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ph-91012

Immune Globulins Prior Authorization Program Summary

Policy Number: PH-91012

This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx, SourceRx-Performance, and Health Insurance Marketplace formularies.

POLICY REVIEW CYCLE

Effective Date	Date of Origin
10-01-2025

FDA LABELED INDICATIONS AND DOSAGE

Agent(s)	FDA Indication(s)	Notes	Ref#
Cutaquig^® 16.5% Subcutaneous injection	Treatment of primary humoral immunodeficiency (PI) in adults and pediatric patients 2 years of age and older		20
Cuvitru™ 20% Subcutaneous injection	Replacement therapy for primary humoral immunodeficiency (PI) in adult and pediatric patients two years of age and older		1
Gammagard™ Liquid 10% Subcutaneous injection	Replacement therapy for primary humoral immunodeficiency (PI) in adult and pediatric patients two years of age or older Maintenance therapy to improve muscle strength and disability in adult patients with multifocal motor neuropathy (MMN) Therapy to improve neuromuscular disability and impairment in adults with chronic inflammatory demyelinating polyneuropathy (CIDP) Limitations of Use: Safety and effectiveness of Gammagard Liquid has not been studied in immunoglobulin-naive patients with CIDP Gammagard Liquid maintenance therapy in CIDP has not been studied beyond 6 months		2
Gammaked™ 10% Subcutaneous injection	Treatment of primary humoral immunodeficiency (PI) in patients 2 years of age and older Treatment of idiopathic thrombocytopenic purpura (ITP) in adults and children Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults		3
Gamunex-C^® 10% Subcutaneous injection	Treatment of primary humoral immunodeficiency (PI) in adults and pediatric patients 2 years of age and older Treatment of idiopathic thrombocytopenic purpura (ITP) in adults and children Treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in adults		4
Hizentra^® 20% Subcutaneous injection	Treatment of primary humoral immunodeficiency (PI) in adults and pediatric patients two years of age or older Maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP)		5
HyQvia® 10% Subcutaneous injection	Treatment of primary immunodeficiency (PI) in adults Maintenance therapy in adults with chronic inflammatory demyelinating polyneuropathy (CIDP)		6
Xembify^® 20% Subcutaneous injection	Treatment of Primary Humoral Immunodeficiency (PI) in patients 2 years of age and older		21

See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm

CLINICAL RATIONALE

Immune Globulins

Immunoglobulin is used to treat a wide variety of diseases, including primary and secondary immunodeficiency states and hematologic and autoimmune disorders. Immunoglobulin is increasingly recognized as a treatment of a variety of medical conditions, not only for its ability to fight infection as a replacement therapy but also for its anti-inflammatory and immunomodulating effects. The appropriate use of immunoglobulin can be life-saving. However, its administration can lead to numerous adverse events and potential additional adverse consequences. Due to finite supply, possible adverse events, and the need for further research in some applications of therapeutic immunoglobulin, it is important for clinicians prescribing immunoglobulin to be familiar with current clinical indications and levels of evidence in support of its use in these conditions.(15)

Primary Immunodeficiency (PI)

Primary immunodeficiencies (PI) are inherited conditions that impact the ability of an immune system to function properly due to absence, deficient or malfunctioning parts of the immune system. PI can cause patients to be more susceptible to infections, immune dysregulation with autoimmune disease and abnormal inflammatory response, and malignancy.(16) Immunoglobulin replacement therapy via the intravenous (IV) or subcutaneous (SC) route is required in patients with certain primary immunodeficiency (PI) diseases characterized by absent or deficient antibody production and, in most cases, recurrent or unusually severe infection. Replacement therapy for agammaglobulinemia and hypogammaglobulinemia in well-described immunodeficiencies such as X-linked agammaglobulinemia (XLA) or common variable immunodeficiency (CVID) is necessary and life-saving. Other more genetically complex PIs, however, may also involve defects in antibody function that contribute to an increased susceptibility to infections.(15) Over 300 distinct primary immunodeficiencies have been described to date with new primary immunodeficiencies being discovered at a rapid rate.(23)

