Immune Globulin

Jurisdiction: J9 MAC Part B. States: Florida, Puerto Rico, US Virgin Islands. Type: Active LCD

Compliance with the provisions in this LCD may be monitored and addressed through post payment data analysis and subsequent medical review audits. History/Background and/or General Information Immune globulin (also referred to as gamma globulin or immunoglobulin) is a therapeutic compound prepared from pools of plasma obtained from several thousand healthy blood donors that contains antibodies to a wide spectrum of antigens. Immune globulin has been utilized for immune deficiencies identified in individuals with inherited or acquired immunodeficiencies and is used for its capacity in combating infection as a replacement therapy and for its anti-inflammatory and immunomodulating effects. The appropriate use of immune globulin can decrease morbidity and mortality and improve quality of life. 1,2 The focus of this LCD is the United States (U.S.) Food and Drug Administration (FDA) approved indications and the off-label indications for immune globulin where the evidence supports such use. Immune globulin products are not generic drugs and products are not interchangeable. A specific product needs to be matched to patient characteristics to ensure patient safety and a change of product should occur only with the active participation of the prescribing provider. 3 The overall coverage of drugs is addressed in the CMS IOM Publication 100-02, Medicare Benefit Policy Manual , Chapter 15, Sections 50.4.1 and 50.4.2 and includes coverage for FDA-approved drugs and unlabeled use of a drug. Covered Indications Immune globulin products will be considered medically reasonable and necessary when administered for treatment of FDA-labeled indications (https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/immune-globulins 4 ). Off-label indications for intravenous immune globulin ( IVIG) products will be considered medically reasonable and necessary in the following situations: Multiple myeloma for recurrent infections with hypogammaglobulinemia and subprotective antibody levels following immunization against diphtheria, tetanus or pneumococcal infection 1,3,5-7 Following treatment of lymphoma utilizing B-cell depleting therapies for recurrent infections with hypogammaglobulinemia and subprotective antibody levels following immunization against diphtheria, tetanus or pneumococcal infection 3 Recipients of hematopoietic stem cell transplants with severe combined immunodeficiency (SCID) or other primary immunodeficiencies who are functionally agammaglobulinemic because of weak B-cell engraftment 3 Recipients of allogeneic hematopoietic stem cell transplantation with chronic graft versus host disease (GVHD), recurring bacterial infections, and subprotective antibody levels following immunization against diphtheria, tetanus or pneumococcal infection 3 Human Leukocyte Antigen (HLA) and ABO desensitization protocols for the prevention of acute humoral rejection in renal transplantation 3 The treatment of antibody mediated solid organ transplant rejection in combination with rituximab and plasma exchange (PE) 3,8 Treatment of hypogammaglobulinemia in solid organ transplants 3 Autoimmune hemolytic anemia (AIHA) when other treatment approaches have failed 9-10 Systemic capillary leak syndrome (SCLS) 11-13 Guillain-Barré syndrome (GBS) in adults 1,3,14-15 Moderate to severe myasthenia gravis (MG) 2-3,10,15-18 Lambert-Eaton myasthenic syndrome (LEMS) in individuals who fail to respond or do not tolerate other treatments 3 Relapsing-remitting multiple sclerosis (MS) 3,19-22 Neuromyelitis optica (Devic syndrome) in individuals with severe relapses not responding to corticosteroids and who are not candidates for PE 3 Stiff-person syndrome (also referred to as stiff-man syndrome) 2-3 Treatment of autoimmune encephalitis, once infection is ruled out, as an alternative in patients who fail to respond or do not tolerate other treatments 23-27 Treatment of Susac syndrome in combination with high-dose intravenous corticosteroids 28 Severe forms of polymyositis resistant to treatment with glucocorticosteroids and immunosuppressants 29-30 Severe forms of inclusion body myositis with dysphagia and individuals are otherwise treatment-resistant 3,29-33 Immune mediated necrotizing myopathy resistant to treatment with glucocorticosteroids and immunosuppressants 29-30 Overlap syndrome with myositis including anti-synthetase syndrome resistant to treatment with glucocorticosteroids and immunosuppressants 29-30 Severe systemic lupus erythematosus (SLE) in individuals who fail to respond or do not tolerate other treatments 10,30 Biopsy-proven autoimmune mucocutaneous blistering diseases in individuals who fail to respond or do not tolerate other treatments and individuals with rapidly progressive disease requiring a faster response than conventional therapy (i.e., pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita) 3,30,34-39 Toxic epidermal necrolysis (TEN) 3,30 Stevens-Johnson syndrome 3,30 Severe scleromyxedema 3,30,40-41 Thyroid eye disease, also referred to as Graves’ disease in patients who have failed treatment with teprotumumab or have contraindications to the use of teprotumumab 3,42-45 Limitations The following are considered not medically reasonable and necessary: The off-label use of subcutaneous immune globulin The off-label use of intravenous immune globulin not listed above in the covered indications AND Immune globulin for the following: Routine use in the immediate peri-transplantation period for the prevention of infection or GVHD following marrow or peripheral blood allogeneic transplantation 3,46 Acute GVHD with hematopoietic stem cell transplantation in the immediate post-transplantation phase 3 Hematopoietic stem cell transplantation in the immediate post-transplantation phase with a history of sinusoidal obstructive syndrome 3,46 Cord blood stem cell transplantation for children or adults 3 Polyneuropathy associated with IgM monoclonal gammopathy 10 Idiopathic neuropathies 10 Brachial plexopathy 10 Adrenoleukodystrophy 10 Amyotrophic lateral sclerosis 10 Critical illness polyneuropathy 10 POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) 10 Please refer to the CMS IOM Publication 100-03, Medicare National Coverage Determinations (NCD) Manual, Chapter 1, Part 4, Section 250.3 Intravenous Immune Globulin for the Treatment of Autoimmune Mucocutaneous Blistering Diseases for additional limitations. Provider Qualifications Services will be considered medically reasonable and necessary when all aspects of care are within the scope of practice of the provider’s professional licensure; and when all procedures are performed by appropriately trained providers in the appropriate setting. Notice: Services performed for any given diagnosis must meet all of the indications and limitations stated in this LCD, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.