Clinical UM Guideline
|Subject:||Immune Globulin (Ig) Therapy|
|Guideline #:||CG-DRUG-09||Current Effective Date:||01/01/2016|
|Status:||Reviewed||Last Review Date:||11/05/2015|
This document addresses immune globulin or immunoglobulin (Ig), which is a blood product that is given for the treatment of primary immunodeficiency diseases featuring low or dysfunctional antibody levels and for certain inflammatory, autoimmune and other diseases featuring low antibody levels. Ig is also used for removal of harmful antibodies and for blocking damage from immune cells. Ig may be administered intravenously (IVIG) or subcutaneously (SCIG).
This document does not pertain to the use of the following:
Note: Please see the following related document for additional information:
Immune globulin (Ig) therapy is considered medically necessary for treatment of individuals with any of the following indications:
Not Medically Necessary:
Immune globulin (Ig) therapy is considered not medically necessary for the indications listed above when criteria are not met.
Immune globulin (Ig) therapy is considered not medically necessary for all other indications not listed above as medically necessary, including but not limited to:
The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.
|90281||Immune globulin (Ig), human, for intramuscular use [when specified for disease treatment as described in this document]|
|90283||Immune globulin, (IgIV), human, for intravenous use|
|90284||Immune globulin, (SCIg), human, for use in subcutaneous infusions, 100 mg each|
|J1459||Injection, immune globulin (Privigen), intravenous, non-lyophilized (e.g., liquid), 500 mg|
|J1460||Injection, gamma globulin, intramuscular, 1 cc [when specified for disease treatment as described in this document]|
|J1556||Injection, immune globulin (Bivigam), 500 mg|
|J1557||Injection, immune globulin, (Gammaplex), intravenous, non-lyophilized (e.g., liquid), 500 mg|
|J1559||Injection, immune globulin (Hizentra), 100 mg|
|J1560||Injection, gamma globulin, intramuscular, over 10 cc [when specified for disease treatment as described in this document]|
|J1561||Injection, immune globulin, (Gamunex-C/Gammaked), non-lyophilized (e.g., liquid), 500 mg|
|J1566||Injection, immune globulin, intravenous lyophilized (e.g., powder), not otherwise specified, 500 mg [Carimune]|
|J1568||Injection, immune globulin, (Octagam), intravenous, non-lyophilized (e.g., liquid), 500 mg|
|J1569||Injection, immune globulin, (Gammagard Liquid), non-lyophilized (e.g., liquid), 500 mg|
|J1572||Injection, immune globulin, (Flebogamma/Flebogamma DIF), intravenous, non-lyophilized (e.g., liquid); 500 mg|
|J1575||Injection, immune globulin/hyaluronidase, (HyQvia), 100 mg immuneglobulin|
|J1599||Injection, immune globulin, intravenous, nonlyophilized (e.g., liquid), not otherwise specified, 500 mg|
|S9338||Home infusion therapy; immunotherapy, administrative services, professional pharmacy services, care coordination, all necessary supplies and equipment, per diem|
When exposed to infection, the human body produces antibodies to fight and create immunity against disease-causing agents, such as viruses and bacteria. These antibodies can sometimes offer protection from illness if an individual is exposed to the same infectious agents in the future. Under many circumstances, an individual's ability to produce immune globulin (Ig) is impaired and the use of other methods to boost the immune system becomes necessary. Ig is a sterilized solution obtained from pooled human blood plasma, which contains the immunoglobulins (or antibodies) to prevent various infectious diseases. Ig is sometimes used to aid in the prevention or progression of an illness by using a donor's antibodies to fight the illness. This process is referred to as passive immunity, as opposed to active immunity, a circumstance in which the human body produces its own antibodies. Passive immunity conveys only temporary protection and should not be confused with receiving an immunization, which provides longer-term protection. The duration of Ig treatment is extremely variable depending upon the condition being treated and the individual receiving the therapy. For some conditions, such as a primary immunodeficiency, treatment is continued indefinitely and diagnosis does not need to be reconfirmed. For some conditions, retreatment may not be needed; however, some individuals may require treatment every 3-4 weeks and others every 6-8 weeks.
