S.Z. Prodanovic

Matrix Metalloproteinases-3 Baseline Serum Levels in Early Rheumatoid Arthritis Patients Without Initial Radiographic Changes: A Two Year Ultrasonographic Study

Objective: To investigate the association of high baseline serum levels of metalloproteinases-3 (MMP-3) with structural damage to hand and feet joints, assessed by ultrasonography (US), in patients with early, treatment-naïve rheumatoid arthritis (RA), without initial X-ray-visible erosions, during 24 months follow-up. Methods: Sixty-three early RA (European League Against Rheumatism/American College of Rheumatology 2010), disease-modifying anti-rheumatic drugs/glucocorticoid naïve patients (mean age 53.4 ± 14.1) with symptom duration ≤12 months, had baseline serum levels of MMP-3 tested. OMERACT US group definition was used to detect the presence, as well as longitudinal diameter of erosions by US at study entry and after 24 months, at the level of wrists, metacarpophalangeal (MCP2/MCP5) joints of both hands, and fifth metatarsophalangeal joints. Results: Complete data were collected from 52 out of 63 patients. High baseline serum levels of MMP-3 (MMP-3-positive) were found in 46/63 patients. 122 bone erosions in total (1.9 bone erosions/patients) were detected by US at baseline visit and 213 erosions (4.3/patients) after 24 months. MMP-3 positive patients had significantly higher total number of erosions than MMP-3-negative (p = 0.039) and higher increase in size of bone erosions in the feet but not in the hand joints after follow-up (OR 4.82 [1.23–18.9], p = 0.024; OR 1.17 [0.320–4.26], p = 0.816 respectively). Conclusion: After 2 years of follow-up, US assessment showed a higher number of new bone erosions in MMP-3-positive compared to MMP-3-negative patients with early RA and no visible initial radiographic changes. High baseline levels of MMP-3 predict significantly higher structural damage progression at the level of feet, but not at the level of hand joints.

AB0243 The Importance of Biomarkers (RF, ACPA and MMP-3) Serum Levels of Rheumatoid Arthritis (RA) in Prediction Bone Erosions in Patients with Early RA and No Visible Radiographic Structural Damages-An Echosonographic Study

Background Rheumatoid factor (RF) and autoantibodies against citrullinated peptides/proteins (ACPA) has been recognized as an important predictor of more severe structural joint damage. Baseline matrix metalloproteinases 3 (MMP-3) serum levels were described as a predictor for the development of joint erosions.Ultrasonography is more sensitive than X-ray in detecting erosions in RA. Objectives to assess the importance of the RF, ACPA and MMP-3 serum levels in prediction of hands and feet bone erosions, detected by ultrasound (US) examination, in patients with early rheumatoid arthritis, without structural damage visible on X-ray. Methods A group of 65 patients (56 female, mean age 53.8±14.6 yrs.) with early RA (Eular/ACR 2010 classification criteria) and ≤1 year duration, (mean duration 3.8 month), were enrolled in the cross sectional clinical study. All patients had been disease-modifying anti-rheumatic drug (DMARDs) and glicocorticoid therapy naïve and had no visible structural damage on hands and feet X-ray. The serological markers of RA were measured: RF (normal concentration<16 U/ml), ACPA (normal concentration<20 IU/ml) and total MMP-3 (normal cut-off range for females: 18–60 ng/ml and males: 24–120 ng/ml). The levels above normal were reted as positive. Ultrasound examination of both hand (wrist, MCP2, MCP5 joints) and MTP5 joints was performed by Esaote My Lab 70 machine using 18 MHz linear probe. Findings of bone erosion were determined according to OMERACT US group definition. Collected data were analyzed in SPSS 16 system. Results Joint bone erosions were found in 59 (90.8%) pts. by US examination. Forty-two (64.6%) pts. were RF positive (mean concentration 88.8±108.2). The mean 2.1 vs.1.6 US bone erosions were detected in RF positive in comparison to RF negative pts. respectively. Forty-six (70.7%) pts. were ACPA positive (mean concentration 467.0±454.4) with mean bone erosions 1.9 vs.1.8 bone erosions in ACPA negative pts. Forty-six out of 63 (73.0%) pts were MMP-3 positive (mean concentration 185.1±241.0) with mean bone erosions 2.1 vs.1.5 bone erosions in MMP-3 negative pts. The 0.500 value of the area under the ROC curve is found for RF, 0.443 for ACPA and 0.627 value for MMP-3. The 75.4% sensitivity, 67% specificity (cut of 99.2 ng/ml) of MMP-3, 71.9% sensitivity, 50% specificity (cut of 232 IU/ml) of ACPA and 66.7% sensitivity, 67% specificity (cut of 79.5 U/ml) of RF were established in predicting US bone erosion. Conclusions Early RA patients with no visible structural damages on X-ray, and increased RF, ACPA and MMP-3 serum levels had higher number of bone erosions assessed by US. Baseline MMP-3 serum levels had the highest sensitivity in predicting joint bone erosions assessed by ultrasound examination. Disclosure of Interest None declared

