Mass General Brigham IVIG Coverage Update

Coverage Criteria and Medical Necessity

inv-01: Primary Immunodeficiency - Initial coverage

Covered when ALL of the following are met for primary immunodeficiency indications

Primary Immunodeficiency categories

SCID/congenital agammaglobulinemia: Pretreatment IgG level <200 mg/dL OR absence/very low number of T cells (CD3 <300/µL) or presence of maternal T cells (SCID)IgG <200 mg/dL; CD3 <300/µL
Wiskott-Aldrich/DiGeorge/other non-SCID combined immunodeficiency: Diagnosis confirmed by genetic or molecular testing (if applicable) AND history of recurrent bacterial infections AND impaired antibody response to pneumococcal polysaccharide vaccine (see Appendix A)
Common Variable Immunodeficiency (CVID): Age ≥4 years AND pretreatment IgG <500 mg/dL or ≥2 SD below the mean for age AND other causes of immune deficiency excluded AND history of recurrent bacterial infectionsIgG <500 mg/dL or ≥2 SD below mean
Other predominant antibody deficiency (including selective IgA/IgM, IgG subclass deficiency, specific antibody deficiency): History of recurrent bacterial infections AND impaired antibody response to pneumococcal polysaccharide vaccine (see Appendix A) AND supporting pretreatment laboratory findings (eg selective IgM <30 mg/dL; IgA <7 mg/dL; IgG subclass values ≥2 SD below mean on ≥2 occasions)Selective IgM <30 mg/dL; IgA <7 mg/dL; IgG subclass ≥2 SD below mean
See Appendix A for vaccine response documentation

inv-02: Primary Immunodeficiency - Re-authorization

Re-authorization criteria for primary immunodeficiency

Re-authorization: At least one of: IgG trough levels monitored at least yearly and maintained at or above the lower range of normal for age; OR a demonstrated reduction in the frequency of bacterial infections since initiation of IVIG therapy; OR prescriber will re-evaluate dose and consider adjustmentIgG trough within normal range for age

Re-authorization of 6 months may be granted

inv-03: Myasthenia Gravis

Myasthenia gravis coverage criteria

Acute/worsening MG: For worsening weakness or acute exacerbation: authorization up to 1 month for acute use (including pre-operative management such as prior to thymectomy). For refractory myasthenia gravis: authorization up to 6 months when member has tried and failed 2 or more standard therapies (eg corticosteroids, azathioprine, cyclosporine, mycophenolate mofetil, rituximab)failed ≥2 standard therapies for refractory MG

inv-04: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

CIDP coverage criteria

CIDP initial: Initial authorization 3 months when disease is progressive or relapsing/remitting for ≥2 months AND diagnosis confirmed by electrodiagnostic studies and CSF evaluation AND moderate to severe functional disabilitydisease ≥2 months

Re-authorization 6 months if significant improvement and IVIG used at lowest effective dose/frequency

inv-05: Dermatomyositis/Polymyositis

Dermatomyositis/Polymyositis coverage criteria

Inflammatory myopathies: Initial authorization 3 months when member has at least 4 specified clinical, laboratory, EMG, or pathologic features AND has failed or is intolerant of standard first-line (corticosteroids) and second-line immunosuppressants, or has a contraindication to them≥4 clinical/lab/EMG/pathologic features

Re-authorization 6 months if significant and maintained improvement

inv-07: B-cell Chronic Lymphocytic Leukemia (CLL)

B-cell CLL prophylaxis coverage criteria

B-cell CLL prophylaxis: Initial authorization 6 months when IVIG is prescribed for prophylaxis of bacterial infections AND pretreatment serum IgG <500 mg/dL AND history of recurrent sinopulmonary infections requiring IV antibiotics or hospitalizationIgG <500 mg/dL

Re-authorization 6 months if infection frequency reduced

inv-09: Multifocal Motor Neuropathy (MMN)

Multifocal Motor Neuropathy (MMN) criteria

MMN: Initial authorization 3 months when progressive multifocal asymmetric weakness without objective sensory loss in ≥2 nerves for ≥1 month AND diagnosis confirmed by electrodiagnostic studiessymptoms ≥1 month

