Intravenous Immune Globulin (IVIG) is a solution of human immunoglobulin
specifically prepared for intravenous infusion. Immunoglobulin contains a
broad range of antibodies that specifically act against bacterial and viral
antigens.  
  
The use of intravenous immune globulin should be reserved for patients with
serious defects of antibody function. The goal is to provide immunoglobulin G
(IgG) antibodies to those who lack them.IVIG infusion may have other effects
beyond simple antibiody replacement. Coverage will be provided for intravenous
immune globulin when it is used in treatment of the following conditions:

**1.Primary Humoral Immunodeficiency Syndromes  
  
** IVIG is indicated for the treatment of patients with primary
immunodeficiency syndromes such as common variable immunodeficiency (CVID),
congenital agammaglobulinemia (X-linked agammaglobulinemia), severe combined
immunodeficiency (SCID), X-linked immunodeficiency with hyperimmunoglobulin M
(IgM), and Wiskott-Aldrich syndrome to replace or boost immunoglobulin G
(IgG).  
  
Common variable immunodeficiency (CVID), also known as acquired
hypogammaglobulinemia, adult-onset hypogammaglobulinemia, and
dysgammaglobulinemia, is characterized by reduced serum immunoglobulins,
impaired antibody responses, and heterogenous clinical features. It is a rare
syndrome, affecting one in 50,000 to one in 200,000 people. In most patients,
the onset is in the second or third decade of life. The most common clinical
presentation of CVID is an increased susceptibility to infection. Because
patients with CVID are predisposed to chronic lung disease and pulmonary
deterioration as a result of chronic or subclinical infection, early
recognition of the diagnosis and initiation of the IVIG therapy are critical.
Patients with CVID can also develop a variety of autoimmune and inflammatory
disorders and are also at risk for inflammatory bowel disease.  
  
Once the diagnosis of CVID is suspected based on clinical presentation,
laboratory confirmation should be made. A low serum IgG level is the most
consistent laboratory abnormality in CVID, with most patients having
concurrent deficiencies of IgA and IgM. However, there are rare instances when
a patient will have normal IgG levels. Therefore, the serum immunoglobulin
measurement alone does not establish a diagnosis of CVID. A definitive
diagnosis of CVID is established when a patient does not demonstrate an
antibody response or rejection to immunization with protein antigens (e.g.,
tetanus) or carbohydrate antigens (e.g., pneumococcal capsular polysaccharides
such as Pneumovax).  
  
The following diagnostic evidence is required to support a diagnosis of CVID:

  * Laboratory reports demonstrating an IgG level of less than 400 mg/dl for the assay utilized, and lack of response to immunization (see below);

  
OR

  * An IgG level greater than or equal to 400mg/dl with evidence of recurrent severe infections with documented antibiotic therapy and lack of response to immunization (see below);
  * Laboratory reports demonstrating a lack of ability to produce an antibody response to a protein antigen (e.g., tetanus) or one of the polysaccharide antigens (e.g., Pneumococcal polysaccharide or H. Influenza type B). Two or more immunizations should have been given in the 12 months prior to laboratory assessment of antibody response. The exception maybe when a severe adverse reaction has occurred with the last immunization and two have been given over 12 month or longer interval. Pneumococcal titers are measured differently among different laboratories with some measuring 4, 5, 6, 12, or 14 serotypes. An adequate response of the serotypes tested should include a two to three fold increase in titers in at least 50 percent of the serotypes.

  
  
Reimbursement will not be provided for the initiation or continuation of
intravenous immune globulin therapy based solely on a low IgG value, there
must be a demonstrated lack of ability to produce an adequate antibody
response to protein or carbohydrate antigens. There is no scientific rationale
for IVIG therapy and it will be considered not medically reasonable and
necessary, when used in patients with normal humoral immunity but with
recurrent infections. The use of IVIG for recurrent viral upper respiratory
infection will not be considered medically reasonable and necessary.
Sinopulmonary disease which merits the use of IVIG is defined as a documented
pneumonia, bronchiectasis, chronic bronchitis, recurrent bacterial or
mycoplasma bronchitis, pneumonitis and documented episodes of acute bacterial
sinusitis requiring extensive and/or recurrent courses of antibiotics. The
goal of using IVIG therapy in this situation to prevent progressive lung
disease and avoid other serious bacterial infections including meningitis,
sepsis, solid organ abscess, osteomylitis, or other bacterial infection of
sufficient severity to merit hospitalization  
  
