BlueCross and BlueShield of Montana Medical Policy/Codes
Extracorporeal Immunoadsorption Using Protein A Columns
Chapter: Therapies
Current Effective Date: August 27, 2013
Original Effective Date: August 27, 2013
Publish Date: May 27, 2013
Revised Dates: This medical document is no longer scheduled for routine literature review and update.
Description

Extracorporeal immunoadsorption (ECI) using protein A columns, also referred to as protein immunoadsorption therapy, consists of highly purified protein A (isolated from Staphylococcus Aureus) that is bonded to a silica matrix.  Plasma is collected from the patient in a pheresis procedure and then passed over the column.  Circulating immune complexes (CICs) and Immunoglobulin G (IgG) bind to protein A and are thus selectively removed from the plasma.  The plasma can then be returned to the patient, thus eliminating the need for a plasma exchange.

Pathogenic levels of IgG and circulating immune complexes are associated with a number of diseases, such as ITP, hemolytic uremic syndrome, and red cell aplasia.  In the past, plasma exchange was used to remove CICs and IgG.  ECI represents a selective removal of pathogenic substances and thus has been investigated as an alternative to plasma exchange, particularly for patients with ITP.  Recently, Immunoadsorption columns have been investigated in patients with rheumatoid arthritis.

The Prosorba Column is a Food and Drug Administration (FDA) approved immunoadsorption Protein A column.  Labeled indications include the following:

  • Therapeutic removal of immunoglobulin G- and IgG (containing circulating immune complexes) from plasma in patients with idiopathic thrombocytopenic purpura having platelet counts less than 100,000mm-3.
  • Therapeutic reduction of the signs and symptoms of moderate to severe rheumatoid arthritis in adult patients with long-standing disease who have failed or are intolerant to disease-modifying anti-rheumatic drugs.

For treatment of ITP, patients typically undergo six treatments over a course of two or up to three weeks.

For treatment of rheumatoid arthritis, patients typically undergo one treatment per week for 12 weeks.

Policy

Prior authorization is recommended. To authorize, call Blue Cross and Blue Shield of Montana (BCBSMT) Customer Service at 1-800-447-7828 or fax your request to the Medical Review Department at 406-441-4624. A retrospective review is performed if services are not prior authorized.

Medically Necessary

BCBSMT may consider extracorporeal immunoadsorption (ECI) using a Protein A column medically necessary as a treatment for patients with idiopathic thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura or hemolytic uremic syndrome unresponsive to other therapies as evidenced by a platelet count:

  • below 20,000, or
  • below 50,000 with evidence of bleeding.

ECI using Protein A columns may be considered medically necessary as a treatment for signs and symptoms of moderate to severe rheumatoid arthritis in adult patients with long-standing disease who have failed or are intolerant to disease-modifying anti-rheumatic drugs (DMARDs).

Investigational

BCBSMT considers other applications of ECI experimental, investigational or unproven, including, but not limited to, treatment of cancer, autoimmune diseases other than rheumatoid arthritis, or for renal transplant recipients.

Federal Mandate

Federal mandate prohibits denial of any drug, device, or biological product fully approved by the FDA as investigational for the Federal Employee Program (FEP). In these instances coverage of these FDA-approved technologies are reviewed on the basis of medical necessity alone. Call the BCBSMT FEP Customer Service Department at 1-800-634-3569 for benefit information.

Rationale for Benefit Administration

This medical policy was developed through consideration of peer reviewed medical literature, FDA approval status, accepted standards of medical practice in Montana, Technology Evaluation Center evaluations, and the concept of medical necessity. BCBSMT reserves the right to make exceptions to policy that benefit the member when advances in technology or new medical information become available.

The purpose of medical policy is to guide coverage decisions and is not intended to influence treatment decisions. Providers are expected to make treatment decisions based on their medical judgment. Blue Cross and Blue Shield of Montana recognizes the rapidly changing nature of technological development and welcomes provider feedback on all medical policies.

When using this policy to determine whether a service, supply or device will be covered please note that member contract language will take precedence over medical policy when there is a conflict.

Rationale

ITP is characterized by rapid platelet destruction and typically appears in young women and also in HIV positive patients.  It is usually a relatively benign disorder in its chronic form, and treatment is usually not needed if the platelet count remains above 50,000/ml.  In cases involving serious bleeding or with platelet counts less than 20,000/ml, ECI has successfully reversed the immune thrombocytopenia by removal and modulation of platelet specific IgG and circulating immune complexes.  Treatment of ITP was the original FDA-labeled indication for extracorporeal immunoadsorption.

In 1999, ECI received an additional FDA-labeled indication for the treatment of "signs and symptoms of moderate to severe rheumatoid arthritis in adult patients with long-standing disease who have failed or are intolerant to disease modifying anti-rheumatic drugs (DMARDS)." DMARDS include:

  • Methotrexate (Rheumatrex),
  • Hydroxychloroquine (Plaquenil),
  • Sulfasalazine (Azulfidine),
  • Gold (Ridaura, Solganal),
  • Azathioprine (Imuran),
  • D-penicillamine (Depen, Cuprimine)
  • Etanercept, and
  • Leflunomide.

The new FDA-labeled indication was based in part on a randomized, double-blind sham placebo controlled trial of 91 patients.  Trial participants had Rheumatoid Arthritis for an average of 15 years and had failed an average of 4.2 DMARDS prior to entry.  Patients received weekly treatments for each of 12 weeks and were followed for an additional seven to eight weeks.  Treatment effect was assessed by the number of tender and swollen joints and pain scores, using a scoring system developed by the American College of Rheumatology.  Improvement was defined as at least a 20% improvement in at least three of the following five criteria:

  • patient pain assessment,
  • patient assessment of global disease activity,
  • physician assessment of global disease activity,
  • patient assessment of physical function, and
  • health functional status questionnaire. 

