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The Prosorba column has been studied as a novel therapy for rheumatoid arthritis in several clinical settings over the last 5 years. In this article, we summarize the pivotal clinical trial study supporting the safety and efficacy of the Prosorba column as it is applied to treatment of rheumatoid arthritis. The Prosorba column is a medical device that contains purified staphylococcal protein A covalently bound to a silica matrix. This device is used to treat patient plasma in conjunction with a plasmapheresis machine. In this ex vivo treatment, blood is withdrawn from the patient, cells are separated from plasma in the machine, and the plasma is passed through the Prosorba column. The plasma then is recombined with the cells and returned to the patient. The Prosorba column was approved for the treatment of idiopathic thrombocytopenic purpura in 1987 and, in 2 open-label trials (1,2), showed promising evidence of efficacy in rheumatoid arthritis. A subsequent Phase 3 pivotal trial demonstrated statistical superiority of Prosorba treatments to sham column apheresis (3). Analysis of the pivotal trial of patients who completed all treatments indicated that 41.7% of the Prosorba treated patients met American College of Rheumatology defined response criteria as compared to 15.6% of the sham treated patients. This difference was significant at a level of p < or = 0.02.

A double-blind, randomized, placebo controlled study was conducted to determine the efficacy of a promising immunoadsorption treatment device containing staphylococcal protein A (Prosorba Immunoadsorption Column, Cypress Bioscience, Inc., San Diego, CA, U.S.A.) in patients with refractory rheumatoid arthritis (RA). Eligibility criteria required adult RA patients who had failed either methotrexate or 2 other disease modifying antirheumatic drugs (DMARD) and who had predefined active disease. All disease-modifying agents were discontinued at least 30 days prior to entry. Patients received 12 weekly procedures after being randomized to the active treatment arm or to the sham treatment arm (apheresis only). Evaluations were double-blinded and occurred at baseline and periodically for 24 weeks thereafter. Primary efficacy was assessed at 7 and 8 weeks after the completion of 12 treatments (at trial Weeks 19 and 20) using the American College of Rheumatology (ACR) definition of improvement (1,2), and results from the assessments at Weeks 19 and 20 were averaged. Ninety-nine randomized patients had a mean disease duration of 15.4 years and received an average of greater than 5 DMARD regimens prior to entry. Analysis of patients who completed all treatments and follow-up indicated that 15 of 36 (41.7%) column-treated patients responded compared to 5 of 32 (15.6%) sham-treated patients (p < or = 0.003). Intent to treat analysis of all patients who were randomized in the study indicated 15 of 52 (28.9%) column-treated patients responded compared to only 5 of 47 (10.6%) patients who received sham treatments (p = .005). Common adverse events (AEs) included joint pain, fatigue, joint swelling, and hypotension. Central line usage was clearly associated with significant AEs during this trial and is not recommended. Hemoglobin, hematocrit, and mean corpuscular volume values decreased similarly in both treatment arms, attributed to phlebotomy for laboratory and scientific studies and to small, repetitive (normal) apheresis losses. Other AEs such as nausea, rash, pruritus, flushing, and fever occurred in 1 to 6% of treatments in each arm (NS). There was no significant increase in AEs in column-treated patients compared to sham-treated patients. Protein A immunoadsorption was proven to be a new therapeutic alternative in patients with severe, refractory disease.

Objective: To evaluate the efficacy and safety of the Prosorba column as a treatment for rheumatoid arthritis (RA) in patients with active and treatment-resistant (refractory) disease., Methods: A sham-controlled, randomized, double-blind, multicenter trial of Prosorba versus sham apheresis was performed in patients with RA who had failed to respond to treatment with methotrexate or at least 2 other second-line drugs. Patients received 12 weekly treatments with Prosorba or sham apheresis, with efficacy evaluated 7-8 weeks after treatment ended. Patients were characterized as responders if they experienced improvement according to the American College of Rheumatology (ACR) response criteria at the efficacy time point. A data safety monitoring board (DSMB) evaluated interim analyses for the possibility of early completion of the trial., Results: Patients in the trial had RA for an average of 15.5 years (range 1.7-50.6) and had failed an average of 4.2 second-line drug treatments prior to entry. After the completion of treatment of 91 randomized patients, the DSMB stopped the trial early due to successful outcomes. Of the 47 patients in the Prosorba arm, 31.9% experienced ACR-defined improvement versus 11.4% of the 44 patients in the sham-treated arm (P = 0.019 after adjustment for interim analysis). When results from 8 additional patients, who had completed blinded treatments at the time of DSMB action, were added to the analysis (n = 99), results were unchanged. The most common adverse events were a short-term flare in joint pain and swelling following treatment, a side effect that occurred in most subjects at least once in both treatment arms. Other side effects, although common, occurred equally as frequently in both treatment groups., Conclusion: Apheresis with the Prosorba column is an efficacious treatment for RA in patients with active disease who have failed other treatments.

Objective: To assess the safety and effectiveness of extracorporeal treatments with protein A (Prosorba) columns in the treatment of patients with severe refractory rheumatoid arthritis (RA) in an open label pilot study., Methods: Fifteen patients with RA who had failed to respond to 2 or more disease modifying antirheumatic drugs were "washed out" for 1-3 months before enrollment into this 6 month pilot study. The treatment schedule called for patients to receive apheresis treatments across staphylococcal protein A columns once a week for 12 weeks. Clinical evaluations of RA activity, defined by Paulus criteria, were conducted at study enrollment (baseline) and monthly throughout the treatment phase. In addition, examinations were conducted at 2, 4, 8, and 12 weeks after the last treatment. Fourteen patients received all 12 scheduled treatments, while one patient received only 10 treatments due to complications secondary to pneumonia., Results: Using Paulus 50% criteria, 9 of 15 (60%) patients were improved at the 4th month, and one more fulfilled >20% Paulus criteria (7%) in the 5th month after starting therapy. The study group reported an average of 2.47 adverse effects per treatment, of which the most common were joint pain and swelling and fatigue of short duration (arthritic flare)., Conclusion: The adverse effects associated with this apheresis based treatment proved to be manageable and of short duration and resolved without sequelae. The results suggest that extracorporeal protein A therapy may have a role in the management of refractory RA, and encouraged the initiation of a larger, blinded, controlled clinical trial.