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August 2000

Use of Staphylococcal Protein A (SPA) Immunoadsorption in Rheumatoid Arthritis and Immune Thrombocytopenic Purpura

Joseph E. Kiss, M.D.
Medical Director, Hemapheresis and Blood Services



Recent Food and Drug Administration (FDA) approval of the staphylococcal protein A (Prosorba) column for treatment-resistant moderate to severe rheumatoid arthritis has prompted increased requests for this therapy by physicians and patients alike.  This edition of the TMU will address the role of SPA immunoadsorption in the only two approved indications for it's use: rheumatoid arthritis (RA)  and immune thrombocytopenic purpura (ITP).  


The Prosorba column consists of 200 mg. of purified staphylococcal protein A covalently linked to a silica matrix.  SPA avidly binds IgG, particularly in the form of IgG-containing circulating immune complexes (CIC). In the "on-line" mode, the column is connected to the plasma return line of a plasmapheresis  instrument; the plasma is perfused through the column at a rate of 10-20 mls/min.  The treated plasma is then recombined with the cellular components and reinfused.  A variable amount of plasma may be processed, depending upon the clinical indication.  As little as 250 mls processed per treatment has been reported to be efficacious in the management of refractory ITP, while most studies reporting the efficacy of Prosorbatreatment in RA processed approximately 1,250 ml of plasma per apheresis.


The basis for the salutary effects of SPA immunoadsorption remains obscure.  Because the column becomes saturated after removal of only ~1 gm of IgG, its efficacy clearly is not based on quantitative immunoglobulin depletion.  Instead, an immunomodulatory effect is believed to occur, resulting from alterations in CIC.   Column treatment appears to reduce the population of small molecular weight CIC.  These CIC may interfere with antigen presentation to T-helper cells, thus blocking  the formation of  "protective" antibodies involved in immune clearance.   CIC may also inhibit the formation of  anti-idiotypic antibodies, which down-regulate autoantibody responses. Alternative hypotheses have also been proposed.


Data from several clinical trials support the efficacy of SPA column treatment in patients with refractory rheumatoid arthritis.  In two non-controlled trials, RA patients treated at approximately weekly intervals had response rates of 54-60%, as assessed by 20% or greater improvement in signs and symptoms.

Because of the complexity of the endpoints for assessing clinical status in RA and the recognized placebo effect of apheresis treatment itself, Felson, studied the efficacy of SPA column treatment in comparison to a control group who received apheresis without column plasma perfusion (i.e., a sham arm) in a randomized double-blind study1.  The treatments wwere performed weekly in patients with RA who had failed to respond to treatment with methotrexate or at least two other second-line drugs (so-called DMARDS, or Disease Modifying Anti-Rheumatic Drugs).  Efficacy was assessed 7-8 weeks after the course of treatment ended.  Improvement was measured according to American College of Rheumatology response criteria.  The trial was stopped after the completion of 91 randomized patients because the safety monitoring board determined a significant advantage existed in favor of SPA.  Of 47 patients in the SPA group, 31.9% experienced improvement in comparison to 11.4% in the control group  (P=0.019).  Most of the responses were seen late in the course of 12 weekly treatments, but lasted a mean of 37 weeks.  SPA therapy may allow RA patients to be managed with fewer or lower doses of DMARDs.  However, procedural issues (i.e., availability, venous access) as well as the expense (about $1000 for each column plus apheresis fees) should also be considered.


The SPA column was approved by the FDA in 1987 for treatment of ITP patients with platelet counts less than 100,000/ml.  Snyder, evaluated 72 patients with initial platelet counts less than 50,000/ml who had failed at least two other therapies2.  They treated patients 2-3 times per week for a total of 6-12 treatments.  A response was reported in 33 (46%); platelet counts rose to over 100,000 in 18 and to 50-100,000/ml in 15 patients, with median time to response of 2 weeks.  Although transient responses of less than one month were seen in 7 (10%), the authors noted the apparent durability of responses in the remaining patients: the mean duration was 8 months, with some responding > 26 months. 