The prevalence of primary immunodeficiencies in the United States is as many as 1:2000 live births. (16) Important signs that may indicate a primary immunodeficiency disease include recurrent, unusual or difficult to treat infections, poor growth or loss of weight, recurrent pneumonia, ear infections or sinusitis, multiple courses of antibiotics or IV antibiotics necessary to clear infections, recurrent deep abscesses of the organs or skin, a family history of primary immunodeficiency disease, swollen lymph glands or an enlarged spleen, autoimmune disease.(23) Diagnosis of primary immunodeficiencies involves laboratory evaluations (Serum IgA, IgG, and IgM levels, circulating T and B lymphocytes and T cell function), measurement of specific antibodies to vaccines, imaging (CT scan of chest detecting pulmonary abnormalities), histology of lymph nodes (reactive follicular or atypical hyperplasia, and granulomatous inflammation), bronchoscopy (infectious processes), and lymph node biopsy.(17)

Diagnostic criteria discussed by the American Academy of Allergy, Asthma and Immunology (AAAAI) for hypogammaglobulinemia include low IgG level (less than 700 mg/dL or more than two standard deviations below the mean) or an inability to mount a significant response to antigenic challenge or both in patients with recurrent bacterial infections coupled with a lack of response to protein or polysaccharide vaccine challenges (i.e., patients who cannot make IgG antibody against diphtheria and tetanus toxoids, pneumococcal polysaccharide vaccine, or both).(14) The European and Pan American Guidelines, state that, the first criterion for CVID requires IgG levels to be two standard deviations below the mean [for the patient's age]. For most laboratories, the lower limit of normal for IgG is 7 - 8 g/L (700 – 800 mg/dL). Impaired vaccine response is the second and most contentious criterion. The last criterion requiring exclusion of secondary causes is the least contentious.(14)

Secondary hypogammaglobulinemia can be caused by a variety of conditions, including gut or renal loss, adverse reactions to drugs, etc.(14) These patients are recommended for immune globulin replacement. The European Society of Immune Deficiencies (ESID) registry has published a working definition for several primary immunodeficiencies (PI) including agammaglobulinemia, severe combined immunodeficiency (SCID), and CVID. The working definition also includes both laboratory values and clinical symptoms. The working definition is based on more recent registry information than the diagnostic requirements discussed by AAAI and is being used by the ESID however neither definition has been validated.(13)

Treatment guidelines published in 2010 from the National Advisory Committee on Blood and Blood Products and Canadian Blood Services concluded there is sufficient evidence that immunoglobulin therapy reduces the rate of infection and hospitalization in patients with primary immune deficiency, which likely leads to a lower mortality and improved quality of life. These guidelines also recommend when considering primary immune deficiency in patients with autoimmune hematological diseases that quantitative IgA, IgG, and IgM levels be drawn and evaluated prior to beginning therapy with immune globulin. Primary immune deficiency may require indefinite therapy.(19)

Chronic inflammatory demyelinating polyneuropathy (CIDP)

Chronic inflammatory demyelinating polyneuropathy (CIDP), also known as chronic inflammatory demyelinating polyradiculoneuropathy, is an acquired autoimmune disorder directed against the myelin sheath of peripheral nerves and nerve roots.(18) CIDP is defined as either typical CIDP or CIDP variants, however, both have demyelination and response to immune therapy in common.(30) The diagnosis of typical CIDP should be considered in patients that present with progressive or relapsing, symmetric, proximal and distal muscle weakness with sensory involvement and areflexia in at least two limbs that progresses for more than 8 weeks. Clinical presentations that vary from typical CIDP in specific limb(s) affected, symmetry, number and extent of limb involvement and sensory versus motor involvement should be considered for CIDP variants.(30)

Electrophysiologic testing developed by the European Federation of Neurological Societies and the Peripheral Nerve Society (EFNS/PNS) is necessary to confirm the diagnosis. Definitive CIDP diagnosis has at least one of the following motor nerve conduction criteria based on electrodiagnostic findings:(30)

