ALYGLO (human immunoglobulin g liquid)
Office-Administration – intravenous (IV) infusion
Diagnosis considered for coverage:
- Primary humoral immunodeficiency: indicated for the treatment of primary humoral immunodeficiency (PI) in adults. This includes, but is not limited to, the humoral immune defect in congenital agammaglobulinemia, common variable immunodeficiency (CVID), X-linked agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiency (SCID)
Coverage Criteria:
For diagnosis of primary humoral immunodeficiency:
- For patients with a primary immunodeficiency syndrome, AND
- Clinically significant functional deficiency of humoral immunity as evidenced by one of the following:
- Documented failure to produce antibodies to specific antigens, OR
- History of significant recurrent infections, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of idiopathic thrombocytopenic purpura:
- Diagnosis of idiopathic thrombocytopenic purpura (ITP), AND
- Documented platelet count of less than 50 x 10^9 / L, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Kawasaki Disease (KD):
- Diagnosis of Kawasaki Disease, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of B-cell chronic lymphocytic leukemia (CLL):
- Diagnosis of B-cell chronic lymphocytic leukemia (CLL), AND
- One of the following:
- Documented hypogammaglobulinemia (IgG less than 500 mg/dL), OR
- History of bacterial infection(s) associated with B-cell CLL, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP):
- Diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) as confirmed by all of the following:
- Progressive symptoms present for at least 2 months, AND
- Symptomatic polyradiculoneuropathy as indicated by one of the following:
- Progressive or relapsing motor impairment of more than one limb, OR
- Progressive or relapsing sensory impairment of more than one limb, AND
- Electrophysiologic findings when three of the following four criteria are present:
- Partial conduction block of 1 or more motor nerve
- Reduced conduction velocity of 2 or more motor nerves
- Prolonged distal latency of 2 or more motor nerves
- Prolonged F-wave latencies of 2 or more motor nerves or the absence of F waves, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Bone Marrow Transplantation (off-label):
- Confirmed allogeneic bone marrow transplant within the last 100 days, AND
- Documented severe hypogammaglobulinemia (IgG less than 400 mg/dL), AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of HIV (off-label):
- Diagnosis of HIV disease, AND
- Patient is less than or equal to 13 years of age, AND
- One of the following:
- Documented hypogammaglobulinemia (IgG less than 400 mg/dL), OR
- Functional antibody deficiency as demonstrated by one of the following:
- Poor specific antibody titers, OR
- Recurrent bacterial infections, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of multifocal motor neuropathy (off-label):
- Diagnosis of multifocal motor neuropathy (MMN) as confirmed by all of the following:
- Weakness with slowly progressive or stepwise progressive course over at least one month, AND
- Asymmetric involvement of two or more nerves, AND
- Absence of both of the following:
- Motor neuron signs
- Bulbar signs, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Relapsing-Remitting Multiple Sclerosis (off-label):
- Diagnosis of relapsing remitting multiple sclerosis (RRMS), AND
- Documentation of an MS exacerbation or progression (worsening) of the patient's clinical status from the visit prior to the one prompting the decision to initiate immune globulin therapy, AND
- Trial and failure, contraindication, or intolerance to two of the following agents:
- Aubagio (teriflunomide)*
- Avonex (interferon beta-1a)*
- Betaseron (interferon beta-1b)*
- Copaxone/Glatopa (glatiramer acetate)*
- Extavia (interferon beta-1b)*
- Gilenya (Fingolimod)*
- Lemtrada (alemtuzumab)*
- Plegridy (peginterferon beta-1a)*
- Rebif (interferon beta-1a)*
- Tecfidera (dimethyl fumarate)*
- Tysabri (natalizumab)*, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
*This agent may require prior authorization.
