O. Sleglova

Serum hyaluronic acid as a potential marker with a predictive value for further radiographic progression of hand osteoarthritis

OBJECTIVE To compare serum levels of hyaluronic acid (HA) between patients with erosive and non-erosive hand osteoarthritis (HOA), and investigate its association with morphological changes and radiographic progression over 2 years. METHODS Fifty-five women with erosive and 33 women with non-erosive HOA were included in this study. All underwent clinical examination, which included assessment of pain, swelling, deformity and deviation of small hand joints and completed health assessment questionnaires. Serum levels of HA were measured by ELISA. Three-phase bone scintigraphy was performed at baseline. Radiographs of both hands were performed at baseline and after 2 years and scored according Kallman grading scale. RESULTS Serum levels of HA were significantly higher in patients with erosive than with non-erosive HOA (P<0.01). It correlated significantly with the number of hand joints with deviations and deformities. HA adjusted for age and disease duration significantly correlated with radiographs at baseline and after 2 years in all patients with HOA (r=0.560 and r=0.542, P<0.01 for both correlations). Although there was an association between HA and radiographic score in erosive disease, after adjustment for confounders it remained no longer significant. HA adjusted for confounders correlated significantly with the late phase in all patients with HOA (r=0.412, P<0.01) and in patients with erosive disease (r=0.320, P<0.05). CONCLUSION HA is increased in patients with erosive HOA and could be proposed as a surrogate marker with a predictive value for further radiographic progression of HOA in general. Further investigation is necessary to confirm these results.

Serum calprotectin (S100A8/9): an independent predictor of ultrasound synovitis in patients with rheumatoid arthritis.

IntroductionCalprotectin, a heterodimeric complex of S100A8/9 (MRP8/14), has been proposed as an important serum biomarker that reflects disease activity and structural joint damage in rheumatoid arthritis (RA). The objective of this cross-sectional study was to test the hypothesis that calprotectin is associated with clinical and ultrasound-determined disease activity in patients with RA.MethodsA total of 37 patients with RA (including 24 females, a mean disease duration of 20 months) underwent a clinical examination and 7-joint ultrasound score (German US-7) of the clinically dominant hand and foot to assess synovitis by grey-scale (GS) and synovial vascularity by power Doppler (PD) ultrasound using semiquantitative 0–3 grading. The levels of serum calprotectin and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined at the time of the ultrasound assessment. We analysed the relationship between serum calprotectin level, traditional inflammatory markers, and ultrasound-determined synovitis.ResultsThe levels of serum calprotectin were significantly correlated with swollen joint count (r = 0.465, p < 0.005), DAS28-ESR (r = 0.430, p < 0.01), ESR (r = 0.370, p < 0.05) and, in particular, CRP (r = 0.629, p < 0.001). Calprotectin was significantly associated with GS (r = 0.359, p < 0.05) and PD synovitis scores (r = 0.497, p < 0.005). Using multivariate regression analysis, calprotectin, adjusted for age and sex, was a better predictor of PD synovitis score (R2 = 0.765, p < 0.001) than CRP (R2 = 0.496, p < 0.001).ConclusionsThe serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of RA disease activity. These results suggest that calprotectin might be superior to CRP for monitoring ultrasound-determined synovial inflammation in RA patients.

Pentosidine, an advanced glycation end-product, may reflect clinical and morphological features of hand osteoarthritis.

The study investigates pentosidine levels, an advanced glycation end-product, in patients with erosive and non-erosive hand osteoarthritis (HOA) and determine its potential association with clinical findings and imaging-defined joint damage. Pentosidine was measured by HPLC in serum and urine of 53 females with HOA (31 erosive and 22 non-erosive HOA) and normalised to the total serum protein or urinary creatinine, respectively. Pain, joint stiffness and disability were assessed by the Australian/Canadian OA hand index (AUSCAN). The hand radiographs scored according to the Kallman grading scale were assessed to determine a baseline value and reassessed after two years. The levels of urine pentosidine, but not of serum pentosidine, were higher in patients with erosive HOA than in non-erosive HOA (p=0.039). Urinary pentosidine correlated with CRP (r=0.302, p=0.031), ESR (r=0.288, p=0.041) and AUSCAN (r=0.408, p=0.003). Serum pentosidine, but not in urine, significantly correlated with the Kallman radiographic score in erosive HOA at the baseline (r=0.409, p=0.022) and after 2 years (r=0.385, p=0.032). However, when corrected for age and disease duration, only correlation between urine pentosidine and AUSCAN remained significant (r=0.397, p=0.004). Our data suggest that serum and urine pentosidine levels may relate to the distinctive clinical and morphological features of HOA.

Serum Calprotectin Discriminates Subclinical Disease Activity from Ultrasound-Defined Remission in Patients with Rheumatoid Arthritis in Clinical Remission

Objective Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation. Methods Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0–1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves. Results The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58–67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity. Conclusion The present study demonstrates the potential of calprotectin to distinguish RA patients in both clinical and ultrasound-defined remission from patients in clinical remission but with residual subclinical disease activity.