Pooled Ig preparations contain many different types of immune globulins (differentiated on the basis of structure and biological activity) that target different specific immune functions of the body. In this way, Ig imparts several types of immune fighting antibodies simultaneously. The anti-inflammatory mechanisms of Ig action remain undetermined. The therapeutic mechanism and the short- and long-term effects may not be the same for each condition.
Since preparations of Ig are derived from donor blood, there are concerns about the potential for contracting diseases, such as hepatitis and HIV. The process used to prepare Ig for use in humans is monitored by the manufacturer and the U.S. Food and Drug Administration (FDA) for the presence of infectious agents. First, the monitoring process begins with the screening of potential donors. Second, all manufacturers use a multi-step process that extracts the desired immune globulins and attempts to remove all other substances. Finally, samples of each batch of Ig are tested for the presence of infectious particles. While all attempts are taken to reduce the risk of infection in the use of Ig, some small risk still exists. Potential recipients of this treatment should take this risk into consideration when contemplating Ig therapy. Different formulations of immune globulin are FDA-approved to be given subcutaneously (SC), intramuscular (IM) or intravenously (IV).
In 2014, the FDA approved HyQvia (Baxter Healthcare Corporation, Westlake, CA), a novel delivery system of subcutaneous recombinant human hyaluronidase-facilitated infusion of immune globulin (IGHy) as a treatment for primary immunodeficiency which includes common variable immunodeficiency (CVID), X-linked agammaglobulinemia, congenital agammaglobulinemia, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies (Product Information Label, 2014). Recombinant hyaluronidase is infused into the subcutaneous tissue to enhance dispersion and absorption of the subsequent infusion of immune globulin. The infusion of IGHy allows increased dosing and infusion volume to achieve monthly dosing of immune globulin into one site. Wasserman and colleagues (2012) reported the efficacy and safety of subcutaneous IGHy was comparable to IVIg based on data from a phase III open-label study with 89 enrolled individuals with primary immunodeficiency. The bioavailability of IGHy was equivalent to IVIg. The primary endpoint of the study was the rate of acute serious bacterial infections (SBIs) which was met with the IGHy SBI rate of 0.025 per subject-year. IGHy had a lower overall infection rate compared to IVIg of 2.97 vs. 4.51 per subject-year, respectively. IGHy had significantly less adverse events compared to IVIg reported at 8.3% compared to 25.0%, respectively. The authors concluded the results of the study supported IGHy provided improved bioavailability compared to the usual SC route, similar bioavailability to the IV route, and less systemic adverse events compared to the IV route. This novel delivery method would allow a single infusion site and provide for self-administration in the home setting.
The development of this document is based on the FDA label, practice guidelines of medical specialty organizations, the published medical literature, and drug compendia off-label indications.
Chronic inflammatory demyelinating polyneuropathy (CIDP)
CIDP is a neurological disorder characterized by progressive weakness and impaired sensory function in the legs and arms. The disorder, which is sometimes called chronic relapsing polyneuropathy, is caused by damage to the myelin sheath (the fatty covering that wraps around and protects nerve fibers) of the peripheral nerves. This myelin damage is often documented by nerve conduction study or nerve biopsy and there is often evidence of elevated cerebral spinal fluid (CSF) protein during the course of the disease. CIDP is difficult to diagnose due to its heterogeneous presentation (both clinical and electrophysiological). Sander and Latov (2003) acknowledged the diagnostic difficulty of CIDP. They attributed this in part to the lack of clarity with the diagnostic criteria for CIDP. Without proper diagnostic criteria, many individuals might remain untreated. In their publication, Sander and Latov (2003) presented the American Academy of Neurology (AAN), Saperstein Diagnostic Criteria and the Inflammatory Neuropathy Cause and Treatment (INCAT) electrodiagnostic criteria.
Although CIDP can occur in both genders at any age, it is more common in young adults. In addition, the disorder occurs more frequently in men than women. CIDP is closely related to Guillain-Barre syndrome and it is considered the chronic counterpart of that acute disease. The FDA approved Gamunex® (Talecris Biotherapeutics, Research Triangle Park, NC) for the treatment of CIDP in September 2008. The FDA based its approval on clinical trials that showed Gamunex was effective at improving certain motor functions for up to 48 weeks after the initial treatment.