For diagnosis of Myasthenia Gravis Exacerbation (off-label):
- Diagnosis of generalized myasthenia gravis, AND
- Evidence of myasthenic exacerbation, defined by one of the following symptoms in the last month:
- Difficulty swallowing, OR
- Acute respiratory failure, OR
- Major functional disability responsible for the discontinuation of physical activity, AND
- Concomitant immunomodulator therapy (e.g., azathioprine, mycophenolate mofetil, cyclosporine), unless contraindicated, will be used for long-term management of myasthenia gravis, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Stiff Person Syndrome (off-label):
- Diagnosis of stiff-person syndrome, AND
- Trial and failure, contraindication or intolerance to GABAergic medication (e.g., baclofen, benzodiazepines), AND
- Trial and failure, contraindication or intolerance to immunosuppressive therapy (e.g., azathioprine, corticosteroids), AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Dermatomyositis and Polymyositis (off-label):
- One of the following diagnoses:
- Dermatomyositis
- Polymyositis, AND
- Trial and failure, contraindication, or intolerance to immunosuppressive therapy (e.g., azathioprine, corticosteroids, cyclophosphamide, methotrexate), AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Guillain-Barre Syndrome (off-label):
- Diagnosis of Guillain-Barre Syndrome, AND
- Patients with severe disease requiring aid to walk, AND
- Onset of neuropathic symptoms within the last four weeks, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Lambert-Eaton Myasthenic Syndrome (off-label):
- Diagnosis of Lambert-Eaton Myasthenic Syndrome (LEMS), AND
- History of failure, contraindication, or intolerance to immunomodulator monotherapy (e.g., azathioprine, corticosteroids), AND
- Concomitant immunomodulator therapy (e.g., azathioprine, corticosteroids), unless contraindicated, will be used for long-term management of LEMS, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Pediatric Acute-Onset Neuropsychiatric Syndrome/Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANS/PANDAS) (off-label):
- Diagnosis of one of the following:
- Pediatric Acute-onset Neuropsychiatric Syndrome (PANS), OR
- Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), AND
- Disease is moderate to severe as defined by distressing symptoms that interfere with daily activities that occupy at least 50 percent (%) of waking hours, AND
- Trial and failure, contraindication, or intolerance to one of the following:
- Corticosteroids (e.g., prednisone, dexamethasone, methylprednisolone), OR
- NSAIDs (e.g., Ibuprofen, naproxen, celecoxib), AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
Reauthorization Criteria:
For diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP):
- Patient demonstrates positive clinical response to therapy as measured by an objective scale (e.g., Modified Rankin, Medical Research Council [MRC] scale), AND
- Documentation of titration to the minimum dose and frequency needed to maintain a sustained clinical effect, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of multifocal motor neuropathy (off-label):
- Patient demonstrates positive clinical response to therapy as measured by an objective scale [e.g., Rankin, Modified Rankin, Medical Research Council (MRC) scale], AND
- Documentation of titration to the minimum dose and frequency needed to maintain a sustained clinical effect, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Relapsing-Remitting Multiple Sclerosis (off-label):
- The prescriber maintains and provides chart documentation of the patient's evaluation, including both of the following:
- Findings of interval examination including neurological deficits incurred, AND
- Assessment of disability (e.g., Expanded Disability Status Score [EDSS], Functional Systems Score [FSS], Multiple Sclerosis Functional Composie [MSFC], Disease Steps [DS]), AND
- Stable or improved disability score (e.g., EDSS, FSS, MSFC, DS), AND
- Documentation of decreased number of relapses since starting immune globulin therapy, AND
- Diagnosis continues to be the relapsing-remitting form of MS (RRMS), AND
- Documentation of titration to the minimum dose and frequency needed to maintain a sustained clinical effect, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Stiff Person Syndrome (off-label):
- Documentation of titration to the minimum dose and frequency needed to maintain a sustained clinical effect, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Dermatomyositis and Polymyositis (off-label):
- Documentation of titration to the minimum dose and frequency needed to maintain a sustained clinical effect, AND
- Trial and failure, contraindication, or intolerance to two of the following
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Guillain-Barre Syndrome (off-label):
- Documentation of titration to the minimum dose and frequency needed to maintain a sustained clinical effect, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
For diagnosis of Lambert-Eaton Myasthenic Syndrome (off-label):
