Immune Globulin Therapy (ARCHIVED)

Policy ID: I-14-051

Section: Injections

Effective Date: June 01, 2019

Revised Date: October 16, 2024

Revision Effective Date: December 08, 2024

Last Reviewed: November 19, 2024

Applies To: Commercial Only

**This policy has been Archived effective December 08, 2024. Click the Archive tab above for more information.**

Policy ID: I-14-051

Section: Injections

Effective Date: June 01, 2019

Revised Date: October 16, 2024

Revision Effective Date: December 08, 2024

Last Reviewed: November 19, 2024

Archived Date: December 08, 2024

Applies To: Commercial Only

Description

Immune globulin is one of five closely-related proteins found in the human body. These proteins are capable of acting as antibodies. Gamma globulin is an intravenous, subcutaneous or intramuscular drug which has IgG antibodies and is used for the prevention and treatment of specific disease.

Policy Application

All claims submitted for this policy will be processed according to the policy effective date and associated revision effective dates in effect on the date of service.

Criteria

Coverage is subject to the specific terms of the member's benefit plan.

Federal Employee Program members (FEP) should check with their Retail Pharmacy Program to determine if prior approval is required by calling the Retail Pharmacy Program at 1-800-624-5060 (TTY: 1-800-624-5077). FEP members can also obtain the list through the www.fepblue.org website.

Subcutaneous Immune Globulin (SCIG) Therapy

Primary Immunodeficiencies

Subcutaneous Immune Globulin (Cutaquig, Cuvitru, Gammagard Liquid, Gammaked, Gamunex-C, Hizentra, HyQvia, or Xembify) may be considered medically necessary when ALL of the following criteria are met:

Individual diagnosed with primary immunodeficiencies [e.g., congenital agammaglobulinemia, hypogammaglobulinemia, common variable immunodeficiency (CVID), severe combined immunodeficiency, Wiskott-Aldrich syndrome, or X-linked agammaglobulinemia (XLA)]; and
Standard therapies have failed, become intolerable, or are contraindicated; and
Laboratory evidence of immunoglobulin deficiency; and
Persistent and severe infections despite treatment with prophylactic antibiotics; and
Documented inability to mount an adequate immunologic response to inciting antigens; and
- Lack of appropriate rise in antibody titer following provocation with a polysaccharide antigen. For example, an adequate response to the pneumococcal vaccine may be defined as at least a four (4)-fold increase in titers for at least 50% of serotypes tested; or
- Lack of appropriate rise in antibody titer following provocation with a protein antigen. For example, an adequate response to tetanus/diphtheria vaccine may be defined as less than a four (4)-fold rise in titers three (3)-four (4) weeks after vaccine administration; and
Other unspecified disorder of immune mechanism may be given individual consideration.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Subcutaneous Immune Globulin (Cutaquig, Cuvitru, Gammagard Liquid, Gammaked, Gamunex-C, Hizentra, HyQvia, or Xembify) may be considered medically necessary for individuals 18 years of age or older when ALL of the following criteria are met:

Individual has confirmed diagnosis of CIDP; and
Individual has demonstrated clinically meaningful response as indicated by documentation of stable or improved symptoms on intravenous immune globulin (IVIG) therapy.

The use of SCIG therapy not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

Procedure Codes

90284

J1551

J1555

J1558

J1559

J1561

J1569

J1575

Intravenous Immune Globulin (IVIG) Therapy

IVIG (Alyglo, Asceniv, Bivigam, Flebogamma DIF, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Octagam, Panzyga, and Privigen) may be considered medically necessary for treatment of ANY ONE of the following conditions when standard therapies have failed, become intolerable, or are contraindicated:

Autoimmune and Inflammatory Disorders

Autoimmune mucocutaneous blistering disease which is severe and progressive including pemphigus, pemphigoid, pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) when an individual has failed treatment with conventional agents such as corticosteroids, azathioprine, and cyclophosphamide.
Dermatomyositis or polymyositis refractory to treatment with corticosteroids; in combination with other immunosuppressive agents; or
Kawasaki disease (mucocutaneous lymph node syndrome); or
Wegener's granulomatosis; or
Neuromyelitis optica as an alternative for those with contraindications or lack of response to first-line treatment.