Motor distal latency prolongation in at least 2 nerves
Reduced motor conduction velocity in at least 2 nerves
Prolonged F-wave latency in at least 2 nerves
Absence of F-waves in at least 2 nerves plus one or more other demyelination criterion listed here in at least 1 other nerve
Partial motor conduction block in at least 2 nerves or in 1 nerve plus one other demyelination criterion listed here except absence of F-waves
Abnormal temporal dispersion in at least 2 nerves
Distal compound muscle action potential (CMAP) duration prolongation in at least 1 nerve plus one other demyelination criterion listed here in at least 1 other nerve

In addition to meeting motor nerve conduction electrodiagnostic criteria, definitive CIDP diagnosis must also be confirmed using sensory conduction testing. Sensory nerve conduction criteria require sensory conduction abnormalities (prolonged distal latency or reduced sensory nerve action potential (SNAP) amplitude or slowed conduction velocity outside of normal limits) in at least two nerves.(30)

EFNS/PNS diagnostic criteria for CIDP also recommends exclusion of other conditions that include:(18)

Lyme disease, diphtheria, or drug or toxin exposure likely caused the neuropathy

Hereditary demyelinating neuropathy
Prominent sphincter disturbance
Diagnosis of multifocal motor neuropathy
Other causes of demyelinating neuropathy (e.g., POEMS syndrome, osteosclerotic myeloma, diabetic and nondiabetic lumbosacral radiculoplexus neuropathy)

Initial treatment for CIDP is immune modulating therapy with IVIG, glucocorticoids, or plasma exchange. Considerations that drive the selection of initial therapy include disease severity, comorbid disorders, venous access, potential adverse effects, availability, and cost. IVIG should be considered instead of a corticosteroid for patients with pure motor CIDP based on evidence of deterioration in these patients soon after initiation of a corticosteroid.(18,30)

Acquired Immune Deficiency secondary to Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is associated with immunosuppression and an increased risk of infection. Infectious complications are influenced by the progressive reduction in immunoglobulin levels (hypogammaglobulinemia) and are common in patients with previously treated CLL. Immune globulin can provide additional protection against infection by supplementing humoral immunity. The administration of immunoglobulin should be restricted to a carefully selected subset of patients with CLL. Patients with CLL, hypogammaglobulinemia, and recurrent bacterial infections should be considered for immunoglobulin replacement.(15,29)

Safety

All immune globulins have a boxed warning for thrombosis. Risk factors include advanced age, prolonged immobilization, hypercoagulable conditions, history of venous or arterial thrombosis, use of estrogens, indwelling vascular catheters, hyperviscosity, and cardiovascular risk factors.(1-6,20,21)

There is a boxed warning for renal dysfunction, acute renal failure and osmotic nephrosis and death in all intravenous immune globulins (IVIG). Patients predisposed to renal dysfunction include those with any degree of preexisting renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, overweight or in patients receiving known nephrotoxic drugs. Renal dysfunction and acute renal failure occur more commonly in patients receiving IVIG products containing sucrose. Alyglo, Asceniv, Bivigam, Cutaquig, Cuvitru, Flebogamma DIF, Gammagard Liquid, Gammagard S/D, Gammaked, Gammaplex, Gamunex-C, Hizentra, HyQvia, Octagam 5%, Octagam 10%, Panzyga, Privigen, and Xembify do NOT contain sucrose.(1-6,20,21)

Adverse events of immune globulin therapy can be difficult to classify due to the diversity of components in the formulation. Mild adverse events are common and may include low grade fever, headache, nausea, malaise, and myalgia. Infusion related reactions such as urticaria and fever can be prevented by pre-medicating patients with diphenhydramine and acetaminophen. Tension headache is the most common adverse event associated with immune globulin use and ranges in frequency from 26%-61%. Migraine headaches also occur.(1-6,20,21)

Aseptic meningitis has been reported in patients receiving immune globulin administered intravenously and subcutaneously. It may occur within several hours to two days following treatment. It typically occurs more frequently in females than males. Discontinuation of immune globulin treatment has resulted remission of AMS within several days without sequelae. Immunoglobulin A-deficient patients with antibodies to IgA are at greater risk of developing severe hypersensitivity and anaphylactic reactions Because immune globulin products are derived from donor plasma, the transmission of infectious particles is possible.(1-6,20,21)

