The requirements of the Horizon BCBSNJ Intravenous Immunoglobulin (IVIG) Therapy Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

[INFORMATIONAL NOTE: Please refer to a separate policy on Respiratory Syncytial Virus Immune Globulin Prophylaxis (RSV-IGIV) -Respigam (Policy #013) and a separate policy on Immune Globulin Subcutaneous (Vivaglobin, Hizentra, Gammagard Liquid, Gamunex-C/Gammaked, and HyQvia for subcutaneous administration) Policy #045) under the Drug Section.]

I. Please refer to a separate policy on Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) under the Drug Section.

II. Intravenous immunoglobulin (IVIG) therapy must be prescribed by the treating physician and requires medical certification.

III. Baseline values for blood urea nitrogen (BUN) and serum creatinine should be obtained within 30 days of request.

IV. IVIG therapy is considered medically necessary for the following conditions which are the FDA-approved indications for use of the drug (FDA-approved labelling may vary depending on the specific product):

A. Primary immunodeficiencies as replacement therapy in members with either:
1. Patient’s IgG level is <200 OR both of the following
2. Patient has a history of multiple hard to treat infections as indicated by at least one of the following:
a. Four or more ear infections within 1 year
b. Two or more serious sinus infections within 1 year
c. Two or more months of antibiotics with little effect
d. Two or more pneumonias within 1 year
e. Recurrent or deep skin abscesses
f. Need for intravenous antibiotics to clear infections
g. Two or more deep-seated infections including septicemia; AND
3. The patient has a deficiency in producing antibodies in response to vaccination; AND
a. Baseline titers were drawn before challenging with vaccination; AND
b. Titers were draw between 4 and 8 weeks of vaccination

[INFORMATIONAL NOTE: The diagnoses of common variable immunodeficiency (CVID), as well as IgG subclass deficiency, are established by excluding other causes of hypogammaglobulinemia and by documenting a clinically significant functional deficiency of humoral immunity as evidenced by a failure to produce antibodies to specific antigens. This includes, but is not limited to, X-linked agammaglobulinemia, congenital hypogammaglobulinemia, severe combined immunodeficiency, X-linked immunodeficiency with hyperimmunoglobulinemia, Wiskott-Aldrich syndrome, and ataxia-telangiectasia. Antibody responses to tetanus, diphtheria, and pneumococcal vaccines should be assessed.

Routine use of IVIG in all patients with an IgG subclass deficiency is not medically necessary. Furthermore, maintenance therapy is not medically necessary for patients with IgG subclass deficiencies who are generally healthy and do not have recurrent infections. IVIG is only medically necessary in patients who have marked (more than two standard deviations below normal) IgG subclass deficiency (with or without IgA deficiency) and who have serious recurrent bacterial infections. The minimum serum concentration of IgG necessary for protection has not been established. The dosage required to achieve and maintain this concentration depends on the individual patient’s metabolic rate for immunoglobulin and the absolute level of immunoglobulin deficiency. Please refer to policy statement V for further clinical information.

Routine use of IVIG is not medically necessary in patients with isolated or selective IgA deficiency especially those with chronic or recurrent infections of the mucous membranes because most of the patients with this condition produce normal quantities of IgG antibodies of all types, do very well on prophylactic antibiotics and have the potential for developing antibodies to IgA that could be responsible for anaphylactic reactions to subsequent administration of blood products that contain IgA; and secretory IgA is not transported from the intravascular compartment to effectively replace IgA at the mucous-membrane surfaces.]

B. Idiopathic Thrombocytopenic Purpura (ITP)
1. For acute disease:
a. Adult and pediatric patients with acute bleeding due to severe thrombocytopenia (platelet count usually less than 30,000/ul); OR,
b. To increase platelet counts prior to invasive surgical procedures, e.g. splenectomy. (Platelets less than 100 X 10⁹/L); OR
c. Patient has severe thrombocytopenia (platelet counts less than 20 X 10⁹/L) and considered to be at risk for intracerebral hemorrhage;
2. Chronic Immune Thrombocytopenia(CIT):
a. The patient is at increased risk for bleeding as indicated by a platelet count less than 30 X 10⁹/L; AND
b. History of failure, contraindication, or intolerance with corticosteroids; AND
c. Duration of illness > 6 months; AND
d. Member age ≥ 10 years (for Flebogamma it is > 2 years)
[INFORMATIONAL NOTE: Adult severe ITP may be defined by the following parameters:
a. Acute ITP with major bleeding, e.g. life-threatening and/or clinically important mucocutaneous bleeding.
b. Acute ITP with severe thrombocytopenia and at high risk for bleeding complications
c. Acute ITP with severe thrombocytopenia and a slow or inadequate response to corticosteroids
d. Acute ITP with severe thrombocytopenia and a predictable risk of bleeding in the future, e.g., a procedure or surgery with high bleeding risk

According to the 2011 American Society of Hematology (ASH) Guidelines:
a. Long courses of corticosteroids are preferred over shorter courses of corticosteroids or IVIG as first-line treatment
b. IVIG or corticosteroids may be used in combination when a greater increase in platelet count is needed
c. Either IVIG or anti-D be used as first line therapy when corticosteroids are contraindicate

High-risk low platelet count (severe thrombocytopenia) is indicated by 1 or more of the following:
• Severe or life-threatening bleeding (eg, intracranial, major gastrointestinal, or extensive mucosal bleeding), with any reduced platelet count.
• Platelet count less than 20,000/mm³ (20 x10⁹/L) with any active bleeding
• Platelet count less than 10,000/mm³ (10 x10⁹/L) with minor purpura or petechiae
• Platelet count less than 5000/mm³ (5 x10⁹/L)
• Low platelet count with hemolytic anemia

According to the 2011 ASH guidelines it is recommended that children with no bleeding or mild bleeding be managed with observation alone regardless of platelet count. Mild bleeding includes skin manifestations such as petechiae and bruising only. For pediatric patients requiring treatment a single dose of IVIG or short course corticosteroids is recommended.]
C. Kawasaki syndrome (when administered within the first ten (10) days of illness) when administered in pediatric patients

