Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis

Javier D. Finkielman, Peter A. Merkel, Darrell Schroeder, Gary S. Hoffman, Robert Spiera, E. William St. Clair, John C. Davis, W. Joseph McCune, Andrea K. Lears, Steven R Ytterberg, Amber M. Hummel, Margaret A. Viss, Tobias D Peikert, John H. Stone, Ulrich Specks

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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-proteinase 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: 8 United States 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% CI, 0.4 to 1.9]; P = 0.67) and pro-PR3-ANCA levels (adjusted hazard ratio, 1.0 [CI, 0.5 to 2.1]; P = 0.99) were not associated with relapse. The proportion of patients who had relapse within 1 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 3 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.

Original languageEnglish (US)
Pages (from-to)611-619
Number of pages9
JournalAnnals of Internal Medicine
Volume147
Issue number9
StatePublished - Nov 6 2007

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Antineutrophil Cytoplasmic Antibodies
Granulomatosis with Polyangiitis
Myeloblastin
Recurrence
Immunosuppressive Agents
Vasculitis

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Finkielman, J. D., Merkel, P. A., Schroeder, D., Hoffman, G. S., Spiera, R., St. Clair, E. W., ... Specks, U. (2007). Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Annals of Internal Medicine, 147(9), 611-619.

Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. / Finkielman, Javier D.; Merkel, Peter A.; Schroeder, Darrell; Hoffman, Gary S.; Spiera, Robert; St. Clair, E. William; Davis, John C.; McCune, W. Joseph; Lears, Andrea K.; Ytterberg, Steven R; Hummel, Amber M.; Viss, Margaret A.; Peikert, Tobias D; Stone, John H.; Specks, Ulrich.

In: Annals of Internal Medicine, Vol. 147, No. 9, 06.11.2007, p. 611-619.

Research output: Contribution to journalArticle

Finkielman, JD, Merkel, PA, Schroeder, D, Hoffman, GS, Spiera, R, St. Clair, EW, Davis, JC, McCune, WJ, Lears, AK, Ytterberg, SR, Hummel, AM, Viss, MA, Peikert, TD, Stone, JH & Specks, U 2007, 'Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis', Annals of Internal Medicine, vol. 147, no. 9, pp. 611-619.
Finkielman JD, Merkel PA, Schroeder D, Hoffman GS, Spiera R, St. Clair EW et al. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Annals of Internal Medicine. 2007 Nov 6;147(9):611-619.
Finkielman, Javier D. ; Merkel, Peter A. ; Schroeder, Darrell ; Hoffman, Gary S. ; Spiera, Robert ; St. Clair, E. William ; Davis, John C. ; McCune, W. Joseph ; Lears, Andrea K. ; Ytterberg, Steven R ; Hummel, Amber M. ; Viss, Margaret A. ; Peikert, Tobias D ; Stone, John H. ; Specks, Ulrich. / Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. In: Annals of Internal Medicine. 2007 ; Vol. 147, No. 9. pp. 611-619.
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title = "Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis",
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-proteinase 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: 8 United States 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{\%} CI, 0.4 to 1.9]; P = 0.67) and pro-PR3-ANCA levels (adjusted hazard ratio, 1.0 [CI, 0.5 to 2.1]; P = 0.99) were not associated with relapse. The proportion of patients who had relapse within 1 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 3 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.",
author = "Finkielman, {Javier D.} and Merkel, {Peter A.} and Darrell Schroeder and Hoffman, {Gary S.} and Robert Spiera and {St. Clair}, {E. William} and Davis, {John C.} and McCune, {W. Joseph} and Lears, {Andrea K.} and Ytterberg, {Steven R} and Hummel, {Amber M.} and Viss, {Margaret A.} and Peikert, {Tobias D} and Stone, {John H.} and Ulrich Specks",
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T1 - Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis

AU - Finkielman, Javier D.

AU - Merkel, Peter A.

AU - Schroeder, Darrell

AU - Hoffman, Gary S.

AU - Spiera, Robert

AU - St. Clair, E. William

AU - Davis, John C.

AU - McCune, W. Joseph

AU - Lears, Andrea K.

AU - Ytterberg, Steven R

AU - Hummel, Amber M.

AU - Viss, Margaret A.

AU - Peikert, Tobias D

AU - Stone, John H.

AU - Specks, Ulrich

PY - 2007/11/6

Y1 - 2007/11/6

N2 - 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-proteinase 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: 8 United States 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% CI, 0.4 to 1.9]; P = 0.67) and pro-PR3-ANCA levels (adjusted hazard ratio, 1.0 [CI, 0.5 to 2.1]; P = 0.99) were not associated with relapse. The proportion of patients who had relapse within 1 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 3 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.

AB - 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-proteinase 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: 8 United States 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% CI, 0.4 to 1.9]; P = 0.67) and pro-PR3-ANCA levels (adjusted hazard ratio, 1.0 [CI, 0.5 to 2.1]; P = 0.99) were not associated with relapse. The proportion of patients who had relapse within 1 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 3 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.

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