Agent	Contraindications
Cutaquig 16.5% SCIG	● History of anaphylactic or severe systemic reactions to human immunoglobulin or other components of Cutaquig (polysorbate 80) ● IgA-deficient patient with antibodies to IgA and a history of hypersensitivity
Cuvitru 20% SCIG	● History of anaphylactic or severe systemic reactions to human immunoglobulin ● IgA-deficient patient with antibodies to IgA and a history of hypersensitivity
Gammagard liquid 10% SCIG/IVIG	● History of anaphylactic or severe systemic reactions to human immunoglobulin ● IgA-deficient patient with antibodies to IgA and a history of hypersensitivity
Gammaked Liquid 10% SCIG/IVIG	● History of anaphylactic or severe systemic hypersensitivity reactions to human immunoglobulin ● IgA-deficient patient with antibodies to IgA and a history of hypersensitivity
Gamunex-C 10% SCIG/IVIG	● History of anaphylactic or severe systemic reactions to human immunoglobulin ● IgA-deficient patient with antibodies to IgA and a history of hypersensitivity
Hizentra 20% SCIG	● Anaphylactic or severe systemic reactions to human immunoglobulin or inactive ingredients of Hizentra, such as polysorbate 80 ● Hyperprolinemia Type I or II (Hizentra contains stabilizer L-proline) ● IgA-deficient patient with antibodies to IgA and a history of hypersensitivity
HyQvia 10% SCIG	● History of anaphylactic or severe systemic reactions to human immunoglobulin ● IgA-deficient patient with antibodies to IgA and a history of hypersensitivity ● Known systemic hypersensitivity to hyaluronidase including Recombinant Human Hyaluronidase of HyQvia ● Known systemic hypersensitivity to human albumin (in the hyaluronidase solution)
Xembify 20% SCIG	● Anaphylactic or severe systemic reactions to human immunoglobulin or inactive ingredients of Xembify such as polysorbate 80 ● IgA-deficient patient with antibodies to IgA and a history of hypersensitivity