The Institute for Transfusion Medicine recently reviewed it's experience using SPA in 24 patients with refractory ITP.   Disease duration ranged from 9 months to 23 years in 22 patients; 2 had disease less than 8 weeks.  All patients were refractory to at least two forms of therapy.  Splenectomy had been performed in 15.  A median of 8 procedures were performed over a 2-3 week period processing 500 mls of plasma.  Treatment responses were defined as both a doubling of the baseline platelet count and a post-treatment platelet count to > 50,000/ml.  The overall response rate was 33%; 7 of the 8 responses achieved platelet increments > 100,000. The two patients with disease duration < 8 weeks (i.e., acute ITP) had continuing responses > 18 months follow-up. Of the 6 patients with longer disease duration, 2 relapsed within 3 months, 2 had continuing responses requiring low-dose corticosteroids or danazol therapy, and 2 had unmaintained responses which lasted > 17 months. In our experience, the overall response rate of 33% is consistent with that previously reported, however, unmaintained remissions in patients with longstanding ITP appear to be uncommon after this treatment. 

A recent consensus guideline published by the American Society of Hematology listed protein A column as an intermediate preference treatment option in patients with refractory ITP and platelet counts less than 10,000/ml3.  Higher preference therapies included intravenous gammaglobulin, accessory splenectomy (where appropriate), danazol, and azathioprine.  Lower preference alternatives  included Rh immune globulin, ascorbic acid, colchicine, cyclosporine, and interferon.  It should be noted that these recommendations were published in 1996, when there was less experience using intravenous Rh immune globulin.


Adverse effects experienced by patients during SPA column treatment vary somewhat with the nature of the underlying disease and the medications the patient is receiving.  Most common adverse events reported in conjunction with treatment of ITP include hypertension, nausea/emesis, chills and/or fever, rash, arthralgias, diarrhea, and abdominal pain.  Symptoms are less common if the patient is receiving prednisone.  Regardless, pretreatment with acetaminophen, 650 mg. and diphenhydramine 25-50 mg. is recommended.  The most common side effects reported in conjunction with RA treatment include joint pain (essentially a "flare") involving the target joints, fatigue, hypertension, nausea, abdominal pain, flushing, and headache.  The possibility of severe reactions exists, including anaphylactoid manifestations, vasculitis, thrombosis, or exacerbation of underlying disease. Most of the serious reactions were reported in the older literature.  However, catheter complications should also be considered as part of the risk/benefit assessment of any patient in whom SPA column therapy is considered. In addition, the column is contraindicated in patients receiving angiotensin-converting enzyme (ACE) inhibitors because of the risk of profound hypotensive reactions.  These drugs inhibit the metabolism of bradykinin, which is formed during column perfusion. 


SPA column therapy is efficacious in some patients with ITP and RA. Appropriate patient selection is essential.  In general, such patients should be refractory to standard modes of therapy (including use of the newer anti-inflammatory medications), and a risk v. benefit v. cost metric should be carefully considered. 


  1. Felson D, Lavalie MP, et al.  The Prosorba column for treatment of refractory rheumatoid arthritis: a randomized, double-blind, SHAM-controlled trial.  Arthritis Rheum. 1999; 42: 2153-59.

  2. Snyder HW, Cochran SK, et al.  Experience with protein A-immunoadsorption in treatment-resistant adult immunothrombocytopenic purpura.  Blood   1992; 79: 2237-45.

  3. George JN, Woolf SH, et al.  Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology.  Blood 1996; 88: 3-40.


Copyright 2000, Institute For Transfusion Medicine

For questions or further information on regarding
SPA immunoadsorption, please contact Joseph E. Kiss, M.D. at The Institute For Transfusion Medicine: 412-209-7326.

Copies of previous Transfusion Medicine Update issues can be obtained from our web page: www.itxm.orgTo be placed on our mailing list for a hard copy, please contact Deborah Small by e-mail: or by phone: (412) 209-7320.