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Title: Infliximab Does Not Improve Antineutrophil Cytoplasm Antibody Associated Vasculitis: Presented at ASN

"Infliximab Does Not Improve Antineutrophil Cytoplasm Antibody Associated Vasculitis: Presented at ASN"

By Bryan DeBusk, PhD SAN FRANCISCO, CA -- November 6, 2007 -- Despite widespread use of infliximab as an additional immunosuppressive agent in patients with antineutrophil cytoplasm antibody (ANCA) associated vasculitis, or ASV, an open-label, phase 2 clinical trial has shown the drug has no benefit for these patients. Matthew D. Morgan, MD, Clinical Lecturer, University of Birmingham, Birmingham, United Kingdom, reported the findings here at Renal Week 2007, the American Society of Nephrology (ASN) Annual Meeting. "There's been a lot of evidence from the basic science research and animal organ studies that suggest that tumour necrosis factor (TNF) is a major cytokine involved in the pathogenesis of ANCA associated vasculitis, and a few case series suggest that anti-TNF treatment should be an effective way of controlling disease," explained Dr. Morgan. "About 3 or 4 years ago there seemed to be more people reporting the use of infliximab on ASV cases but without any real trial evidence to suggest that it was an effective treatment, so we wanted to run a phase 2 clinical trial to actually see whether we could see any advantage to using infliximab as adult therapy in addition to cyclophosphamide," he added. To examine the question, Dr. Morgan and his colleagues enrolled 16 patients with active ASV and no life- or organ-threatening disease in an open-label, phase 2 clinical trial and treated them with 5 mg/kg infliximab at weeks 0, 2, 6, and 10, plus standard immunosuppression therapy, and followed their progress for 12 months. A comparison group of 17 patients who refused infliximab or had life- or organ-threatening disease were matched for age, gender, ethnicity, and ANCA type, pattern, and specificity, and received only standard immunosuppression therapy. Activity of the disease was measured with the Birmingham Vasculitis Activity Score (BVAS) and serum level of C-reactive protein (CRP), and organ damage was assessed using the Vasculitis Damage Index (VDI). Median BVAS was similar in the two groups at the outset and throughout the study, while CRP was higher at the outset in the group receiving only immunosuppression therapy (122 vs 42 in the group with infliximab; [P =.034). Both groups had similar CRP levels by week 2 and remained similar throughout the remainder of the study.

Rates of infection were similar in both groups, and two patients with infliximab and one patient with immunosuppression only experienced a clinical relapse during the study. Three patients in each group died during the study (one on immunosuppression only died of the disease, one on infliximab died of metastatic pancreatic cancer, and the other patients succumbed to sudden death at home).

At the conclusion of the follow up period both groups had similar VDI scores (infliximab + immunosuppression = 2; immunosuppression only = 2.5; no statistical difference).

"The infliximab should have had a built-in advantage in terms of disease remission and organ damage," remarked Dr. Morgan. "But actually we found that there was no difference between the two groups; infliximab didn't appear to confer any advantage over cyclophosphamide and prednisolone therapy... On the other hand, there didn't appear to be any harm to giving infliximab, either."

[Presentation Title: Infliximab as Additional Therapy in Anti-Neutrophil Cytoplasm Antibody (ANCA) Associated Vasculitis. Abstract SU-PO922]

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