CurrentBlue Cross Blue Shield - MassachusettsPolicy 310

Intravenous and Subcutaneous Immunoglobulin Therapy (IVIG/SCIG)

Medical necessity and coverage guidance for IVIG and SCIG therapies for Blue Cross Blue Shield of Massachusetts commercial members, including indications, requirements, and related administrative notes.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyIntravenous and Subcutaneous Immunoglobulin Therapy (IVIG/SCIG)

Policy CodePolicy 310

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization (use BCBSMA Formulary Exception/Prior Authorization form) and include required clinical documentation; many members must fill immunoglobulin prescriptions at an in‑network specialty pharmacy.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

sufficient evidenceIndications with sufficient evidence

insufficientIndications with insufficient evidence

preferred listPreferred home infusion list

network requiredRetail specialty pharmacy requirement

2Related policies referenced

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Coverage Criteria for IVIG and SCIG

Medically Necessary Indications

Covered when criteria below are met for specified indications

Primary immunodeficiency (IVIG/SCIG)

Required diagnostic and clinical documentation: Documented inability to mount an adequate immunologic response to inciting antigens; laboratory evidence of immunoglobulin deficiency; persistent and severe infections despite prophylactic antibiotics; ordered by or in consultation with a Board-certified Clinical Immunologist or Infectious Disease Specialist.

Chronic lymphocytic leukemia (CLL): Individuals with CLL who have immunoglobulin G (IgG) levels < 400 mg/dL and persistent bacterial infections are eligible for IVIG.

Autoimmune and inflammatory conditions (IVIG): Individuals meeting indication-specific criteria for IVIG, including but not limited to: acute severe idiopathic thrombocytopenic purpura (ITP) or chronic ITP (disease ≥6 months, symptomatic, persistent thrombocytopenia despite corticosteroids and splenectomy, platelet thresholds as specified); Kawasaki syndrome; Guillain-Barre syndrome (adult) as an alternative to plasma exchange; Wegener granulomatosis; multifocal motor neuropathy; chronic inflammatory demyelinating polyneuropathy (CIDP) with progressive symptoms ≥2 months; Eaton-Lambert myasthenic syndrome after failure of anticholinesterase agents and/or corticosteroids; neuromyelitis optica when refractory or contraindicated to first-line therapy; myasthenic exacerbation when plasma exchange is contraindicated; severe refractory myasthenia gravis after failure of other agents; severe autoimmune mucocutaneous blistering diseases refractory to conventional agents; warm antibody hemolytic anemia refractory to prednisone and splenectomy; dermatomyositis/polymyositis refractory to corticosteroids in combination with other immunosuppressives; catastrophic antiphospholipid syndrome.

SCIG covered indications: Subcutaneous immunoglobulin therapy (SCIG) is medically necessary for primary immunodeficiency states that meet the same diagnostic/laboratory criteria as IVIG and for CIDP where specified; other SCIG applications are considered investigational.

Alloimmune and transplant-related uses: IVIG is covered for select alloimmune indications, including neonatal alloimmune thrombocytopenia and hemolytic disease of the fetus/newborn, and in specific transplant-related contexts (eg, select hematopoietic cell transplant or solid-organ transplant situations) when criteria in the policy are met.

Indications with sufficient evidence

Covered when evidence supports improved net health outcome (examples provided in document):

Examples of indications with sufficient evidence: Primary humoral immunodeficiency; recurrent bacterial infections with hypogammaglobulinemia in chronic lymphocytic leukemia; HIV-infected children with recurrent bacterial infections associated with hypogammaglobulinemia; immune thrombocytopenic purpura (ITP); Guillain-Barre syndrome (GBS); Kawasaki disease; chronic inflammatory demyelinating polyneuropathy (CIDP) [IVIG]; multifocal motor neuropathy (MMN); Eaton-Lambert myasthenic syndrome; severe refractory myasthenia gravis and myasthenic exacerbation (when plasma exchange contraindicated); toxic shock syndrome; autoimmune mucocutaneous blistering diseases; dermatomyositis/polymyositis (refractory); neonatal alloimmune thrombocytopenia.

