Blue Cross Blue Shield - Iowa IVIG Coverage Update

Coverage and Medical Necessity Criteria

Primary Immunodeficiency

Covered when ALL of the following are met for initial authorization (may be granted for 6 months):

Eligible primary diagnoses: Severe combined immunodeficiency (SCID) or congenital agammaglobulinemia; Wiskott-Aldrich syndrome, DiGeorge syndrome, ataxia-telangiectasia or other non-SCID combined immunodeficiency; Common variable immunodeficiency (CVID); Hypogammaglobulinemia, IgG subclass deficiency, selective IgA or IgM deficiency, or specific antibody deficiency

Each diagnosis has specific laboratory or testing subcriteria

SCID/ congenital agammaglobulinemia subcriteria: Diagnosis confirmed by genetic or molecular testing OR pretreatment IgG level < 200 mg/dL OR absence/very low T cells (CD3 < 300/µL) or presence of maternal T cells (SCID only)IgG < 200 mg/dL; CD3 < 300/µL

Wiskott-Aldrich/DiGeorge/ataxia-telangiectasia subcriteria: Diagnosis confirmed by genetic/molecular testing (if applicable) AND history of recurrent bacterial infections AND impaired antibody response to pneumococcal polysaccharide vaccine

See Appendix A for vaccine response details

CVID subcriteria: Age ≥ 2 years AND other causes of immune deficiency excluded AND pretreatment IgG < 500 mg/dL or ≥ 2 SD below mean for age AND history of recurrent bacterial infections AND impaired antibody response to pneumococcal polysaccharide vaccineIgG < 500 mg/dL or ≥2 SD below mean for age

Other antibody deficiencies subcriteria: History of recurrent bacterial infections AND impaired antibody response to pneumococcal polysaccharide vaccine AND one of the following pre-treatment laboratory findings: (i) IgG < 500 mg/dL or ≥2 SD below mean for age; (ii) selective IgA deficiency (IgA < 7 mg/dL) with normal others; (iii) selective IgM deficiency (IgM < 30 mg/dL) with normal others; (iv) IgG subclass deficiency ≥2 SD below mean on ≥2 occasions with normal total IgG/IgM; or (v) specific antibody deficiency with normal total IgG/IgA/IgM)IgG < 500 mg/dL (one pathway) or specified subclass/IgA/IgM thresholds

See Appendix A for vaccine response details

Re-authorization for primary immunodeficiency: Demonstrated reduction in frequency of bacterial infections since initiation of IG therapy AND yearly monitoring of IgG troughs maintained at or above the lower range of normal for age OR prescriber will re-evaluate dose and consider adjustment

Re-authorization may be granted for 6 months when met

Myasthenia Gravis

Covered when ONE of the following is met:

Acute/worsening or pre-operative MG: IG prescribed for worsening weakness (increase in diplopia, ptosis, blurred vision, dysarthria, dysphagia, difficulty chewing, impaired respiration, fatigue, limb weakness) OR acute exacerbation (severe swallowing difficulty or respiratory failure) OR pre-operative management prior to thymectomy

Authorization of 1 month may be granted

Refractory MG: Member has tried and failed 2 or more standard therapies (e.g., corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, rituximab)

Authorization of 6 months may be granted

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Covered when ALL of the following are met for initial authorization:

CIDP initial criteria: Disease course progressive or relapsing/remitting for ≥2 months AND moderate to severe functional disability AND diagnosis confirmed by electrodiagnostic studies and CSF evaluation

Initial authorization of 3 months

CIDP re-authorization: Significant improvement in disability and maintenance of improvement since initiation of IG therapy AND IG used at the lowest effective dose and frequency

Re-authorization of 6 months

Dermatomyositis and Polymyositis

Covered when ALL of the following are met for initial authorization:

Diagnostic criteria: Member has at least 4 specified clinical, laboratory, biopsy, or EMG features (e.g., proximal muscle weakness; elevated CK or aldolase; muscle pain; myogenic EMG changes; anti-synthetase antibodies; non-destructive arthritis; systemic inflammatory signs; biopsy compatible with inflammatory myositis)

Treatment history: Standard first-line (corticosteroids) and second-line (immunosuppressants) have been tried and were unsuccessful or not tolerated, OR member is unable to receive these therapies due to contraindication

