Session Information
Date: Sunday, November 8, 2015
Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
Calprotectin (MRP8/MRP14, S100A8/A9) is a protein abundant in cytosol of granulocytes and monocytes/macrophages and released during cell activation. It reflects clinical disease activity in patients with rheumatoid arthritis (RA). Ultrasonography (US) is sensitive for detecting synovitis (grey scale, GS) and vascularization (power Doppler, PD). There is only published one small study showing associations between calprotectin and US in RA patients.
To study the associations between calprotectin and a comprehensive US examination as well as clinical/laboratory variables and to explore the responsiveness of calprotectin to biologics in a large cohort of RA patients.
Methods:
A total of 141 patients with RA (mean (SD) age of 50.3 (13.3) years and disease duration 9.9 (8.6) years, 81% women, 77% anti-CCP positive) starting different biologic medication (including 66,7% anti-TNF) were examined at baseline and after 1, 2, 3, 6 and 12 months for calprotectin, CRP, ESR, clinical variables as well as US of 36 joints and 4 tendons (wrist (incl. RU, IC, RU), MCP 1-5, PIP 2-3, elbow, knee, ankle, MTP 1-5, ECU and tib.post. tendons bilaterally). Both GS and PD pathology were scored semi-quantitatively 0-3 by one sonographer (HBH) (Siemens Antares Excellence version, 5-13MHz probe, PRF 391Hz, no updates during the study). At each examination EDTA-plasma was frozen at -80 degrees, and all calprotectin concentrations were analyzed at the same time (normal levels ≤ 900 µg/L). Changes from baseline were assessed by Wilcoxon T-test, differences between groups by Mann-Whitney and correlations by Spearman’s rank.
Results:
All variables decreased significantly from baseline (table 1) (p<0.001). Calprotectin had higher correlations with CRP during the study (range r=0.46-0.76), than with ESR (range r= 0.31-0.56), while the correlations between ESR and CRP was 0.47-0.69 (all correlations p<0.001). Prednisolone users at baseline (55%, median 7.5 mg) had higher levels of calprotectin (p=0.006), sum score GS (p=0.02) and number of swollen joints (p=0.02), while no differences were found between the groups for ESR, CRP or the other variables. Calprotectin was highly associated with US scores during the study, with higher correlations than ESR or CRP (table 2).
|
|
Baseline |
1 month |
2 months |
3 months |
6 months |
12 months |
|
Calprotectin µg/L |
1149 (698-1949) |
739 (501-1223) |
659 (436-1105) |
673 (443-1122) |
653 (409-982) |
637 (453-954) |
|
ESR mm/h |
22 (11-35) |
14 (7-26) |
14 (8-28) |
16 (7-24) |
14 (7-21) |
14 (7-21) |
|
CRP mg/L |
6 (2-12) |
2 (1-7) |
2 (1-5) |
2 (1-5) |
1 (1-5) |
2 (1-4) |
|
GSUS sum score |
27 (17-43) |
24 (15-37) |
23 (14-37) |
21 (13-32) |
18 (12-27) |
17 (11-25) |
|
PDUS sum score |
11 (4-24) |
9 (3-17) |
6 (3-17) |
7 (2-14) |
5 (1-11) |
4 (1-8) |
|
Assessor’s global VAS (study nurse) |
27 (18-38) |
20 (10-30) |
17 (11-26) |
15 (10-25) |
13 (8-20) |
13 (8-20) |
|
DAS28 |
4.4 (3.1-5.4) |
3.6 (2.7-4.7) |
3.2 (2.6-4.4) |
3.2 (2.3-4.2) |
2.9 (2.3-3.7) |
2.8 (2.1-3.9) |
|
Number of swollen joints (of 32) |
6 (3-11) |
4 (2-9) |
4 (2-7) |
3 (1-7) |
2 (0-5) |
1 (0-4) |
|
Number of tender joints (of32) |
4 (2-11) |
4 (1-9) |
3 (0-7) |
3 (0-7) |
1 (0-4) |
1 (0-5) |
|
Patient’s global VAS |
46 (20-67) |
25 (10-46) |
22 (8-36) |
19 (5-37) |
16 (5-33) |
19 (6-33) |
|
|
Sum score Grey scale 36 joints and 4 tendons |
Sum score power Doppler 36 joints and 4 tendons |
||||||||||
|
|
Baseline |
1 month |
2 months |
3 months |
6 months |
12 months |
Baseline |
1 month |
2 months |
3 months |
6 months |
12 months |
|
Calprotectin |
0.59** |
0.51** |
0.50** |
0.37** |
0.48** |
0.25* |
0.62** |
0.53** |
0.53** |
0.46** |
0.47** |
0.31** |
|
ESR |
0.19* |
0.04 |
0.06 |
0.01 |
0.19* |
0.01 |
0.30** |
0.14 |
0.15 |
0.12 |
0.21* |
0.15 |
|
CRP |
0.41** |
0.21* |
0.30** |
0.18* |
0.33** |
0.20* |
0.47** |
0.23* |
0.33** |
0.26* |
0.35** |
0.30** |
Conclusion:
In this first large study exploring calprotectin and US, calprotectin was found to be highly associated with both sum GS and PD scores. In addition, calprotectin was not suppressed by use of prednisolone like CRP/ESR and it was highly responsive to biologic medication. These findings support the use of calprotectin as an inflammatory marker in RA patients.
To cite this abstract in AMA style:
Hammer HB, Nordal HH, Kvien TK. Calprotectin (MRP8/MRP14), a Major Leukocyte Protein, Is Highly Associated to Ultrasound Detected Synovitis and Is Responsive to Biologic Treatment [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/calprotectin-mrp8mrp14-a-major-leukocyte-protein-is-highly-associated-to-ultrasound-detected-synovitis-and-is-responsive-to-biologic-treatment/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/calprotectin-mrp8mrp14-a-major-leukocyte-protein-is-highly-associated-to-ultrasound-detected-synovitis-and-is-responsive-to-biologic-treatment/