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MP 8.02.03 Extracorporeal Immunoadsorption Using Protein A Columns

Medical Policy
Section
Therapy
Original Policy Date
11/1/98
Last Review Status/Date
Reviewed with literature search/April 2006
Issue
2:2006
Return to Medical Policy Index

Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.


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 is passed over the column. Circulating immune complexes (CICs) and immunoglobulin (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 idiopathic thrombocytopenic purpura (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 the 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 an immunoadsorption protein A column approved by the U.S. Food and Drug Administration (FDA). Labeled indications include (1) therapeutic removal of immunoglobulin G- and IgG-containing circulating immune complexes from plasma in patients with idiopathic thrombocytopenic purpura having platelet counts less than 100,000 mm-3, and (2) therapeutic reduction of the signs and symptoms of moderate to severe rheumatoid arthritis in adult patients with longstanding disease who have failed or are intolerant to disease-modifying anti-rheumatic drugs. According to manufacturer’s information obtained during the 2008 policy update the Prosorba column is no longer sold worldwide; activities for the replacement Immunosorba column focus on Europe and there is no sales activity in the US market.
NOTE: This policy does not address the role of ECI in the transplant setting.


Policy

Extracorporeal immunoadsorption may be considered medically necessary as a treatment of patients with idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, or hemolytic uremic syndrome unresponsive to other therapies with either of the following:

  • a platelet count below 20,000 OR
  • a platelet count below 50,000 with evidence of bleeding

Extracorporeal immunoadsorption may be considered medically necessary as a 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.

Other applications of extracorporeal immunoadsorption are investigational including, but not limited to, treatment of cancer, or autoimmune diseases other than rheumatoid arthritis.

Note: This policy does not address the role of ECI in the transplant setting.


Policy Guidelines

For treatment of idiopathic thrombocytopenia, patients typically undergo given treatments 6 times over the course of 2 to 3 weeks.

For treatment of rheumatoid arthritis, patients typically undergo 1 treatment per week for 12 weeks.

Disease-modifying antirheumatic drugs include: methotrexate (Rheumatrex), hydroxycholoroquine (Plaquenil), sulfasalazine (Azulfidine), gold (Ridaurs, Solganal), azathioprine (Imuran), D-penicillamine (Depen, Cupirmine), etanerecept (Enbrel), and leflunomide (Arava).

The apheresis portion of the procedure may be coded as CPT code 36516:

Therapeutic apheresis, with extracorporeal selective adsorption or selective filtration and plasma reinfusion.


Benefit Application

BlueCard/National Account Issues

No applicable information.


Rationale

Idiopathic thrombocytopenic purpura (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 not needed if the platelet count remains above 50,000/ml. In cases involving more 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. (1) 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), hydroxycholoroquine (Plaquenil), sulfasalazine (Azulfidine), gold (Ridaurs, Solganal), azathioprine (Imuran), D-penicillamine (Depen, Cupirmine), etanercept, and leflunomide.

Approval from the FDA was based in part on a randomized, double-blind sham placebo-controlled trial of 91 patients. (2) 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 up for an additional 7 to 8 weeks. Treatment effect was assessed by the number of tender and swollen joints and pain scores, according to a scoring system developed by the American College of Rheumatology. Improvement was defined as at least a 20% improvement in the tender joint count, at least 20% improvement in swollen joint count, and at least 20% improvement in at least 3 of the following 5: patient pain assessment, patient global assessment of disease activity, physician global assessment of disease activity, patient assessment of physical function, and a 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, 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. (3) Hemolytic uremic syndrome is considered part of the spectrum of thrombotic thrombocytopenic purpura (TTP). Patients treated with immunoadsorption columns have achieved a definite increase in platelet count, decrease of hemolysis, and stabilization of renal function. (4, 5) 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 effectiveness of the treatment. (6) Similarly, there are scattered reports of using ECI to treat other autoimmune diseases, such as systemic lupus erythematosus, but the literature is inadequate to permit conclusions. (7)

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. (8)

2006 Update

A literature search was performed for the period of 2003 through January 2006. No additional published studies were identified that would prompt reconsideration of the policy statement. Therefore the policy statement is unchanged.