Hematologic

Idiopathic thrombocytopenia purpura (ITP):
- Diagnosis of acute, severe ITP; and
- Alternate etiologies of thrombocytopenia have been ruled out; and
- Individual has one of the following:
  - Major bleeding (e.g., life-threatening bleeding and/or clinically important mucocutaneous bleeding); or
  - Severe thrombocytopenia and is at high risk for bleeding complications; or
  - Severe thrombocytopenia and a slow or inadequate response to corticosteroids; or
  - Severe thrombocytopenia and a predictable risk of bleeding in the future (e.g., a procedure or surgery with a high bleeding risk); or
- Treatment of chronic ITP; in individuals with BOTH of the following:
  - Duration of disease has been at least six (6) months; and
  - Individual has persistent thrombocytopenia despite treatment with corticosteroids; or
Fetal/neonatal alloimmune thrombocytopenia; or
Hemolytic disease of the fetus and newborn (e.g. erythroblastosis fetalis); or
Post allogeneic bone marrow transplant setting; or
Individuals with hypogammaglobulinemia and/or recurrent bacterial infections secondary to acute lymphoblastic leukemia or multiple myeloma with an IgG level less than 400mg/dL; or
Individuals with hypogammaglobulinemia and/or recurrent bacterial infections secondary to chronic lymphocytic leukemia or small lymphocytic lymphoma with ONE of the following:
- Individual has an IgG level less than 200mg/dL: or
- Individual has an IgG level less than 500mg/dL and individual has recurrent sinopulmonary infections requiring IV antibiotics or hospitalizations; or
- Individual has both of the following:
  - Individual has a history of multiple hard to treat infections as indicated by at least one of the following:
    - Four (4) or more ear infections within 12 months; or
    - Two (2) or more serious sinus infections within 12 months; or
    - Two (2) or more months of antibiotics with little effect; or
    - Two (2) or more pneumonias within 12 months; or
    - Recurrent, organ or deep skin abscesses; or
    - Persistent thrush in the mouth or fungal infections on the skin; or
    - Need for intravenous antibiotics to clear infections; or
    - Two (2) or more deep-seated infections; and
  - Individual has a deficiency in producing antibiotics in response to vaccination, titers were drawn before challenging with vaccination, and titers were drawn between four (4) and eight (8) weeks of vaccination; or
Warm antibody autoimmune hemolytic anemia, refractory to corticosteroids; or
Antiphospholipid syndrome; or
Severe anemia due to parvovirus B19; or

Infectious Disease

Prevention of infection in EITHER of the following:
- Prevention of infection in pre-term (less than 37 weeks gestational age) and/or low birth weight (less than 2500g) neonates; or
- Neonates predisposed to group B streptococcal infections; or
Toxic shock syndrome caused by staphylococcal or streptococcal organisms refractory to conventional therapy; or
HIV infected individuals; or
Individuals with primary defective antibody synthesis; or

Neuroimmunological

Chronic inflammatory demyelinating polyneuropathy (CIDP) in individuals with progressive symptoms for at least two (2) months when ALL of the following criteria are met:
- Progressive or relapsing motor and/or sensory dysfunction of more than one (1) limb or a peripheral nerve nature, developing over at least two (2) months; and
- Hypo- or areflexia (usually involving all four (4) limbs); and
- Nerve conduction studies strongly supportive of demyelination with at least ONE of the following (consistent with EFNS/PNS guidelines further defined in Professional Statements and Societal Positions section below:
  - Motor distal latency prolongation in at least two (2) nerves; or
  - Reduction of motor conduction velocity in at least two (2) nerves; or
  - Prolongation of F-wave latency in at least two (2) nerves; or
  - Absence of F-waves in at least two (2) nerves; or
  - Motor conduction block in at least one (1) nerve; or
  - Abnormal temporal dispersion in at least two (2) nerves; or
  - Distal CMAP duration prolongation in at least one (1) nerve; or
Multifocal motor neuropathy in patients with anti GM1 antibodies or conduction block; or
Myasthenia gravis chronic, severe, refractory to standard therapy (i.e., azathioprine, steroids); or
Guillain Barre syndrome (acute infective polyneuritis); or
Myasthenic crisis; or
Lambert-Eaton myasthenic syndrome when there is failure, contraindication, or intolerance to other therapies (i.e. anticholinesterase and diaminopyridine); or
Relapsing-remitting multiple sclerosis (RRMS) when ALL the following criteria are met:
- Other therapy (e.g., interferon beta, glatiramer) has failed, become intolerable, and/or is contraindicated; and
- The individual has impaired function measured by a standard clinical scale and/or objective findings on a physical exam at the time of initial therapy; and
- Documentation of an MS exacerbation or progression (worsening) of the individual's clinical status from the visit prior to the one prompting the decision to initiate immune globulin therapy; or
Stiff person syndrome not controlled by at least one (1) other therapy; or