Chronic Lymphocytic Leukemia (CLL)
The National Comprehensive Cancer Network® (NCCN®) clinical practice guidelines for Non-Hodgkin's Lymphoma (2015) recommends the use of IVIg for individuals with a serum IVIG <500 mg/dL who also have recurrent sinopulmonary infections which require IV antibiotics or hospitalization.
Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children were published by the Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children (2013) for the Department of Health and Human Services. IVIg was the primary prophylaxis recommended to prevent serious bacterial infections (such as, Streptococcus pneumoniae and other invasive bacteria) in children with HIV-infection and hypogammaglobulinemia (IgG < 400 mg/dL).
IgG Subclass Deficiency
There are five types or classes of immunoglobulin: IgG, IgA, IgM, IgD and IgE. The most prevalent immunoglobulin present in the body is IgG. The IgG class of antibodies is itself composed of four different subtypes of IgG molecules called the IgG subclasses. These are designated IgG1, IgG2, IgG3, and IgG4. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) jointly published the Practice Parameter for the Diagnosis and Management of Primary Immunodeficiency where IgG subclass deficiency (IGGSD) diagnostic criteria were addressed (Bonilla, 2005):
IGGSD is defined as an abnormally low level of 1 or more IgG subclasses in patients with normal levels of total IgG and IgM; IgA level may also be low. IGGSD is defined as 1 or more IgG subclass levels are 2 standard deviations (SD) below the age-adjusted mean.
The Practice Parameter also notes the diagnosis of IGGSD is controversial, and the presence of one or more IgG subclasses alone is "Generally not considered sufficient for a diagnosis of immunodeficiency." In individuals with recurrent infections and one or more low levels of IgG subclasses, a demonstrable impairment in antibody response to vaccination or natural exposure is considered the most important determinant of disease (Bonilla, 2005).
Primary humoral immunodeficiency includes many disorders that result from defects in the immune system. The origin for CVID, a type of primary immunodeficiency, is uncertain. CVID is a heterogenous subset of hypogammaglobulinemia conditions. Frequent infectious complications include respiratory tract infections, otitis media, sinusitis, bronchitis and recurrent pneumonias. Lower respiratory tract infections include bronchiectasis, granulomatous lung disease and lymphocytic interstitial pneumonitis. The Practice Parameter (Bonilla, 2005) notes hallmarks of CVID include IgG levels that are reduced to greater than 2 SDs below the mean. Diagnosis of CVID should be considered in individuals "Older than 2 years with recurrent upper and/or lower respiratory tract infections with encapsulated (H. influenza, S penumoniae) or atypical (Mycoplasma species) bacteria." In updated reviews of CVID, it was noted when diagnosing CVID, IgG is typically below 5 g/L and this threshold was recommended (Ameratunga, 2013; Salzer, 2012).
For individuals with protein losing enteropathy (PLE) or nephrotic syndrome, there are large losses of serum protein either into the GI tract or the urine. The resultant hypogammaglobulinemia and depressed or poorly functioning IgG has not been shown to be improved with IG replacement therapy. There is no evidence of increased rates or more severe infections in these individuals compared with those of similar co-morbidities. It is generally recommended that correction of the underlying disorder is the appropriate treatment of these IgG deficiencies.
Individuals with Wiskott-Aldrich syndrome (WAS) have humoral abnormalities which include dysgammaglobulinemia and impaired production of specific antibodies. Individuals with WAS have some degree of impaired vaccine antibody responses.
X-linked immunodeficiency and severe combined immunodeficiency (SCID) are primary immunodeficiencies. Individuals with SCID and X-linked immunodeficiency do not have the sufficient specific immunity and are prone to opportunistic infections.
The American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) Foundation guideline, Clinical practice guideline: Adult sinusitis (2015) concluded that treatment with IVIg for chronic sinusitis or recurrent acute rhinosinusitis in those with humoral immune deficiency requires more research.
