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Abstract Number: 2870

Higher Disease Activity and Serum Levels Of Angiogenic Factors In Patients With Rheumatoid Arthritis In Clinical Remission With Synovitis On Ultrasound

Julio Ramirez1, Virginia Ruiz-Esquide2, Isaac Pomés3, Raquel Celis4, Jaume Pomés3, Sonia Cabrera1, M. Victoria Hernández5, Oscar M Epis6, Jose L. Pablos7, Raimon Sanmarti1 and Juan D. Cañete2, 1Arthritis Unit. Rheumatology Department, Hospital Clínic of Barcelona, Barcelona, Spain, 2Rheumatology, Hospital Clinic, Barcelona, Spain, 3Radiology, Hospital Clínic, Barcelona, Spain, 4Arthritis Unit, Rheumatology Department, Arthritis Unit, Rheumatology Dpt, Hospital Clinic of Barcelona and IDIBAPS, Barcelona, Spain, 5Arthritis Unit, Department of Rheumatology, Hospital Clinic, Barcelona, Barcelona, Spain, 6A.O. Ospedale Niguarda Cà Granda, Milan, Italy, 7Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (I+12), Madrid, Spain

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Angiogenesis, remission, rheumatoid arthritis (RA) and ultrasonography

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Session Information

Title: Rheumatoid Arthritis - Clinical Aspects VII: Remission, Flare and Outcome Measures in Rheumatoid Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

To identify and characterize subclinical synovitis in patients with rheumatoid arthritis in clinical remission using power Doppler ultrasound and serum levels of angiogenic factors.

Methods:

We selected patients with rheumatoid arthritis in clinical remission (defined as DAS28-ESR<2.6) tested by two independent rheumatologists. Clinical, epidemiological, demographic and serological data were analyzed. Ultrasonography of knees and hands (wrists, metacarpophalangeal [MCP], proximal interphalangeal [PIP], flexor and extensor tendons of the hand) was performed by a radiologist with an ultrasound scanner (Acuson Antares, Siemens AG, Erlangen, Germany) with a linear probe of 10.5 MHz. Synovial hypertrophy and power Doppler signal were scored (grades 0-3). Synovial hypertrophy >2 plus power Doppler signal was classified as active synovitis.

Serum levels of angiogenic factors were determined by Quantibody® Human Array (RayBiotech, Inc, Norcross, GA, USA).

Results:

Fifty-five patients were included of whom 25 (45.4%) met criteria for active synovitis. The most-affected joints were the wrist and second MCP. Patients with active synovitis on ultrasound had significantly higher DAS28-CRP (p=0.020) and only 12% were taking oral glucocorticoids (< 5 mg/day) compared with 40% of patients without active synovitis. No other clinical differences were found (Table 1). Patients with active synovitis had significantly-higher serum levels of angiogenic factors: angiopoietin-2 (p=0.038), VEGF-D (p=0.018), PIGF (p=0.043), SDF-1 (p=0.035), MMP-2 (p=0.027) and bFGF (p=0.007) (Table 1).

Table 1. Clinical, demographic and biological data of the 55 patients, stratified according the presence or not of active synovitis as defined by ultrasound*.

 

All n=55

HS + Doppler(active synovitis) n=25

No HS+Doppler    (no active synovitis) n=30

p–value

Age (years)

52 (44-62)

51 (43-61)

55 (46-65)

0.275

Women, n (%)

42 (76)

17 (68)

25 (83)

0.155

Disease duration (months)

90.0 (56.2-150.3)

86.3 (57.1-166.9)

93.7 (50.8-148.9)

0.649

RF, n (%)

39 (71)

18 (72)

21 (70)

0.555

ACPA, n (%)

47 (86)

23 (92)

24 (80)

0.193

DAS283v-ESR

2.03 (1.67-2.44)

2.24 (1.88-2.57)

1.92 (1.55-2.21)

0.060

DAS283v-CRP

1.42 (1.37-1.59)

1.54 (1.38-1.71)

1.40 (1.17-1.49)

0.020

mHAQ

0.1 (0.0-0.4)

0.1 (0.0-0.3)

0.0 (0.0-0.4)

0.564

ESR (mm/1h)

9 (6-16)

10 (7-20)

9 (6-12)

0.493

CRP (mg/dL)

0.10 (0.03-0.35)

0.11 (0.03-0.50)

0.09 (0.04-0.27)

0.722

Glucocorticoids, n (%)

15 (27)

3 (12)

12 (40)

0.020

Biological Therapy, n (%)

23 (42)

9 (36)

14 (47)

0.301

DMARDs, n (%)

44 (80)

21(84)

23 (77)

0.233

ANG-2 (pg/mL)

726 (579-1027)

880 (659-1152)

702 (525-881)

0.038

VEGF-D (pg/mL)

32096 (17759-239749)

63479 (26346-600000)

27544 (9813-87872)

0.018

PlGF (pg/mL)

288 (147-994)

452 (180-1501)

237 (115-730)

0.043

SDF-1 (pg/mL)

280 (115-1648)

750 (157-3420)

165 (80-1127)

0.035

MMP-2 (pg/mL)

2738 (1909-4109)

3762 (2101-5779)

2403.5 (1870-3448)

0.027

bFGF (pg/mL)

314 (267-521)

383 (285-762)

295 (260-327)

0.007

 *Data are expressed as median (IQR) or as percentage. HS: synovial hypertrophy; RF: rheumatoid factor; ACPA: anti-citrullinated protein/peptide antibodies; DAS28: disease activity score; mHAQ: modified Health Status Questionnaire; ESR: erythrocyte sedimentation rate; DMARD: disease modifying anti-rheumatic drugs. ANG-2: angiopoietin-2; VEFG: vascular endothelial growth factor; PIGF: Placental Growth Factor. SDF: Stromal-cell derived factor-1; MMP-2: matrix metalloproteinase-2; bFGF: basic fibroblast growth factor.

Conclusion:

Around half of patients with RA in clinical remission presented active synovitis on  ultrasound. These patients have greater disease activity and higher serum levels of angiogenic factors. These findings are clinically and physiopathologically consistent and may help identify active synovitis in RA patients in clinical remission.

 This study is supported by a grant from Ministry of Economy, ISCIII, FIS 11/01890  and RD12/0006/0016 (JDC)


Disclosure:

J. Ramirez,
None;

V. Ruiz-Esquide,
None;

I. Pomés,
None;

R. Celis,
None;

J. Pomés,
None;

S. Cabrera,
None;

M. V. Hernández,
None;

O. M. Epis,
None;

J. L. Pablos,
None;

R. Sanmarti,
None;

J. D. Cañete,
None.

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