AB0317 Do Cigarette Smoking Patients Have More Severe Early Rheumatoid Arthritis

Background Smoking in association with genetic factor can facilitate production of auto antibodies against citrullinated peptide and lead rheumatoid arthritis (RA) development (1). Objectives To investigate the influence of cigarette smoking on severity of early rheumatoid arthritis. Methods The 63 (85.7% female) early RA patients, mean age of 53.79±14.1 yrs. were enrolled in prospective observational study. All pts fulfilled EULAR/ACR 2010 criteria for diagnosis of early RA, had disease duration ≤12 months (in average 3.6 months) and have been without structural changes on radiography of hands and foot. Patients were treatment naïve for disease modifying anti-rheumatic drugs (DMARDs) and steroids. RA activity was assessed by the 28-joint disease activity score (DAS28-ESR) and bone erosions of hands and feet estimated by echosonography at the baseline, when early RA diagnosis was established and after 6 months of MTX (15 mg per week) therapy. Ultrasound examination was done by ESAOTE My Lab70 machine using 8-18 MHz linear probe according to OMERACT recommendations. The severity of smoking was estimated by pack/year: light (smoking ≤5 pack/yrs); moderate (5-20 pack/yrs) and heavy (≥20 pack/yrs), Anova statistical method was performed in data processing. Results The total 33 (52.4%) early RA pts had never smoked, 11 (17.4%) pts. had stopped smoking at list 2 years before early RA onset. Nineteen (30.2%) pts. were current smokers. Three (4.8%) pts were a light-smokers, thirteen (20.6%) pts. were a moderate-smokers and three (4.8%) pts were a heavy smokers. Initially, there was no statistical difference between group of RA non-smokers, light-smokers, moderate or heavy-smokers pts regarding value of DAS28 score (mean value: 5.7; 6.5; 5.2; 6.1 respectively, p=0.387) and number of echo erosions (mean value: 2.4; 1.7; 2.3; 3.3 respectively, p=0.814). The group of moderate and heavy-smokers had statistically significant less decrease in DAS28 score than non-smokers and light-smokers (mean value: 0.9; 0.9; 1.7; 3.2 respectively, p<0.05) after 6 months of treatment. However, there was no statistically significant difference between heavy-smokers and moderate-smokers in comparison to non-smokers and light-smokers in increasing number of new echo erosions (mean value: 1.7; 0.2; 0.3; 1.0 respectively, p>0.05) after six months of therapy with MTX. Conclusions After 6 months of MTX 15 mg/week treatment of sixty-three patients with early rheumatoid arthritis, non-smokers and light-smokers had significantly higher decrease of DAS28 score in comparison with group of moderate and heavy smokers. Number of new erosions observed by ultrasound was not significantly different between these groups. References Klareskog L, Stolt P, Lundberg K et al. Smoking May Trigger HLA–DR (Shared Epitope)–Restricted Immune Reactionsto Autoantigens Modified by Citrullination, Arthritis & Rheumatism 2006; 54 (1): 38–46. Disclosure of Interest None declared

FRI0043 Is ACPA and RF Finding Sensitive Marker of MTP5 Erosive Disease in Early Rheumatoid Arthritis Patients without X-RAY Changes?

