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This article defines coding and coverage
for intravenous immune globulin (IVIG) including off-label indications.
National Government Services Local Coverage Determination (LCD) “Coverage
of Drugs and Biologicals for Label and Off-Label
Uses” allows coverage for off-label indications only if the United States
Pharmacopeia Drug Information (USP-DI), the American Hospital Formulary
Services (AHFS) and/or Thomson Healthcare DrugPoints®
(as described in the LCD) define such indications or if National Government
Services has published an article or LCD expanding such coverage. Providers
may request approval for additional off-label indications by submitting
this request in writing with supporting medical literature. The
aforementioned National Government Services LCD, which describes the requirements
for such a request, can be accessed on our contractor Web site at
www.NGSMedicare.com or on the Medicare Coverage Database at www.cms.hhs.gov/mcd.
Abstract:
Intravenous immune globulin is a sterile solution of human immunoglobulins specifically prepared for intravenous
infusion. Immunoglobulin contains a broad range of antibodies that
specifically act against bacterial and viral antigens.
Indications:
The use of intravenous immune globulin should be reserved for patients with
serious defects of antibody function. The goal is to provide immune
globulin to those who lack it. Medicare will provide coverage of
intravenous immune globulin when it is used in the treatment of the
following conditions:
- Primary humoral immunodeficiency:
- Congenital agammaglobulinemia,
- Common
variable immunodeficiency,
- Wiskott-Aldrich
syndrome,
- X-linked agammaglobulinemia, or
- Severe
combined immunodeficiency.
Blood level results, which demonstrate a significant deficiency in gamma
globulin levels, must be drawn before the initial treatment. A serum trough
IgG level should be measured every 3 months,
before the infusion, and the dose of intravenous immune globulin adjusted
accordingly. Infusions are usually given every 4 weeks, but the interval
should be adjusted, depending on the serum trough IgG
concentrations and the patient’s clinical condition. Serum trough levels
should be maintained at 400-600mg/dl, a value close to the lower limit of
normal. Rarely does a patient need his or her serum trough level greater
than 600 mg/dl. If greater levels are needed, documentation should support
the rationale.
- Recurrent severe infection and
documented severe deficiency or absence of IgG
subclass.
For IgG subclass deficiency, a serum IgG subclass trough level should be monitored at
least every three months prior to the dose of intravenous immune
globulin, along with clinical progress of signs and symptoms for which
intravenous immune globulin therapy is required.
- Clinically significant
functional deficiency of humoral immunity as
evidenced by documented failure to produce antibodies to specific
antigens and a history of recurrent infections.
For functional deficiency, the deficient antibody (ies)
should be monitored at least every 3 months, prior to the dose of
intravenous immune globulin, along with clinical progress of signs and
symptoms for which intravenous immune globulin therapy is required.
- Immune
thrombocytopenic purpura (ITP):
Acute ITP:
- Management
of acute bleeding due to severe thrombocytopenia (platelet counts
less than 30,000/µl); or
- To increase
platelet counts prior to invasive major surgical procedures (e.g., splenectomy); or
- In patients
with severe thrombocytopenia (platelet counts less than 20,000/µl)
considered to be at risk for intracerebral
hemorrhage.
Dosage guidelines:
- 1,000 mg/kg
body weight given on 1 or 2 consecutive days; or
- 400 mg/kg
body weight given on each of 2-5 consecutive days
Chronic refractory ITP:
IVIG is indicated for chronic ITP only when all of the following conditions
are met:
- Prior
treatment with corticosteroids and splenectomy;
and
- Duration of
illness less than 6 months; and
- Age of 10
years or older; and
- No
concurrent illness/disease explaining thrombocytopenia; and
- Platelet
counts persistently at or below 20,000/µl.
Dosage guidelines:
- Initial - 1
or 2g/kg body weight (total cumulative dose) given in equal amounts
over 2-5 days
- Maintenance
- 800 - 1,000 mg/kg body weight administered no more frequently than
every 2-6 weeks as determined by serial platelet counts.
- Chronic lymphocytic leukemia with associated hypogammaglobulinemia:
To initiate intravenous immunoglobulins for
this disease, the IgG level should be less
than 600 mg/dl, or there should be evidence of specific antibody
deficiency and the presence of repeated bacterial infections.
- Symptomatic
human immunodeficiency virus (HIV) in patients less than 13 years of
age, who are immunologically abnormal with
CD4+ lymphocyte count of 200/mm 3 or greater.
