Journal
ARTHRITIS AND RHEUMATISM
Volume 65, Issue 9, Pages 2441-2449Publisher
WILEY-BLACKWELL
DOI: 10.1002/art.38044
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Funding
- Immune Tolerance Network (NIH), an international clinical research consortium headquartered at the University of California San Francisco [N01-AI-15416, ITN021AI]
- NIH (National Institute of Allergy and Infectious Diseases) [N01-AI-15416, ITN021AI]
- Juvenile Diabetes Research Foundation
- Genentech
- Biogen Idec
- NIH (Mayo Clinic: National Center for Research Resources Clinical and Translational Science) [RR-024150-01]
- NIH (Johns Hopkins University: National Center for Research Resources Clinical and Translational Science) [RR-025005, K23-AR-052820, K24-AR-049185, RR-025771, M01-RR-00533, K24-AR-02224]
- Arthritis Foundation
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000439] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000533, M01RR001066, UL1RR024150, UL1RR025005, UL1RR025771] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI088635, N01AI015416, U01AI067075] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [K24AR049185, K24AR002224, K23AR052820] Funding Source: NIH RePORTER
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Objective. To evaluate the reasons that complete remission is not achieved or maintained with original treatment in some patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with rituximab (RTX) or with cyclophosphamide/azathioprine (CYC/AZA). Methods. The Rituximab in AAV trial was a randomized, double-blind, placebo-controlled trial comparing the rate of remission induction among patients treated with RTX (n = 99) and patients treated with CYC followed by AZA (n = 98). Glucocorticoids were tapered over a period of 5 months. The primary outcome measure was lack of disease activity without glucocorticoid treatment at 6 months. To determine the most important reason for failure to achieve the primary outcome, 7 hierarchical categories of reasons were defined retrospectively (uncontrolled disease, adverse event leading to therapy discontinuation, severe flare, limited flare, Birmingham Vasculitis Activity Score for Wegener's Granulomatosis >0, prednisone treatment at any dosage, and other). Results. Although remission (lack of disease activity) was achieved in 170 of the 197 patients (86%) in the first 6 months, the primary outcome measure was not achieved in 42%. There were 3 deaths. Twenty-four percent of the patients failed to achieve the primary end point due to active disease: 10 (5%) experienced uncontrolled disease in the first month and 37 (19%) experienced flares after initial improvement. In the majority of such patients, treatment with blinded crossover or according to best medical judgment led to disease control. Ninety-one percent of patients who had uncontrolled disease or experienced a severe flare had proteinase 3 (PR3)-ANCA. When patients with uncontrolled disease were excluded from analysis, those who were PR3-ANCA positive were found to experience fewer flares when treated with RTX compared to CYC/AZA (8 of 59 [14%] versus 20 of 62 [32%]; P = 0.02). Neither ANCA titers nor B cell counts predicted disease flare. Conclusion. Current treatment regimens are largely successful in controlling AAV, but in approximately one-fourth of patients, active disease persists or recurs in the first 6 months despite treatment. PR3- ANCA positivity is a risk factor for recurrence or persistence of severe disease. ANCA titers and B cell detectability are poor predictors of both disease relapse and disease quiescence in the first 6 months.
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