D. Chronic Lymphocytic Leukemia (CLL) as replacement therapy in members with either:
1. Patient’s IgG level is <200 OR both of the following
2. Patient has a history of multiple hard to treat infections as indicated by at least one of the following:
a. Four or more ear infections within 1 year
b. Two or more serious sinus infections within 1 year
c. Two or more months of antibiotics with little effect
d. Two or more pneumonias within 1 year
e. Recurrent or deep skin abscesses
f. Need for intravenous antibiotics to clear infections
g. Two or more deep-seated infection including septicemia; AND
3. The patient has a deficiency in producing antibodies in response to vaccination; AND
a. Baseline titers were drawn before challenging with vaccination; AND
b. Titers were draw between 4 and 8 weeks of vaccination

E. Chronic inflammatory demyelating polyneuropathy (CIDP) if ALL of the following criteria has been met:

[INFORMATIONAL NOTE: Patients with very mild symptoms which do not or only slightly interfere with activities of daily living may be monitored without treatment.]
• Patient’s disease course is progressive or relapsing and remitting for 2 months or longer; AND
• Patient has abnormal or absent deep tendon reflexes in upper or lower limbs; AND
• Electrodiagnostic testing indicating demyelination based on the criteria below:
  • Partial motor conduction block in at least two motor nerves or in 1 nerve plus one other demyelination criterion listed here in at least 1 other nerve; OR
  • Distal CMAP duration increase in at least 1 nerve plus one other demyelination criterion listed here in at least 1 other nerve; OR
  • Abnormal temporal dispersion conduction must be present in at least 2 motor nerves OR
  • Reduced conduction velocity in at least 2 motor nerves; OR
  • Prolonged distal motor latency in at least 2 motor nerves; OR
  • Absent F wave in at least two motor nerves plus one other demyelination criterion listed here in at least 1 other nerve; OR
  • Prolonged F wave latency in at least 2 motor nerves ; AND
• Refractory to or intolerant of corticosteroids (e.g. prednisolone, prednisone) given in therapeutic doses over at least three months; AND
• Baseline in strength/weakness has been documented using objective clinical measuring tool (e.g. INCAT, Medical Research Council (MRC) muscle strength,6 MWT, Rankin, Modified Rankin) and renewals will require current results
  
[INFORMATIONAL NOTE: Patients with very mild symptoms which do not or only slightly interfere with activities of daily living may be monitored without treatment.]
F. Multifocal motor neuropathy (MMN) - in members with
• Complete or partial conduction block or abnormal temporal dispersion conduction must be present in at least 2 motor nerves with accompanying normal sensory nerve conduction study across the same nerve that demonstrated the conduction block; AND
• Patient has progressive multi-focal weakness (without sensory symptoms); AND
• Baseline in strength/weakness has been documented using objective clinical measuring tool (e.g. INCAT, Medical Research Council (MRC) muscle strength,6 MWT, Rankin, Modified Rankin) and renewals will require current results

Examples of specific medically necessary "off-label" use of IVIG that is supported by sufficient clinical evidence published in the medical literature are listed below. Medical certification from the prescribing physician is required and must include a statement of medical necessity, the diagnosis, and clinical history reflecting the therapeutic regimens previously provided and their outcomes.
A. HEMATOLOGY:
1. Anemia, autoimmune hemolytic (AIHA) - members with warm-type AIHA that does not respond to corticosteroids and splenectomy
2. Thrombocytopenia, neonatal alloimmune (NAIT)- neonates with severe immune thrombocytopenia if other interventions are unsuccessful or contraindicated; maternal antenatal infusion may be considered.
3. Thrombocytopendia, fetal alloimmune (FAIT) - Coverage is provided until delivery for one or more of the following:
• Previous fetal alloimmune thrombocytopenia (FAIT) pregnancy;
• Family history of the disease; OR
• Screening reveals platelet alloantibodies
4. Hemolytic Disease of the Fetus and Newborn (HDFN) - members with severe hyperbilirubinemia or if total serum bilirubin is rising despite intensive phototherapy
5. Multiple Myeloma as replacement therapy in members with either:
a. Patient’s IgG level is <200 OR both of the following
b. Patient has a history of multiple hard to treat infections as indicated by at least one of the following:
i. Four or more ear infections within 1 year
ii. Two or more serious sinus infections within 1 year
iii. Two or more months of antibiotics with little effect
iv. Two or more pneumonias within 1 year
v. Recurrent or deep skin abscesses
vi. Need for intravenous antibiotics to clear infections
vii. Two or more deep-seated infections including septicemia; AND
c. The patient has a deficiency in producing antibodies in response to vaccination; AND
i. Baseline titers were drawn before challenging with vaccination; AND
ii. Titers were draw between 4 and 8 weeks of vaccination
B. INFECTIOUS DISEASES (Prophylaxis: Infections):
1. Transplantation, solid organ - CMV-seronegative recipients of CMV-seropositive organs. Coverage is provided for one or more of the following:
• Suppression of panel reactive anti-HLA antibodies prior to transplantation;
• Treatment of antibody mediated rejection of solid organ transplantation; or
• Prevention or treatment of viral infections (e.g. cytomegalovirus (CMV), Parvo B-19 virus, and Polyoma BK virus); or

2. HIV infection, children (< 13 years old) and adult- for prevention of serious infections in members who meet Centers for Disease Control (CDC) criteria B (HIV-infected patients with symptomatic conditions that are attributed to and/or are complicated by HIV infection), and criteria C (patients has or has had with clinical conditions that are included in the AIDS surveillance case definition).
• IVIG is prescribed for prophylaxis of bacterial infections AND
• Member has hypogammaglobulinemia(pretreatment IgG <400 mg/dl) OR history of recurrent bacterial infections (>2 serious bacterial infections in a 1-year period despite cART and antibiotic prophylaxis)
3. Toxic shock syndrome

C. INFECTIOUS DISEASES (Treatment: Infections):
1. For the treatment of acute myocarditis – in neonates, infants, children, and adolescents