A total of 31.93% of patients in the treatment arm showed improvement compared to 11.4% in the sham/placebo group.  Among those experiencing improvement during the trial, the median duration of response was 32 weeks.  Originally, the investigators had planned to enroll 178 patients but at an interim analysis the trial was stopped early due to the significant comparative improvement in the treatment group.

ECI has also been used in the treatment of hemolytic uremic syndrome, which is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and progressive renal failure (thought to be related to circulating immune complexes).  Patients treated with immunoadsorption columns have achieved a definite increase in platelet count, decrease of hemolysis, and stabilization of renal function.  ECI has also been investigated as a technique to reduce the number of antibodies reactive against human lymphocyte antigens in highly sensitized potential kidney transplant recipients.  While a number of case series have been reported, there are inadequate data to validate the treatment effectiveness.  Similarly, there are scattered reports of using ECI to treat various autoimmune diseases, such as systemic lupus erythematosus, but the literature is inadequate to permit conclusions.

Various malignancies have also been treated with ECI.  The proposed rationale is that cancer patients are known to have depressed immune functions due to various factors in the plasma and that ECI might remove these blocking antibodies and immune complexes.  Fennelly and colleagues conducted a phase II trial of ECI in patients with metastatic breast cancer and reported that ECI was not associated with antitumor activity and that patients with breast cancer did not appear to have higher levels of circulating immune complexes compared to normal controls.

2005 Update

A literature search was performed for the period of 2003 through 2005.  No additional published studies were identified that would prompt reconsideration of the policy statement.  Therefore the policy statement is unchanged.

Coding

Disclaimer for coding information on Medical Policies           

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy.  They may not be all-inclusive.           

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers.  Only the written coverage position in a medical policy should be used for such determinations.           

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes
99.76, 283.11, 287.30, 287.31, 287.32, 287.33, 287.39, 446.6, 714.0
Procedural Codes: 36515
References
  1. Mittleman, A.  Treatment of patients with HIV thrombocytopenia and hemolytic uremic syndrome with protein a (Prosorba Column) immunoadsorption.  Seminals of Hematology (1989); 26 (supplement 2): 15-18.
  2. Palmer, A., Taube, D., et al.  Removal of anti-HLA antibodies by extracorporeal immunoadsorption to enable renal transplantation Lancet (1989 January) 7:10-12.
  3. Hakim,R.M., Milford, E., et al.  Extracorporeal removal of anti-HLA antibodies in transplant candidates.  American Journal of Kidney Disease (1990) 16:423-31.
  4. Schneider, M., Berning, T., et al.  Immunoadsorbant plasma perfusion in patients with systemic lupus erythematosus. Journal of Rheumatology (1990) 17:900-07.
  5. Snyder, H.W., Cochran, S.K., et al.  Experience with protein A immunoadsorption in treatment resistant adult immune thrombocytopenic purpura.  Blood (1992) 2237-45.
  6. Snyder, H.W., Mittelman, A., et al.  Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein Immunoadsorption of plasma.  Cancer (1993) 71:1882-92.
  7. Weisenhutter, C.W., B.L. Irish.  Treatment of patients with refractory rheumatoid arthritis with extracorporeal protein A immunoadsorption columns: A pilot trial.  Journal of Rheumatology (1994)  21:804-12.
  8. Fennelly,D.W., L. Norton.  A phase II trial of extracorporeal plasma immunoadsorption of patient plasma with Prosorba columns for treating metastatic breast cancer.  Cancer (1995) 75:2099-102.
  9. Cher, L.M., Hochberg, F.H., et al.  Therapy for paraneoplastic neurologic syndromes in six patients with protein A column immunoadsorption.  Cancer (1995) 75(7):1678-83.
  10. Batchelor, T.T., M. Platten.   Immunoadsorption therapy for paraneoplastic syndromes. Journal of Neurooncology (1998)  40(2):131-6.
  11. Hickstein, H., Korten, G., et al.  Protein A immunoadsorption (i.e.) in renal transplantation patients with vascular rejection. Transfusion Science (1998) 19 supplement:53-7.
  12. Borghardt, E.J., Kirchertz, E.J., et al.  Protein A immunoadsorption in chemotherapy associated hemolytic-uremic syndrome. Transfusion Science (1998) 19 supplement:5-7.
  13. Strand, V.  Recent Advances in the Treatment of Rheumatoid Arthritis. Clinical Cornerstone (1999) 2(2):38-50.
  14. Department of Health and Human Services, FDA Approval Letter: Prosorba Column (March 15, 1999).
  15. Felson, D.  The Prosorba Column for Treatment of Refractory Rheumatoid Arthritis. Arthritis and Rheumatism (October 1999)42(10):2153-2159.
  16. Caldwell, J.  A pilot study using a Staph Protein A Column (Prosorba) to treat refractory rheumatoid arthritis. The Journal of Rheumatology (1999) 26-8.
  17. Extracorporeal Immunoadsorption Using Protein A Columns.  Chicago, Illinois: Blue Cross Blue Shield Association Medical Policy Reference Manual, Medicine. (2005 January) Therapy 8.02.03.
History
May 2013  New 2013 BCBSMT medical policy.  Considered possibly investigational. 
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Extracorporeal Immunoadsorption Using Protein A Columns