Objectives To evaluate bone erosions of MTP5 joints in early rheumatoid arthritis (RA) patients (pts) without structural radiographic changes by echosonography and to investigate clinical importance of autoantibodies against citrullinated peptides/proteins (ACPA) and rheumatoid factor (RF) in its detection. Methods A group of 120 patients (85 female) with early RA (≤1 year duration, mean duration 5.4 month, (Eular 2010 classification criteria) were enrolled in the cross sectional study. None of the patients had erosions on radiographs of hands and feet and were not previously treated with DMARDs and/or glucocorticoid. Ultrasound (US) examination of MTP5 joints was performed by Esaote My Lab 70 machine equipped with 8-18 MHz linear probe. Finding of bone erosion was defined according to OMERACT US group definition. The following laboratory parameters in sera of pts were monitored: presence and concentration of ACPA, presence of RF, erythrocyte sedimentation rate (ESR) and level of CRP. Collected data were analyzed in SPSS 16 system. Results A 240 MTP5 joints out of 120 pts were assesed by US.The MTP5 bone erosion was found at 74 (61.7%) pts. Among 120 pts 88 pts were ACPA positive with 257.1 IU/ml mean concentration and 83 pts were RF positive. There was no statistically significant difference between group of pts with and without US detected bone erosions regarding age of pts (56.9 yr. vs 52.5 yr, p=0.333), duration of RA (5.8 vs 4.8 months, p=0.712) and ESR (60.2 vs 50.5, p=0.825). Patients with MTP 5 US detected bone erosion had statistically significant higher concentration of ACPA than pts without US detected bone erosions, (323.8 vs 151.3, p=0.005) and higher level of CRP (39.7 g/l vs 25.3 g/l, p=0.024). Sixty-one ACPA positive pts and 13 ACPA negative had US detected MTP5 bone erosions in opposite to 27 ACPA positive and 19 ACPA negative pts without them. The difference was statistically significant (p=0.01). Fifty-five pts with MTP5 US detected bone erosion had positive RF and 19 pts had RF negative in contrast to 28 RF positive and 18 RF negative pts without them. The difference was not statistically significant (p=0.155). The 0.66 value of the area under the ROC curve was found for ACPA and 0.57 value for RF. The 66% sensitivity and 61% specificity of ACPA and 74% sensitivity and 29% specificity of RF was established in detection of US MTP5 bone erosion for value on 174 of cut off. Conclusions Erosions of MTP 5 joints were detected by echosonography in 62% of early rheumatoid arthritis patients without erosions visible on X-ray. ACPA positivity was weakly associated with presence of MTP5 erosions. There was no significant correlation between US bone erosions and RF positivity. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4252

AB0968 Construct Validity of New Ultrasound Score Intended to Measure Damage of Small Joints in Patients with Rheumatoid Arthritis