When IVIG is indicated in immunodeficient individuals (as defined above), with
recurrent or chronic bacterial sinusitis, the medical record must document
findings diagnostic of, or highly suggestive of, recurrent or chronic
bacterial sinus infection. Such findings may include, but are not limited to,
fever, unilateral purulent nasal discharge and unilateral facial pain."
Absence of these findings will not preclude the use of IVIG, however,
documentation will be considered insufficient to justify medical necessity
when antibiotic therapy is prescribed routinely during the first few days of
symptoms in the absence of these findings, or in the instance where antibiotic
therapy is prescribed by phone without the benefit of an examination by a
physician (or qualified non-physician practitioner). The fact that antibiotic
therapy is prescribed for an episode of sinusitis will not be considered, in
and of itself, evidence of bacterial sinus infection. IVIG is never indicated
and therefore not reasonable and necessary for the treatment of simple viral
rhinosinusitis, even in immunodeficient individuals and even if recurrent.
Recurrent rhinosinustis is defined as the occurrence of four or more episodes
of acute rhinosinustis per year with interim symptom resolution. Chronic
sinusitis is defined as an episode of rhinosinustis that persists for greater
than 12 weeks.  
  
Patients who have been receiving long term IVIG therapy for Primary Humoral
Immunodeficiency Syndromes may have undergone diagnostic testing in the remote
past, the results of which may no longer be available. Repeat testing for the
purpose of re-confirming the diagnosis is not necessary. Similarly, repeat
testing with new technology, not available at the time or original testing for
the purpose of diagnostic confirmation is also not necessary. The medical
record must document that the patient has been receiving long term IVIG
therapy .  
  
Dosage Guidelines:  
  
The dosing regimen for patients with CVID is not standardized, but is based
primarily on the clinical response. Generally, checking trough levels of IgG
and functional antibody levels are not medically necessary more frequently
than every 3-6 months. A patient will generally receive initial IVIG doses of
400-600 mg/kg every 3-4 weeks titrating the dose and interval to achieve serum
trough levels of at least 400 mg/dl or 300 mg/dl above the baseline IgG level.
Documentation should support the rationale for a serum trough level greater
than 300 mg above the baseline IgG. IVIG replacement in these patients is
usually life-long.  
  
Maintenance doses exceeding the 400-600 mg/kg range may be covered, but only
if the desired clinical response to 400-600 mg/kg is clearly documented as
inadequate as evidenced by serum trough levels below 400mg/dl.  
  
  

  * Congenital agammaglobulinemia (X-linked agammaglobulinemia) is an inherited deficiency that appears in the first 3 years of life and occurs in one out of 10,000 people. Quantitative immunoglobulins show marked deficits or absence of all five immunoglobulin classes. Peripheral blood B-lymphocytes are usually absent.
  * Severe combined immunodeficiency (SCID) is a rare and fatal inherited syndrome that has an incidence of approximately one in 1,000,000 people. The typical case involves an infant less than one year of age. The lymphocyte counts are significantly below normal, the levels of B- and T-lymphocytes are absent or below normal, the lymphocyte response to mitogen is absent or below normal, and the quantitative measurements of IgG, IgA, and IgM show marked deficits.
  * X-linked immunodeficiency with hyperimmunoglobulin M (IgM) is similar to X-linked agammaglobulinemia, however, these patients sometimes have lymphoid hyperplasia. The concentrations of serum IgG, IgA, and IgE are very low, whereas the serum IgM concentration is either normal or, more frequently, greatly elevated and polyclonal.
  * Wiskott-Aldrich syndrome is an X-linked recessive syndrome characterized by eczema, thrombocytopenia purpura with normal-appearing megakaryocytes but small defective platelets, and undue susceptibility to infection. Patients usually present during infancy. Survival beyond the teens is rare.

  
For congenital agammaglobulinemia (X-linked agammaglobulinemia), severe
combined immunodeficiency (SCID), X-linked immunodeficiency with
hyperimmunoglobulin M (IgM), and Wiskott-Aldrich syndrome, the dosage
variability is based on a patient's condition and disease type, providers must
adhere to the current clinical standard of practice and recommended dosage in
current literature. Any time there is a departure from the standard dosing,
the rationale for this must be documented in the medical record.  
  