Indications with insufficient evidence / not routinely recommended

Not routinely covered / insufficient evidence for routine use:

Examples of indications with insufficient evidence: Routine prophylactic IVIG for hematopoietic cell transplantation; IVIG for many solid organ transplant prophylaxis or for treatment of antibody-mediated rejection (evidence insufficient/conflicting); IVIG for neonatal sepsis prophylaxis or treatment; IVIG for adult sepsis (heterogeneous evidence); IVIG for systemic lupus erythematosus (SLE); relapsing-remitting multiple sclerosis (RRMS); toxic epidermal necrolysis (TEN)/Stevens-Johnson syndrome (SJS); inclusion body myositis; paraproteinemic neuropathy; chronic fatigue syndrome; acute myocarditis; refractory recurrent pericarditis; postpolio syndrome; necrotizing fasciitis; autism spectrum disorder; complex regional pain syndrome; many other miscellaneous indications where controlled evidence is lacking or inconsistent.

Coverage conditional on medical necessity criteria

Coverage depends on meeting the policy's medical necessity criteria for the listed codes

General coverage precondition: Inclusion of a code in this policy list does not itself guarantee coverage. The above medical necessity criteria MUST be met for the listed HCPCS/CPT/ICD codes to be covered for Commercial Members; providers should refer to the member's contract and submit required prior authorization and documentation.

The policy notes that while SCIG is an established replacement therapy for primary immunodeficiency, many applications of SCIG are considered investigational. Specifically, the document lists CIDP under Autoimmune and Inflammatory Conditions and explicitly states that other applications of SCIG therapy are considered INVESTIGATIONAL (no coverage) unless the policy’s clinical criteria are met.

Separately, the policy reiterates the primary immunodeficiency entry criteria that apply to both IVIG and SCIG: documented inability to mount an adequate immunologic response, laboratory evidence of immunoglobulin deficiency, and persistent, severe infections despite prophylactic antibiotics; orders should be by or in consultation with a Board-certified Clinical Immunologist or Infectious Disease Specialist.

The policy includes an extensive "Miscellaneous" list of conditions for which IVIG is not indicated or for which evidence is lacking. Examples called out include autism spectrum disorder, complex regional pain syndrome, paraproteinemic neuropathy, acute myocarditis, chronic fatigue syndrome, refractory recurrent pericarditis, postpolio syndrome, noninfectious uveitis, necrotizing fasciitis, thrombotic thrombocytopenic purpura, aplastic anemia, and many other listed disorders—these are presented as conditions with insufficient evidence or not established for IVIG therapy.

Policy history entries provide context for coverage decisions and clarifications over time. Notable history items include additions and coding updates for specific products (eg, Asceniv, Xembify, Cutaquig), movement of HyQvia to non-preferred status, and a specific clarification in 4/2023 that the policy does not cover organ rejection. These historical notes explain prior editorial changes that inform the current scope and coding clarifications.

The document includes an extensive reference list supporting clinical conclusions and coverage determinations. References cited include clinical practice guidelines (eg, EFNS/PNS for CIDP), FDA resources on immune globulins, evidence-based reviews of IVIG use in primary immune deficiency, and multiple randomized trials and systematic reviews that underpin policy statements.

The endnotes summarize historical evidence reviews and the policy’s relationship to national Blue Cross Blue Shield policies and other expert recommendations; these endnotes are used to justify investigational designations and to explain how earlier technology assessments informed the policy.

Endnotes and references in the policy indicate that several indications are classified as investigational or off-label based on National Blue Cross Blue Shield policies and other cited guidance. The policy’s endnotes explicitly reference BCBSA national policy documents and consensus statements as the basis for some investigational/off-label determinations.

The policy documents an apparent inconsistency: while CIDP is listed as a covered indication for IVIG, other applications of SCIG therapy are described as investigational and CIDP is specifically noted under the Autoimmune and Inflammatory Conditions section as an example where SCIG applications are considered investigational. Providers should therefore reconcile product-specific statements against the policy’s clinical criteria when requesting coverage.

Randomized trials and systematic reviews summarized in the policy show that IVIG did not prevent recurrent spontaneous abortion. Multiple RCTs comparing IVIG to placebo found no beneficial effect for preventing spontaneous pregnancy loss; based on that evidence the policy does not support IVIG for recurrent spontaneous abortion.

The policy emphasizes that the inclusion of procedure or product codes in the document is for informational purposes only and does not imply coverage. Coverage for the listed HCPCS/CPT codes is contingent on meeting the policy’s medical necessity criteria; omission of required clinical criteria may result in non-coverage or denial.

The reference list includes randomized trial evidence demonstrating a lack of benefit for IVIG in certain indications—an example cited is a randomized trial showing that IVIG is ineffective for chronic fatigue syndrome. Such trial data are used in the policy to support non-coverage or investigational designations for those conditions.

