Vasculitis
PR3-ACNA Little Help in Guiding Wegener Granulomatosis Treatment
By Michael M. Ward, MD
Abstract
Background: The utility of antineutrophil cytoplasmic antibody (ANCA) levels to guide the management of patients with Wegener granulomatosis remains controversial.
Objective: To determine whether pro–pro-teinase 3 (PR3)-ANCA levels are a better measure of disease activity than mature–PR3-ANCA levels, whether decreases in either level are associated with shorter time to remission, and whether increases are followed by relapse.
Design: Prospective, observational cohort study.
Setting: Eight U.S. medical centers that participated in a treatment trial for Wegener granulomatosis.
Patients: 156 patients with Wegener granulomatosis enrolled during periods of active disease.
Measurements: PR3-ANCA levels (by capture enzyme-linked immunosorbent assay) and disease activity (by the Birmingham Vasculitis Activity Score for Wegener granulomatosis).
Results: The ANCA levels were only weakly associated with disease activity across patients. The longitudinal association within patients was stronger, but changes in ANCA levels explained less than 10% of the variation in disease activity. Decreases in mature– and pro–PR3-ANCA levels were not statistically significantly associated with shorter time to remission, and increases in mature–PR3-ANCA levels (adjusted hazard ratio, 0.8 [95% confidence interval (CI), 0.4–1.9]; p=0.67) and pro–PR3-ANCA levels (adjusted hazard ratio, 1.0 [CI, 0.5–2.1]; p=0.99) were not associated with relapse. The proportion of patients who had relapse within one year of an increase in PR3-ANCA levels was 40% for mature-PR3 (CI, 18% to 56%) and 43% for pro-PR3 (CI, 22% to 58%).
Limitations: Samples were collected approximately every three months. Sensitivity and specificity of ANCA levels for detecting remission and relapse could not be calculated because each patient had different follow-up times.
Conclusion: Pro–PR3-ANCA is no better than mature–PR3-ANCA as a measure of Wegener granulomatosis activity. Decreases in PR3-ANCA levels are not associated with shorter time to remission, and increases are not associated with relapse. These findings suggest that ANCA levels cannot be used to guide immunosuppressive therapy.
Commentary
While the value of ANCA, and specifically antibodies to PR3-ANCA, as a diagnostic test for Wegener granulomatosis is undisputed, there have been conflicting data and ongoing debate about whether serum concentrations of these antibodies correlate with clinical disease activity, and whether increases in antibody concentration among patients with quiescent disease predict imminent relapse.
This prospective observational study, the largest to examine this question to date, found little relationship between within-patient changes in PR3-ANCA levels and clinical disease activity, assessed on a median of 11 visits over 34 months, among patients with active disease undergoing immunosuppressive treatment.