Dosage Guidelines:

  * A patient will generally receive initial IVIG doses of 400-600 mg/kg every 3-4 weeks titrating the dose and interval to achieve serum trough levels of at least 500 mg/dl or 300 mg/dl above the baseline IgG level. IVIG replacement in these patients is usually life-long.
  * Maintenance doses exceeding the 400-600 mg/kg range may be covered, but only if the desired clinical response to 400-600 mg/kg is clearly documented as inadequate as evidenced by serum trough levels below 400mg/dl.

  
**  2\. **IVIG in Children with Human Immunodeficiency Virus (HIV) Disease who
do not have ITP**  
  
** IVIG may be medically necessary to reduce significant bacterial infections
when all three primary criteria and one of the secondary criteria are met:  
  
Primary criteria:  
  
1.Age less than 13 years  
2.IgG level less than 400 mg/dl  
3.Entry CD4+ lymphocyte cell count is greater than or equal to 200/mm3  
  
Secondary criteria:  
  
1.Two or more bacterial infections in a 1-year period despite antibiotic
chemoprophylaxis with TMP-SMZ or another active agent  
  
2.The child has received two doses of measles vaccine and lives in a region
with a high prevalence of measles  
  
3.The child has chronic bronchiectasis whose immunological response is
suboptimal to antimicrobial and pulmonary therapy  
  
4.The child has immune abnormalities with symptomatic or asymptomatic HIV, as
evidenced by a lack of ability to produce an antibody response to immunization
with protein antigens (e.g., tetanus) or carbohydrate antigens (e.g.,
pneumococcal capsular polysaccharides. such as, Pneumovax).  
  
Dosage guideline: For pediatric (HIV) Infection is 400-mg/kg body weight given
every 28 days to prevent serious bacterial infection. Claims reimbursed with
dosages in larger or decreased frequency of administration are subject to
medical review, like any service.  
  
5\. Neurological Disorders  
  
IVIG is indicated for the treatment of patients with neurological disorders
such as Guillain-Barre' syndrome, relapsing-remitting multiple sclerosis,
chronic inflammatory demyelinating polyneuropathy (and variant syndromes such
as Multifocal Motor Neuropathy), myasthenia gravis, refractory polymyositis,
and refractory dermatomyositis. However, it is noted that not all patients
with these diagnoses require treatment with IVIG.  
  
IVIG therapy will only be considered medically reasonable and necessary for
these neurological disorders when there is evidence of rapid progression of
the disease or relapse or when other forms of treatment have failed or are
contraindicated. The physician must document the rationale for the choice of
therapy and consider disease activity, concurrent illness, venous access, side
effects and drug availability in the decision of which therapy to prescribe
and in what sequence.  
  
For each of these diseases, the diagnosis of the disorder must be unequivocal.
There must be clinical (history, quantitative examination),
electrophysiological motor-sensory nerve conductions, electromyography (EMG),
cerebrospinal fluid (CSF), and when necessary, biopsy (muscle-nerve) data to
support the diagnosis. This must be clearly documented in the medical record
and conclusions based upon this information must be consistent with accepted
standards of care, in order for IVIG treatment to be considered reasonable and
necessary.  
  
Once IVIG treatment is initiated, meticulous documentation of progress is
required. If there is initial improvement, and continued treatment is
necessary, quantitative assessment to monitor the progress is required (e.g.,
ADL measurements). Changes in these parameters must be clearly documented.
Subjective or experiential improvement alone is insufficient to either
continue IVIG or to expect coverage.  
  
There must be evidence of an attempt to wean the dosage when improvement has
occurred. This "weaning" may be either a reduction in the frequency of
administration and/or a reduction in dosage. There must be an attempt to stop
the IVIG infusion if improvement is sustained with dosage reduction. If
improvement does not occur with IVIG, then IVIG therapy is not indicated and
should be discontinued. Generally, objective clinical improvement should occur
within three months of the start of the IVIG therapy. If objective clinical
improvement does not occur within this time frame, further administration of
IVIG will be considered not medically reasonable and necessary.  
  
Maintenance dosing for neurologic disorders should be individualized such that
the minimum dose required to maintain clinical response is used for those
patients who require chronic therapy. Where it is necessary to administer
larger doses than noted in the dosage guidelines, the medical record must
document that such higher doses are required to maintain response. Such
documentation must include evidence that lower doses are not efficacious in
producing the needed functional response for any individual patient.  
  