Endnotes reiterate that certain IVIG uses are considered investigational or off-label per Blue Cross Blue Shield Association policy and related guidance. The policy cites specific national policy references and consensus documents in its endnotes to support these classifications.

Coding and Product Listings

SCIG agents (product names listed)NDC

Hizentra	human immunoglobulin g liquid, subcutaneous (preferred agent listed)
Cuvitru	immune globulin subcutaneous (non-preferred agent)
Cutaquig	immunoglobulin g solution, subcutaneous
HyQvia	immune globulin infusion, subcutaneous (non-preferred agent)

HCPCS codes (informational list)HCPCS

C9072	Injection immune globulin Asceniv 500 mg
J0850	Injection cytomegalovirus immune globulin intravenous (human) per vial [Cytogam]
J1459	mg.
J1551	.
J1554	Injection, immune globulin (Asceniv) 500 mg
J1555	Injection immune globulin (Cuvitru) 100 mg
J1556	Injection immune globulin Bivigam 500 mg
J1557	500 mg
J1558	Injection, immune globulin Xembify, 100 mg
J1559	Injection immune globulin Hizentra 100 mg

1–10 of 19

1/2

The policy lists examples of immune globulin products and links them to the HCPCS coding tables included for informational purposes. Product examples referenced in the coding and definitions sections include brand names such as Asceniv, Cuvitru, Xembify, Hizentra, Gamunex, and others; corresponding HCPCS entries are provided in the coding appendix but coverage remains subject to meeting the clinical criteria in the policy.

Prior Authorization, Documentation, and Submission

Prior Authorization

Prior Authorization and Specialty Pharmacy

Prior authorization is required for medications and infusion services described in this policy. For coverage determination, physicians may call Pharmacy Operations (Phone: 1-800-366-7778) or submit the Formulary Exception/Prior Authorization form by fax (1-800-583-6289) or mail to Blue Cross Blue Shield of Massachusetts Pharmacy Operations Department, 25 Technology Place, Hingham, MA 02043. Many non-Medicare BCBSMA members (other than MedexB; Blue MedicareRx, Medicare Advantage plans that include prescription drug coverage) are required to have prescriptions filled at a participating retail specialty pharmacy in BCBSMA's specialty pharmacy network.

Phone: 1-800-366-7778
Fax: 1-800-583-6289
Mail: BCBSMA Pharmacy Operations Dept, 25 Technology Place, Hingham, MA 02043
Retail specialty pharmacy fill requirement applies to many non-Medicare members

Note

Prior authorization informed by payer and CMS guidance

Prior authorization decisions are informed by BCBSMA policy criteria and may reference applicable Centers for Medicare & Medicaid Services (CMS) National Coverage Determinations and Blue Cross Blue Shield Association national policies. Coverage is contingent on meeting the medical necessity criteria in this policy and may require review of CMS guidance when relevant.

Background and Rationale

Intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) are pooled human immunoglobulin G preparations used both as replacement therapy for primary humoral immunodeficiency and as an immunomodulatory therapy in selected autoimmune, alloimmune, and inflammatory conditions. Appropriate use requires documentation of immunoglobulin deficiency or refractory disease and specialist involvement, and product-specific coding and prior authorization processes apply.

Definitions

Primary immunodeficiency — definition and examples as key/value

DefinitionPrimary immunodeficiency: conditions characterized by laboratory immunoglobulin deficiency and inability to mount an adequate immunologic response to antigens (examples: congenital agammaglobulinemia, severe combined immunodeficiency, X-linked agammaglobulinemia, X‑linked hyper‑IgM syndrome, hypogammaglobulinemia, common variable immunodeficiency, Wiskott‑Aldrich syndrome, ataxia telangiectasia).

Diagnostic requirementsDocumented inability to mount an adequate immunologic response to inciting antigens AND laboratory evidence of immunoglobulin deficiency AND persistent, severe infections despite prophylactic antibiotics.

Ordering requirementOrdered by or in consultation with a Board‑certified Clinical Immunologist or Infectious Disease Specialist.

Related secondary conditionAlso includes individuals with chronic lymphocytic leukemia who have IgG < 400 mg/dL and persistent bacterial infections.

Chronic idiopathic thrombocytopenic purpura (ITP) — definition and clinical thresholds

Revision History and References

2025-07policy updateLatest

HyQvia moved to non-preferred status.