REFERENCES

Number	Reference
1	Cuvitru prescribing information. Takeda Pharmaceuticals America, Inc. February 2025.
2	Gammagard Liquid prescribing information. Takeda Pharmaceuticals America, Inc. September 2024.
3	Gammaked prescribing information. Kedrion USA. January 2020.
4	Gamunex-C prescribing information. Grifols Therapeutics Inc. January 2020.
5	Hizentra prescribing information. CSL Behring AG. April 2023.
6	HyQvia prescribing information. Takeda Pharmaceuticals America, Inc. September 2024.
7	Jolles S, Sewell W, Misbah S. Clinical uses of intravenous immunoglobulin. Clin Exper Immunol. 2005;142:1-11.
8	El-Shanawany T, Sewell W, Misbah S, et al. Current clinical uses of intravenous immunoglobulin. Clin Med. 2006;6(4):356-359.
9	Orange J, Hossny E, Weiler C, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol. 2006;117(4):S525-S553.
10	Pierce L, Jain N. Risks associated with the use of intravenous immunoglobulin. Trans Med. Rev. 2003;17(4):241-251.
11	Hamrock D. Adverse events associated with intravenous immunoglobulin therapy. Int Immunopharmacol. 2006;6:535-542.
12	Rubella. Centers for Disease Control and Prevention (CDC). Available at https://www.cdc.gov/rubella/about/index.html.
13	ESID registry. Working definitions for clinical diagnosis of PID. Available at: https://esid.org/?s=Working+definitions+for+clinical+diagnosis+of+PID
14	Ameratunga R, Woon ST, Gills D, et al. New diagnostic criteria for common variable immune deficiency (CVID), which may assist with decisions to treat with intravenous or subcutaneous immunoglobulin. Clinical and Experimental Immunology. July 2013;174:203-211.
15	Perez EE, Orange JS, Bonilla F, et al. Update on the use of immune globulin in human disease: a review of evidence. J Allergy Clin Immunol 2017;139(3):s1-46.
16	Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol 2015;136(5):1186-1205,1205e1-1205e78.
17	Immune Deficiency Foundation Diagnostic & Clinical Care Guidelines for Primary Immunodeficiency Diseases Third Edition. 2015.
18	Ryan M, Ryan SJ. Chronic inflammatory demyelinating polyneuropathy: considerations for diagnosis, management, and population health. Am J Manag Care. 2018 Sep;24(17 Suppl):S371-S379. PMID: 30312032.
19	Shehata N, Palda V, Bowen T, et al. The Use of Immunoglobulin Therapy for Patients with Primary Immune Deficiency: An Evidence-Based Practice Guideline. Transfusion Medicine Reviews 2010;24(1) Suppl 1:S28-S50.
20	Cutaquig Prescribing information. Pfizer Labs. November 2021.
21	Xembify Prescribing information. Grifols USA LLC. July 2024.
22	Jeffrey Modell Foundation Medical Advisory Board, 2013. 10 Warning Signs of Primary Immunodeficiency. Jeffrey Modell Foundation, New York, NY
23	American Academy of Allergy Asthma & Immunology. Primary Immunodeficiency. Accessed at https://www.aaaai.org/conditions-and-treatments/primary-immunodeficiency-disease
24	Orange JS, Ballow M, Stiehm, et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: A working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol Vol 130 (3).
25	Emerson GG, Herndon CN, Sreih AG. Thrombotic complications after intravenous immunoglobulin therapy in two patients. Pharmacotherapy. 2002;22:1638-1641.
26	Department of Health (London). Clinical Guidelines for Immunoglobulin Use: Update to Second Edition. August, 2011.
27	Provan, Drew, et al. "Clinical guidelines for immunoglobulin use." Department of Health Publication, London (2008).
28	Dantal J. Intravenous Immunoglobulins: In-Depth Review of Excipients and Acute Kidney Injury Risk. Am J Nephrol 2013;38:275-284.
29	NCCN Drugs & Biologics Compendium. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2022. National Comprehensive Cancer Network, 2022. Accessed October 2022.
30	Van den Bergh, P. Y., van Doorn, P. A., Hadden, R. D., Avau, B., Vankrunkelsven, P., Allen, J. A., Attarian, S., Blomkwist‐Markens, P. H., Cornblath, D. R., Eftimov, F., Goedee, H. S., Harbo, T., Kuwabara, S., Lewis, R. A., Lunn, M. P., Nobile‐Orazio, E., Querol, L., Rajabally, Y. A., Sommer, C., & Topaloglu, H. A. (2021a). European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint task force—second revision. European Journal of Neurology, 28(11), 3556–3583. https://doi.org/10.1111/ene.14959.

POLICY AGENT SUMMARY PRIOR AUTHORIZATION

Target Brand Agent(s)	Target Generic Agent(s)	Strength	Targeted MSC	Available MSC	Final Age Limit	Preferred Status

Hyqvia	immun glob inj	10 GM/100ML ; 2.5 GM/25ML ; 20 GM/200ML ; 30 GM/300ML ; 5 GM/50ML	M ; N ; O ; Y	N
Gammagard liquid ; Gammaked ; Gamunex-c	immune globulin (human) iv or subcutaneous soln	1 GM/10ML ; 10 GM/100ML ; 2.5 GM/25ML ; 20 GM/200ML ; 30 GM/300ML ; 40 GM/400ML ; 5 GM/50ML	M ; N ; O ; Y	N
Cuvitru ; Hizentra	immune globulin (human) subcutaneous inj	1 GM/5ML ; 10 GM/50ML ; 2 GM/10ML ; 4 GM/20ML ; 8 GM/40ML	M ; N ; O ; Y	N
Hizentra	immune globulin (human) subcutaneous inj ; immune globulin (human) subcutaneous sol pref syr ; immune globulin (human) subcutaneous soln pref syr	1 GM/5ML ; 10 GM/50ML ; 2 GM/10ML ; 4 GM/20ML	M ; N ; O ; Y	N
Cutaquig	immune globulin (human)-hipp subcutaneous inj	1 GM/6ML ; 1.65 GM/10ML ; 2 GM/12ML ; 3.3 GM/20ML ; 4 GM/24ML ; 8 GM/48ML	M ; N ; O ; Y	N
Xembify	immune globulin (human)-klhw subcutaneous inj	1 GM/5ML ; 10 GM/50ML ; 2 GM/10ML ; 4 GM/20ML	M ; N ; O ; Y	N