Primary immune deficiency syndromes, including combined immunodeficiencies

Individual diagnosed with primary immunodeficiencies [e.g., congenital agammaglobulinemia (total IgG less than 200mg/dl), hypogammaglobulinemia, common variable immunodeficiency (CVID), severe combined immunodeficiency, Wiskott-Aldrich syndrome, or X-linked agammaglobulinemia (XLA)]; and
Laboratory evidence of immunoglobulin deficiency; and
Persistent and severe infections despite treatment with prophylactic antibiotics; and
Documented inability to mount an adequate immunologic response to inciting antigens; and
Other unspecified disorder of immune mechanism may be given individual consideration; or

Transplantation

Prior to solid organ transplant, for treatment of individuals at high risk of antibody-mediated rejection (AMR) after steroid or other immunosuppressant failure, including highly sensitized individuals, and those receiving an ABO incompatible organ; or
Renal transplantation for prevention or treatment of acute humoral rejection; or
Following solid organ transplant, for treatment of AMR; or

Compendia Sources

IVIG therapy may be considered medically necessary for treatment of any of the current category 1 or 2A NCCN recommendations.

The use of IVIG therapy not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

Procedure Codes

90283

J1459

J1554

J1556

J1557

J1561

J1566

J1568

J1569

J1572

J1576

J1599

Reauthorization Criteria

Continuation of therapy with immune globulin may be considered medically necessary with the following criteria are met:

The individual has been previously approved for immune globulin through Blue Cross Blue Shield of North Dakota's review process; and
The individual is being treated for a covered diagnosis; and
The prescriber has provided documentation that the individual has demonstrated disease stability or beneficial response to therapy.

The use of immune globulin therapy not meeting the criteria as indicated in this policy is considered experimental/investigational and therefore non-covered because the safety and/or effectiveness of this service cannot be established by the available published peer-reviewed literature.

Procedure Codes

90283

90284

J1459

J1551

J1554

J1555

J1556

J1557

J1558

J1559

J1561

J1566

J1568

J1569

J1572

J1575

J1576

J1599

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the United States Food and Drug Administration (U.S. FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines.

Diagnosis Codes

Covered diagnosis codes for procedure codes J1459, J1554, J1556, J1557, J1561, J1566, J1568, J1569, J1572, and J1576

