CurrentPremera BluecrossPolicy N/A

Immune Globulin Therapy (IVIG and SCIG)

Defines medical necessity, site-of-service review criteria, covered indications and investigational/excluded uses for intravenous (IVIG) and subcutaneous (SCIG) immune globulin therapies and coding/documentation and authorization periods. Applies to listed commercial products and addresses site of service considerations for members >=13 years, with Alaska fully insured exception.

Policy Summary

PayerPremera Bluecross

PolicyImmune Globulin Therapy (IVIG and SCIG)

Policy CodePolicy N/A

Change TypeMultiple additions, clarifications and code updates

Effective Date

Next Review Date

Key ActionObtain pre-approval and submit clinical documentation (diagnosis, labs, objective response measures) and ensure site-of-service review for members age >=13 as applicable.

POLICY UPDATE CHANGES

Last revised date indicated as Jun 10, 2025 NZA; policy includes new J-code J1552 effective 01/01/2025.

Updated IgG level requirements from <400 mg/dL to <500 mg/dL across initial criteria.

Added treatment for certain individuals with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).

Added re-authorization requirement to have an IgG '2300 mg/dL' (source text likely contains typographical error).

Added site-of-service review requirements for several products (Asceniv, Cutaquig, Panzyga, Alyglo).

Added Yimmugo and other products to the policy and associated HCPCS code J3590.

Removed requirement to have recurrent or persistent infections from humoral immunodeficiency coverage criteria.

Clarified that medications listed are subject to the product's FDA dosage and administration.

Added measles post-exposure prophylaxis treatment for certain individuals (effective October 3, 2025).

Clarified Site of Service Medical Necessity criteria applicability to injection drugs (effective October 3, 2025).

ManyCovered Indications (listed)

ManyInvestigational/Not Covered Indications

>=13Age threshold for SOS review

12 moMax non-formulary exception duration

multipleHCPCS/J-codes history

Coverage Summary

Background: This policy addresses use of pooled intravenous immune globulin (IVIG) and subcutaneous immune globulin (SCIG) for primary and secondary immunodeficiency and a range of autoimmune and inflammatory disorders. IVIG is treated as a medical benefit, while SCIG may be either a pharmacy or medical benefit depending on contract/benefit language.

Scope: The policy excludes preparations used for passive immunization to specific antigens (examples: CMV, hepatitis A, hepatitis B, measles, RSV, rubella, varicella). Site-of-Service (SOS) review applies to medical benefit reviews for members aged 13 years and older; the SOS criteria do NOT apply to Alaska fully insured members per the Alaska exception. Reviewers will apply the policy’s site-of-service and medical necessity criteria to IVIG (medical benefit) and apply contract/benefit rules to determine whether SCIG is pharmacy or medical benefit.

Reference thresholds and authorization durations (see policy brief): key laboratory and clinical thresholds and the documented authorization timeframes are referenced in the policy (including IgG thresholds and specified authorization durations); these headline thresholds and durations are taken from the brief and should be consulted in the policy for exact numeric values and authorization windows.

Key thresholds and quick facts

IgG threshold — secondary humoral immunodeficiencyIgG < 500 mg/dL

Agammaglobulinemia definitionTotal IgG < 200 mg/dL

Persistent hypogammaglobulinemia definitionTotal IgG < 500 mg/dL or ≥2 standard deviations below normal on at least 2 occasions

CIDP diagnostic timeframe thresholdProgressive or relapsing motor/sensory symptoms for >2 months

ITP adult platelet thresholdPlatelet count < 10,000/mm3 (or < 30,000/mm3 with additional criteria)

CRS temperature thresholdTemperature ≥ 38°C (part of CRS grade 3–4 criteria)

IVIG starting dose (primary immunodeficiency)IVIG 400–600 mg/kg per 4 weeks

SCIG starting dose (primary immunodeficiency)SCIG 100–150 mg/kg per week

Maintenance IVIG dose (CLL guidance)0.3–0.5 g/kg monthly to maintain IgG ≥ 500 mg/dL

Age threshold for site-of-service (SOS) reviewSOS review applies to individuals aged ≥13 years (Alaska fully insured members excluded)

Maximum non-formulary exception authorization durationUp to 12 months

Provider notification window for effective policy changes90 days prior to effective date

Re-authorization IgG requirement (noted update)Policy history notes added re-authorization requirement mentioning an IgG '2300 mg/dL' (source lists this numeric string; likely typographical error)

Medical-Necessity Criteria

Site of Service Medical Necessity

Site of Service Medical Necessity criteria applies to members aged 13 and older except Alaska fully insured members (see note below).