CLIENT SUMMARY – PRIOR AUTHORIZATION

Target Brand Agent Name(s)	Target Generic Agent Name(s)	Strength	Client Formulary
Cutaquig	immune globulin (human)-hipp subcutaneous inj	1 GM/6ML ; 1.65 GM/10ML ; 2 GM/12ML ; 3.3 GM/20ML ; 4 GM/24ML ; 8 GM/48ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance
Cuvitru ; Hizentra	immune globulin (human) subcutaneous inj	1 GM/5ML ; 10 GM/50ML ; 2 GM/10ML ; 4 GM/20ML ; 8 GM/40ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance
Gammagard liquid ; Gammaked ; Gamunex-c	immune globulin (human) iv or subcutaneous soln	1 GM/10ML ; 10 GM/100ML ; 2.5 GM/25ML ; 20 GM/200ML ; 30 GM/300ML ; 40 GM/400ML ; 5 GM/50ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance
Hizentra	immune globulin (human) subcutaneous inj ; immune globulin (human) subcutaneous sol pref syr ; immune globulin (human) subcutaneous soln pref syr	1 GM/5ML ; 10 GM/50ML ; 2 GM/10ML ; 4 GM/20ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance
Hyqvia	immun glob inj	10 GM/100ML ; 2.5 GM/25ML ; 20 GM/200ML ; 30 GM/300ML ; 5 GM/50ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance
Xembify	immune globulin (human)-klhw subcutaneous inj	1 GM/5ML ; 10 GM/50ML ; 2 GM/10ML ; 4 GM/20ML	Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx ; SourceRx-Performance

PRIOR AUTHORIZATION CLINICAL CRITERIA FOR APPROVAL

Module

Clinical Criteria for Approval

TARGET AGENT(S)

Preferred Agent(s)	Nonpreferred Agent(s)
Hyqvia Xembify Hizentra	Cutaquig Cuvitru Gammagard liquid Gammaked Gamunex-c

Initial Evaluation

Target Agent(s) will be approved when ONE of the following is met:

ONE of the following:
1. The patient has a diagnosis of Primary Immunodeficiency (PID)/Wiskott-Aldrich syndrome [e.g., x-linked agammaglobulinemia, common variable immunodeficiency, transient hypogammaglobulinemia of infancy, IgG subclass deficiency with or without IgA deficiency, antibody deficiency with near normal immunoglobulin levels) and combined deficiencies (severe combined immunodeficiencies, ataxia-telangiectasia, x-linked lymphoproliferative syndrome)] AND BOTH of the following:
  1. The patient is 2 years of age or older AND
  2. ONE of the following:
    1. The patient’s IgG level is less than 200 mg/dL OR
    2. BOTH of the following:
      1. The patient has a history of multiple hard to treat infections as indicated by at least ONE of the following:
        
        Four or more ear infections within 1 year
        
        Two or more serious sinus infections within 1 year
        
        Two or more months of antibiotics with little effect
        
        Two or more pneumonias within 1 year
        
        Recurrent or deep skin abscesses
        
        Persistent thrush in the mouth or fungal infection on the skin
        
        Need for intravenous antibiotics to clear infections
        
        Two or more deep-seated infections including septicemia AND
      2. The patient has a deficiency in producing antibodies in response to vaccination and BOTH of the following:
        