D. NEUROLOGY:
1. Guillain-Barre syndrome - IVIG may be considered as an equivalent alternative to plasma exchange in children and adults with severe Guillain-Barre syndrome who require aid to walk within 2 to 4 weeks from the onset of neuropathic symptoms
• Disease is severe (individual requires assistance to walk)
• Onset of symptoms are recent (less than 1 month)
• Approval will be granted for a maximum of 2 rounds of therapy within 6 weeks on onset
• Authorization is valid for 2 months only
2. Myasthenia gravis (MG) - members with severe MG to treat acute severe decompensation (respiratory or bulbar compromise) when other treatments have been unsuccessful or are contraindicated
• Failure of conventional therapy alone (corticosteroids azathioprine, cyclosporine and/or cyclophosphamide)
• Treatment will include combination therapy with corticosteroids or other immunosuppressant (e.g. azathioprine, mycophenolate, cyclosporine, methotrexate, tacrolimus, cyclophosphamide, etc.
3. Acute disseminated encephalomyelitis – in patients who do not respond to or have a contraindication to high-dose corticosteroids

E. RHEUMATOLOGY:
1. Dermatomyositis / Polymyositis - members with severe active illness for whom other interventions have been unsuccessful or intolerable if ALL of the following criteria has been met:
• Proximal weakness in all upper and/or lower limbs; AND
• Diagnosis confirmed by muscle biopsy; AND
• Patient has failed a trial of corticosteroids (i.e. prednisone); AND
• Patient has failed a trial of immunosuppressants (i.e. MTX, azathioprine); AND
• Documented baseline per physical exam
2. Stiff Person Syndrome
• Individual positive for anti-GAD antibodies
• Severe disability in carrying out daily activities with baseline physical exam documented
• Failure of two of the following therapies:
  • Benzodiazepines (e.g., diazepam, clonazepam)
  • Baclofen

F. MISCELLANEOUS:
1. Autoimmune Mucocutaneous Blistering Diseases – including pemphigus, pemphigoid, pemphigus vulgaris, pemphigus foliaceus, in patients with severe, progressive disease despite treatment with conventional agents (corticosteroids, azathioprine, cyclophosphamide, etc.) when diagnosis has been confirmed by biopsy
2. Eaton-Lambert myasthenic syndrome – in patients who have failed to respond to anticholinesterase medications and/or corticosteroids.
3. Management of Immune-Checkpoint Inhibitor Related Toxicity
• Patient has been receiving therapy with an immune checkpoint inhibitor (e.g. nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, etc); AND
• Patient has one of the following toxicities related to immunotherapy:
  • Myasthenia gravis refractory to high-dose corticosteroids
  • Severe transverse myelitis
  • Moderate or severe Guillain-Barre Syndrome or peripheral neuropathy toxicity used in combination with pulse-dose methylprednisolone
  • Severe pneumonitis refractory to methylprednisolone after 48 hours of therapy
  • Encephalitis used in combination with pulse-dose methylprednisolone
  • Severe inflammatory arthritis refractory to 14 days of high-dose corticosteroid therapy
4. Allogeneic bone marrow recipients to prevent graft-versus-host disease and bacterial infections when IgG level are less than 400 mg/dL.

A. HEMATOLOGY:
1. Anemia, aplastic
2. Anemia, Diamond-Blackfan
3. Factor VIII inhibitors, acquired
4. Hemophagocytic syndrome
5. Leukemia, acute lymphoblastic
6. Thrombocytopenia, nonimmune
7. Heparin-induced thrombocytopenia
8. Thrombotic Thrombocytopenic Purpura (TTP)/Hemolytic Uremic Syndrome (HUS)
9. Transfusion reaction, hemolytic
10. von Willebrand's syndrome, acquired
11. Hyperbilirubinemia due to Rh hemolytic disease
B. INFECTIOUS DISEASES (Prophylaxis: Infections):
1. Surgery or trauma
2. Sinusitis, chronic
3. Otitis media, recurrent
C. INFECTIOUS DISEASES (Treatment: Mortality):
1. Neonates, high-risk hypogammaglobulinemic
2. Surgery or trauma, adults
3. Cytomegalovirus infection treatment and prophylaxis
4. Treatment of neonatal sepsis
D. NEUROLOGY:
1. Motor neuron syndromes
2. Multiple sclerosis
3. Myelopathy, HTLV-I associated
4. Neuropathy, paraproteinemic
5. Plexopathy, progressive lumbosacral
6. Amyotrophic lateral sclerosis (ALS)
7. Autism
8. Opsoclonus-myoclonus
9. POEMS syndrome (acronym for polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes)
10. Alzheimer’s disease
11. Complex-regional pain syndrome
E. OBSTETRICS:
1. Spontaneous abortion (recurrent)
2. Failed conception or repeated IVF failure
[INFORMATIONAL NOTE: A variety of immunologic tests may precede the initiation of IVIG therapy. These tests, including various subsets of lymphocytes, HLA testing, and lymphocyte functional testing (i.e., natural killer cell assays and embryo cytotoxicity test), are research tools that explore subtle immunologic disorders that may contribute to maternal immunologic tolerance of the fetus. However, there are no clinical data that indicates that the results of these tests can be used in the management of patients to reduce the incidence of recurrent spontaneous abortion, particularly since IVIG therapy has not been shown to be an effective therapy.]
F. PULMONOLOGY:
1. Asthma and inflammatory chest disease
G. RHEUMATOLOGY:
1. Arthritis, rheumatoid (adult and juvenile)
2. Myositis, Inclusion body
H. MISCELLANEOUS:
1. Adrenoleukodystrophy
2. Behcet's syndrome
3. Burns or thermal injury
4. Chronic fatigue syndrome
5. Cystic fibrosis
6. Diabetes mellitus
7. Endotoxemia
8. Heart block, congenital
9. Nephropathy, membranous
10. Nephrotic syndrome
11. Ophthalmopathy, euthyroid
12. Oral use of IVIG
13. Otitis media, recurrent
14. Renal failure, acute
15. Sinusitis, chronic
16. PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections)
17. Paraneoplastic syndrome
18. Asthma
19. Narcolepsy
20 Syndenham’s chorea
21 Prostate cancer
22 Colon cancer
23 Melanoma
24. Neonatal jaundice

A. At the following calculated dosing recommendations:
• Actual body weight in patients weighing up to 100kg with a BMI <30 kg/m² OR
• Adjusted body weight if one or more of the following criteria are met:
  • If BMI =/ >30 kg/m² OR
  • If the patients actual body weight is >20% over the patients ideal body.