A48.3

B20

B34.3

C90.00

C90.01

C90.02

C91.10

C91.11

C91.12

D47.Z1

D59.11

D59.13

D68.312

D68.61

D69.3

D69.49

D80.0

D80.1

D80.2

D80.3

D80.4

D80.5

D80.6

D80.7

D80.8

D80.9

D81.0

D81.1

D81.2

D81.6

D81.7

D81.9

D82.0

D82.3

D83.0

D83.1

D83.2

D83.8

D83.9

D84.81

D84.821

D84.822

D84.89

D89.89

D89.9

G25.82

G35

G36.0

G61.0

G61.81

G61.82

G61.89

G61.9

G65.0

G70.00

G70.01

G70.80

G70.81

G73.1

L10.0

L10.2

L12.0

L12.1

L12.30

L12.35

L13.8

L51.1

L51.2

L51.3

M30.3

M31.30

M31.31

M33.00

M33.01

M33.02

M33.09

M33.10

M33.11

M33.12

M33.13

M33.19

M33.20

M33.21

M33.22

M33.29

M33.90

M33.91

M33.92

M33.99

M35.9

M36.0

O36.8210

O36.8211

O36.8212

O36.8213

O36.8214

O36.8215

O36.8219

O36.8220

O36.8221

O36.8222

O36.8223

O36.8224

O36.8225

O36.8229

O36.8230

O36.8231

O36.8232

O36.8233

O36.8234

O36.8235

O36.8239

O36.8290

O36.8291

O36.8292

O36.8293

O36.8294

O36.8295

O36.8299

O98.711

O98.712

O98.713

O98.719

P07.00

P07.01

P07.02

P07.03

P07.10

P07.14

P07.15

P07.16

P07.17

P07.18

P07.20

P07.21

P07.22

P07.23

P07.24

P07.25

P07.26

P07.30

P07.31

P07.32

P07.33

P07.34

P07.35

P07.36

P07.37

P07.38

P07.39

P55.8

P55.9

P61.0

T86.00

T86.01

T86.02

T86.03

T86.09

T86.10

T86.11

T86.12

T86.13

T86.19

T86.20

T86.21

T86.22

T86.23

T86.290

T86.298

T86.30

T86.31

T86.32

T86.33

T86.39

T86.40

T86.41

T86.42

T86.43

T86.49

T86.5

T86.810

T86.811

T86.812

T86.818

T86.819

T86.830

T86.831

T86.832

T86.838

T86.839

T86.850

T86.851

T86.852

T86.858

T86.859

T86.890

T86.891

T86.892

T86.898

T86.899

T86.90

T86.91

T86.92

T86.93

T86.99

V50.8

Z94.0

Z94.1

Z94.2

Z94.3

Z94.4

Z94.5

Z94.6

Z94.7

Z94.81

Z94.82

Z94.83

Z94.84

Z94.89

Z94.9

Covered diagnosis codes for procedure codes J1551, J1555, J1558, J1559, and J1575

D80.0

D80.1

D80.2

D80.3

D80.4

D80.5

D80.6

D80.7

D80.8

D80.9

D81.0

D81.1

D81.2

D81.6

D81.7

D81.9

D82.0

D82.3

D82.8

D82.9

D83.0

D83.1

D83.2

D83.8

D83.9

G61.81

Professional Statements and Societal Positions Guidelines

Product

Route

Procedure Code

Alyglo

J1599

Asceniv®

J1554

Bivigam®

J1556

Cutaquig®

J1551

Cuvitru®

J1555

Flebogamma® DIF

J1572

Gammagard® Liquid

IV, SC

J1569

Gammagard S/D

J1566

Gammaked ^TM

IV, SC

J1561

Gammaplex®

J1557

Gamunex®-C

IV, SC

J1561

Hizentra®

J1559

HyQvia®

J1575

Octagam®

J1568

Panzyga®

J1576

Privigen®

J1459

Xembify®

J1558

Motor nerve conduction criteria per the European Academy of Neurology/ Peripheral Nerve Society:

Strongly supportive of demyelination:

At least one of the following:
- Motor distal latency prolongation greater than or equal to 50% above ULN in two nerves (excluding median neuropathy at the wrist from carpal tunnel syndrome), or
- Reduction of motor conduction velocity greater than or equal to 30% below LLN in two (2) nerves, or
- Prolongation of F-wave latency greater than or equal to 20% above ULN in two (2) nerves (greater than or equal to 50% if amplitude of distal negative peak CMAP less than 80% of LLN), or
- Absence of F-waves in two (2) nerves (if these nerves have distal negative peak CMAP amplitudes greater than or equal to 20% of LLN) plus greater than or equal to one (1) other demyelinating parameter in greater than or equal to one (1) other nerve, or
- Motor conduction block: greater than or equal to 30% reduction of the proximal relative to distal negative peak CMAP amplitude, excluding the tibial nerve, and distal negative peak CMAP amplitude greater than or equal to 20% of LLN in two (2) nerves; or in one (1) nerve plus greater than or equal to one (1) other demyelinating parameter except absence of F-waves in greater than or equal to one (1) other nerve, or
- Abnormal temporal dispersion: greater than 30% duration increase between the proximal and distal negative peak CMAP (at least 100% in the tibial nerve) in greater than or equal to two (2) nerves, or
- Distal CMAP duration (interval between onset of the first negative peak and return to baseline of the last negative peak) prolongation in greater than or equal to one (1) nerve plus greater than or equal to one (1) other demyelinating parameter in greater than or equal to one (1) other nerve