  * Guillain-Barre' syndrome is an acute, frequently severe, and fulminant inflammatory demyelinating polyneuropathy that occurs at a rate of approximately one case in a million per month. An infection generally precedes the onset of neuropathy by 1 to 3 weeks. A small proportion occurs within 1 to 4 weeks of a surgical procedure. The clinical features include ascending paralysis, hyporeflexia or areflexia, parasthesias, and elevated spinal fluid protein levels. Pain, particularly in the back and extremities may be reported in up to two thirds of cases. Electrophysiologic evidence includes prolonged or absent F waves and absent H reflexes. Increased distal latencies, conduction blocks with temporal depression of motor responses also occur followed by slowing of nerve conduction velocities. Intravenous administration of high-dose immunoglobulin given over 5 days has been proven effective.

  
Dosage Guidelines: 1,000 mg/kg body weight daily for two days; or 400 mg/kg
body weight daily for five days.  
  
  

  * Multiple Sclerosis that is relapsing-remitting is characterized by unpredictable recurrent attacks of neurological dysfunction. Attacks generally evolve over days to weeks and may be followed by complete, partial, or no recovery. Patients with a relapsing-remitting course experience no progression of neurological impairment between attacks. The age of onset is generally between 15 and 60 years. IVIG has not as yet been shown to be clinical benefit in patients with progressive forms of multiple sclerosis. IVIG will be covered for the treatment of multiple sclerosis only when there is clear documentation of relapsing remitting disease.

  
Dosage Guidelines: Usual dosing is 200-400 mg/kg every 4 weeks.  
  

  * Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) includes a group of chronic progressive or relapsing, inflammatory demyelinating peripheral neuropathies that are manifested by physiological abnormalities such as partial conduction block,slowed nerve conduction velocities manifested by prolonged distal motor latencies and/or delayed or absent F waves, or dispersion of compound muscle action potentials. Clinical features include chronic progressive or relapsing symmetric weakness with sensory loss and high spinal fluid protein levels. In addition, IVIG may be approved for CIDP patients, who had no response or an inadequate response to corticosteroids, who have experienced unacceptable side effects to the use of corticosteroids and dosage reduction is not clinically feasible or have contraindications to steroids. The physician will be required to substantiate the contraindication(s) in the medical record.

  
  
Dosage Guidelines for:  
  

  * Initial therapy - 400 mg/kg body weight per day for five days
  * Maintenance therapy - 250-400 mg/kg body weight no more frequently than every two weeks.

  
**  6\. ** Myasthenia gravis is a disorder of neuromuscular transmission
characterized by fluctuating weakness and fatigability. It is attributed to
blockage of the acetylcholine receptor at the neuromuscular end-plates by
anti-acetylcholine receptor autoantibodies. The diagnosis of myasthenia gravis
is confirmed by a positive Tensilon test. Anticholinesterase drugs or
thymectomy are generally the first treatments for this condition  
  
IVIG is indicated in those patients with myasthenia gravis who have failed to
respond to, or have intolerable side effects to acetylcholinesterase
inhibitors, are either refractory to corticosteroids over a 6 week period;
have been unable to successfully taper corticosteroids below moderately high
doses; or develop severe side effects due to steroid therapy; and have also
failed at least one immunosuppressive agent (e.g., azathiprime, Methotrexate,
cyclophosphamide, cyclosporine). Thymectomy must be considered in patients who
have evidence of thymoma prior to the use of IVIG. IVIG will be considered
medically reasonable and necessary as a first line therapy for Myasthenic
crisis or preoperatively for planned thymectomy. Length of treatment with IVIG
will vary due to the remittent and recurrent nature of this condition.  
  
Dosage Guidelines: At this time, there is no clearly established dozing
regimen, although many studies have reported success with a dose of 400 mg/kg
weight per day for five days.  
  
 **7.** Polymyositis and dermatomyositis are conditions in which the skeletal
muscle is damaged by a nonsuppurative inflammatory process dominated by
lymphocytic infiltration. Polymyositis begins acutely or insidiously with
muscle weakness, tenderness, and discomfort. Proximal muscles more often than
distal muscles are affective. Dermatomyositis involves characteristic skin
changes that may precede or follow the muscle syndrome and include a localized
or diffuse erythema, maculopapular eruption, scaling eczematoid dermatitis, or
rarely, an exfoliative dermatitis. The classic lilac-colored (heliotrope)
usually manifested on the eyelids, bridge of the nose, cheeks (butterfly
distribution), forehead, chest, elbows, knees and knuckles, and around the
nailbeds. Periorbital edema is frequent.  
  