Initial authorization of 3 months

Re-authorization: Significant improvement in disability and maintenance of improvement since initiation of IG therapy

Re-authorization of 6 months

Idiopathic Thrombocytopenic Purpura (ITP)

Covered when ALL of the following per clinical scenario are met:

Newly diagnosed ITP (children): Significant mucosal or moderate/severe bleeding OR high risk for bleeding OR rapid increase in platelets required (e.g., for surgery)

Authorization of 1 month for children; provide risk factors per Appendix B

Newly diagnosed ITP (adults): Platelet count < 30,000/mcL OR platelet count < 50,000/mcL with significant bleeding/high risk for bleeding/need for rapid platelet increase AND corticosteroid therapy contraindicated or IG used alone or with corticosteroidplatelets < 30,000/mcL (or <50,000/mcL with qualifying features)

Authorization of 1 month for adults

Chronic/persistent ITP (≥3 months): Platelet count < 30,000/mcL OR platelet count < 50,000/mcL with significant bleeding/high risk/need for rapid platelet increase AND relapse after prior response to IG or inadequate response/intolerance/contraindication to corticosteroid or anti-D therapy

B-cell Chronic Lymphocytic Leukemia (CLL)

Covered when ALL of the following are met for initial authorization (6 months):

CLL prophylaxis criteria: IG prescribed for prophylaxis of bacterial infections AND history of recurrent sinopulmonary infections requiring IV antibiotics or hospitalization AND pretreatment serum IgG < 500 mg/dLIgG < 500 mg/dL

Re-authorization of 6 months requires reduction in infection frequency

Prophylaxis of Bacterial Infections in Pediatric HIV

Covered when ANY of the following initial criteria are met (authorization up to 6 months):

Pediatric HIV prophylaxis: a) Primary prophylaxis with pretreatment serum IgG < 400 mg/dL; b) Secondary prophylaxis for history of recurrent serious bacterial infections (>2 serious infections in 1 year); c) Failure to form antibodies to common antigens (e.g., measles, pneumococcal, H. influenzae type b); d) Lives in high-measles area with no antibody response after two MMR doses; e) Single-dose post-exposure request for measles; f) Chronic bronchiectasis suboptimally responsive to antimicrobial/pulmonary therapyIgG < 400 mg/dL (for primary prophylaxis)

Re-authorization of 6 months may be granted when reduction in bacterial infection frequency is demonstrated

Prophylaxis of Bacterial Infections in BMT/HSCT Recipients

Covered when ALL of the following are met for initial authorization (6 months):

BMT/HSCT criteria: IG prescribed for prophylaxis of bacterial infections AND either (i) IG requested within the first 100 days post-transplant OR (ii) pretreatment serum IgG < 400 mg/dLIgG < 400 mg/dL (one pathway)

Re-authorization of 6 months may be granted when reduction in frequency of bacterial infections is demonstrated

H. Prophylaxis of Bacterial Infections in HIV-Infected Pediatric Patients

Initial authorization up to 6 months when ANY of the following apply:

HIV pediatric prophylaxis initial: a) primary prophylaxis with pretreatment serum IgG < 400 mg/dL; b) secondary prophylaxis for history of recurrent bacterial infections (>2 serious bacterial infections in 1 year); c) failure to form antibodies to common antigens (e.g., measles, pneumococcal, H. influenzae type b); d) lives in area with high measles prevalence and no antibody response after two MMR doses; e) single-dose post-exposure to measles; f) chronic bronchiectasis suboptimally responsive to antimicrobial/pulmonary therapyIgG < 400 mg/dL (for primary prophylaxis)

Re-authorization of 6 months may be granted when reduction in bacterial infection frequency is demonstrated

H. Prophylaxis of Bacterial Infections in BMT/HSCT Recipients

Initial authorization of 6 months when ALL of the following are met:

BMT/HSCT prophylaxis: a) IG prescribed for prophylaxis of bacterial infections; b) either (i) IG requested within first 100 days post-transplant OR (ii) pretreatment serum IgG < 400 mg/dLIgG < 400 mg/dL (one pathway)

Re-authorization of 6 months may be granted when reduction in frequency of bacterial infections is demonstrated

I. Multifocal Motor Neuropathy (MMN)

Initial authorization of 3 months when ALL are met:

MMN initial: Progressive, multifocal, asymmetrical weakness without objective sensory loss in ≥2 nerves for ≥1 month AND diagnosis confirmed by electrodiagnostic studies

Electrodiagnostic confirmation required for initial authorization; re-authorization 6 months when significant improvement maintained

J. Guillain-Barre Syndrome (GBS)

Authorization of 2 months total when BOTH are met:

GBS authorization: Severe disease with significant weakness (e.g., inability to stand/walk without aid, respiratory weakness) AND onset of neurologic symptoms < 4 weeks from anticipated start of therapy

Authorization limited to 2 months total

K. Lambert-Eaton Myasthenic Syndrome (LEMS)

Initial authorization of 6 months when ALL are met:

LEMS initial: Diagnosis confirmed by neurophysiology OR positive anti-P/Q VGCC antibody; anticholinesterases and amifampridine tried and unsuccessful or not tolerated; AND weakness is severe or venous access for plasmapheresis is difficult

Re-authorization of 6 months may be granted when member is responding

L. Kawasaki Syndrome

Authorization:

Kawasaki: Pediatric members with Kawasaki syndrome may be granted authorization of 1 month

M. Fetal/Neonatal Alloimmune Thrombocytopenia (F/NAIT)

Authorization:

F/NAIT: Authorization of 6 months may be granted for treatment of fetal/neonatal alloimmune thrombocytopenia

N. Parvovirus B19-induced PRCA

Authorization:

PRCA: Authorization of 6 months may be granted for severe, refractory anemia associated with bone marrow suppression and parvovirus B19 viremia

Confirmation of parvovirus B19 required per documentation guidance

O. Stiff-person Syndrome

Authorization of 6 months when BOTH are met:

Stiff-person: Diagnosis confirmed by anti-glutamic acid decarboxylase (GAD) antibody testing AND inadequate response to first-line treatment (benzodiazepines and/or baclofen)

Authorization of 6 months may be granted

P. Management of immune checkpoint inhibitor-related toxicities

Authorization of 1 month when ALL are met:

ICI toxicities: Moderate or severe adverse event to a PD-1 or PD-L1 inhibitor AND offending medication held or discontinued AND member has one or more listed severe adverse events (e.g., myocarditis, Stevens-Johnson syndrome, pneumonitis, myasthenia gravis, GBS, encephalitis, severe inflammatory arthritis, steroid-refractory myalgias/myositis)

Authorization of 1 month may be granted

Q. Acquired Red Cell Aplasia

Authorization:

Acquired Red Cell Aplasia: Authorization of 6 months may be granted for acquired red cell aplasia

R. Acute Disseminated Encephalomyelitis

Authorization:

ADEM: Authorization of 6 months may be granted for acute disseminated encephalomyelitis in members with insufficient response or contraindication to IV corticosteroids

S. Autoimmune Mucocutaneous Blistering Disease

Authorization of 6 months when ALL are met:

Blistering disease: Diagnosis proven by biopsy and confirmed by pathology report AND condition is rapidly progressing, extensive, or debilitating AND member has failed or experienced significant complications from standard treatment (corticosteroids, immunosuppressive agents)

Includes pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita

T. Autoimmune Hemolytic Anemia

Authorization:

Autoimmune hemolytic anemia: Authorization of 6 months may be granted for warm-type autoimmune hemolytic anemia in members who do not respond to or have a contraindication to corticosteroids or splenectomy

U. Autoimmune Neutropenia

Authorization:

Autoimmune neutropenia: Authorization of 6 months may be granted where treatment with GCSF is not appropriate

V. Birdshot Retinochoroidopathy

Authorization:

Birdshot retinochoroidopathy: Authorization of 6 months may be granted for disease not responsive to immunosuppressives (e.g., corticosteroids, cyclosporine)

W. BK Virus Associated Nephropathy

Authorization:

BK virus nephropathy: Authorization of 6 months may be granted for BK virus associated nephropathy

X. Churg-Strauss Syndrome

Authorization:

Churg-Strauss: Authorization of 6 months may be granted for severe, active Churg-Strauss syndrome as adjunctive therapy when failure, intolerance, or contraindication to other interventions has occurred

Y. Enteroviral Meningoencephalitis; Z. HLH or MAS

Authorizations:

Enteroviral meningoencephalitis: Authorization of 6 months may be granted for severe cases of enteroviral meningoencephalitis

HLH/MAS hypogammaglobulinemia: Authorization of 6 months may be granted for treatment of hypogammaglobulinemia in HLH or MAS when total IgG < 400 mg/dL or 2 SD below the mean for agetotal IgG < 400 mg/dL or 2 SD below mean for age

AA. Hemolytic Disease of Newborn

Authorization:

Hemolytic disease of newborn: Authorization of 6 months may be granted for isoimmune hemolytic disease in neonates

Indications with authorization durations and criteria

Authorization may be granted for the following conditions with the noted durations and criteria:

Enteroviral Meningoencephalitis: Authorization of 6 months may be granted for severe cases of enteroviral meningoencephalitis.

HLH or MAS with hypogammaglobulinemia: Authorization of 6 months may be granted when total IgG is less than 400 mg/dL or two standard deviations below the mean for age.IgG < 400 mg/dL or <-2 SD

Hemolytic Disease of Newborn: Authorization of 6 months may be granted for isoimmune hemolytic disease in neonates.

HIV-associated Thrombocytopenia (pediatric): Authorization of 6 months for pediatric members with IgG < 400 mg/dL and one of listed clinical criteria (recurrent infections despite prophylaxis, measles vaccination + high-prevalence region, thrombocytopenia despite ART, chronic bronchiectasis refractory to therapy, or T4 ≥200/mm3).

Continuation/Reauthorization

Continuation of Therapy

Continuation criteria: Authorization may be granted for continuation when: A) for conditions with reauthorization criteria listed under 'Criteria for Approval', members currently receiving IG therapy meet the applicable reauthorization criteria for their condition; OR B) for all other conditions, all members (including new members) must meet initial authorization criteria.

IVIG is considered not medically necessary for members who do not meet the criteria above

Dosing/Admin guidance and supporting appendices

Policy guidance and supporting appendices (no explicit stepwise medical necessity criteria in this segment):

Dosing and administration: Approvals may be subject to dosing limits in accordance with FDA-approved labeling, accepted compendia, and/or evidence-based practice guidelines.

See dosing guidance and administered product labeling

Appendix A: Impaired vaccine response: Age ≥ 2 years: impaired antibody response demonstrated to pneumococcal polysaccharide vaccine; not established for children < 2 years; excludes therapy initiated in the hospital setting.

Appendix A

Appendix B: Bleeding risk factors: Examples of risk factors include anticipated procedural blood loss, certain comorbidities, mandated anticoagulation, and high-risk professions or lifestyles.

Appendix B

Use of IVIG for pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorder associated with group A streptococci (PANDAS) is classified as experimental, investigational, or unproven and is therefore excluded from coverage under this policy.

The policy specifies that certain indications are considered experimental, investigational, or unproven; providers should consult the specific indications listed in the policy and supporting appendices when determining whether IVIG is an appropriate therapy for a given pediatric neuropsychiatric presentation.

Appendix A defines impaired antibody response to pneumococcal polysaccharide vaccine for members age 2 years and older and explicitly excludes therapy initiated in the hospital setting when that impaired vaccine response is the basis for IVIG consideration.

For clarity, Appendix A's definition of impaired pneumococcal vaccine response states that the appendix does not apply to IVIG therapy initiated in the hospital setting; therapies begun during inpatient care are excluded from the Appendix A pathway.

This inventory entry is a placeholder; refer to the policy exclusions and Appendix A for specific limits on pediatric uses and other indications considered experimental or not established.

When the clinical criteria in this policy are not met, IVIG is considered not medically necessary and is not covered. Continuation requests must meet the applicable reauthorization criteria; new or other requests must meet initial authorization criteria.