Jordan and colleagues (2004) reported outcomes of a randomized, double-blind, placebo-controlled clinical trial for the reduction of anti-HLA antibody levels and improvement of transplant rates with IVIg. A total of 101 participants with end stage renal disease (ESRD) and highly sensitized to HLA antigens (panel reactive antibody [PRA] greater than or equal to 50% monthly for 3 months) were enrolled in a National Institutes of Health (NIH) sponsored trial (IG02). Participants received either IVIg 2 gm/kg monthly for 4 months or an equivalent volume of placebo with additional infusions at 12 and 24 months after entry, if not transplanted. If transplanted, additional infusions were given monthly for 4 months. Baseline PRA levels were similar in both groups. However, IVIg significantly reduced PRA levels in the IVIg group compared with placebo. Sixteen IVIg participants (35%) and 8 placebo participants (17%) were transplanted. Rejection episodes occurred in 9 of 17 IVIg and 1 of 10 placebo subjects. Seven graft failures occurred (4 IVIg; 3 placebo) among adherent participants with similar 2-year graft survival rates (80% IVIg; 75% placebo). With a median follow-up of 2 years after transplant, the viable transplants functioned normally. The authors concluded that IVIg is better than placebo in reducing anti-HLA antibody levels and improving transplantation rates in highly sensitized individuals with ESRD.
In a review, Jordan and colleagues (2011) addressed clinical applications of Ig in solid organ transplantation, and suggested that IVIg has a much broader ability to regulate cellular immunity and is a modifier of complement activation and injury. Published clinical data addresses the use of IVIg in desensitization and treatment of antibody-mediated rejection (AMR) and are supportive for use in kidney transplant recipients, but no clinical trials using IVIg in sensitized individuals have been performed. Additionally, the available data regarding the use of IVIg for desensitization and treatment of AMR in cardiac and lung allograft recipients is not conclusive. The authors pointed out that desensitization (immunomodulation) pre- and post-solid organ transplantation requires a coordinated approach so that AMR and infectious complications are minimized. There are currently no FDA approved drugs/protocols for desensitization.
Kobashigawa and colleagues (2009) reported recommendations from an international consensus conference addressing those who are sensitized and awaiting heart transplant. The 71-member panel examined diagnostic and treatment regimes from transplant centers and reached consensus for anti-HLA antibody screening and testing methodology. The desensitization recommendations pre-transplant included IVIg, plasmapheresis, and possibly rituximab.
Kobashigawa and colleagues (2011) reported recommendations from an international consensus conference addressing antibody mediated rejection (AMR) in heart transplantation. The conference participants noted that the problem of AMR is due to the many different features of AMR making the current methods for diagnosis and treatment difficult. The panel examined diagnostic and treatment regimens from transplant centers and the published literature. Regarding the use of IVIg, initial treatment for AMR may include high dose corticosteroids, plasmapheresis and IVIg.
A guideline addressing the use of Ig for sensitized individuals undergoing solid organ transplantation (SOT) was developed by the Canadian Blood Services and the National Advisory Committee of Blood and Blood Products of Canada and provides the following recommendations regarding non-kidney solid organ transplantation:
The committee further stated:
There is limited methodologically rigorous evidence for the use of IV Ig for solid organ transplantation. Future studies are needed to delineate the effect of IV Ig on desensitization using standardized methods for desensitization; the effect of IV Ig on acute rejection rates, graft survival, and overall survival; the use of the combined modality IV Ig and PP compared either to PP or IV Ig alone; and the optimum dosage of IV Ig (Shehata, 2010).
Other Proposed Uses:
Alzheimer's disease (AD) is an irreversible, neurodegenerative disease that primarily affects older adults and is the most common form of dementia. AD is definitely diagnosed only after death, through autopsy of the brain tissue and corroborating with clinical measures. However, prior to death, individuals with memory problems and other symptoms may lead to a diagnosis of "possible or probable Alzheimer's disease" (National Institute on Aging [NIA] and the National Institutes of Health [NIH], 2015). Key features reported in the AD brain include atrophy, loss of neurons, deposition of amyloids in specific regions, neuritic plaques and neurofibrillary tangles (Dodel, 2010). However, the specific cause and development of AD is unclear. Amyloid-beta (Aβ) protein deposition in the CSF and CSF tau are two biomarkers being investigated in the pathophysiological process of AD, and these biomarkers are also being studied as potential targets to treat AD. However, at this time, the NIA- Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease do not recommend the use of AD biomarkers tests for routine diagnostic purposes, but may be useful in "investigational studies, clinical trials, and as an optional clinical tool for use where available, and when deemed appropriate by the clinician." There is a lack of biomarker standardization for AD and additional studies of biomarkers are recommended to "determine their value and validity in practice and research settings (McKhann, 2011)."