2025-02clarification

Clarified coding for Immunodeficiency States.

2025-01content update

Added a preferred section to the Subcutaneous immunoglobulin (SubQ IG) section of the policy.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyIntravenous and Subcutaneous Immunoglobulin Therapy (IVIG/SCIG)

Policy CodePolicy 310

Change TypeNo material changes

Effective DateN/A

Next Review DateN/A

SourceLink

On This Page

BCBSMA policy clinical criteria must be met for coverage of listed codes
CMS NCDs and BCBSA national policies may inform prior authorization decisions

Denial Risk

Investigational Indications

Requests for use of subcutaneous immunoglobulin (SCIG) or other immunoglobulin therapies for investigational indications, or indications not supported by the clinical criteria in this policy, may be denied or routed for Individual Consideration (exception request). Provide supporting clinical documentation for review.

Investigational or off-label indications may be denied or require Individual Consideration
Include clinical rationale and supporting literature when requesting an exception

Documentation Required

Medical necessity must be met for listed codes

Medical necessity criteria in this policy must be met for the codes listed in the Coding/Endnotes section to be covered. Inclusion of a code in the document is informational and does not by itself guarantee coverage — verify member contract benefits at time of service.

The above medical necessity criteria MUST be met for the listed CPT/HCPCS/ICD codes to be covered
Verify member contract benefits to determine coverage and reimbursement

Note

None stated in these reference and endnote sections

The References and Endnotes sections contain bibliographic citations and historical notes but do not list additional provider action items beyond those specified in this PROVIDER ACTIONS section.

References provide supporting literature and CMS citations
Endnotes provide historical policy revision context

Prior Authorization

Form submission requirement

Home infusion therapy requires completion and submission of the BCBSMA Home Infusion Therapy Prior Authorization Form. BCBSMA employees should fax the completed form to (617) 246-4013. Incomplete or missing information on the form may delay or prevent authorization.

BCBSMA employee fax for Home Infusion Therapy form: (617) 246-4013
Complete all required fields (company, contact, provider #, patient ID, diagnosis, prescribing physician, therapy details, dates, physician signature)
Incomplete forms may delay or prevent authorization

Documentation Required

Specialist Ordering Requirement

Orders for immunoglobulin therapies should be placed by, or in consultation with, a Board-certified Clinical Immunologist or an Infectious Disease Specialist when indicated by the clinical criteria in this policy.

Ordered by or in consultation with a Board-certified Clinical Immunologist or Infectious Disease Specialist

Documentation Required

Immunodeficiency Documentation

For primary immunodeficiency and related indications, documentation must include laboratory evidence of immunoglobulin deficiency and documented inability to mount an adequate immunologic response to inciting antigens, plus history of persistent and severe infections despite prophylactic antibiotics where applicable.

Laboratory evidence of immunoglobulin deficiency
Documented inadequate immune response to antigens (see Policy Guidelines)
History of persistent, severe infections despite prophylactic antibiotics

Note

This part of the document contains bibliographic references

This section includes bibliographic references supporting the policy criteria and clinical guidance. Providers may cite these references in Individual Consideration/exception requests as supporting literature.

Selected peer-reviewed articles, society guidelines, and CMS NCD citations are listed in the References
Providers may include these or other reputable literature when requesting Individual Consideration

Documentation Required

Required documentation on prior authorization form

The prior authorization form and Individual Consideration requests should include supporting clinical documentation: specific names and strengths of formulary alternatives tried, dates of use, clinical response and reason for failure or intolerance, clinical notes, and relevant peer-reviewed literature or guideline references.

Names and strengths of formulary alternatives tried and dates
Description of response or reason for failure/intolerance
Clinical notes and supporting statements
Clinical literature or guideline references (eg, AHFS-DI, Lexi-Drug, Clinical Pharmacology, Micromedex, Drugdex)

Step Therapy

Step therapy for some autoimmune indications

Step therapy requirements apply for some autoimmune indications: for example, IVIG for certain autoimmune conditions may be considered only after failure of corticosteroids and splenectomy or other specified first-line therapies as outlined in the clinical criteria. Pharmacy Operations manages Step Therapy and Quality Care Dosing programs and may use prescription claims to confirm prior use of preferred alternatives.