Use the following dosing formulas to calculate the adjusted body weight (round dose to nearest 5 gram increment in adult patients):

Dosing formulas

BMI = 703 x (weight in pounds/height in inches2)

IBW(kg) for males = 50 + [2.3 (height in inches – 60)]

IBW(kg) for females = 45.5 + [2.3 x (height in inches – 60)]

Adjusted body weight = IBW + 0.5 (actual body weight – IBW)

B. The following clinical information is provided as a guide in the use of IVIG in the treatment of the following conditions based on the current literature and FDA approved package inserts:
1. Primary immunodeficiencies - the minimum serum concentration of IgG necessary for protection has not been established. While serum IgG concentrations may not necessarily correlate with prevention of infection, IgG concentrations <200 mg/dL may increase a member's risk for sudden and overwhelming bacterial infection, while concentrations >400 mg/dL may provide protection against infection. The dosage required to achieve and maintain this concentration depends on the individual member's metabolic rate for immunoglobulin and the absolute level of immunoglobulin deficiency. Serum IgG concentrations should be monitored before each IVIG-infusion, until each subclass concentration is within the normal range, and annually thereafter. IVIG therapy should be discontinued if the total IgG and IgG subclass concentrations are in the normal range for the particular age group to determine whether they will remain normal.

The usual recommended dose of IVIG is 200-800 mg/kg body weight given every 3-4 weeks. Initial doses may be administered at 200-400 mg/kg body weight or infusions may be given at more frequent intervals until clinical response is adequate or the level of IgG in the serum is sufficient.
2. Immune/ Idiopathic Thrombocytopenic Purpura (ITP) - either of two therapeutic regimens may be followed. IVIG may be administered at 400 mg/kg/d for 5 days or infusion of 1 g/kg/d for 1-2 days in adult patients. In pediatric population the dose may be administered at a dose of 400 mg/kg/d daily for 2-5 days superceded by short course with a single dose of 0.8 to 1 g/kg with possible repeat treatment based on the short-term platelet response. The need for additional doses can be determined by clinical response and platelet count.
3. Kawasaki syndrome - a single dose regimen of 1g/kg body weight given over 10 hours, or a multi-dose regimen of 400 mg/kg body weight per day for 4 consecutive days. Either treatment regimen should be administered or started within the first 10 days of illness.
4. Chronic Lymphocytic Leukemia (CLL) - usual recommended dose is 400 mg/kg body weight given every 3- 4 weeks.
5. Chronic inflammatory demyelating (CIDP): initial loading dose is 2g/kg given in divided doses over 2 to 5 consecutive days, followed by a maintenance dose of 1g/kg given over 1 day OR as 2 divided doses on 2 consecutive days, every 3 weeks.
6. Multifocal motor neuropathy (MMN): Dose range 0.5 to 2.4 grams/kg/month based on clinical response

• Patient continues to meet initial review criteria; AND
• Documentation of disease response is submitted; AND
• Absence of unacceptable toxicity from the drug (e.g.: thrombosis, renal dysfunction, aseptic meningitis syndrome, hemolytic anemia) AND
· Blood urea nitrogen (BUN) and serum creatinine obtained within the last 6 months and the concentration and rate of infusion adjusted accordingly; AND
• Patient meets the following additional criteria for the indications listed below:
  • Primary Immune Deficiency and Chronic Lymphocytic Leukemia
    • Disease response as evidenced by one or more of the following:
      • Decrease in the frequency of infection
      • Decrease in the severity of infection
  • Chronic Immune Thrombocytopenia
    • Disease response as indicated by the achievement and maintenance of a platelet count of at least 50 X 10⁹/L as necessary to reduce the risk for bleeding
  • Chronic Inflammatory Demyelinating Polyneuropathy
    • Renewals will be authorized for patients that have demonstrated a clinical response to therapy based on an objective clinical measuring tool (e.g. INCAT, Medical Research Council (MRC) muscle strength,6 MWT, Rankin, Modified Rankin)
  • Multifocal Motor Neuropathy
    • Renewals will be authorized for patients that have demonstrated a clinical response to therapy based on an objective clinical measuring tool (e.g. INCAT, Medical Research Council (MRC) muscle strength,6 MWT, Rankin, Modified Rankin)
  • Allogeneic Bone Marrow or Stem Cell Transplant
    • Patient’s IgG is less than or equal to 400mg/dL; AND
    • Therapy does not exceed 360 days past patient’s allogeneic bone marrow transplantation; AND
    • May only be renewed for coverage up to 360 days post patient’s allogeneic bone marrow transplantation
• There should be an attempt made to decrease/wean the dosage when improvement has occurred.
• If disease response does not occur with the initial IVIG therapy, continued IVIG infusion will not be considered medically necessary.

**Note: Bullet 1 of the policy section referring to Site of Administration for Infusion and Injectable Prescription Medications (Policy #142) does not apply for Medicare Advantage Products.

Medicaid Coverage
For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Intravenous Immunoglobulin (IVIG) Therapy
IVIG (Intravenous Immunoglobulin) Therapy
Therapy, Intravenous Immunoglobulin (IVIG)

References:
1. Physicians' Desk Reference. Montvale, NJ: Medical Economics Co Inc; 53rd Edition. 1999.

2. Daya S, Gunby J, Clark DA. Intravenous immunoglobulin therapy for recurrent spontaneous abortion: a meta-analysis. Am J Reprod Immunol. February 1998;39(2):69-76.

3. Stephenson MD, Dreher K, Houlihan E, Wu V. Prevention of unexplained recurrent spontaneous abortion using intravenous immunoglobulin: a prospective, randomized, double-blinded, placebo-controlled trial. Am J Reprod Immunol. February 1998;39(2):82-88.