- Documentation of titration to the minimum dose and frequency needed to maintain a sustained clinical effect, AND
- Trial and failure, contraindication, or intolerance to two of the following:
- Gammagard
- Gammaplex
- Gamunex-C
- Privigen, AND
- Prescribed by or in consultation with a physician who has specialized expertise in managing patients on immune globulin therapy (e.g., immunologist, hematologist, neurologist)
Coverage Duration:
For diagnosis of primary humoral immunodeficiency:
- 1 year
For diagnosis of idiopathic thrombocytopenic purpura:
- 6 months
For diagnosis of Kawasaki Disease (KD):
- 1 month
For diagnosis of B-cell chronic lymphocytic leukemia (CLL):
- 1 year
For diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP):
- Initial: 6 months
- Reauthorization: 1 year
For diagnosis of Bone Marrow Transplantation (off-label):
- 1 year
For diagnosis of HIV (off-label):
- 1 year
For diagnosis of multifocal motor neuropathy (off-label):
- Initial: 1 year
- Reauthorization: 1 year
For diagnosis of Relapsing-Remitting Multiple Sclerosis (off-label):
- Initial: 1 year
- Reauthorization: 1 year
For diagnosis of Myasthenia Gravis Exacerbation (off-label):
- 3 months
For diagnosis of Stiff Person Syndrome (off-label):
- Initial: 1 year
- Reauthorization: 1 year
For diagnosis of Dermatomyositis and Polymyositis (off-label):
- Initial: 1 year
- Reauthorization: 1 year
For diagnosis of Guillain-Barre Syndrome (off-label):
- Initial: 3 months
- Reauthorization: 1 year
For diagnosis of Lambert-Eaton Myasthenic Syndrome (off-label):
- Initial: 1 year
- Reauthorization: 1 year
For diagnosis of Pediatric Acute-Onset Neuropsychiatric Syndrome/Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANS/PANDAS) (off-label):
- 6 months
Dosing:
For diagnosis of primary humoral immunodeficiency:
- Recommended dose:
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- Significant differences in the half-life of IgG among patients with PI may necessitate the dose and frequency of immunoglobulin therapy to vary from patient to patient. Determine the proper dose and frequency by monitoring clinical response.
Authorization is not covered for the following:
The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.
Additional Information:
- Guidelines from the British Committee for Standards in Haematology [11] and the National Comprehensive Cancer Network [16] state that IVIG therapy may be beneficial in patients with recurrent infections. Clinical studies show that IVIG reduces the number of bacterial infections, but not viral or fungal infections. [24]
- Based on inclusion criteria from Molica et al. [14]
- According to published data, there appears to be no difference in efficacy among IVIG, plasma exchange, and corticosteroids. [15, 17, 20]
- A controlled trial indicated that treatment with IVIG beyond three months was associated with a delayed recovery of humoral immunity, and the rate of infections after two years of treatment was increased significantly in IVIG recipients. [25] Centers for Disease Control and Prevention, Infectious Disease Society of America, and American Society of Blood and Marrow Transplantation guidelines recommended routine IVIG use to prevent bacterial infections among BMT recipients with unrelated marrow grafts who experience severe hypogammaglobulinemia (e.g., IgG < 400 mg/dl) within the first 100 days after transplant. [21]
- The American Academy of Neurology recommends that IVIG is for patients with GBS who require aid to walk within 2 weeks from the onset of neuropathic symptoms. [40]
- The effectiveness of IVIG for moderate-to-severe but stable myasthenia gravis, or for moderate exacerbations of myasthenia gravis have not been demonstrated in adequately controlled trials. [48] IVIG may be as effective as plasma exchange for patients with acute exacerbations of myasthenia gravis. [45] The indications for the use of IVIG are the same as those for plasma exchange: to produce rapid improvement to help the patient through a difficult period of myasthenic weakness. It has the advantages of not requiring special equipment or large-bore vascular access. [59] The usual dose of immune globulin is 400 mg per kilogram per day for five successive days. The improvement rate after immune globulin treatment, calculated from eight published reports, was 73 percent, but this figure is likely to be biased by selective reporting of positive uncontrolled trials. In patients who respond, improvement begins within four to five days. The effect is temporary but may be sustained for weeks to months, allowing intermittent long-term therapy in patients with otherwise refractory disease.
- Guidelines from the American Academy of Neurology [42] state that interferon Beta or glatirimer are appropriate treatments for patients who have relapsing-remitting multiple sclerosis. The guidelines state that it is only possible that IVIG reduces the attack rate in RRMS, and that current evidence suggests IVIG is of little benefit with regard to slowing disease progression.