        Titers were drawn before challenging with vaccination AND
        
        Titers were drawn between 4 and 8 weeks of vaccination OR
2. The patient has a diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) AND ALL of the following:
  1. The requested agent is Hizentra or Hyqvia AND
  2. The patient is 18 years of age or older AND
  3. BOTH of the following:
    1. The prescriber has assessed baseline disease severity utilizing an objective measure/tool (e.g., INCAT, Medical Research Council (MRC) muscle strength, 6-MWT, Rankin, Modified Rankin, etc.) AND
    2. ONE of the following:
      1. The requested agent will be used as initial maintenance therapy for prevention of disease relapses after treatment and stabilization with intravenous immunoglobulin (IVIG) OR
      2. The requested agent will be used for re-initiation of maintenance therapy after experiencing a relapse and requiring re-induction therapy with IVIG OR
3. The patient has a diagnosis of Acquired Immune Deficiency secondary to Chronic Lymphocytic Leukemia AND ONE of the following:
  1. The patient’s IgG level is less than 200 mg/dL OR
  2. BOTH of the following:
    1. The patient has a history of multiple hard to treat infections as indicated by at least ONE of the following:
      1. Four or more ear infections within 1 year
      2. Two or more serious sinus infections within 1 year
      3. Two or more months of antibiotics with little effect
      4. Two or more pneumonias within 1 year
      5. Recurrent or deep skin abscesses
      6. Persistent thrush in the mouth or fungal infection on the skin
      7. Need for intravenous antibiotics to clear infections
      8. Two or more deep-seated infections including septicemia AND
    2. The patient has a deficiency in producing antibodies in response to vaccination and BOTH of the following:
      1. Titers were drawn before challenging with vaccination AND
      2. Titers were drawn between 4 and 8 weeks of vaccination AND
ONE of the following:
1. The requested agent is a preferred agent OR
2. The requested agent is a non-preferred agent AND ONE of the following:
  1. The patient has tried and had an inadequate response to a preferred agent (medical records required) OR
  2. The patient has an intolerance or hypersensitivity to a preferred agent that is NOT expected to occur with the requested agent (medical records required) OR
    1. The patient has an FDA labeled contraindication to ALL preferred IVIG agents that is NOT expected to occur with the requested agent (medical records required) OR
    2. There is support for the use of the non-preferred agent over the preferred agents for the requested indication

Length of Approval: 6 months

Renewal Evaluation

Target Agent(s) will be approved when BOTH of the following are met:

The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation review] AND
ONE of the following:
1. The patient has a diagnosis of Primary Immunodeficiency (PID)/Wiskott-Aldrich syndrome [e.g., x-linked agammaglobulinemia, common variable immunodeficiency, transient hypogammaglobulinemia of infancy, IgG subclass deficiency with or without IgA deficiency, antibody deficiency with near normal immunoglobulin levels) and combined deficiencies (severe combined immunodeficiencies, ataxia-telangiectasia, x-linked lymphoproliferative syndrome)] AND the prescriber has provided information showing disease response as evidence by ONE or more of the following:
  1. Decrease in the frequency of infection OR
  2. Decrease in the severity of infection OR
2. The patient has a diagnosis of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) AND ONE of the following:
  1. There is support indicating the patient has demonstrated a beneficial clinical response to maintenance therapy, without relapses, based on an objective clinical measuring tool (e.g., INCAT, Medical Research Council (MRC) muscle strength, 6-MWT, Rankin, Modified Rankin, etc.) OR
  2. The patient is re-initiating maintenance therapy after experiencing a relapse while on Hizentra or HyQvia AND BOTH of the following:
    1. The patient improved and is stabilized on IVIG treatment AND
    2. The patient was NOT receiving maximum dosing of Hizentra or HyQvia prior to relapse OR
3. The patient has a diagnosis of Acquired Immune Deficiency secondary to Chronic Lymphocytic Leukemia AND the prescriber has provided information showing disease response as evidence by BOTH of the following:
  1. ONE of the following:
    1. Decrease in frequency of infection OR
    2. Decrease in the severity of infection AND
  2. The patient is at a decreased risk of infection as a result of treatment necessitating continued therapy AND
ONE of the following:
1. The requested agent is a preferred agent OR
2. The requested agent is a non-preferred agent AND ONE of the following:
  1. The patient has tried and had an inadequate response to a preferred agent (medical records required) OR
  2. The patient has an intolerance or hypersensitivity to a preferred agent that is NOT expected to occur with the requested agent (medical records required) OR
  3. The patient has an FDA labeled contraindication to ALL preferred agents that is NOT expected to occur with the requested agent (medical records required) OR
  4. There is support for the use of the non-preferred agent over the preferred agents for the requested indication

Length of Approval: 12 months

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.