4. Kiehl MG, Stoll R, Broder M, et al. A Controlled Trial of Intravenous Immune Globulin for the Prevention of Serious Infections in Adults With Advanced Human Immunodeficiency Virus Infection. Arc Intern Med. December 1996;156:2545-2550.

5. Ratko TA, Burnett DA, Foulke GE, Matuszewski KA, Sacher RA, et al. Recommendations for Off-Label Use of Intravenously Administered Immunoglobulin Preparations. JAMA. June 21, 1995; 273(23): 1865-70.

6. Fadal RG. Chronic Sinusitis, Steroid-Dependent Asthma, and IgG Subclass and Selective Antibody Deficiencies. Otolaryngology-Head and Neck Surgery. September 1993; 109(3): 606-10.

7. Shackelford PG. IgG Subclasses: Importance in Pediatric Practice. Pediatrics in Review. August 1993; 14(8): 291-96.

8. Herrod HG. Management of the Patient with IgG Subclass Deficiency and/or Selective Antibody Deficiency. Annals of Allergy. January 1993; 70: 3-11.

9. American Society of Hospital Pharmacists. ASHP Therapeutic Guidelines for Intravenous Immune Globulin. Clin Pharm. Feb 1992; Vol 11: 117-36.

10. Oates JA, Wood AJJ. The Use of Intravenous Immune Globulin in Immunodeficiency Diseases. The New England Journal of Medicine. July 11, 1991; 325(2): 110-17.

11. American Hospital Formulary Service Drug Information, 2001.

12. United States Pharmacopoeia Drug Information, 2000.

13. Cooper MD, Schroeder Jr. HW: Primary Immune Deficiency Diseases, in Harrison’s Principles of Internal Medicine, 15th ed, E Braunwald et al (eds). New York, McGraw-Hill, 2001.

14. Hill JA, Scott RT Jr. Immunologic tests and IVF: "Please, enough already". Fertility and Sterility 2000 Sep;74(3):439-442.

15. Stephenson MD, Fluker MR. Treatment of repeated unexplained in-vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial. Fertility and Sterility 2000 Dec;74(6):1108-1113.

16. Ghazeeri GS, Kutteh WH. Immunological testing and treatment in reproduction: frequency assessment of practice patterns at assisted reproduction clinics in the USA and Australia. Human Reproduction 2001;16(10):2130-2135.

17. Perino A, Vassiliadis A, Vucetich A, et al. Short-term therapy for recurrent abortion using intravenous immunoglobulins: results of a double-blind placebo-controlled Italian study. Human Reproduction 1997;12(11):2388-2392.

18. Jablonowska B, Selbing A, Palfi M, et al. Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study. Human Reproduction 1999;14(3):838-841.

19. Branch DW, Porter TF, Paidas MJ, et al. Obstetric uses of intravenous immunoglobulin: successes, failures, and promises. J Allergy Clin Immunol 2001 Oct;108(4 Suppl):S133-S138.

20. Porter TF, Scott JR. Alloimmune causes of recurrent pregnancy loss. Semin Reprod Med 2000;18(4):393-400.

21. Daya S, Gunby J, Porter F, et al. Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage. Human Reprod Update 1999 Sep-Oct;5(5):475-482.

22. Mackay IR, Rosen FS. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med. 2001 Sep;345(10):747-755.

23. Chen C, Danekas LH, Ratko TA, et al. A multicenter drug use surveillance of intravenous immunoglobulin utilization in US academic health centers. Ann Pharmacother 2000 Mar;34(3):295-299.

24. Spring PJ, Spies JM. Myasthenia gravis: options and timing of immunomodulatory treatment. BioDrugs 2001;15(3):173-183.

25. Howard JF Jr. Intravenous immunoglobulin for the treatment of acquired myasthenia gravis. Neurology 1998;51(6):S30-S36.

26. Lisak RP. Intravenous immunoglobulins in multiple sclerosis. Neurology 1998;51(6):S25-S29.

27. Poehlau D. Treatment of chronic progressive multiple sclerosis with intravenous immunoglobulins - interim results on drug safety of an ongoing study. IVIG study group. Mult Scler 2000 Oct;6 Suppl 2:S21-S23.

28. Dalakas MC. Controlled studies with high-dose intravenous immunoglobulin in the treatment of dermatomyositis, inclusion body myositis, and polymyositis. Neurology 1998;51(6):S37-S45.

29. Broliden K. Parvovirus B19 infection in pediatric solid-organ and bone marrow transplantation. Pediatr Transplant 2001 Oct;5(5):320-330.

30. Lindenbaum Y, Kissel JT, Mendell JR. Treatment approaches for Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Neurol Clin 2001 Feb;191(1):187-204.

31. Hahn AF. Treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulin. Neurology 1998;51(6):S16-S21.

32. Sater RA, Rostami A. Treatment of Guillain-Barre syndrome with intravenous immunoglobulin. Neurology 1998;51(6):S9-S15.

33. Colsky AS. Intravenous immunoglobulin in autoimmune and inflammatory dermatoses. A review of proposed mechanisms of action and therapeutic applications. Dermatol Clin 2000 Jul;18(3):447-457.

34. Sorensen PS, Wanscher B, Jensen CV, et al. Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis. Neurology 1998;50:1273-1281.

35. Achiron A, Gabbay U, Gilad R, et al. Intravenous immunoglobulin treatment in multiple sclerosis. Neurology 1998;50:396-402.

36. Achiron A, Pras E, Gilad R, et al. Open Controlled Therapeutic Trial of Intravenous Immune Globulin in Relapsing-Remitting Multiple Sclerosis. Arch Neurol 1992 Dec;49:1233-1236.

37. Achiron A, Gilad R, Margalit R, et al. Intravenous gammaglobulin treatment in multiple sclerosis and experimental autoimmune encephalomyelitis: delineation of usage and mode of action. J Neurol Neurosurg Psychiatry 1994 Nov;57 Suppl:57-61.