Re-authorization 6 months if significant and maintained improvement

inv-10: Guillain-Barre Syndrome (GBS)

Guillain-Barre Syndrome (GBS) criteria

GBS: Authorization of 2 months total when member has severe disease with significant weakness (eg unable to stand/walk without aid or respiratory weakness) AND onset of neurologic symptoms <4 weeks from anticipated therapy startonset <4 weeks

inv-11: Lambert-Eaton Myasthenic Syndrome (LEMS)

Lambert-Eaton Myasthenic Syndrome (LEMS) criteria

LEMS: Initial authorization 6 months when diagnosis confirmed by neurophysiology or positive anti–P/Q-type VGCC antibody AND anticholinesterases and amifampridine tried and failed or not tolerated, or severe weakness or difficult venous access for plasmapheresis

Re-authorization 6 months when responding to therapy

inv-13: Stiff-person Syndrome (initial authorization)

Covered when ALL of the following are met for Stiff-person Syndrome

Stiff-person Syndrome criteria: 1) Diagnosis confirmed by anti–glutamic acid decarboxylase (GAD) antibody testing; AND 2) Inadequate response to first-line treatment (benzodiazepines and/or baclofen)

Authorization of 6 months may be granted.

inv-14: Immune checkpoint inhibitor-related neurologic adverse events

Covered when ALL of the following are met for management of immune checkpoint inhibitor-related nervous system adverse events

Immune checkpoint inhibitor-related neurologic toxicity: 1) Member experienced a moderate or severe adverse event to a PD-1 or PD-L1 inhibitor; AND 2) The offending medication has been held or discontinued; AND 3) Member experienced one or more of the following nervous system adverse events: pneumonitis, myasthenia gravis, peripheral neuropathy, encephalitis, transverse myelitis, or severe inflammatory arthritis

Authorization of 1 month may be granted.

inv-15: Autoimmune Mucocutaneous Blistering Disease

Covered when ALL of the following are met for Autoimmune Mucocutaneous Blistering Disease

Autoimmune mucocutaneous blistering disease: 1) Diagnosis proven by biopsy and confirmed by pathology report; AND 2) Condition is rapidly progressing, extensive, or debilitating; AND 3) Member has failed or experienced significant complications from standard treatment (corticosteroids, immunosuppressive agents)

Authorization of 6 months may be granted.

inv-16: Fetal/Neonatal Alloimmune Thrombocytopenia

Covered when treating Fetal/Neonatal Alloimmune Thrombocytopenia (F/NAIT)

F/NAIT: Authorization of 6 months may be granted for treatment of F/NAIT.

inv-17: Parvovirus B19–induced PRCA

Covered when treating Parvovirus B19–induced Pure Red Cell Aplasia (PRCA)

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

inv-18: HLH or MAS

Covered when ALL of the following are met for HLH or MAS–related hypogammaglobulinemia

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

inv-19: Hypogammaglobulinemia from CAR-T therapy

Covered when ALL of the following are met for CAR-T therapy–related hypogammaglobulinemia

CAR-T associated hypogammaglobulinemia: Authorization of 6 months may be granted for members with IgG ≤ 400 mg/dL receiving CAR-T therapy (tisagenlecleucel or axicabtagene ciloleucel) within 45 daysIgG <= 400 mg/dL; within 45 days of CAR-T

inv-20: Autoimmune Hemolytic Anemia

Covered when ALL of the following are met for Autoimmune Hemolytic Anemia

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

inv-21: Acute Disseminated Encephalomyelitis

Covered when ALL of the following are met for Acute Disseminated Encephalomyelitis (ADEM)

ADEM: Authorization of 6 months may be granted for ADEM in members who have had an insufficient response to intravenous corticosteroid treatment

inv-22: Kawasaki Syndrome

Covered when ALL of the following are met for Kawasaki Syndrome (pediatric)

Kawasaki Syndrome: Authorization of 1 month may be granted for pediatric members with Kawasaki syndrome

inv-23: Additional specified indications

Covered (authorization durations noted) for other listed indications when clinical context supports use