- Bone marrow
transplantation:
Indications for intravenous immunoglobulin would include:
- The
transplantation was for a Medicare covered indication; and
- The patient
is 20 years of age or older; and
- The patient
was seropositive for cytomegalovirus (CMV)
before transplantation; or
- The patient
was seronegative, had seronegative
marrow donors, and was undergoing allogeneic
transplantation for hematologic neoplasms.
Dosage guidelines:
- The normally
recommended dose of IgG is 500mg/kg,
- Treatment
would begin 7 days prior to the transplant and would be repeated on
day 2 before transplantation,
- Following transplantation,
treatment would be repeated weekly for 90 days
- Solid organ
transplantation:
Indications for intravenous immunoglobulin would include:
- The
transplantation was for a Medicare covered indication; and
- The patient
was seronegative for cytomegalovirus (CMV)
before transplantation; and the donor is seropositive.
- Kawasaki disease (mucocutaneous lymph node syndrome):
Acute and chronic inflammatory demyelinating
polyradiculoneuropathy, Guillain-Barre
syndrome, myasthenia gravis, immune thrombocytopenic purpura in pregnancy, multifocal
motor neuropathy (MMN), and dermatomyositis.
It should be noted that not all patients with these diseases require
treatment with IVIG. IVIG may be recommended for these conditions in
the following situations:
- When there
is difficulty with venous access for plasmapheresis;
or
- Other
therapy has failed or is contraindicated; or
- For rapidly
progressive forms of these diseases.
- Immune
thrombocytopenic purpura in pregnancy:
Pregnant women with this disease are at risk for delivering
thrombocytopenic infants. Protection of the fetus becomes an important
consideration in management of a pregnant woman with immune
thrombocytopenic purpura. Intravenous
immunoglobulin can be recommended in any of the following cases:
- Pregnant
women who have previously delivered infants with autoimmune
thrombocytopenia;
- Pregnant
women who have platelet counts less than 75,000/mm 3 during the
current pregnancy; or
- Pregnant
women with past history of splenectomy.
- Treatment of
autoimmune mucocutaneous blistering
diseases:
IVIG is covered for treatment of the following biopsy-proven
conditions:
- Pemphigus vulgaris,
- Pemphigus foliaceus,
- Bullous pemphigoid,
- Mucous
membrane pemphigoid (a.k.a., cicatrical pemphigoid),
or
- Epidermolysis bullosa acquisita
Patients must meet at least one of the following criteria:
- Failed
conventional therapy,
- Conventional
therapy is contraindicated, or
- Have rapidly
progressive disease in which a clinical response could not be
affected quickly enough using conventional agents. In these
situations, IVIG therapy would be given along with conventional
treatment(s) and the IVIG would be used only until conventional
therapy could take effect.
In addition, IVIG for the treatment of autoimmune mucocutaneous
blistering disease must be used only for short-term therapy and not as a
maintenance therapy (CMS Publication 100-03, Medicare National
Coverage Decisions Manual, Chapter 1, Section
250.3).
- Scleromyxedema is covered for
patients whose treatment with more traditional measures has failed.
- Humoral or vascular
allograft rejection.
- Hemolytic uremic
syndrome.
- Hemolytic anemia:
Patients 18 years of age or younger with hemolytic anemia and patients
with hepatomegaly or hepatosplenomegaly
will be considered for coverage on an individual consideration basis.
Documentation of hepatomegaly or hepatosplenomegaly must be kept in the chart.
Claims for infusion of IVIG for patients with hemolytic anemia, over
18 and without hepatomegaly or hepatosplenomegaly, or with splenomegaly
alone will be denied as not medically necessary.
- Polymyositis and dermatomyositis:
- The patient
must be unresponsive to steroids and immunosuppressants;
or intolerant to steroids and/or immunosuppressives;
or have serious side effects from steroids and/or immunosuppressives.
The IVIG will be used to decrease the doses of other drugs that are
needed for treatment.
- The
patient’s record must show that there was a measurable response
within 6 months of use of IVIG, or its use will no longer be
considered medically necessary.
- Sensitized
renal transplant recipients:
IVIG and/or plasmapheresis are used in
several sequential treatments pre or post transplant to help with
patients sensitized to living or cadaveric
organ donors. This attempts to modify panel reactive antibody level
(PRA), a crossmatch result, with prevention
and/or treatment of organ rejection.