Diagnostic studies to support a diagnosis of polymyositis or dermatomyositis
include an elevated creatine phosphokivase (CPK), an abnormal electromyography
(EMG), and/or an abnormal muscle biopsy. The differential diagnosis of
polymyositis and dermatomyositis includes other entities which may cause
muscle weakness including drug induced myopathy, necrotizing myopathy,
hypothyroidism, HIV infection, myasthenia gravis, inherited metabolic
myopathies and the muscular dystrophies. Diagnostic studies, along with the
history and physical examination must clearly document the diagnosis to be
polymyositis or dermtomyositis.  
  
IVIG is indicated in those patients with polymyositis or dermatomyositis who
are either refractory to corticosteroids over a 6 week period administered as
Prednisone 1 mg/kg or equivalent; have been unable to successfully taper
corticosteroids below moderately high doses even with the addition of other
immunosupressive agents; or develop severe side effects due to steroid
therapy; and have also failed at least one immunosuppressive agent (e.g.,
azathioprime, Methotrexate, cyclophosphamide, cyclosperine). Patients who fail
to show a response to initial therapies are considered to have resistant
disease. Resistant disease is defined by a lack of normalization of the serum
creatine kinase (CK) by 4-6 weeks and/or a failure to regain muscle strength
in three months. Before treatment with IVIG, consideration should be given to
alternative diagnoses. Length of treatment with IVIG will vary due to the
remittent and recurrent nature of these conditions. The need for continuation
of IVIG must be documented and would be demonstrated by continued decreased
muscle strength, elevated CPKs, and/or EMG abnormalities.  
  
Dosage Guidelines: 1,000 mg/kg body weight daily for two days every four weeks
or 400mg/kg body weight for five days every four weeks in patients intolerant
of high-dose therapy.  
  
Note: For patients who are unable to tolerate corticosteroid or
immunosuppressive agents, or in the rare instance that these agents are
contraindicated for the patient, treatment for polymyositis or dermatomyositis
will be covered only if medical record documentation clearly indicates the
reason that the patient cannot take the corticosteroid or immunosuppressive
agent  
  
 **Other Disorders**  
  
 **a. Chronic Lymphocytic Leukemia**  
  
Chronic lymphocytic leukemia is a disorder of accumulation of mature-appearing
lymphocytes in blood marrow and other organs. The symptoms usually develop
gradually and include fatigue, shortness of breath with activity, weight loss,
or frequent infections of the skin, lungs, kidneys, or other sites. Recurrent
infections are a frequent complication.  
  
IVIG is indicated for the prevention of recurrent bacterial infections and an
immunoglobulin G (IgG) level of less then 600 mg/dl in patients with
hypogammaglobulinemia associated with B-cell chronic lymphocytic leukemia
(CLL) in order to help correct the patient's immunity deficiency.  
  
Dosage guideline for this disease process is 400 mg/kg body weight given every
3 - 4 weeks.  
  
**b. Hematopoetic Stem Cell Transplantation (HSCT)**  
  
IVIG is indicated to prevent the risk of acute graft-versus-host disease,
associated interstitial pneumonia (infectious or idiopathic) and infections
(e.g., cytomegalovirus infections [CMV], varicella-zoster virus infection, and
recurrent bacterial infection) after HSCT in patients 20 years of age or older
during the first 100 days after transplantation. It is not indicated in HSCT
patients younger than 20 years of age, nor is it recommended for autologous
transplants.  
  
Dosage guideline is 500 mg/kg body weight given on days -7 and -2 pre-
transplantation, then weekly through day 90 post-transplantation.  
  
 **c .Kawasaki Disease (mucocutaneous Lymph Node Syndrome)**  
  
Kawasaki disease is an acute childhood vasculitis, the diagnosis of which is
made based on clinical criteria. These criteria include fever of at least five
(5) days duration and at least four (4) of the following: (1) polymorphic
exanthem, (2) changes in the oropharynx such as fissured lips and strawberry
tongue without discrete lesions, (3) changes in the extremities such as edema
of the hands and feet and erythema of the palms and soles, (4) bilateral
conjunctival infection without exudate, and (5) cervical lymphadenopathy,
often singular and unilateral. IVIG is indicated for the treatment of Kawasaki
disease when used in conjunction with aspirin.  
  