Other covered indications: Acquired red cell aplasia; autoimmune neutropenia when G-CSF inappropriate; birdshot retinochoroidopathy refractory to immunosuppressives; BK virus associated nephropathy; enteroviral meningoencephalitis (severe); hemolytic disease of the newborn; HIV-associated thrombocytopenia with specified criteria; hyperimmunoglobulinemia E syndrome for severe eczema; severe active Churg-Strauss as adjunctive therapy after failure/intolerance/contraindication to other interventions

Most list authorization of 6 months.

inv-24: Hypogammaglobulinemia from CAR-T therapy

Covered when ALL of the following are met

CAR-T associated hypogammaglobulinemia: Member receiving CAR-T therapy (tisagenlecleucel or axicabtagene ciloleucel) within 45 days AND IgG ≤ 400 mg/dL6 months authorization

inv-25: Multiple Myeloma

Multiple myeloma with recurrent infections: Member with multiple myeloma AND recurrent, serious infections despite use of prophylactic antibiotics6 months authorization

inv-26: Neonatal Hemochromatosis

Neonatal hemochromatosis prophylaxis: Pregnant member with history of prior pregnancy ending in documented neonatal hemochromatosis6 months authorization

inv-27: Opsoclonus-myoclonus

Opsoclonus-myoclonus indications: Paraneoplastic opsoclonus-myoclonus-ataxia associated with neuroblastoma OR refractory opsoclonus-myoclonus as last-resort treatment6 months authorization

inv-28: PANDAS/PANS

PANDAS/PANS in pediatrics: Pediatric diagnosis of PANDAS or PANS documented by or in consultation with a pediatric psychiatrist or pediatric neurologist3 months authorization

inv-29: Post-transfusion Purpura

Post-transfusion purpura: Diagnosis of post-transfusion purpura1 month authorization

inv-30: Rasmussen Encephalitis

Rasmussen encephalitis AND symptoms not improved with antiepileptic drugs and corticosteroids6 months authorization

inv-31: Renal Transplantation

Renal transplantation with incompatibility: Member undergoing renal transplant from a live donor with ABO incompatibility or positive crossmatch6 months authorization

inv-32: Secondary Immunosuppression

Secondary immunosuppression with IgG threshold: Member has secondary immunosuppression associated with major surgery, hematological malignancy, extensive burns, or collagen-vascular disease AND IgG <400 mg/dL6 months authorization

inv-33: Solid Organ Transplantation

Solid organ transplantation for allosensitized members: Solid organ transplant candidate who is allosensitized6 months authorization

inv-34: Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome

Severe TEN/SJS: Severe toxic epidermal necrolysis or Stevens-Johnson syndrome1 month authorization

inv-35: Toxic Shock Syndrome

Toxic shock syndrome criteria: Staphylococcal or streptococcal toxic shock syndrome that is refractory to several hours of aggressive therapy OR has an undrainable focus OR persistent oliguria with pulmonary edema1 month authorization

inv-36: Systemic Lupus Erythematosus

Severe active SLE: Severe, active systemic lupus erythematosus AND inadequate response, intolerance, or contraindication to first- and second-line therapies6 months authorization

inv-37: Toxic Necrotizing Fasciitis (Group A Strep)

Toxic necrotizing fasciitis due to group A streptococcus: Member with fasciitis due to invasive group A streptococcal infection1 month authorization

inv-38: Continuation of Therapy

Continuation authorization criteria and required conditions

Continuation of therapy: Members currently receiving IVIG must meet applicable reauthorization criteria for their condition; for all other conditions members must meet initial authorization criteriaauthorization per applicable reauthorization criteria

Continuation approvals require meeting applicable reauthorization criteria; initial approvals and reauthorizations are based on diagnosis under Coverage Guidelines

Exceptions: There are no special coverage exceptions listed beyond standard prior authorization requirements. Authorization decisions require documentation demonstrating the member meets the applicable coverage criteria and enrollment timing where specified; requests that lack required documentation (for example, proof the member is new to the plan within the past 90 days when applicable) may be denied.