(LFF 2 Hz) median greater than 8.4 ms, ulnar greater than 9.6 ms, peroneal greater than 8.8 ms, tibial greater than 9.2 ms
(LFF 5 Hz) median greater than 8.0 ms, ulnar greater than 8.6 ms, peroneal greater than 8.5 ms, tibial greater than 8.3 ms
(LFF 10 Hz) median greater than 7.8 ms, ulnar greater than 8.5 ms, peroneal greater than 8.3 ms, tibial greater than 8.2 ms
(LFF 20 Hz) median greater than 7.4 ms, ulnar greater than 7.8 ms, peroneal greater than 8.1 ms, tibial greater than 8.0 ms

Weakly supportive of demyelination as in only one nerve.

ND Committee Review

Internal Medical Policy Committee 1-22-2020

Changed Policy to precertification policy

Internal Medical Policy Committee 5-19-2020 Revision

Updated order of IVIG procedure codes, and
Added reauthorization criteria

Internal Medical Policy Committee 7-22-2020

Added new code J1558 for Xembify - Effective July 01, 2020 , and
Revised reauthorization criteria - Effective August 01, 2020

Internal Medical Policy Committee 9-21-2020

Added codes 90281 and 90284 to policy, and
Updated diagnosis codes

Internal Medical Policy Committee 1-19-2021 - Effective January 01, 2021

Added new code C9072 for immune globulin (Asceniv)

Internal Medical Policy Committee 3-17-2021 - Effective April 01, 2021

Added new code J1554 for immune globulin (Asceniv), and
Removed code C9072 from policy

Internal Medical Policy Committee 9-21-2021

Added code J1566 to covered diagnosis codes for procedure codes section

Internal Medical Policy Committee 5-24-2022

Added product chart and product names to SCIG and IVIG criteria,
Updated criteria and diagnosis codes,
Removed 90281 as this is IM immune globulin and J1562 as this product is discontinued

Internal Medical Policy Committee 7-21-2022 Effective July 1, 2022

Added new code, J1551, for Cutaquig, to the policy

Internal Medical Policy Committee 7-26-2023 - Effective July 1, 2023

Added new code J1576 for Panzyga to the policy

Internal Medical Policy Committee 7-26-2023 - Effective September 01, 2023

Removed Carimune NF due to product discontinuation by the manufacturer
Added Compendia sources statement for IVIG therapy 'Drug may be considered medically necessary for treatment of any of the current category 1 or 2A NCCN recommendations.'
Added diagnosis code M33.13 for J1459, J1554, J1556, J1557, J1561, J1566, J1568, J1569, J1572, and J1576

Internal Medical Policy Committee 1-16-2024 - Effective March 01, 2024

Added new IVIG, Alyglo, to the policy
Removed splenectomy from IVIG Hematologic

Internal Medical Policy Committee 7-16-2024 - Effective September 01, 2024

Updated hematologic individuals with hypogammaglobulinemia and/or recurrent bacterial infections criteria

Internal Medical Policy Committee 11-19-2024 Effective December 08, 2024

Archived policy

Links

References (PDF)

Disclaimer

Current medical policy is to be used in determining a Member's contract benefits on the date that services are rendered. Contract language, including definitions and specific inclusions/exclusions, as well as state and federal law, must be considered in determining eligibility for coverage. Members must consult their applicable benefit plans or contact a Member Services representative for specific coverage information. Likewise, medical policy, which addresses the issue(s) in any specific case, should be considered before utilizing medical opinion in adjudication. Medical technology is constantly evolving, and the Company reserves the right to review and update medical policy periodically.

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Medical Policies Quick Search

Immune Globulin Therapy (ARCHIVED)

This policy has been Archived effective December 08, 2024. Click the Archive tab above for more information.

Description

Policy Application

Criteria

Diagnosis Codes

Covered diagnosis codes for procedure codes J1459, J1554, J1556, J1557, J1561, J1566, J1568, J1569, J1572, and J1576

Covered diagnosis codes for procedure codes J1551, J1555, J1558, J1559, and J1575

Professional Statements and Societal Positions Guidelines

ND Committee Review

Links

Disclaimer

**This policy has been Archived effective December 08, 2024. Click the Archive tab above for more information.**