Billing and Coding

Covered HCPCS/J-codes (selected list)HCPCSCovered

J1459

Injection, immune globulin (Privigen), intravenous, nonlyophilized (e.g., liquid), 500 mg

Covered HCPCS/J-codesHCPCSCovered

J1552	Injection, immune globulin (alyglo), 500 mg (effective 1/1/2025)
J1553	Injection, immune globulin (yimmugo), 100 mg
J1556	Injection, immune globulin (Bivigam), 500 mg
J1557	Injection, immune globulin, (Gammaplex), intravenous, nonlyophilized (e.g., liquid), 500 mg
J1561	Injection, immune globulin, (Gamunex), intravenous, non-lyophilized, (e.g., liquid), 500 mg
J1566	Injection, immune globulin, intravenous, lyophilized (e.g., powder), 500 mg
J1568	Injection, immune globulin, (Octagam), intravenous, non-lyophilized, (e.g., liquid), 500 mg
J1569	Injection, immune globulin, (Gammagard liquid), intravenous, non-lyophilized, (e.g., liquid), 500 mg
J1572	Injection, immune globulin, (Flebogamma), intravenous, non-lyophilized, (e.g., liquid), 500 mg
J1554	Injection, immune globulin, (Asceniv), 500 mg (effective 04/01/2021)

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Unclassified codes for product-specific reportingHCPCS | CPT | mixed

J3590	Unclassified biologic (when specified as Yimmugo [immune globulin intravenous, humandira])
C9399	Unclassified drugs or biologicals (when specified as Yimmugo [immune globulin intravenous, human-dira])

IgG threshold — authorization criterion

Threshold definitionTotal serum IgG less than 400 mg/dL or two standard deviations below the mean for age.

Usage contextsApplied as an authorization threshold across multiple indications including HLH/MAS, pediatric HIV prophylaxis, BMT/HSCT recipients, CAR-T–related hypogammaglobulinemia, and secondary immunosuppression.

Re-authorization relevanceRe-authorization decisions for some indications (e.g., BMT/HSCT, pediatric HIV) reference meeting or reassessment of this IgG threshold alongside clinical response.

IgG level — numeric threshold

Numeric levelIgG < 400 mg/dL.

Indications citing this level

Prior Authorization, Documentation, and Prescribing Actions

Prior Authorization

Prior Authorization Required

Prior authorization is required for IVIG for covered indications. Benefits are determined by the member's contract and IVIG will be reviewed for medical necessity only when the benefit exists and no contract exclusions apply (this policy may not apply to certain federal programs). Approvals are conditioned on meeting the diagnosis-specific criteria below, submitting required documentation, and adhering to dosing/billing rules.

Prior authorization required for all covered IVIG indications listed in the policy.
Verify member eligibility and contract limitations before submitting a prior authorization request.
Denials may be issued if the member does not meet the specific criteria set forth in the policy.

Documentation Required

Documentation Required per Indication

Submit documentation specific to the diagnosis to support the medical necessity review. Required items vary by indication and must be provided at initial authorization and, when requested, for re-authorization.

Background and Scope

Intravenous immune globulin (IVIG) is used to replace or modulate immunoglobulins for a range of primary and secondary immunodeficiency states and selected autoimmune, inflammatory, and neurologic disorders. This policy aligns coverage with FDA-approved indications and accepted compendial uses and requires documentation of diagnosis, relevant laboratory testing (including vaccine response when applicable per Appendix A), and adherence to indication-specific authorization durations and reauthorization requirements. Continuation typically requires meeting reauthorization criteria and demonstration of clinical benefit or maintained therapeutic biomarkers.

Definitions and Diagnostic Thresholds

Primary immunodeficiency — included disorders

Included disordersSevere combined immunodeficiency (SCID) and congenital agammaglobulinemia (e.g., X-linked or autosomal recessive agammaglobulinemia).

Additional combined immunodeficienciesWiskott-Aldrich syndrome, DiGeorge syndrome, ataxia-telangiectasia, and other non-SCID combined immunodeficiencies (diagnosis confirmed by genetic/molecular testing when applicable).

Antibody deficiency syndromesCommon variable immunodeficiency (CVID), hypogammaglobulinemia (unspecified), IgG subclass deficiency, selective IgA deficiency, selective IgM deficiency, and specific antibody deficiency.

Required supporting findingsHistory of recurrent bacterial infections and impaired antibody response to pneumococcal polysaccharide vaccine (see Appendix A); specific laboratory criteria apply per diagnosis (e.g., pretreatment IgG thresholds for SCID/CVID/other antibody deficiencies).

CIDP — diagnostic support requirements

OpenPayer

Intravenous Immune Globulin (IVIG)

Coverage and Medical Necessity Criteria

Billing and Coding

Prior Authorization, Documentation, and Prescribing Actions

Background and Scope

Definitions and Diagnostic Thresholds