Background Gray scale ultrasound (US) detects from 2 up to 9 times more erosions on B mode scans than standard radiographs of hand and feet in patients with rheumatoid arthritis (RA). Nowadays, mainly for research purposes, US erosions of small joints were semiquantitatively scored 0–3 according to the Szkudlarek and Scoring by UltraSound Structural erosion (ScUSSe) systems, respectively. Objectives To assess the construct validity of new US erosion score (USES) and ability of new method to detect erosions of small joints in patients with RA as well as to suggest a new USES for erosion quantification. Methods Sixty-three patients (48 females and 15 males) with clinically active disease were prospectively recruited at the Institute of Rheumatology, Belgrade, Serbia. All of them were treated with Methotrexate, or with other DMARDs, including biologic agents. The study was conducted in agreement with the Declaration of Helsinki and was approved by relevant ethics committee. The mean age of patients (S.D.) was 54.7 (12.7) years (range 24-78 years) and the mean disease duration was 28.8 (29.0) months (range 4-156 months). Forty-six pts (73.0%) were rheumatoid factor positive, and 45 pts (71.4%) anti-CCP positive. The patients underwent clinical and laboratory assessment, along with blinded power Doppler US (PDUS) and grey-scale (GS) US (GSUS) examination. A GSUS examination for presence, total surface, and total volume of erosions on 22 joints (2 wrists, 10 metacarpophlangeal joints – MCPs, and 10 metatarsophalangeal joints – MTPs) was performed by two independent examiners, blinded to clinical findings. GSUS examinations were based on standard EULAR reference scans, using US workstation Esaote My Lab 70xvg with 18 MHz linear probe. Surface USES (sUSES) was calculated as a sum of multiplications of long axis with short axis diameters of erosions, and volumetric USES (vUSES) as a sum of multiplications of long axis diameter, short axis diameter, and depth diameter of erosions. Results Five thousand five hundred and forty-four joint quadrants and 1386 joints were examined by two ultrasound operators. Erosions were detected by US in 264 (19,0%) joints. Strong positive linear correlation was found between s USES, vUSES and standard radiographic damage index, such as Sharp van der Heijde score (r=0.66, and r=0.67, respectively, p<0.001). Correlations between sUSES and vUSES with DAS28, HAQ, levels of ESR and CRP were weak and statistically insignificant, except between sUSES with serum levels of CRP (r=0.30, p<0.02). Conclusions Owing to our findings of strong positive linear correlation with the most utilized radiographic score (Sharp van der Heijde score), surface and volumetric ultrasound erosion scores showed at least decent ability to measure damage of hand and feet joints in patients with rheumatoid arthritis. Our next step in development of ultrasound erosion scores will be assessment of reliability and sensitivity to change of these scores in patients with early rheumatoid arthritis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2918

SAT0201 Relationship of Matrix Metalloproteinase-3 With Pulmonary and Joint Involvement in Scl-70 Positive Systemic Sclerosis Patients

Background Extracellular matrix degradation is regulated mainly by matrixmetalloproteinases (MMPs). MMP-3 can degrade many components of the extracellular matrix and an increase in serum MMP-3 concentration has been proposed as a synovial derived marker of inflammation. Objectives To determine matrix metalloproteinase-3 (MMP-3) serum levels in anti Scl 70 positive patients with systemic sclerosis (SSc) and to study clinical significance and the relationship between MMP-3 and pulmonary and joint involvement Methods Forty-seven anti-Scl 70 antibodies positive patients with systemic sclerosis (43 female, 4 male) and 50 healthy controls were included in the study. All SSc patients underwent standard assessment, including laboratory tests, physical examination with joint assessment, chest X-ray and pulmonary functional tests, including diffusion capacity for carbon monoxide (DLco) and forced vital capacity (FVC). Levels of MMP-3 were measured with specific ELISA kit (Aeskulisa DF) with normal range between 18-60 ng/ml for female and 24-120ng/ml for male. Results SSc patients had significantly higher MMP-3 concentration compared to healthy donors 122.64±188.40 vs. 57.4±46.79, p<0.001. Twenty-two (46.8%) SSs pts had increased MMP-3 levels above normal range and those had more frequently pulmonary fibrosis (p<0.001) and arthritis (p<0.001). Patients with increased levels of MMP-3 had significantly more frequently reduction in DLco <75% predicted (p<0.001). Conclusions In 47 patient with systemic sclerosis and anti-Scl 70 positive antibodies, high levels of MMP-3 significantly positively correlate with pulmonary fibrosis, DLCo < 75% predicted and joint involvement (arthritis). Disclosure of Interest None Declared