38. Fazekas F, Deisenhammer F, Strasser-Fuchs S, et al. Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group. Lancet 1997 Mar;349(9052):589-593.

39. Yamada H, Morikawa M, Kato EH, et al. Pre-conceptional natural killer cell activity and percentage as predictors of biochemical pregnancy and spontaneous abortion with normal chromosome karyotype. Am J Reprod Immunol 2003 Oct;50(4):351-4.

40. Shakhar K, Ben-Eliyahu S, Lowenthal R, et al. Differences in number and activity of peripheral natural killer cells in primary versus secondary recurrent miscarriage. Fertile Steril 2003 Aug;80(2):368-75.

41. Morikawa M, Yamada H, Kato EH, et al. Massive intravenous immunoglobulin treatment in women with four or more recurrent spontaneous abortions of unexplained etiology: down-regulations of NK cell activity and subsets. Am J Immunol 2001 Dec;46(6):399-404.

42. Kwak JY, Kwak FM, Gilman-Sachs A, et al. Immunoglobulin G infusion treatment for women with recurrent spontaneous abortions and elevated CD56+ natural killer cells. Early Pregnancy 2000 Apr;4(2):154-64.

43. Coulam CB, Goodman C. Increased pregnancy rates after IVF/ET with intravenous immunoglobulin treatment in women with elevated circulating C56+ cells. Early Pregnancy 2000 Apr;4(2):90-8.

44. Robinson P, Anderson D, Brouwers M, et al. Evidence-Based Guidelines on the Use of Intravenous Immune Globulin for Hematologic and Neurologic Conditions. Transfusion Medicine Reviews 2007 Apr;21(2 Suppl 1):S3-S8.

45. Anderson D, Ali K, Blanchette V, et al. Guidelines on the Use of Intravenous Immune Globulin for Hematologic Conditions. Transfusion Medicine Reviews 2007 Apr;21(2 Suppl 1):S9-S56.

46. Feasby T, Banwell B, Benstead T, et al. Guidelines on the Use of Intravenous Immune Globulin for Neurologic Conditions. Transfusion Medicine Reviews 2007 Apr;21(2 Suppl 1):S57-S107.

47. Perlmutter SJ, Leitman SF, Garvey MA, et al. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder amd tic disorders in childhood. Lancet 1999 Oct 2;354(9185):1153-8.

48. Snider LA, Swedo SE. PANDAS: current status and directions for research. Mol Psychiatry 2004 Oct;9(10):900-7.

49. Leonard HL, Swedo SE. Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS). Int J Neuropsychopharmacol 2001 Jun;4(2):191-8.\

50. Kurlan R, Kaplan EL. The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) etiology for tics and obsessive-compulsive symptoms: hypothesis or entity? Practical considerations for the clinician. Pediatrics 2004 Apr;113(4):883-6.

51. Dodel R, Neff F, Noelker C, et al. Intravenous immunoglobulins as a treatment for Alzheimer’s disease: rationale and current evidence. Drugs. 2010 Mar 26; 70(5):513-528.

52. MICROMEDEX® Healthcare Series - DRUGDEX® Evaluations: Immune Globulin. March 18, 2010 . [Available at: http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS/F3BF43/DUPLICATIONSHIELDSYNC/0D10B8/ND_PG/PRIH/ND_B/HCS/SBK/2/ND_P/Main/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/0693/ContentSetId/31/SearchTerm/immune%20globulin%20/SearchOption/BeginWith ] Accessed February 28, 2019.

53. Shimoni Z, Niven MJ, Pitlick S, et al. Treatment of West Nile virus encephalitis with intravenous immune globulin. Emerg Infect Dis 2001;7:759.

54. ClinicalTrials.gov. Efficacy of High-dose Intravenous Immunoglobulin Therapy for Hyperbilirubinemia Due Rh Hemolytic Disease. [Available from: http://clinicaltrials.gov/ct2/show/NCT00288600?term=immunoglobulin&rank=5 ] [cited 31 Mar 2010]

55. ClinicalTrials.gov. A Phase III study evaluating safety and effectiveness of immune globulin intravenous (IGIV 10%) for the treatment of mild to moderate Alzheimer’s disease. [ Available from: http://clinicaltrials.gov/ct2/show/NCT00818662?term=immunoglobulin&rank=64 ] [ cited 31 Mar 2010]

56. ClinicalTrials.gov. Intravenous Immunoglobulins in Complex-regional Pain Syndrome (PAINLESS). [ Available from: http://clinicaltrials.gov/ct2/show/NCT00949065?term=complex+regional+pain+syndrome&rank=8 ] [ cited 31 Mar 2010]

57. ClinicalTrials.gov. Intravenous Immunoglobulins as Effective Treatment in Sydenham's Chorea. [ Available from: http://clinicaltrials.gov/ct2/show/NCT00615797?term=immunoglobulin&rank=20 ] [ cited 31 Mar 2010]

58. ClinicalTrials.gov. IVIG in the Treatment of Metastatic Cancers of the Prostate, Colon and Melanoma. [ Available from: http://clinicaltrials.gov/ct2/show/NCT00294476?term=IVIG&rank=20 ] [ cited 31 Mar 2010]

59. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117(16):4190-4207.

60. Provan D, Stasi R, Newland A, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010; 115 (2): 168-186.

61. Hughes RA, Wijkicks EF, Barohn R, et al. Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: immunotherapy for Guillain- Barre syndrome. Neurology. 2003;61(6):736-740.

62. Goodin DS, Frohman EM, Garmany GP, et al. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002 Jan 22;58(2):169-78.

63. Elovaara I, Apostolski S, van Doorn P, et al. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurologic diseases. European Journal of Neurology 2008; 15:893-908.

64. Gajdos P, Tranchant C, Clair B, et al; Myasthenia Gravis Clinical Study Group. Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin: a randomized double-blind clinical trial. Arch Neurol. 2005;62(11):1689-1693.

65. Rnager J, Ravnborg M, Hermansen I, Vorstrup S. Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis. Artif Organs. 2001;25(12):967-973.