Applicable population
- Member age >= 13 years (site-of-service review applies).
- Exception: Alaska fully insured members — SOS Medical Necessity criteria does NOT apply; refer to infusion and injection drug Medical Necessity criteria only.
Medically necessary sites of service
- Physician's office

Evidence, Guidelines and Indications

Indications with sufficient evidence to improve net health outcome

IVIG/SCIG is considered to improve net health outcome for the following conditions based on RCTs, systematic reviews, meta-analyses, or multiple observational studies:

Toxic shock syndrome (Streptococcal toxic shock syndrome) — evidence: small RCT and multiple observational studies; showed reductions in mortality.

Immune thrombocytopenia (ITP) — evidence: multiple RCTs, systematic review, meta-analysis; IVIG improved platelet counts compared with corticosteroids.

Guillain-Barre syndrome (GBS) — evidence: multiple RCTs, systematic review, meta-analysis; IVIG similar outcomes to plasma exchange.

Kawasaki disease — evidence: multiple RCTs, systematic review, meta-analysis; IVIG decreased new coronary artery abnormalities.

Coding

CPTCPT

90283	Immune globulin (IGIV), human; for intravenous use.
90284

HCPCS / J-codes (Immune globulin products)HCPCS

J1459
J1551	Injection, immune globulin (Cutaquig) 100 mg
J1552	Injection, immune globulin (Alyglo), 500 mg (new code effective 01/01/2025)
J1554	Injection, immune globulin (Asceniv), 500 mg
J1555	Injection, immune globulin (Cuvitru), 100 mg
J1556	Injection, immune globulin (Bivigam), 500 mg
J1557	Injection, immune globulin (Gammaplex), intravenous, non-lyophilized liquid, 500 mg
J1558	Injection, immune globulin (Xembify), 100 mg
J1559	Injection, immune globulin (Hizentra), 100 mg
J1561	Injection, immune globulin (Gamunex/Gamunex-C/Gammaked), non-lyophilized liquid, 500 mg

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FDA-approved IVIG/SCIG products (examples listed)mixed

Asceniv	ADMA Biologics — example FDA-approved IVIG product
Bivigam	ADMA Biologics — example FDA-approved IVIG product
Flebogamma DIF	Instituto Grifols — IVIG
Gammagard Liquid	Takeda — IVIG/SCIG
Gammagard S/D	Takeda — IVIG
Gammaked	Kedrion Biopharma — IVIG/SCIG
Gammaplex	Bio Products Lab — IVIG
Gamunex-C	Grifols Therapeutics — IVIG/SCIG
Octagam	Octapharma — IVIG
Panzyga	Pfizer — IVIG

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HCPCS / J-codes referenced in history (added/removed over time)HCPCS

J1459	added 01/13/09
J1551	added 07/01/22
J1552	replaced J1599 for Alyglo (removed/added 12/01/24 - 01/01/25)
J1554	added 04/07/21
J1555	added 01/01/18
J1556	added 02/01/16
J1557	added 01/27/12
J1558	added 07/01/20
J1562	removed (date not specified)
J1566	removed, later re-added 03/01/24, then removed again per 01/01/25 note; market removal referenced

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Provider Actions & Billing Rules

Prior Authorization

Prior authorization required

Pre-approval required. Submit request for review and receive authorization prior to initiation of IVIG/SCIG therapy or other immune globulin infusions. Authorizations will specify approved diagnosis, dosing limits, duration, and any site-of-service limitations.

Documentation Required

Clinical documentation required

Clinical documentation must be submitted with the authorization request to support medical necessity. Include relevant history, prior therapies and responses, baseline labs, and objective measures as applicable to the diagnosis (e.g., IgG levels, antibody responses, platelet counts). For re-authorization requests, provide documentation of clinical benefit and objective measures per condition-specific criteria.