2008 Update

A literature search for studies published between February 2006 and March 2008 was performed. No additional studies were identified. A review of plasma exchange in rheumatoid arthritis (9) suggests that despite good results with protein A columns, their use was supplanted by the biologic disease-modifying anti-rheumatic drugs (such as tumor necrosis factor alpha inhibitors) due to efficacy, convenience and practicality.
Because there is no current sales activity for protein A columns in the US, the status of this policy is being changed to no further review.

 

References:

  1. Snyder HW, Cochran SK, Balint JP et al. Experience with protein A-immunoadsorption in treatment-resistant adult immune thrombocytopenic purpura. Blood 1992; 79(9):2237-45.
  2. Felson DT, LaValley MP, Baldassare AR et al. The Prosorba column for treatment of refractory rheumatoid arthritis: a randomized, double-blind, sham-controlled trial. Arthritis Rheum 1999; 42(10):2153-9.
  3. Mittelman A, Bertram J, Henry DH et al. Treatment of patients with HIV thrombocytopenia and hemolytic uremic syndrome with protein A (Prosorba Column) immunoadsorption. Semin Hematol 1989; 26(2 suppl 1):15-8.
  4. Snyder HW, Mittelman A, Oral A et al. Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma. Cancer 1993; 71(5):1882-92.
  5. Hakim RM, Milford E, Himmelfarb J et al. Extracorporeal removal of anti-HLA antibodies in transplant candidates. Am J Kidney Dis 1990; 16(5):423-31.
  6. Palmer A, Taube D, Welsh K et al. Removal of anti-HLA antibodies by extracorporeal immunoadsorption to enable renal transplantation. Lancet 1989; 1(8628):10-2.
  7. Schneider M, Berning T, Waldendorf M et al. Immunoadsorbent plasma perfusion in patients with systemic lupus erythematosus. J Rheumatol 1990; 17(7):900-7.
  8. Fennelly DW, Norton L, Sznol M et al. A phase II trial of extracorporeal plasma immunoadsorption of patient plasma with PROSORBA columns for treating metastatic breast cancer. Cancer 1995; 75(8):2099-102.
  9. Seror R, Pagnoux C, Guillevin L. Plasma exchange for rheumatoid arthritis. Transfus Apher Sci 2007:36(2);195-9.

     

 

Codes

Number

Description

CPT  36515  Therapeutic apheresis; with extracorporeal immunoadsorption and plasma reinfusion 
ICD-9 Procedure  99.76  Extracorporeal immunoadsorption 
ICD-9 Diagnosis  283.11  Hemolytic-uremic syndrome 
  287.3  Primary thrombocytopenia (includes idiopathic thrombocytopenic purpura) 
446.6 Thrombotic microangiopathy (includes thrombotic thrombocytopenic purpura)
  714.0  Rheumatoid arthritis 
HCPCS  No code   
Type of Service  Medicine   
Place of Service  Outpatient   


Index

Extracorporeal Immunoadsorbent Therapy
ITP, Extracorporeal Immunoadsorbent (Prosorba) Therapy
Prosorba Column
Rheumatoid Arthritis, Extracorporeal Immunoadsorbent (Prosorba) Therapy


Policy History

Date Action Reason
11/01/98 Add to Medicine section New policy
12/1/99 Replace policy Policy statement revised to include new FDA-approved indication
7/12/02 Replace policy Policy reviewed without literature review; new review date only
10/03/03 Replace policy Policy reviewed by consensus without literature review; no changes in policy
04/1/05 Replace policy Policy reviewed with literature search; no change in policy statement
09/27/05 Replace policy Typographical errors corrected (ECI) and statement about kidney transplant removed from the investigational policy statement as it conflicted with the statement that this policy does not address ECI in the transplant setting.
04/25/06 Replace policy Policy reviewed with literature search. No change in policy statement. Reference number 2 updated
04/09/08 Replace policy  Policy updated with literature search, no change in policy statement. Since there is no longer US sales activity, policy status changed to no further review. Reference 9 added.


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