The use of IVIg as a treatment and prevention for AD has been investigated in phase I and II clinical trials in individuals with mild to moderate AD. The results have been mixed and there is currently an ongoing phase III randomized trial in progress. A review by Loeffler (2013) notes the results from an unpublished placebo-controlled, phase III trial reported no significant difference in the rate of cognitive decline between the IVIg treatment group and the placebo group.
IVIg products consist of pooled plasma and contains different volumes of antibodies, including Aβ and tau antibodies, but the quantity and specific mechanism of action is still unclear. There is a lack of published data from large trials demonstrating the long-term efficacy and safety of IVIg to treat or prevent AD.
Immune Optic Neuritis (ON)
Ig has been studied for treatment of autoimmune optic neuropathy, specifically, optic neuritis (ON). Roed and colleagues (2005) conducted a randomized controlled trial of 68 participants receiving IVIg (n=34) and a control group (n=34) to investigate whether IVIg treatment in the acute phase of ON could improve visual outcome and reduce disease activity as measured by magnetic resonance imaging (MRI) 6 months after disease onset. Infusions were given at days 0, 1, 2, 30, and 60. Contrast sensitivity, visual acuity, and color vision were measured at baseline and after 1 week, 1 month, and 6 months. Pattern reversal visual evoked potential studies and gadolinium-enhanced MRI were performed at baseline and after 1 and 6 months. There was no difference in the primary outcome, contrast sensitivity after 6 months, between participants randomized to treatment with IVIg or placebo. In addition, there was no significant difference in the secondary outcome measures, improvement in the visual function measures and MRI, at any time during follow-up. Results showed no effect of IVIg on long-term visual function following acute optic neuritis, nor was there an effect of IVIg treatment in reducing latency on visual evoked potentials.
The American Academy of Neurology (AAN) guideline (Goodin, 2008) Disease modifying therapies in multiple sclerosis, addresses IVIg for the treatment of multiple sclerosis and states:
The studies of intravenous immunoglobulin (IVIg), to date, have generally involved small numbers of patients, have lacked complete data on clinical and MRI outcomes or have used methods that have been questioned. It is, therefore, only possible that IVIg reduces the attack rate in RRMS (Type C recommendation*). The current evidence suggests that IVIg is of little benefit with regard to slowing disease progression (Type C recommendation*).
*Type C recommendation C—Possibly effective, ineffective or harmful for the given condition in the specified population.
The American Academy of Allergy Asthma and Immunology (AAAAI), in their Work Group Report on the appropriate use of intravenously administered immunoglobulin (2005) states:
IVIG may also be a potentially effective second line treatment in relapsing-remitting multiple sclerosis, although the optimal dosage remains to be established.*
*AAAAI Position Statements and Work Group Reports are not to be considered to reflect current AAAAI standards or policy after five years from the date of publication. For reference only. January 2005
Neuromyelitis Optica (NMO)
Ig has been proposed for treatment of neuromyelitis optica (NMO), which is a rare disease syndrome of the central nervous system (CNS) that affects the optic nerves and spinal cord. In the disease process of NMO, the immune system cells and antibodies attack and destroy myelin cells in the optic nerves and the spinal cord. NMO leads to loss of myelin, which is a fatty substance that surrounds nerve fibers facilitating neural signals to move from cell to cell. NMO can also damage nerve fibers and leave areas of degraded tissue. The cause of NMO is not clear. Individuals with NMO develop optic neuritis, which causes pain in the eye and vision loss. Spinal cord complications include transverse myelitis, which causes weakness, numbness, and sometimes paralysis of the arms and legs, along with sensory disturbances and loss of bladder and bowel control. There are no published clinical trials demonstrating efficacy of Ig treatment. Published literature consists of case reports and case series (Bakker, 2004; Ii, 2008; Okada, 2007).