Include baseline and most recent relevant laboratory results (e.g., IgG, IgA, IgM, IgG subclasses, antibody titers)

Definitions

Site of Service (SOS): Location where the drug is administered (hospital-based outpatient, infusion center, physician's office, or home). SOS criteria apply to medical benefit reviews and to members age 13+ exclusion for Alaska fully insured members.

CRS grade 3 or 4: Documented criteria include temperature ≥ 38°C, hypotension requiring ≥1 vasopressor, and hypoxia requiring high-flow oxygen or positive pressure/ventilation.

IVIG: Intravenous immunoglobulin therapy — pooled human immunoglobulin administered intravenously for immune replacement or modulation; considered a medical benefit in the policy.

SCIG: Subcutaneous immunoglobulin therapy — human immunoglobulin administered subcutaneously, used for maintenance in some conditions; may be pharmacy or medical benefit depending on contract.

NAC/CBS: National Advisory Committee on Blood and Blood Services (Canadian Blood Services) — named guideline source referenced in the policy.

AAAAI: American Academy of Allergy, Asthma, and Immunology — named guideline source referenced in the policy.

Medicare Determinations

Number	Name	Effective Year	Type
CMS 2002 NCD	IVIG for autoimmune mucocutaneous blistering diseases	2002	NCD
250.3	IVIG for autoimmune mucocutaneous blistering diseases	2002	NCD

Revision History

07/09/2024interim_review

Interim review approved July 9, 2024: clarified IVIG coverage for Guillain-Barre syndrome; added treatment for certain individuals with MOG antibody–associated disease (MOGAD); updated IgG level requirements across initial criteria from <400 mg/dL to <500 mg/dL; added a re-authorization requirement language referencing an IgG value (source text records 'have an IgG 2300 mg/dL').

12/23/2024interim_review

Interim review approved December 23, 2024: clarified that medications listed are subject to the product's FDA dosage and administration prescribing information; removed HCPCS code J1599 and replaced it with new code J1552 for Alyglo.

01/01/2025policy_update

Policy Summary

PayerPremera Bluecross

PolicyImmune Globulin Therapy (IVIG and SCIG)

Policy CodePolicy N/A

Change TypeMultiple additions, clarifications and code updates

Effective Date

Next Review Date

Key ActionObtain pre-approval and submit clinical documentation (diagnosis, labs, objective response measures) and ensure site-of-service review for members age >=13 as applicable.

On This Page

Home infusion (when criteria met)

Hospital-based outpatient setting / outpatient hospital IV infusion department — considered medically necessary for the initial course or re-initiation after >= 6 months, or when no outpatient infusion center within 50 miles or no contracted home infusion agency will travel to the home, or hospital is the only facility offering the infusion.

Situations requiring hospital-based outpatient setting

Increased risk of complications (e.g., known cardiac condition with symptomatic arrhythmia; significant respiratory disease or FVC <= 40%; unstable renal function; difficult or unstable vascular access; acute mental status changes impacting safety).
Known history of severe adverse drug reactions and/or anaphylaxis to prior treatment with a related or similar drug.
Cytokine Release Syndrome (CRS) grade 3 or 4 evidenced by ALL of the following: Temperature >= 38°C; hypotension requiring >= 1 vasopressor; hypoxia requiring high-flow oxygen device or positive pressure ventilation.

IVIG — Humoral Immunodeficiency States (Therapeutic use)

IVIG — Humoral Immunodeficiency States (Therapeutic use).

ALL of the following

IVIG may be considered medically necessary for therapeutic use in humoral immunodeficiency states (for example: ALL, CLL, lymphoma, multiple myeloma) when ALL of the following are present:
Documented IgG level < 500 mg/dL.
The individual is receiving or at risk due to anti‑B cell immunotherapy (e.g., rituximab, CAR‑T, or hematopoietic stem cell transplant [HCT]) that impairs humoral immunity.