Dosage guideline: 400 mg/kg body weight for four (4) consecutive days or a
single infusion of 2,000 mg/kg body weight.  
  
 **d. Autoimmune Hemolytic Anemia**  
  
Autoimmune hemolytic anemia is an acquired anemia induced by the binding of
autoantibodies and/or a complement to the red cells. Signs and symptoms may
include, but are not limited to, weakness, fatigue, exertional dyspnea,
pallor, jaundice, tachycardia, splenomegaly, hepatomegaly, and anemia. In the
majority of patients, this disease can be controlled by steroid therapy alone,
by splenectomy or by a combination of these.  
  
In this condition, intravenous immune globulin is indicated only for those
patients who have failed to respond to other forms of therapy and/or require
rapid cessation of hemolysis due to severe or life threatening manifestations
of this condition. Other therapies showing treatment efficacy include
corticosteroids, immunosuppressive and cytotoxic agents and monoclonal
antibodies such as Rituximab. Duration of treatment is generally a short
course of 3-5 weeks. Realizing dosage may vary based on patient's individual
situation; dosage must be in keeping with the recommended current literature
and standard of practice.  
  
Dosage guidelines: Realizing dosage may vary based on a patient's individual
situation, the dosage must be in keeping with the recommended dosage in
current literature and the standard of practice. Any time there is a departure
from the standard dosing, the rationale for this must be documented in the
medical record.  
  
 **e. Autoimmune Neutropenia**  
  
Autoimmune neutropenia is a hematologic disorder in which there is a decreased
number of neutrophilic leukocytes in the blood due to an autoimmune mechanism.
The disease is usually benign and self-limiting, and treatment beyond
antibiotics is not frequently required. Occasionally, however, it is marked by
repeated infection. IVIG may be recommended for the treatment of an absolute
neutrophil count less than 800mm with recurrent bacterial infections.  
  
Dosage guidelines are 1 to 2 g/kg of IVIG over 1 to 2 days.  
  
**f. Autoimmune Mucocutaneous Blistering Diseases**  
  
Effective October 1, 2002, IVIG is covered for the treatment of biopsy-proven
(1) Pemphigus Vulgaris, (2) Pemphigus Foliaceus, (3) Bullous Pemphigoid, (4)
Mucous Membrane Pemphigoid (a.k.a., Cicatricial Pemphigoid), and (5)
Epidermolysis Bullosa Acquista for the following patient subpopulations:  
  
1\. Patients who have failed conventional therapy such as corticosteroids
(prednisone at not less than 1 mg/kg or equivalent), azathioprine or
mycophenolate mofetil;  
  
2\. Patients in whom conventional therapy is otherwise contraindicated; or  
  
3\. Patients with rapidly progressive disease in whom a clinical response
could not be affected quickly enough using conventional agents. In such
situations IVIG therapy would be given along with conventional treatment(s)
and the IVIG would be used only until the conventional therapy could take
effect.  
  
Dosage guidelines: 2,000 mg/kg body weight per month divided into 1 to 5
doses.  
  
In addition, IVIG for the treatment for autoimmune mucocutaneous blistering
diseases must be used only for short-term therapy and not as a maintenance
therapy.  
  
 **g. Multiple Myeloma**  
  
IVIG is indicated in patients with multiple myeloma to reduce the incidence of
recurrent bacterial infection when the patient is in the plateau phase of the
disease and there is evidence of immunodeficiency as indicated by a serum IgG
level <600mg/dl and a history of one documented, serious bacterial infection
requiring IV antibiotic therapy in the previous six months or two or more such
infections in the previous one year. IVIG will also be considered medically
necessary when there has been a failure to mount an appropriate IgG humoral
response to pneumococcal vaccine. IVIG therapy is not considered medically
reasonable and necessary during primary induction chemotherapy or during a
relapse of the disease  
  
  
IVIG is considered medically reasonable and necessary for the following off-
label indications:  
  

  * Stiff-man syndrome. Please refer to the utilization guidelines and documentation requirements for specific criteria related to coverage.
  * Hypogammaglobulinemia with NNI (non neutropenic infection) induced by certain agents (All criteria must be met):

1\. Recent treatment with rituximab in combination with cytotoxic chemotherapy  
2\. Laboratory proven hypogammaglobulinemia and an absolute neutrophil count
over 1,000.  
3\. Acute infection requiring hospitalization or an infection lasting over 2
weeks in spite of antibiotics or an infection relapsing immediately after
discontinuation of antibiotics.  
4\. Dose: 400-600 mg/kg one time that can be repeated at a standard interval
based on laboratory assessment of IG levels and persistence of non neutropenic
infection.

