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  • Title: Predictors of relapse and treatment resistance in antineutrophil cytoplasmic antibody-associated small-vessel vasculitis.
    Author: Hogan SL, Falk RJ, Chin H, Cai J, Jennette CE, Jennette JC, Nachman PH.
    Journal: Ann Intern Med; 2005 Nov 01; 143(9):621-31. PubMed ID: 16263884.
    Abstract:
    BACKGROUND: Predictors of treatment resistance and relapse have not been well described in antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis. OBJECTIVE: To identify clinical, pathologic, and serologic predictors of treatment resistance and relapse in a community-based cohort of patients with ANCA-associated vasculitis. DESIGN: Cohort of patients identified at or near the time of biopsy diagnosis and followed as clinically indicated. SETTING: The Glomerular Disease Collaborative Network. PATIENTS: 350 patients who received a new diagnosis of ANCA-associated vasculitis between 1985 and 2003 and were followed for a median of 49 months. MEASUREMENTS: Patients were categorized according to whether they had antiproteinase-3 (anti-PR3) antibodies or antimyeloperoxidase (anti-MPO) antibodies. Organ involvement was determined by biopsy or by well-defined clinical criteria. Treatment resistance was defined as progressive decline in kidney function with active urine sediment or the persistence or appearance of extrarenal manifestations. Relapse was defined as the time to the resurgence of vasculitic symptoms. RESULTS: Treatment resistance affected 23% of 334 treated patients and was associated with female sex, black ethnicity, and presentation with severe kidney disease (odds ratio per serum creatinine elevation of 100 micromol/L [1.13 mg/dL], 1.28 [95% CI, 1.16 to 1.39]). The following factors were associated with relapse in 258 (77%) patients who attained remission: seropositivity for anti-PR3 antibodies (hazard ratio, 1.87 [CI, 1.11 to 3.14]) and disease of the lung (hazard ratio, 1.71 [CI, 1.04 to 2.81]) or upper respiratory tract (hazard ratio, 1.73 [CI, 1.04 to 2.88]). Relapses occurred in 26% of patients with no risk factors versus 73% of patients with all 3 risk factors (hazard ratio, 3.7 [CI, 1.4 to 9.7]). Among 143 patients attaining remission who subsequently stopped all immunosuppressant therapy, relapse rates were similar for those who had received cyclophosphamide therapy for 6 months or less (34%) compared with those treated for a longer duration (35%), even after adjusting for risk factors for relapse (hazard ratio, 1.41 [CI, 0.80 to 2.50]). LIMITATIONS: The cohort mostly included patients with biopsy-proven kidney disease. Patients were not followed with uniform treatment protocols, and only limited information about their clinical course before diagnosis was available. CONCLUSIONS: Female or black patients, or those with severe kidney disease, may be resistant to initial treatment more often than other patients with ANCA-associated small-vessel vasculitis. Increased risk for relapse appears to be related to the presence of lung or upper airway disease and anti-PR3 antibody seropositivity.
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