IVIG — Primary Immunodeficiency States

IVIG — Primary Immunodeficiency States. IVIG may be considered medically necessary when ALL of the following are present:

ALL of the following

Laboratory evidence of immunoglobulin deficiency indicated by ONE of the following:
ANY of the following
- Agammaglobulinemia: total IgG < 200 mg/dL.
- Persistent hypogammaglobulinemia: total IgG < 500 mg/dL, or ≥2 standard deviations below normal, on at least 2 occasions.
- Absence of B lymphocytes.
Documented inability to mount an adequate immunologic response to inciting antigens as indicated by ONE of the following:
ANY of the following
- Lack of appropriate rise in antibody titer following provocation with a polysaccharide antigen.
- Lack of appropriate rise in antibody titer following provocation with a protein antigen.
Persistent and severe infections despite appropriate treatment including prophylactic antibiotics.

IVIG — Specific Antibody Deficiency (SAD)

IVIG — Specific Antibody Deficiency (SAD). Note: source text truncated in original for part of the serotype wording — below preserves age-specific serotype thresholds and available vaccine-response criteria.

ALL of the following

Immunological evaluation with documented normal serum IgG, IgG subclasses, IgA, and IgM.
Normal responses to protein antigens (e.g., tetanus and diphtheria toxoid) measured approximately 4 weeks after immunization.
Inadequate responsiveness to pneumococcal polysaccharide vaccine (e.g., Pneumovax23) measured 4–8 weeks after vaccination as demonstrated by age-specific serotype thresholds:
Pneumococcal vaccine response thresholds
- Age < 6 years: < 50% of serotypes protective (>= 1.3 mcg/mL per serotype is considered protective).
- Age >= 6 years: inadequate response defined by percentage of serotypes not achieving >= 1.3 mcg/mL per serotype (source text truncated; use clinical judgment and immunology consultation).
Recurrent, significant bacterial sinopulmonary infections despite pneumococcal vaccination and failure or inadequate response to prophylactic antibiotics.
Documented management of underlying conditions (e.g., asthma, allergic rhinitis) with appropriate controller therapy (nasal or inhaled glucocorticoids, bronchodilators, or antihistamines) when applicable.

IVIG — Other Covered Indications

IVIG — Other Covered Indications. IVIG may be considered medically necessary for the following conditions when specified subcriteria are met.

ANY of the following

Measles post-exposure prophylaxis
- Documented indication for measles post‑exposure prophylaxis per public health guidance.
Severe anemia associated with parvovirus B19
- Documented diagnosis of severe anemia due to human parvovirus B19 infection.
Toxic shock syndrome (TSS)
- Documented diagnosis of toxic shock syndrome.
Blistering diseases (pemphigoid, mucous membrane pemphigoid, pemphigus vulgaris/foliaceus, IgA pemphigus)
- Severe, progressive disease AND failure of, contraindication to, or intolerance of conventional agents (e.g., corticosteroids and immunosuppressive agents such as azathioprine, cyclophosphamide, mycophenolate).
Immune thrombocytopenia (ITP) — Adults
- Platelet count < 10,000/mm3 and individual considered at risk for severe bleeding or intracranial bleeding; OR
- Platelet count < 30,000/mm3 AND one of the following: need to rapidly increase platelets due to bleeding, major surgery planned, or risk of intracranial bleeding; OR not a candidate for splenectomy or relapse post-splenectomy.
- Failure, contraindication, or intolerance to corticosteroids.*
Immune thrombocytopenia (ITP) — Pediatric
- Platelet count < 30,000/mm3 AND one of the following: need to rapidly increase platelets due to bleeding, major surgery planned, or risk of intracranial bleeding; OR prevention of bleeding in the first 12 months after diagnosis.
- See policy 5.01.566 Pharmacotherapy of Thrombocytopenia for additional details.
Guillain-Barré syndrome (adult and pediatric)
- Documented diagnosis and clinical indication per neurology guidance (policy text continues in other sections).
Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Meets established diagnostic criteria (e.g., AAN or other accepted CIDP criteria) and failure or intolerance of first‑line therapies when applicable.
Stiff person syndrome
- Documented diagnosis of stiff person syndrome and clinical indication for IVIG per neurology guidance.

IVIG — Not Medically Necessary

IVIG — Not Medically Necessary. The following are explicit exclusions.

ANY of the following

Multiple sclerosis (IVIG is not medically necessary for treatment of multiple sclerosis).
Other indications with sufficient evidence of lack of benefit per guideline and evidence review (see Conditions with insufficient or negative evidence).

