ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2159

Correlation of a Multi-Biomarker Disease Activity Response Assessment to Disease Activity Score 28 (C-Reactive Protein) Response Assessment and Omeract Ramris Scores in a Placebo-Controlled Rheumatoid Arthritis Clinical Trial with Abatacept (ASSET)

DJ Haney1, G. Cavet2, P. Durez3, R. Alten4, Gerd Burmester5, P. P. Tak6, Anca Catrina7, C. Gaillez8, M. Le Bars8, S. Connolly9 and R. Townsend9, 1Crescendo Bioscience Inc., South San Francisco, CA, 2Crescendo Bioscience, Inc., South San Francisco, CA, 3Université Catholique de Louvain, Brussels, Belgium, 4Schlosspark-Klinik, University Medicine, Berlin, Germany, 5Charité-Universitätsmedizin, Berlin, Germany, 6Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands; GlaxoSmithKline, Stevenage, United Kingdom, 7Department of Medicine, Karolinska Institute, Stockholm, Sweden, 8Bristol-Myers Squibb, Rueil Malmaison, France, 9Bristol-Myers Squibb, Princeton, NJ

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Rheumatoid Arthritis Treatment - Small Molecules, Biologics and Gene Therapy

Session Type: Abstract Submissions (ACR)

Background/Purpose: A novel multi-biomarker disease activity (MBDA) score has been validated and is a tool for monitoring disease activity in RA.1 Here, we evaluate the relationship between MBDA scores and both clinical and MRI assessments in patients (pts) from the ASSET trial (NCT00420199) who received abatacept (ABA) or placebo (pbo). Methods: Fifty pts with active RA, baseline (BL) DAS28-CRP >3.2 or Tender Joint Count and Swollen Joint Count >6 and CRP >upper limit of normal and inadequate response to MTX were randomly assigned 1:1 to receive ABA or pbo plus MTX, administered intravenously at BL; Days 15, 29; and every 28 days up to and including Day 113.2 Concentrations of 12 serum biomarkers including inflammatory cytokines and receptors (IL-6, TNF-RI), growth factors (EGF, VEGF-A), matrix metalloproteinases (MMP-1, MMP-3), skeletal-related protein (YKL-40), hormones (leptin, resistin), acute phase proteins, and markers of systemic inflammation (CRP and SAA1) were measured in pt serum at BL, 2 and 4 wks to calculate MBDA scores between 1 and 100. Disease activity measures (DAS28-CRP) were evaluated at BL, Wks 2 and 4, and every 4 wks until Wk 16, EULAR response was assessed at Week 16, and OMERACT RAMRIS scores (components: erosion, osteitis, and synovitis scores) were evaluated at BL and Mth 4. Associations between MBDA scores and DAS28-CRP, and between MBDA scores and OMERACT RAMRIS scores, were evaluated post hoc using Spearman’s rank correlation. The relationships of early changes in DAS28-CRP and MBDA score with subsequent EULAR response were evaluated by two-sample t-test. Comparisons of changes in disease activity  scores between treatment arms were evaluated by two-sample t-tests. Results: Statistically significant correlations were observed between DAS28-CRP and MBDA score (r=0.47, p<0.001, n=146; all time points combined), and between change in DAS28-CRP and change in MBDA score from BL to Wk 4 (r=0.58, p<0.001, n=48). Pts in the ABA + MTX  arm experienced significantly greater improvements in MBDA score and DAS28-CRP versus pbo + MTX arm at Wk 4 (p=0.003 in each case). A significant association between change in DAS28-CRP from BL to Wk 4 and EULAR good response at Wk 16 (p=0.02) was observed, as well as a marginally significant association between change in MBDA at Wk 4 and good EULAR response at Wk 16 (p=0.05). There was a significant correlation between MBDA score and OMERACT RAMRIS synovitis and osteitis scores at BL (Table).

Conclusion: In the ASSET trial, pts receiving abatacept had a better improvement in both clinical disease activity and disease activity biomarkers than pts in the pbo group. The MBDA score was correlated with disease activity and the OMERACT RAMRIS synovitis and osteitis scores. Monitoring of changes in MBDA score may be useful in RA pts in combination with clinical assessment.

1. Bakker MF, et al. Ann Rheum Dis 2012;doi:10.1136/annrheumdis-2011-200963 2. Conaghan P, et al. Ann Rheum Dis 2011;70(Suppl 3):151  

Disease activity measure Synovitis Osteitis Erosion
Correlation P value n Correlation P value n Correlation P value n
MBDA score 0.34 0.02 47 0.36 0.01 47 0.27 0.06 47
DAS28-CRP 0.08 0.60 47 0.10  0.52 47 0.10 0.49 47
 

Disclosure:

D. Haney,

Crescendo Bioscience,

1,

Crescendo Bioscience,

3;

G. Cavet,

Crescendo Bioscience,

1,

Crescendo Bioscience,

3;

P. Durez,

BMS (less than US$2000),

8;

R. Alten,

Abbott, Bristol-Myers Squibb, Novartis, Pfizer, UCB,

2,

Abbott, Bristol-Myers Squibb, Novartis, Pfizer, UCB,

5,

Abbott, Bristol-Myers Squibb, Novartis, Pfizer, UCB,

8;

G. Burmester,

Abbott, BMS, MSD, Pfizer, Roche, MSD,

2,

Abbott, BMS, MSD, Pfizer, Roche, MSD,

5,

Abbott, BMS, MSD, Pfizer, Roche, MSD,

8;

P. P. Tak,

Employee of GSK,

3;

A. Catrina,
None;

C. Gaillez,

Full time BMS Employee,

3;

M. Le Bars,

Bristol-Myers Squibb,

1,

Bristol-Myers Squibb,

3;

S. Connolly,

Own BMS stock,

1,

Full time employee of BMS,

3;

R. Townsend,

Bristol-Myers Squibb,

1,

Bristol-Myers Squibb,

3.

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