Route of Administration
Multiple immune globulin products are available for use via IV, SC administration.
Several prospective trials, including both children and adults, have demonstrated that subcutaneous immune globulin (SCIG) is as effective as intravenous immune globulin (IVIG) in protecting individuals with primary immunodeficiency from infection. In addition, a randomized crossover trial directly compared the two forms of therapy in 40 individuals with primary antibody deficiencies and found no statistically significant difference in the number of infections reported.
In most cases, only IVIG is used when high doses are required in acute situations, such as Kawasaki disease and immune thrombocytopenia (ITP); it is also generally used in chronic motor neuropathy or autoimmune diseases.
There are some advantages to SCIG compared to IVIG, including diminished systemic reactions both during administration and after longer term use, no requirement for premedication, delivery of more even serologic levels due to regularity of dosing, allows for self-administration at home after training, and usefulness when venous access is limited.
HyQvia (Baxter HealthCare, Inc., Westlake, CA) is a recombinant human hyaluronidase-facilitated SCIG of Gammagard, which allows for increased dispersion and absorption of the IG due to breakdown of hyaluron in the SC tissue, and thereby allowing larger, less frequent dosing. Non-neutralizing antibodies to the hyaluronidase component occurs in some individuals, though their significance and cross-reactivity is currently unclear.
IM Ig is usually only used for single dosing or for short term treatment during local outbreaks.
Black Box Warnings and Precautions
Black Box Warnings from the product information labels (2013-2015) for the intravenous Ig formulations include the following:
Additional warnings and precautions from the production information labels (2013) include the following:
The subcutaneous Ig product information labels (2013) note reactions similar to other immune globulin products may occur. The most common adverse reactions with subcutaneous injections include local reactions (that is, swelling, redness, heat, pain and itching at the injection site).
Please see specific product information labels for additional warnings and precautions.
Antibody: Specialized gamma globulin proteins found in the blood or lymph that act as an immune defense against foreign agents (antigens).
Antigen: A substance, that when introduced into the body stimulates the production of an antibody. Antigens include toxins, bacteria, foreign blood cells, and the cells of transplanted organs.
Refractory disease: Illness or disease that does not respond to treatment.
Standard deviation: A measure of variability from the average or mean. In laboratory testing results, the average may be expressed as one measurement or as a "reference range" for acceptable values between two measurements. The upper and lower measurements reported are usually two standard deviations from the mean.
Peer Reviewed Publications:
Government Agency, Medical Society, and Other Authoritative Publications:
Intravenous Immune Globulin, Human (IVIg)
The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.
|Reviewed||11/05/2015||Medical Policy & Technology Assessment Committee (MPTAC) review.|
|Reviewed||11/04/2015||Hematology/Oncology Subcommittee review. Updated Discussion/General Information and References sections. Updated Coding section with 01/01/2016 HCPCS changes; also removed ICD-9 codes.|
|Revised||05/07/2015||MPTAC review. Clarified medically necessary criterion S2 – added tetanus as an example of immunization. Added recombinant human hyaluronidase-facilitated immune globulin (IGHy) formulation information and HyQvia to the document. Updated Discussion, Definitions, References, Coding and Index sections.|
|Revised||11/13/2014||MPTAC review. Clarified medically necessary criteria for reference range for IgG sub-class deficiency, CVID and primary humoral immunodeficiency.|