IVIG — Investigational / Not Covered Indications

IVIG — Investigational / Not Covered Indications. The following conditions are considered investigational or not covered.

ANY of the following

Listed neurologic, rheumatologic, infectious, and other conditions with insufficient evidence supporting IVIG use (refer to Evidence Review and Conditions with insufficient or negative evidence section for full list).

SCIG

Subcutaneous Immune Globulin (SCIG).

ALL of the following

SCIG is covered when IVIG criteria are met and SCIG is an appropriate route for administration for the condition diagnosed.
Other uses of SCIG that do not meet IVIG coverage criteria are considered investigational or not covered.

Authorization durations

Authorization durations.

ALL of the following

Initial authorization: duration per indication-specific guidance (commonly 6–12 months for chronic indications; short duration for acute indications as clinically appropriate).
Re-authorization: based on documented clinical response and ongoing need; generally requires documentation of benefit and interval labs/assessments as applicable.
Non-formulary exception requests: duration will be limited to the timeframe clinically necessary and consistent with medical necessity; when requested for non-formulary product due to shortage or clinical need, authorization may be granted for a shorter interval subject to review.

Granulomatosis with polyangiitis (Wegener granulomatosis) — evidence: systematic reviews and RCT; more responders at 3 months.

Chronic inflammatory demyelinating polyneuropathy (CIDP) — evidence: systematic review and RCTs; IVIG showed clinically meaningful reductions in disability.

Multifocal motor neuropathy (MMN) — evidence: multiple RCTs and meta-analysis; IVIG reduced disability and improved muscle strength.

Lambert-Eaton myasthenic syndrome — evidence: RCT and observational studies; IVIG improved muscle strength.

Neuromyelitis optica spectrum disorder (refractory to first-line treatments) — evidence: multiple observational studies; IVIG may benefit refractory cases, particularly children.

Severe refractory myasthenia gravis or myasthenic exacerbation — evidence: multiple RCTs and systematic review; IVIG reduced disability and improved muscle strength.

Autoimmune mucocutaneous blistering diseases — evidence: two RCTs and systematic review; improvements in >90% in some reports.

Neonatal alloimmune thrombocytopenia — evidence: multiple RCTs and systematic review; IVIG demonstrated increased platelet counts.

Stiff person syndrome — evidence: small randomized crossover study; IVIG decreased stiffness and improved function.

Indications supported by specialty society guidance

Evidence is insufficient for routine use of IVIG/SCIG for the following conditions (observational data, small trials, or negative trials):

Sepsis (general) — evidence insufficient.

Severe anemia associated with human parvovirus B19 — evidence limited to case series; evidence insufficient.

CIDP (SCIG for CIDP maintenance) — evidence limited; insufficient to draw conclusions about relative efficacy.

Relapsing-remitting multiple sclerosis — IVIG no longer considered treatment of choice; evidence insufficient.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson Syndrome (SJS) — pooled analyses did not find mortality benefit; insufficient evidence.

Inclusion body myositis — RCTs failed to show improvements; insufficient evidence.

Systemic lupus erythematosus — mainly retrospective data; insufficient evidence.

Immune optic neuritis — two RCTs failed to show vision improvement; insufficient evidence.

Crohn disease — case reports only; insufficient evidence.

citations([

Evidence summary: The policy cites a broad evidence base including randomized controlled trials (RCTs), systematic reviews and meta-analyses, practice guidelines, and observational studies across conditions. Examples include RCTs and meta-analyses for neonatal and adult sepsis, Cochrane and other systematic reviews for Guillain-Barre syndrome, Kawasaki disease, CIDP, multifocal motor neuropathy and ITP, and multiple RCTs/observational series for toxic shock syndrome and other indications.

Guidelines and society recommendations are also referenced extensively (e.g., NAC/CBS, AAN, AAAAI, NCCN, AHA, CMS NCD), and numerous PMIDs and guideline sources are listed in the policy references to support condition-specific conclusions.

