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Paul A. Monach,
Gunnar Tomasson,
Ulrich Specks,
John H. Stone,
David Cuthbertson,
Jeffrey Krischer,
Linna Ding,
Fernando C. Fervenza,
Barri J. Fessler,
Gary S. Hoffman, [......],
Carol A. Langford,
Mark Mueller,
Philip Seo, E. William St.Clair,
Robert Spiera,
Nadia Tchao,
Steven R. Ytterberg,
Yi-Zhong Gu,
Ronald D. Snyder,
Peter A. Merkel
[show abstract]
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ABSTRACT: Objective
To identify biomarkers that distinguish between active antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) and remission in a manner superior or complementary to established markers of systemic inflammation.Methods
Markers of vascular injury and angiogenesis were measured before and after treatment in a large clinical trial in AAV: 163 subjects enrolled in the Rituximab in ANCA-Associated Vasculitis trial were screened for the present study. Serum levels of E-selectin, intercellular adhesion molecule 3 matrix metalloproteinase protein 1 (MMP-1), MMP-3, MMP-9, P-selectin, thrombomodulin, and vascular endothelial growth factor were measured at study screening (time of active disease) and at month 6. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels had been measured at the time of the clinical visit. The primary outcome measure was the difference in marker level between screening and month 6 among patients whose disease was in remission (Birmingham Vasculitis Activity Score for Wegener's granulomatosis [BVAS/WG] score of 0) at month 6.ResultsAll patients had severe active vasculitis at screening (mean ± SD BVAS/WG score 8.6 ± 3.2). Among the 123 patients whose disease was clinically in remission at month 6, levels of all markers except E-selectin showed significant declines. MMP-3 levels were also higher among the 23 patients with active disease at month 6 than among the 123 patients whose disease was in remission. MMP-3 levels correlated weakly with ESR and CRP levels.Conclusion
Many markers of vascular injury and angiogenesis are elevated in severe active AAV and decline with treatment, but MMP-3 appears to distinguish active AAV from remission better than the other markers studied. Further study of MMP-3 is warranted to determine its clinical utility in combination with conventional markers of inflammation and ANCA titers.
Arthritis & Rheumatism 11/2011; 63(12):3988 - 3997. · 7.87 Impact Factor
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Alfred D. Mahr,
Tuhina Neogi,
Michael P. Lavalley,
John C. Davis,
Gary S. Hoffman,
W. Joseph Mccune,
Ulrich Specks,
Robert F. Spiera, E. William St.Clair,
John H. Stone,
Peter A. Merkel
[show abstract]
[hide abstract]
ABSTRACT: Objective
To assess the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) with respect to its selection and weighting of items.Methods
This study used the BVAS/WG data from the Wegener's Granulomatosis Etanercept Trial. The scoring frequencies of the 34 predefined items and any “other” items added by clinicians were calculated. Using linear regression with generalized estimating equations in which the physician global assessment (PGA) of disease activity was the dependent variable, we computed weights for all predefined items. We also created variables for clinical manifestations frequently added as other items, and computed weights for these as well. We searched for the model that included the items and their generated weights yielding an activity score with the highest R2 to predict the PGA.ResultsWe analyzed 2,044 BVAS/WG assessments from 180 patients; 734 assessments were scored during active disease. The highest R2 with the PGA was obtained by scoring WG activity based on the following items: the 25 predefined items rated on ≥5 visits, the 2 newly created fatigue and weight loss variables, the remaining minor other and major other items, and a variable that signified whether new or worse items were present at a specific visit. The weights assigned to the items ranged from 1 to 21. Compared with the original BVAS/WG, this modified score correlated significantly more strongly with the PGA.Conclusion
This study suggests possibilities to enhance the item selection and weighting of the BVAS/WG. These changes may increase this instrument's ability to capture the continuum of disease activity in WG.
Arthritis & Rheumatism 06/2008; 59(6):884 - 891. · 7.87 Impact Factor
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John H. Stone,
Gary S. Hoffman,
Peter A. Merkel,
Yuan-I Min,
Misty L. Uhlfelder,
David B. Hellmann,
Ulrich Specks,
Nancy B. Allen,
John C. Davis,
Robert F. Spiera,
Leonard H. Calabrese,
Fredrick M. Wigley,
Nicola Maiden,
Robert M. Valente,
John L. Niles,
Kenneth H. Fye,
Joseph W. McCune, E. William St.Clair,
Raashid A. Luqmani
[show abstract]
[hide abstract]
ABSTRACT: Objective
To refine and validate the Birmingham Vasculitis Activity Score (BVAS) as a disease-specific activity index for Wegener's granulomatosis (WG).Methods
Sixteen members of the International Network for the Study of the Systemic Vasculitides (INSSYS) revised the BVAS, with 3 goals: to reduce the redundancy of some component items, to enhance its ability to capture important disease manifestations specific to WG, and to streamline the instrument for use in clinical research. We defined the items and weighted them empirically as either minor (e.g., nasal crusting = 1 point) or major (e.g., alveolar hemorrhage = 3 points). We then validated the new, disease-specific BVAS/WG in 2 simulation exercises and a clinical case series that involved 117 patients with WG.ResultsWe removed 38 items from the original BVAS, revised 9 items, and added 7 new items. Correlations between the scores on the BVAS/WG and the physician's global assessment (PGA) of disease activity were high, even when patients in remission were excluded. In the clinical case series, Spearman's rank correlation coefficient between the BVAS/WG and the PGA was r = 0.81 (95% confidence interval 0.73–0.87). The interobserver reliability using intraclass (within-case) correlation coefficients in the 2 simulation exercises was r = 0.93 for the BVAS/WG and r = 0.88 for the PGA in the first and r = 0.91 for the BVAS/WG and r = 0.88 for the PGA in the second. There was no significant observer effect in the scoring of the BVAS/WG or the PGA. The discriminant validity of the BVAS/WG was good: r = 0.73 (95% confidence interval 0.43–0.83).Conclusion
The BVAS/WG is a valid, disease-specific activity index for WG. Tested in simulation exercises and in actual patients, the BVAS/WG correlates well with the PGA, is sensitive to change, and has good inter- and intraobserver reliability. The INSSYS will use the BVAS/WG to assess the primary outcome in a phase II/III trial of etanercept in WG.
Arthritis & Rheumatism 03/2001; 44(4):912 - 920. · 7.87 Impact Factor
