Predictors of Relapse and Treatment Resistance in Antineutrophil Cytoplasmic Antibody–Associated Small-Vessel Vasculitis

1 November 2005 | Volume 143 Issue 9 | Pages 621-631

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 µmol/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.

Editors' Notes Context Patients with antineutrophil cytoplasmic autoantibody (ANCA)–associated small-vessel vasculitis sometimes experience relapses and resistance to glucocorticoid and cyclophosphamide treatment. Contribution This study followed 350 patients with ANCA-associated vasculitis for a median of 49 months. Of 258 patients attaining remission, 109 (42%) relapsed. Upper or lower respiratory tract disease and proteinase-3 ANCA seropositivity were associated with increased risk for relapse. Of 334 treated patients, 77 (23%) had progressive disease despite treatment. Severe kidney disease, black ethnicity, and female sex were associated with an increased risk for treatment resistance. Cautions The participants were primarily selected on the basis of their condition being identified by renal biopsy. —The Editors

 

Author and Article Information

From the University of North Carolina, Chapel Hill, North Carolina.

Acknowledgments: The authors thank the physicians and medical staff who participate in the Glomerular Disease Collaborative Network and the patients who made this study possible.

Grant Support: In part by a grant from the National Institutes of Health, National Institute of Diabetes & Digestive & Kidney Diseases (program project number P01-DK58335).

Potential Financial Conflicts of Interest: Grants received: S.L. Hogan (National Institutes of Health), R.J. Falk (National Institutes of Health), C.E. Jennette (National Institutes of Health), J.C. Jennette (National Institutes of Health), P.H. Nachman (National Institutes of Health).

Requests for Single Reprints: Susan L. Hogan, PhD, MPH, Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, CB 7156, 7024B Burnett-Womack, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7156; e-mail, slh{at}med.unc.edu.

Current Author Addresses: Drs. Hogan, Falk, and Nachman, Ms. Chin, and Ms. Jennette: Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center, CB 7156, 7024B Burnett-Womack, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7156.

Dr. Cai: School of Public Health, CB 7400, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7400.

Dr. Jennette: Department of Pathology and Laboratory Medicine, CB 7525, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525.

Author Contributions: Conception and design: S.L. Hogan, R.J. Falk, J.C. Jennette, P.H. Nachman.

Analysis and interpretation of the data: S.L. Hogan, R.J. Falk, H. Chin, J. Cai, J.C. Jennette, P.H. Nachman.

Drafting of the article: S.L. Hogan, R.J. Falk, J.C. Jennette, P.H. Nachman.

Critical revision of the article for important intellectual content: S.L. Hogan, R.J. Falk, H. Chin, J. Cai, C.E. Jennette, J.C. Jennette, P.H. Nachman.

Final approval of the article: S.L. Hogan, R.J. Falk, H. Chin, J. Cai, C.E. Jennette, J.C. Jennette, P.H. Nachman.

Provision of study materials or patients: R.J. Falk, P.H. Nachman.

Statistical expertise: S.L. Hogan, H. Chin, J. Cai.

Obtaining of funding: S.L. Hogan, R.J. Falk.

Administrative, technical, or logistic support: S.L. Hogan, R.J. Falk, J. Cai, C.E. Jennette.

Collection and assembly of data: S.L. Hogan, R.J. Falk, C.E. Jennette, P.H. Nachman.

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