Provide prior treatment history and reasons for IVIG (failure/intolerance to conventional therapies)

For ITP maintenance re-evaluation: document platelet trend and clinical bleeding risk; provide objective platelet counts at re-evaluation intervals

Documentation Required

Biopsy-proven diagnosis required for blistering diseases

Some conditions require disease confirmation by tissue diagnosis. For autoimmune mucocutaneous blistering diseases (pemphigus, mucous membrane pemphigoid, bullous pemphigoid, IgA pemphigus), provide biopsy-proven diagnosis (histopathology and direct immunofluorescence) with submitted request to meet coverage criteria.

Biopsy-proven diagnosis required for autoimmune mucocutaneous blistering diseases: histology and direct immunofluorescence results must be included

Documentation Required

Dose and monitoring documentation

Dose and monitoring documentation must be included in the medical record and submitted with authorization and re-authorization. For chronic maintenance IVIG (e.g., ITP maintenance), document dosing schedule, cumulative dose, interval between infusions, and clinical response. Re-evaluation intervals should be specified: maintenance IVIG for chronic ITP must be re-evaluated periodically with documentation of ongoing need (including platelet counts and bleeding symptoms) to support continuing authorization.

Document dose, infusion dates, and monitoring labs
For chronic ITP maintenance IVIG: include re-evaluation interval and serial platelet counts demonstrating continued need

Billing Rule

Site-of-service review applicability and Alaska exception

Site-of-service review applies to IV and injectable immune globulin administration for members aged 13 and older; the site-of-service determination (office, infusion center, home, or hospital outpatient) will be made based on the clinical criteria in this policy. The Site of Service Medical Necessity criteria do NOT apply to Alaska fully insured members; for those members refer to the infusion and injection drug Medical Necessity criteria only.

Site-of-service review applies for members age 13 and older
SOS Medical Necessity criteria do not apply to Alaska fully insured members

Billing Rule

Site-of-service rules and exceptions

Site-of-service exceptions: hospital-based outpatient setting is considered medically necessary for initial infusions (first 90 days) or re-initiation after ≥6 months when clinically indicated, or when clinical conditions increase infusion risk (e.g., severe cardiac/pulmonary disease, unstable renal function, difficult vascular access, severe cognitive impairment, prior severe infusion reaction). For cytokine release syndrome (CRS) grade 3–4, hospital-based outpatient setting is required.

Hospital-based outpatient setting may be required for initial course (first 90 days) or re-initiation after ≥6 months
Hospital-based setting indicated for CRS grade 3–4 or other high-risk clinical conditions

Billing Rule

J3590 and coding guidance

When billing for IVIG/SCIG services, follow the current policy code listing and payer guidance. If using miscellaneous drug code J3590, report J3590 with the drug name and NDC or supply documentation as required by payer. Check the current coding table for the appropriate HCPCS/NDC.

If reporting J3590, include drug name and NDC per current policy guidance
Follow current policy code listing for specific HCPCS/NDC codes

Prior Authorization

Authorization duration and effective-dates/provider notification

Non-formulary exception approvals or other non-standard authorizations may be granted for up to 12 months. Changes to coverage, site-of-service rules, or prior authorization requirements become effective only after providers have been notified; allow a 90-day provider-notification period before changes are applied to existing authorizations.

Non-formulary exception duration: up to 12 months
Policy or coverage changes: effective after 90-day provider notification period

01/01/2025 updates effective for dates of service on or after Jan 1, 2025: coding updates and policy clarifications noted in history (including code replacements and confirmation of FDA dosing applicability).

01/01/2025 (code effective date)code_addition

New HCPCS/J-code J1552 (Alyglo) noted as new code effective 01/01/2025 for reporting Alyglo.

12/01/2024interim_review

Interim review approved November 12, 2024 (effective Dec 1, 2024 action reflected in history): added Yimmugo to the policy and added HCPCS code J3590 to report Yimmugo; added treatment for certain individuals in humoral immunodeficiency state with ALL; removed requirement for recurrent or persistent infections from humoral immunodeficiency coverage criteria.

06/10/2025revisedLatest

Last revised Jun 10, 2025 NZA (approved June 10, 2025; effective following 90-day provider notification): added J1552 (Alyglo) noted as new code effective 01/01/2025; added measles post-exposure prophylaxis treatment for certain individuals (effective October 3, 2025); clarified Site of Service Medical Necessity criteria applicability to injection drugs effective October 3, 2025; effective dates to follow 90-day provider notification.