**h. Chronic Graft versus Host Disease (GVHD)**



IVIG is indicated in patient with chronic GVHD who meet all of the following
criteria



  1. Laboratory proven hypogammaglobulinemia with IgG levels <400 mg/dl.

  2. At least one acute infection requiring hospitalization and/or parenteral antibiotics

  3. Confirmed diagnosis of chronic GVHD

  4. At least 100 days post transplant.





  

Expansion of coverage to treat secondary hypogammaglobulinemia to any
medication that may cause this laboratory finding

The literature reviewed shows the following evidence



  1. There is an association between the administration of certain pharmaceuticals and the development of hypogammaglobulinemia.

  2. Not all forms of secondary hypogammaglobulinemia confer an increased risk of infection

  3. There is insufficient evidence to conclude that IVIG reduces the incidence or severity of infection in patients with drug induced secondary hypogammaglobulinemia.





Adding coverage for IVIG for hematopoietic stem cell transplantation (HSCT)



  1. The evidence is sufficient to conclude that the complications of stem cell transplantation are independent of the source of stem cells.





Adding coverage for IVIG for hypogammaglobulinemia for Graft vs. Host Disease
(GVHD)



  1. There is sufficient evidence to conclude that patients who require ongoing immunosuppression for the treatment of chronic GVHD are at increased risk when compared to their peers who do not require such treatment.

  2. There is sufficient evidence that such patients who are hypogammaglobulinemic (IgG < 400 mg/d)  and have experienced one serious infection may benefit from treatment of IVIG

  3. There is insufficient evidence that prophylactic treatment of HSCT patients with IVIG provides a benefit in the absence of hypogammaglobulinemia

  

  
  
  


1.Use of IVIG for the treatment of secondary hypogammaglobulinemia induced by
various medications.



While evidence from the peer reviewed medical literature documents an
association between various agents which suppress the immune system and low
immunoglobulin levels, the literature does not address whether this finding
equates to a higher incidence of serious and/or life threatening infections or
that the administration of immune globulin offers a beneficial effect by
reducing either the frequency of said infections, or the morbidity/mortality
associated with them



2.Use of IVIG for hypogammaglobulinemia associated with hematopoetic stem cell
transplant (HSCT).

The Infectious Disease Society of America (IDSA) in their guideline for
preventing infectious complications among HSCT recipients, defines HSCT to
include any stem cell transplant, regardless of type or source.  While there
are differences in the risks and complications of HSCT between different
sources, the effects on immune function are similar.  In light of this, CGS
will no longer cover indications for bone marrow transplant (BMT) recipients
only, but will extend the same coverage currently in place of BMT recipients,
to all HSCT receipients.





3\. Use of IVIG  for hypogammaglobulinemia associated with complications of
HSCT such as graft vs. host disease (GVHD).



The ISDA guidelines provides a summary of evidence which supports that risk of
infection is, among other things, related to the presence or absence of GVHD.
Patients with chronic GVHD, who require ongoing immunosuppressive therapy to
prevent complications of GVHD, may have ongoing impaired immunity as
demonstrated by any number of objective tests.  This being said, the ISDA does
not recommend routine administration of IVIG during the first 100 days post
transplant and indicates that IVIG treatment as prophylaxis "may be
considered" in patients with IgG levels <400 mg/dl.  We note the quality of
evidence on their scale (graded CIII) does not meet the reasonable and
necessary criteria of 1862(a)(1)(A) which supports the decision not to add
this indication as covered.  The same applies to routine prophylaxis in the
absence of confirmed hypogammaglobulinemia in patients >100 days post
transplant.  There is however, support for the use of IVIG in patients with
chronic GVHD with confirmed hypogammaglobulinemia (IgG < 400 mg/dl) and who
have experienced at least one serious infection.