66. Wolfe GI, Barohn RJ, Foster BM, et al; Myasthenia Gravis-IVIG Study Group. Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis. Muscle Nerve. 2002;26(4):549-552.

67. Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial. Neurology. 2007;68(11):837-841.

68. Whitington PF and Kelly S. Outcome of pregnancies at risk for neonatal hemochromatosis is improved by treatment with high dose intravenous immunoglobulin. Pediatrics 2008; 121 (6): e1615-e1621.

69. Neunert C, Wendy L, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011; 117: 4190-4207.

70. Provan D, Stasi R, Adrian C, et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010; 115: 168-186.

71. Hematology GRG. Milliman Care Guidelines [Internet] (16^th Edition).2012 Feb Accessed at: http://careweb.careguidelines.com/ed16/grg/0798010b.htm. [accessed 2012 Jul 9]

72. George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 2011;117:4190-4207.

73. Skeie GO, Apostolski S, Evoli A, et al. Guidelines for the treatment of autoimmune neuromuscular transmission disorders. Eur J Neurol. 2006;13(7):691-699.

74. Van den Bergh PY, Hadden RD, Bouche P, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies [trunc]. Eur J Neurol 2010 Mar;17(3):356-63

75. Patwa HS, Chaudhry V, Katzberg H, et al. Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2012 Mar 27;78(13):1009-15.

76. French CIDP Study Group. Recommendations on diagnostic strategies for chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Neurosurg Psychiatry 2008; 79: 115–118.

77. Donofrio PD, Berger A, Brannagan TH, et al. Consensus statement: The use of intravenous immunoglobulin in the treatment of neuromuscular conditions report of the AANEM ad hoc committee. Muscle Nerve. 2009;40:890-900.

78. Feasby T, Banwell B, Benstead T, et al. Guidelines on the use of intravenous immune globulin for neurologic conditions. Transfus Med Rev. 2007;21(2 suppl 1):S57-107.

79. Gajdos P, Tranchant C, Clair B, et al; Myasthenia Gravis Clinical Study Group. Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin: a randomized double-blind clinical trial. Arch Neurol. 2005;62(11):1689-1693.

80. Elovaara I, et al. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases: EFNS task force on the use of intravenous immunoglobulin in treatment of neurological diseases. European Journal of Neurology 2008;15(9):893-908.

81. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision. J Peripher Nerv Syst. 2010 Dec;15(4):295-301. doi: 10.1111/j.1529-8027.2010.00290.x.

82. Hahn AF, Bolton CF, Pillay N, et al. Plasma exchange therapy in chronic inflammatory demyelinating polyneuropathy. A double-blind, sham controlled, cross-over study. Brain 1996;119:1055–66.

83. The National Institute of Child Health and Human Developments Intravenous Immunoglobulin Study Group. Intravenous immune globulin for the prevention of bacterial infections in children with symptomatic human immunodeficiency virus infection. N Engl J Med. 1991 Jul 11;325(2):73-80.
84. Centers for Disease Control and Prevention. Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children. MMWR 2009;58(No. RR-11):11-12.

85. Wolfe GI, Barohn RJ, Foster BM, et al; Myasthenia Gravis-IVIG Study Group. Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis. Muscle Nerve. 2002;26(4):549-552.

86. Hughes RA, Wijdicks EF, Barohn R, et al; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: immunotherapy for Guillain-Barré syndrome: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2003;61(6):736-740.

87. Hughes RA, Swan AV, Raphael JC, Annane D, van Koningsveld R, van Doorn PA. Immunotherapy for Guillain-Barré syndrome: a systematic review. Brain. 2007;130(pt 9):2245-2257.

88. Bussel, JB et al. Antenatal management of alloimmune thrombocytopenia with Intravenous Immunoglobulin: A randomized trial of he low dose steroid to intravenous immunoglobulin. Am J Obstet Gynecol 1996; 174 1414-23.

89. Ratko TA, Burnett DA, The Univ Hospital Consortium Expert Panel for the Off-label Use of Polyvalent Intravenously Administered Immunoglobulin Preparations, et al. Recommendations for the off-label use of intravenously administered immunoglobulin preparations. JAMA 1995; 273:1865-70.

90. Ahmed AR, Spigelman Z, Cavacine LA et al. Treatment of pemphigus vulgaris with rituximab and intravenous immune globulin. N Eng J Med 2006; 1772-9

91. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114:297-316

92. Gottstein R, Cooke R. Systematic Review of intravenous immunoglobulin in haemolytic disease of the newborn. Arch Dis Child Fetal Neonatal Ed 2003; 88:F6-10

93. Anderson D, Ali K, Blanchette V, et al. Guidelines on the use of intravenous immune globulin for hematologic conditions. Transfus Med Rev. 2007;21(2 Suppl 1):S9-56.

94. 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 Suppl): S525-53.

95. Stasi R, Evangelista ML, Stipa E, et al. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thrombosis and Haemostasis 2008;99(1):4-13.

96. Amagai M, Ikeda S, Shimizu H, et al. A randomized, double-blind trial of intravenous immunoglobulin for pemphigus. J Am Acad Dermatol 2009; 60:595-602

97. Ahmed AR. Intravenous immunoglobulin therapy in the treatment of patients with pemphigus vulgaris unresponsive to conventional immunosuppressve treatment. J Am Acad Dermatol 2001; 45:679-90.

98. Hughes R, Bensa S, Willison H, Van den Bergh P, Comi G, Illa I, Nobile-Orazio E, van Doorn P, Dalakas M, Bojar M, Swan A; Inflammatory Neuropathy Cause and Treatment (INCAT) Group. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy. Ann Neurol. 2001 Aug;50(2):195-201.

99. Zinman L, Ng E, Bril V. IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial. Neurology. 2007 Mar 13;68(11):837-41.

100. Koski CL, Baumgarten M, Magder LS, et al. Derivation and validation of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy. Journal of the Neurological Sciences 2009; 277:1-8.

101. H.S. Patwa, V. Chaudhry, H. Katzberg, et al. Evidence-based guideline: Intravenous immunoglobulin in the treatment of neuromuscular disorders: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2012; 78; 1009-1015.