For Autoimmune mucocutaneous blistering disease the policy requires histologic confirmation: diagnosis proven by biopsy and confirmed by pathology report before authorization will be granted. Documentation of prior trials or intolerance to standard therapies (eg, corticosteroids, immunosuppressive agents) and the disease being rapidly progressing, extensive, or debilitating is also required.

Note: Appendix A excludes therapy initiated in the hospital setting. For impaired antibody response to pneumococcal polysaccharide vaccine, the appendix also specifies age-based testing criteria (not established for children <2 years).

Operational update: continuation request language was revised to remove the prior blanket inclusion of new members. The policy now requires documentation of member enrollment timing for certain started/stabilized situations; where applicable, authorization may be limited to members who are new to the plan within the past 90 days and are currently receiving treatment with the requested medication.

Initial approvals and reauthorizations are granted based on the diagnosis-specific Coverage Guidelines. Requests that do not meet the diagnosis-based criteria listed in the policy will not be approved.

Provider Requirements, Documentation, and Authorization Details

Prior Authorization

Prior Authorization and Specialty Pharmacy

Prior authorization is required for IVIG products listed; these medications are designated specialty and must be filled at a contracted specialty pharmacy. Requests without required prior authorization may be denied.

Specialty medications must be filled at a contracted specialty pharmacy
Contact: Medical and Specialty Medications Phone: 877-519-1908; Fax: 855-540-3693
Non-specialty medications contact: Phone: 800-711-4555; Fax: 844-403-1029

Prior Authorization

New-member Timing and Continuation Impacts

Authorization may be granted for members who are new to the plan within the past 90 days and are currently receiving treatment with the requested medication. Requests that lack documentation that the member is new to the plan within the past 90 days and currently receiving treatment may be denied. Continuation approvals can be affected if the member does not meet the new-member timing requirements.

Documentation required showing member enrolled in plan within the past 90 days for "new-to-plan" continuation requests

Product Listings, Thresholds, and Codes

IgG threshold for HLH/MAS

HLH / MAS IgG ThresholdTotal IgG < 400 mg/dL or two standard deviations below the mean for age

IgG threshold for CAR-T related hypogammaglobulinemia

CAR-T related hypogammaglobulinemia IgG ThresholdIgG < 400 mg/dL (authorization of 6 months may be granted for members receiving CAR-T therapy within 45 days)

IgG — 400 mg/dL threshold reference

Reference IgG Threshold400 mg/dL

Definitions and Clinical Thresholds

IVIG — Intravenous Immune Globulin (IVIG) — pooled IgG given intravenously for replacement and immunomodulatory therapy.

DefinitionIntravenous Immune Globulin (IVIG) — pooled IgG given intravenously for replacement and immunomodulatory therapy.

Primary usesReplacement therapy for primary and secondary immunodeficiencies and passive immunity by increasing antibody titers

Immunomodulatory actionMay act via interference with Fc receptors for treatment of autoimmune cytopenias and immune thrombocytopenia (ITP)

Hypogammaglobulinemia threshold — IgG less than 400 mg/dL or two standard deviations below the mean for age is cited as an indication threshold for HLH/MAS

Definition/thresholdHypogammaglobulinemia defined as IgG less than 400 mg/dL or ≥2 standard deviations below mean for age

Indication example

Background and Clinical Rationale

Intravenous immune globulin (IVIG) is pooled immunoglobulin G administered intravenously to provide replacement IgG for primary and secondary immunodeficiencies, passive immunity against pathogens, and immune modulation in certain autoimmune and inflammatory conditions (for example via Fc receptor interference). IVIG is used across a range of FDA-labeled and compendial indications and dosing/authorization durations vary by condition.

Policy Changes and Revision History

2024-10-15operational_updateLatest

Added requirement that member must be new to the plan within the past 90 days for certain provisions; effective date noted in review history.

2024-08-14product_addition_and_policy_clarification

Added Alyglo to the policy and clarified step therapy language.

2023-07-01criteria_revision

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Intravenous Immune Globulin (IVIG) — coverage criteria