- Treatment for CIDP includes corticosteroids such as prednisone, which may be prescribed alone or in combination with immunosuppressant drugs. [58] Plasmapheresis and intravenous immunoglobulin (IVIG) therapy are effective. IVIG may be used even as a first-line therapy. Physiotherapy may improve muscle strength, function and mobility, and minimize the shrinkage of muscles and tendons and distortions of the joints.
- Subcutaneous formulations of immune globulin are available for the treatment of patients with primary immune deficiency. Subcutaneous infusions may be an alternative for patients with adverse effects to intravenous infusions of immune globulin or with poor venous access. Other advantages include decreased cost of administration, independence from scheduled home nursing visits, better maintenance of intravenous immune globulin trough levels, and a serum IgG profile (smaller variation in the peak and trough IgG concentrations compared to intravenous administration) that is similar to that in a normal population. Disadvantages include more frequent infusions and local reactions. [6]
- There are good data to show that all immune globulins (IVIG/SCIG) are effective for primary immunodeficiency. There are no data for SCIG for indications other than PI. Efficacy is a class effect for all immune globulins products. It is appropriate to combine all IVIG/SCIG products as they are used interchangeably for PI; can combine all IVIG for other indications. Gamastan S/D (IMIG) has unique indications and should be available on the formulary. [74]
- IVIG has been used in children with symptomatic human immunodeficiency virus (HIV) infection who are immunosuppressed in association with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) in an attempt to control or prevent infections and improve immunologic parameters. Results of studies in adults and children with symptomatic HIV infection indicate that IVIG, used in dosages similar to those used for replacement therapy in patients with primary immunodeficiencies, reduces the incidence of recurrent bacterial infections and sepsis, including upper respiratory tract infections. [75]
- The ACIP, American Academy of Pediatrics (AAP), Centers for Disease Control (CDC), National Institutes of Health (NIH), HIV Medicine Association of the Infectious Diseases Society of America (IDSA), Pediatric Infectious Diseases Society, and other experts state that HIV-infected infants and children who have hypogammaglobulinemia (IgG less than 400 mg/dL) should receive IVIG (400 mg/kg once every 2-4 weeks) to prevent serious bacterial infections. [75]
- Per expert consultant regarding MS: IVIG is only used in acute, severe MS. IVIG is used for bad relapses of MS with significant neurological dysfunction when a patient is breaking through their regular maintenance medications. It takes about 3 months to see if there is improvement in MS and one cannot say a patient has failed a medication if they have a breakthrough episode of MS within this 3 month period [86].
- Per expert consultant regarding multifocal motor neuropathy: the European Federation of Neurological Societies (EFNS) guidelines [88] as outlined on page 344 and in the table are fairly reasonable: 1. Weakness with slowly progressive or stepwise progressive course 2. Asymmetric involvement of two or more nerves 3. Absence of upper motor neuron signs and bulbar signs [87].
- Per expert consultant regarding MS: there are no data to support the initial length of IVIG treatment in MS. I would suggest 3 months and then reevaluate. An appropriate length of time for reauthorization of IVIG is 12 months. Patients who receive IVIG for RRMS should be in acute exacerbation, should have tried steroids, have documentation of inability to tolerate other disease modifying drugs, as well as show progression of disease. IVIG should be used 2nd or 3rd line if other injectable disease modifying drugs are not tolerated. Guidelines do not support IVIG as first line treatment for MS [87].
- Per expert consultant regarding CIDP: It is important to reevaluate a patient after initial treatment. Some patients may need changes in dosing intervals due to wearing off of a dose within 2-3 weeks. Treatment can be lifelong for some patient [87].
- Per expert consultant regarding dermatomyositis: It is reasonable to ask a patient to try steroids prior to treatment with IVIG. [87]
- Per expert consultant regarding MG: IVIG should be used in patients with moderate to severe myasthenia gravis with acute exacerbation. Most MDs favor plasma exchange for maintenance therapy in MG patients. Myasthenic exacerbation = myasthenic crisis. [87]
Policy Updates:
- 9/1/2024 (policy effective date) – New policy approved by WHA P&T Committee. (P&T, 8/20/2024) (P&T meeting date)
References:
- Alyglo Prescribing Information. GC Biopharma USA, Inc. Teaneck, NJ 07666, December 2023.
Last review date: September 1, 2024