efficacy endpoints in EPIT randomized trials and extensions.

Allergoid — Definition

AllergoidAn allergenic protein chemically modified (e.g., with formaldehyde) to reduce IgE reactivity; available and licensed in Europe but not marketed in the United States.

AvailabilityNot available in the U.S.; primarily a European product formulation.

Intended effectDesigned to decrease IgE binding while retaining immunogenicity for desensitization purposes.

Epicutaneous Immunotherapy (EPIT) — Definition

EPIT definitionEpicutaneous immunotherapy (EPIT): daily application of a skin patch delivering small amounts of allergen (e.g., peanut 250 μg patch in trials) intended to desensitize individuals to food allergens.

Trial contextStudied in randomized trials (PEPITES, PEPITES/PEOPLE) with daily home application after initial supervised application; outcomes measured by DBPCFC eliciting dose changes and responder rates.

Safety notesLocal patch-site reactions are common; systemic reaction rates and long-term effectiveness vary across studies.

Enzyme Potentiated Desensitization (EPD) — Definition

EPD definitionEnzyme potentiated desensitization (EPD): a patented European immunotherapy (Epidyme) using mixtures of multiple allergens administered in-office; not marketed or FDA-approved in the U.S. and lacking supporting clinical trial evidence.

Regulatory statusNot approved in the United States; FDA has banned importation of EPD.

EvidenceClinical trial evidence supporting efficacy is lacking.

Population / Intervention — SLIT Evidence Review

Population/InterventionPopulation: individuals with food allergy. Intervention (for SLIT evidence review): sublingual immunotherapy (SLIT).

ComparatorComparators include standard care, SCIT, or oral immunotherapy depending on study design and question.

OutcomesOutcomes of interest include symptoms, quality of life, hospitalizations, medication use, treatment-related morbidity and mortality, and desensitization as an intermediate outcome.

Outcomes of Interest

Primary outcomes of interestClinical outcomes: symptoms, quality of life, hospitalizations, medication use, treatment-related morbidity and mortality.

Intermediate outcomeDesensitization (increased eliciting dose on food challenge) used as an intermediate efficacy measure.

Safety outcomesTreatment-related morbidity including systemic reactions, skin reactions, gastrointestinal events, serious adverse events, and discontinuations.

AERD / NSAID Hypersensitivity Management — Definition

AERD managementAspirin challenge or desensitization is recommended in select patients with NSAID-induced urticaria/angioedema or AERD when diagnostic uncertainty exists or when aspirin therapy is needed for cardioprotection, pain relief, or control of nasal polyp regrowth.

PrecautionsPrecautions during aspirin desensitization include frequent monitoring of lung function and management of bronchospasm; continued daily aspirin required to maintain tolerance.

Loss of toleranceGaps in aspirin dosing >48 hours may lead to loss of tolerance; after ~5 days all patients may react and require repeat desensitization.

Drug Desensitization — Definition (Reiteration)

Drug desensitization (reiteration)Procedures to induce temporary tolerance to an implicated chemotherapeutic, biologic, or other drug when the drug is the preferred therapy and no effective alternative exists.

ApproachMay include slowed infusion, graded dose escalation, premedication, or formal desensitization protocols depending on reaction type and drug.

Evidence and successEvidence is limited but desensitization is an established option with reported high success rates in case series and practice guidelines supporting use.

Allergen Immunotherapy — Common CPT/HCPCS Codes

Common allergen immunotherapy CPT codesExamples include 95115, 95117, 95120, 95125, 95130–95134 for venom, 95144, 95145–95149 (supervision/preparation), 95165, and 95170.

Unlisted code95199 is identified as the unlisted allergy/clinical immunologic service or procedure (e.g., sublingual immunotherapy) when no specific code applies.

Other codesAlso includes a specific test code 0604U (bradykinin peptides LC-MS/MS) referenced in code listings.

Annual review and policy revision completed in February 2024.

2023-02Policy revised/annual review

Annual review and policy revision completed in February 2023.

2022-02Policy revised/annual review

Annual review and policy revision completed in February 2022.

2021-11Interim review and policy revised

Interim review and policy revision conducted in November 2021.

2021-02Policy revised/annual review

Annual review and policy revision completed in February 2021.

2020-02Policy revised/annual review

Annual review and policy revision completed in February 2020.

2019-02Policy revised/annual review

Annual review and policy revision completed in February 2019.

2018-02Policy revised/annual review

Annual review and policy revision completed in February 2018.

2017-02Policy revised/annual review

Annual review and policy revision completed in February 2017.

2016-04Policy revised/annual review

Annual review and policy revision completed in April 2016.

2016-01Interim review and policy revised

Interim review and policy revision conducted in January 2016.

2015-05Policy revised/annual review

Annual review and policy revision completed in May 2015.

2014-05Policy revised/annual review

Annual review and policy revision completed in May 2014.

2013-07Policy revised/annual review

Annual review and policy revision completed in July 2013.

2012-09Policy revised/annual review

Annual review and policy revision completed in September 2012.

2011-09Policy revised/annual review

Annual review and policy revision completed in September 2011.