102. Sullivan KM, Storek J, Kopecky KJ, et al. A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery. Biol Blood Marrow Transplant 1996;2:44-53.

103. Alejandria MM, Lansang MA, Dans LF, Mantaring JB. Intravenous immunoglobulin for treating sepsis and septic shock. Cochrane Database Syst Rev 2002;CD001090.

104. American College of Obstetricians and Gynecologists (ACOG), Committee on Practice Bulletins -- Obstetrics. Thrombocytopenia in pregnancy. ACOG Practice Pattern No. 6. Washington, DC: ACOG; September 1999.

105. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. MMWR 2000;49(No. RR-10):1-128.

106. Emerson GG, Herndon CN, Sreih AG. Thrombotic complications after intravenous immunoglobulin therapy in two patients. Pharmacotherapy. 2002;22:1638-1641.

107. Department of Health (London). Clinical Guidelines for Immunoglobulin Use: Update to Second Edition. August, 2011.

108. Provan, Drew, et al. "Clinical guidelines for immunoglobulin use." Department of Health Publication, London (2008).

109. 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).

110. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 Evidence-based practice guidelines for immune thrombocytopenia. Blood April 2011; Vol 117 (16).

111. Jeffrey Modell Foundation Medical Advisory Board, 2013. 10 Warning Signs of Primary Immunodeficiency. Jeffrey Modell Foundation, New York, NY.

112. Centers for Disease Control and Prevention. Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children. MMWR 2009;58(No. RR-11):11-12.

113. Wimperis J, et al. National Health Service. Clinical Guidelines for Immunoglobulin Use: second edition update. Available from: https://www.gov.uk/​government/​uploads/​system/​uploads/​attachment_data/​file/​153238/​dh_131107.pdf

114. Koleba T, Ensom MH. Pharmacokinetics of intravenous immunoglobulin: a systematic review. Pharmacotherapy. 2006;26(6);813-827

115. Hodkinson J, et al. Therapeutic immunoglobulin should be dosed by clinical outcome rather than by body weight in obese patients. Clinical & Experimental Immunology, 2015; 181: 179–187.

116. Anderson C, Olson J, et al. Correlation of weight-based I.V. immune globulin doses with changes in serum immunoglobulin G levels. Am J Health-System Pharm. 2015. DOI 10.2146/ajhp140171. 1079-2082.

117. Shapiro R. Subcutaneous immunoglobulin therapy in obese patients with primary immunodeficiency: a retrospective analysis of administration by infusion pump or subcutaneous rapid push. 2013. Clinical and Experimental Immunology, 173: 365–371.

118. Leonard M, White D. Acute stroke with high-dose intravenous immune globulin. Am J Health-Syst Pharm. 2007; 64:1611-4.

119. Leonard M, Lehman M, Travis D, et al. Intravenous Immune Globulin (IVIG) A Review of Formulary Restrictions. Cleveland Clinic Pharmacotherapy Update From the Department of Pharmacy. Vol XI, No I January 2008.

120. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 2017 Mar;139(3S):S1-S46.

121. Privigen ( Immune Globulin Intravenous) [Prescribing Information]. CSL Behring LLC. Berne, Switzerland. March 2019.

122. Bivigam [package insert]. Biotest Pharmaceuticals. Boca Raton, FL. July 2019.

123. Flebogamma® 10% DIF [package insert]. Instituto Grifols. Barcelona, Spain. September 2019.

124. Flebogamma® 5% DIF [package insert]. Instituto Grifols. Barcelona, Spain. September 2019.

125. Gammagard Liquid [package insert]. Baxalta US Inc. Westlake Village, CA. June 2016.

126. Gammagard S/D [package insert]. Baxalta, US Inc. Westlake Village, CA. September 2016.

127. Gamunex®-C. [package insert]. Grifols Therapeutics, Inc. Research Triangle, NC. January 2020.

128. Gammaked [package insert]. Grifols Therapeutics, Inc. Research Triangle, NC. June 2018.

129. Gammaplex [package insert]. Bio Products Laboratory Ltd. Durham, NC. December 2016.

130. Octagam [package insert]. Octapharma USA, Inc. Hoboken, NJ. August 2018.

131. NCCN Drugs & Biologics Compendium (NCCN Compendium®) Management of Immunotherapy-Related Toxicities, Version 1.2018, February 28, 2019. National Comprehensive Cancer Network, 2019.

132. Postow, MA. Managing Immune Checkpoint-Blocking Antibody Side Effects. American Society of Clinical Oncology Education Book. 2015; 76-83.

133. Williams TJ, Benavides DR, Patrice KA. Association of Autoimmune Encephalitis with combined immune checkpoint inhibitor treatment for metastatic cancer. JAMA Neurol. 2016;73(8):928-933. doi:10.1001/jamaneurol.2016.1399.

134. Panzyga [package insert]. Octapharma USA, Inc. Hoboken, NJ. August 2018.

135. Clinical Pharmacology. ICIG. Available at https://www.clinicalkey.com/pharmacology/monograph/311?sec=monindi. Accessed March 2019.

136. AHFS Drug Information. Immune Globulin. Available athttp://online.statref.com/Document.aspx?docAddress=vnXD8fDmET1JHwjnz0SFPA!!&SessionId=2B59A14EPLIXOCWA&Scroll=1&goBestMatch=true&Index=2&searchContext=ivig|c0||10|1|0|0|0|0||c0#H&1&ChaptersTab&vnXD8fDmET1JHwjnz0SFPA!!&a277013&1. Accessed March 2019.

137. McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific statement for health professionals from the American Heart Association. Circulation 2017;135:e927-e999.

138. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol. 2017 Mar;139(3S):S1-S46.

139. Asceniv [package insert]. ADMA Biologics. Ramsey, NJ. April 2019

140. Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143-1238. doi: 10.1016/j.bbmt.2009.06.019. [PubMed 19747629]

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

90281
90283
90288
90291
90386

J1459
J1555
J1556
J1557
J1559
J1561
J1566
J1568
J1569
J1572
J1575
J1599