Some autoimmune indications require prior failure of corticosteroids and splenectomy where specified
Pharmacy Operations enforces Step Therapy and Quality Care Dosing
Prescription claims may be used to verify prior use of formulary alternatives

DefinitionChronic idiopathic thrombocytopenic purpura (ITP): autoimmune platelet destruction with persistent thrombocytopenia described in policy as acute severe ITP or chronic ITP with disease duration ≥6 months, symptomatic, and persistent thrombocytopenia despite corticosteroids and splenectomy.

Platelet thresholdsAdult: platelet count < 20,000 per microliter; Child: platelet count < 30,000 per microliter (criteria for chronic ITP treatment consideration).

Treatment failure requirementPersistent thrombocytopenia despite treatment with corticosteroids and splenectomy is required for chronic ITP to meet IVIG criteria.

ContextPolicy references guideline sources and practice guidelines in endnotes when describing ITP criteria and use of IVIG.

IVIG/SCIG — definition of products and usage

DefinitionIVIG/SCIG: nonspecific pooled human immunoglobulin G preparations derived from donor plasma administered intravenously (IVIG) or subcutaneously (SCIG) for passive immunity and immune modulation.

Scope of reviewThe review addresses IVIG and SCIG nonspecific pooled preparations; it does not consider preparations for passive immunization to specific antigens.

UsesUsed to treat primary and secondary immune deficiency states and various autoimmune and inflammatory disorders by providing broad-spectrum IgG antibodies.

Immune globulin products — examples related to HCPCS and product names

HCPCS examplesPolicy lists immune globulin HCPCS and CPT codes for informational use; inclusion does not guarantee coverage—medical necessity criteria must be met for coverage.

Product examplesNamed products appearing in the policy and references include Asceniv, Hizentra, Cuvitru, Xembify, Gamunex, Flebogamma, Panzyga, Carimune/Panglobulin and others cited in coding and references.

Coding noteProviders should report services using current procedure and diagnosis codes; the document includes an informational list of HCPCS codes and product descriptions but is not exhaustive.

IVIG — brief definition and citation context

DefinitionIVIG: intravenous immunoglobulin preparations derived from pooled human plasma used for replacement therapy in immunodeficiency and as immunomodulatory therapy in selected autoimmune and inflammatory conditions.

Evidence contextIVIG preparations are studied and cited across multiple trials, systematic reviews, and guidelines referenced in the policy (see citations and practice parameters).

Administration routeAdministered intravenously as nonspecific pooled IgG preparations; policy distinguishes IVIG from SCIG based on route and certain indications.

Off-label / Investigational use — definition based on endnotes and BCBSA policy

DefinitionOff‑label / Investigational use: certain IVIG and SCIG indications are designated as off‑label or investigational per Blue Cross Blue Shield Association policy and the policy endnotes; these uses lack sufficient evidence to determine net health benefit.

Reference basisEndnotes cite BCBSA national policy 8.01.05 and other historical guidance as the basis for classifying some uses as off‑label or investigational.

Implication for coverageRequests for indications considered investigational or off‑label may be denied and are subject to individual consideration; inclusion of a code does not imply coverage without meeting medical necessity criteria.

2024-08clarification

Policy clarified with Blue Cross Blue Shield Association.

2024-04content update

Alyglo added to Medical Utilization Management (Medical UM).

2023-11criteria update

Updated criteria for Myasthenia Gravis and updated individual consideration to align with 118E MGL §51A.

2023-04clarification

Clarified that the policy does not cover Organ Rejection.

2021-12review

BCBSA national medical policy review conducted; new references added (no changes to policy statements).

2021-02state mandate update

Updated to add PANDAS & PANS in line with state mandate.

2020-12review

BCBSA national medical policy review conducted; new references added (no changes to policy statements).

2020-04content update

Asceniv added to the policy.

2019-11content update

Xembify added to the policy.

2019-07content update

Cutaquig added to the policy.

2018-08guideline alignment

Updated to include Association coverage statement for Neuromyelitis Optica and blistering disease.

2017-10coding clarification

Clarified coding information and updated Walgreens Specialty name.

2017-07content update

AllCare added to Pharmacy Specialty list.

The policy’s reference list is extensive and numbered; the document notes a substantial bibliography including clinical trials, practice guidelines, systematic reviews, and national policy citations. Endnote counts and cross-references are included in the endnotes section to document the evidence base supporting coverage and investigational determinations.

The endnotes explicitly reference National Blue Cross Blue Shield policies and other national guidance as the basis for some investigational or off-label determinations. These endnote citations are used in the policy to align BCBSMA coverage positions with referenced national policy and expert recommendations.