- Sepsis
- Kidney
disease
- Cytomegalovirus
infection
- von Willebrand disorder
- Uveitis
- Toxic shock
syndrome
- Respiratory syncytial virus infection
Indications expanded by this
Article:
In many neurological illnesses, IVIG has been of benefit although such use
is off-label from FDA approved indications. Studies with acceptable or
sound methodological bases have shown that IVIG can halt and reverse
progression in the conditions listed above. In a few neurological
conditions, such as multifocal motor neuropathy
(MMN), and dermatomyositis, IVIG may be of
benefit. It is well to remember that some of the more recently defined
conditions do not have a specific ICD-9-CM code. We find there is
potential for misunderstanding and lack of clarity with regard to IVIG
usage in neurological diseases. Therefore, before undertaking this therapy,
please direct attention to the following requirements.
The diagnosis of the neurological disorder must be well supported in the
medical record documentation. There must be a clinical history with a
physical examination; electrophysiological motor-sensory nerve conduction
study, e.g., electromyography (EMG); cerebral spinal fluid (CSF), serum immunoprotein, and where necessary, biopsy
(muscle-nerve) data to support the diagnosis. The reason for choosing IVIG
as a treatment must be well supported on review of records. Previous
treatment failures with alternative agents should be documented.
After initiation of treatment, if there is initial improvement, and
continued treatment is necessary, then quantitative assessment to monitor
progress is required. Quantitative monitoring may use any accepted measure,
such as medical research council (MRC) scale and activities of daily living
(ADL) measurements. Changes in these measures must be clearly documented.
Subjective or experiential improvement alone is insufficient to support
continued use of IVIG.
Clinical monitoring takes clear precedence over laboratory monitoring. If
clinical improvement is evident, then laboratory monitoring solely to guide
IVIG therapy will not be medically necessary.
There must be an attempt made to wean the dosage when improvement has
occurred. 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 infusion should not continue.
In cases of MMN and dermatomyositis, inclusion
body myositis (IBM) and polymyositis
(PM), coverage determination will require individual consideration.
Dosage Guidelines:
- 2g/kg is a
common initial empirical dose
We leave the choice of division of total initial dosage and rate of
infusion to the treating physician. A decision to provide maintenance
infusions must be justified through clear documentation as delineated
above. We do not advocate a particular maintenance dosage schedule, but we
do require literature support for a specific schedule chosen for each
patient.
Stiff-man syndrome may be treated with IVIG when/if standard
treatment with Diazepam is no longer effective.
Limitations:
IVIG coverage benefits will not be extended for the treatment of:
- Erythroblastosis,
- Secondary
thrombocytopenia,
- Epilepsy,
- Amyotrophic
lateral sclerosis (ALS),
- Paraneoplastic neurological
syndromes,
- Undiagnosed
neuropathy, or
- Weakness and
malignancies with no causal link to coexisting neurological
dysfunctions.
Claims submitted for procedures performed at unusually frequent intervals
or high dosages may be reviewed for medical necessity.
If coverage of IVIG is denied, the administration and pre-administration
services associated with IVIG will also be denied.
Documentation Requirements:
Medical record documentation maintained by the treating physician must
clearly document the medical necessity to initiate intravenous immune
globulin therapy and the continued need thereof. Required documentation of
medical necessity should include:
- history and
physical;
- office/progress
notes(s);
- test results
with written interpretation;
- accurate
weight in kilograms should be documented prior to the
infusion, since the dosage is based on a mg/kg dosage;
- documentation
of prior treatment therapies (where appropriate or
referenced by this policy);
- evidence of
blood level results demonstrating a significant deficiency
in gammaglobulin levels prior to initial
treatment (where appropriate
or referenced by this policy);
- history of
recurrent and severe infections;
- current
effectiveness of IVIG therapy; and
- goals and/or
treatment plan
Documentation must be available to Medicare upon request.
Coding Guidelines:
General Guidelines for claims submitted to Carriers or
Intermediaries:
- When
administering IVIG to patients over continuous days, providers should
report each day’s dosage on a separate line of coding, using the
appropriate date of service with the units reported in the NOS field
of the claim form.
- When
separately identifiable evaluation and management services are
provided and documented on the same day as intravenous administration,
they may be billed using modifier 25.
For claims submitted to the carrier:
For providers who bill the carrier, IVIG is payable in an office setting
(11) and independent clinic (49).
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