|Revised||05/14/2014||Hematology/Oncology Subcommittee review. Clarified medically necessary language for IgG sub-class deficiency (IgG1, IgG2, IgG3, IgG4). Revised medically necessary indications by addressing common variable immunodeficiency (CVID) separately from other primary humoral immunodeficiencies. Updated criteria for common variable immunodeficiency (CVID). Updated criteria for primary humoral immunodeficiency - other (e.g., congenital agammaglobulinemia, X-linked immunodeficiency, severe combined immunodeficiency [SCID] or Wiskott-Aldrich syndrome [WAS]). Updated Discussion and Reference sections.|
|Revised||02/13/2014||MPTAC review. Revised formatting for medically necessary indications. Updated Discussion/General Information, Coding, and Reference Sections. Black Box warnings updated. Updated trade names in Index section: removed Vivaglobin, Gamunex, and updated Flebogamma DIF.|
|01/01/2014||Updated Coding section with 01/01/2014 HCPCS changes; removed C9130 deleted 12/31/2013.|
|Revised||02/14/2013||MPTAC review. Clarified acronyms in Clinical Indication section. Discussion/General Information and Reference sections updated. Added Bivigam, black box warnings and precautions. Updated Coding section with 04/01/2013 HCPCS changes.|
|Revised||02/16/2012||MPTAC review. Medically necessary clinical indications for primary humoral immunodeficiency clarified to address initial, pretreatment, total IgG.|
|Revised||11/17/2011||MPTAC review. Definitions section added. Discussion/General Information section updated.|
|Revised||11/16/2011||Hematology/Oncology Subcommittee review. Medically necessary criteria revised for CLL bacterial infection and Ig levels and secondary hypoglobulinemia Ig levels, as well as medically necessary criteria for IVIg treatment prior to solid organ transplant. Discussion/General Information and References updated. Updated Coding section with 01/01/2012 HCPCS changes; removed C9270 deleted 12/31/2011.|
|Revised||08/18/2011||MPTAC review. Added additional information to the FDA labeled medically necessary criteria. Multiple sclerosis, immune optic neuropathy, chronic lymphocytic leukemia when Ig levels are normal, non kidney solid organ transplant for desensitization or rejection added as not medically necessary. Discussion/General Information and References updated.|
|Revised||11/18/2010||MPTAC review. Title and medically necessary criteria changed to address Immune Globulin (Ig) Therapy. Medically necessary criteria also clarified for Ig use in hypogammaglobulinemia /recurrent bacterial infection associated with B-cell chronic lymphocytic leukemia. Additional information about Ig product examples and routes of administration added to Discussion/General Information. References updated. Updated Coding section to include 01/01/2011 HCPCS changes.|
|Revised||11/19/2009||MPTAC review. Diagnostic criteria added for CIDP and MMN. Place of service removed. Discussion and references updated.|
|Revised||11/20/2008||MPTAC review. CIDP moved from off label indications to medically necessary criteria. Discussion and references updated. Updated Coding section with 01/01/2009 HCPCS changes.|
|10/01/2008||Updated Coding section with 10/01/2008 ICD-9 changes.|
|Reviewed||02/21/2008||MPTAC review. Discussion/General Information updated with AAN and AAAAI IVIg for MS position; AAO Head and Neck Surgery IVIg for PID position. References updated. Updated Coding section with 04/01/2008 HCPCS changes.|
|01/01/2008||Updated Coding section with 01/01/2008 HCPCS changes; removed HCPCS J1567, Q4087. Q4088, Q4091, Q4092 deleted 12/31/2007.|
|10/01/2007||Updated Coding section with 10/01/2007 ICD-9 changes.|
|07/01/2007||Updated Coding section with 07/01/2007 HCPCS changes.|
|Reviewed||03/08/2007||MPTAC review. References updated. Coding updated; removed HCPCS J1563, J1564, Q9941, Q9942, Q9943, and Q9944, deleted 12/31/2005.|
|01/01/2006||Updated Coding section with 01/01/2006 CPT/HCPCS changes|
|11/18/2005||Added reference for Centers for Medicare & Medicaid Services (CMS) -National Coverage Determination (NCD).|
|Revised||07/14/2005||MPTAC review. Revision based on Pre-merger Anthem and Pre-merger WellPoint Harmonization.|
|Pre-Merger Organizations||Last Review Date||Document Number||Title|
|Anthem, Inc.||09/18/2003||DRUG.00013||Intravenous Immune Globulin Therapy|
|WellPoint Health Networks, Inc.||04/28/2005||2.09.17||Intravenous Immunoglobulin as a Treatment of Recurrent Spontaneous Abortion and Associated Laboratory Tests|
|12/02/2004||Pharmacology Toolkit||Intravenous Immune Globulin|