Relationship between serum calprotectin (S100A8/9) and clinical, laboratory and ultrasound parameters of disease activity in rheumatoid arthritis: A large cohort study

Background Calprotectin may be a sensitive biomarker of rheumatoid arthritis (RA) disease activity. Objectives In the current study, we investigated whether calprotectin is a better biomarker than CRP for predicting clinical activity and ultrasound parameters in patients with RA. Methods A total of 160 patients with RA underwent clinical (swollen joint count—SJC, tender joint count—TJC, Disease Activity Score—DAS28, Clinical Disease Activity Index—CDAI, and simplified Disease Activity Index—SDAI) and ultrasound (German US7) examination. Clinical and laboratory measures were correlated with ultrasound findings using Spearman´s correlation coefficient. Differences in serum calprotectin levels in patients with variable disease activity according to the DAS28-ESR and CDAI scores were assessed using ANOVA. Multivariate regression analysis was used to determine the predictive values of calprotectin, CRP and SJC for CDAI and PD US synovitis scores. Results Serum calprotectin was significantly associated with DAS28-ESR (r = 0.321, p<0.001), DAS28-CRP (r = 0.346, p<0.001), SDAI (r = 0.305, p<0.001), CDAI (r = 0.279, p<0.001) scores and CRP levels (r = 0.556, p<0.001). Moreover, calprotectin was significantly correlated with GS (r = 0.379, p<0.001) and PD synovitis scores (r = 0.419, p<0.001). The multivariate regression analysis showed that calprotectin is a better predictor of the CDAI score and PD US synovitis than CRP. Conclusions The results of this study support an additional role of calprotectin in assessing inflammatory activity in patients with RA.

Chronic Low Back Pain: Current Pharmacotherapeutic Therapies and a New Biological Approach

Chronic low back pain (CLBP) syndrome represents one of the leading causes of long-term disability worldwide. The prevalence of CLBP has been rising significantly in relation to increasing average life expectancy. CLBP results from chronification of acute low back pain. There are many factors contributing to the CLBP crisis; common etiopathogenetic factors include e.g., functional blockage of intervertebral joints. The treatment of CLBP is complex. An important part of treatment consists of pain pharmacotherapy, for which several groups of drugs are used. The problem lies in the side effects of many of these traditionally used medications. Therefore, new and safer treatment methods are being sought. Innovative options for CLBP pharmacology include injections containing collagen, which can be combined with other traditionally used drugs, which helps reduce dosages and increase the overall safety of CLBP therapy.

Lower serum clusterin levels in patients with erosive hand osteoarthritis are associated with more pain

BackgroundThe aims of this study were to analyse the serum concentrations of clusterin (CLU) in patients with hand osteoarthritis (OA) and in healthy controls, to compare CLU levels between patients with erosive and non-erosive disease, and to examine the association of CLU levels with clinical and laboratory parameters.MethodsA total of 135 patients with hand OA (81 with erosive and 54 with non-erosive disease) and 53 healthy individuals were included in this study. All patients underwent clinical and hand joint ultrasound examination. The Australian/Canadian (AUSCAN) hand osteoarthritis index, algofunctional index and a visual analogue scale (VAS) for the measurement of pain were assessed. Serum levels of CLU were measured by an enzyme-linked immunosorbent assay (ELISA).ResultsSerum levels of CLU were significantly lower in patients with hand OA than in control subjects (p < 0.0001). In addition, patients with erosive hand OA had significantly lower CLU levels than those with non-erosive disease (p = 0.044). Negative correlations between CLU levels and pain as assessed by the AUSCAN score and the VAS were found in patients with erosive hand OA (r = − 0.275; p = 0.013 and r = − 0.220; p = 0.049, respectively).ConclusionThe present study demonstrates that lower concentrations of CLU are found in hand OA patients than in healthy individuals, especially in those with erosive disease, and that CLU concentrations have a negative association with hand pain.

OP0053 Bone loss and cardiovascular risk in patients with erosive and non-erosive hand osteoarthritis

Background Hand osteoarthritis (OA) and its more severe subset erosive hand OA are common causes of pain and morbidity. Some metabolic factors were suggested to be implicated in erosive disease. Furthermore, few studies investigated differences in systemic bone loss and cardiovascular risk factors between erosive and non-erosive hand OA. Objectives To compare bone mineral density (BMD) and major cardiovascular risk factors between patients with erosive and non-erosive hand OA in a cross-sectional study. Methods Patients with symptomatic disease fulfilling the American College of Rheumatology (ACR) criteria for hand OA were included in this study. Erosive hand OA was defined by at least one erosive interphalangeal joint. All patients underwent clinical assessments of joint swelling and radiographs of both hands. DEXA examination of lumbar spine, total femur and femur neck was performed. Metabolic risk factors (body mass index, hypertension, diabetes, dyslipidaemia) were collected. Patients were examined at baseline, one-year and two years follow-up. Results Altogether, 129 patients (12 male) with symptomatic nodal hand OA were included in this study and followed between April 2012 and January 2017. Out of these patients, 72 had erosive disease. The disease duration (p<0.01) was significantly higher in patients with erosive compared with non-erosive disease at baseline. Patients were taking symptomatic slow acting drugs (SYSADOA) twice a year, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics on demand. Baseline population characteristics did not differ between both groups. Osteoporosis (T-score <-2.5 SD) was diagnosed in 12.5% (9/72) of patients with erosive hand OA and in 8.06% (5/57) of patients with non-erosive hand OA. Although bone mineral density did not significantly differ between the groups, T-scores of lumbar spine (-0.46 vs. -1.04 SD, p<0.001), total femur (-0.36 vs. -1.20 SD, p<0.001) and femur neck (-0.92 vs. -1.20 SD, p<0.01) were significantly lower in patients with erosive compared with non-erosive disease. After two years, the decrease in T- score of lumbar spine was significantly higher in patients with erosive compared with non-erosive hand OA (-0.08 SD vs. 0.07SD, p<0.01; total difference between groups is 10.92%). The decrease of T-score in femur neck, total femur and the decrease of BMD (g/cm2) in all regions were also higher, although not significantly, in patients with erosive compared with non-erosive hand OA. In addition, more patients with erosive compared with non-erosive hand OA were treated for dyslipidaemia at baseline and after two years (32% vs. 28% and 32% vs.30%, p<0.01 for both comparisons). Conclusions These results suggest that patients with erosive hand OA are at risk for development of general bone loss and cardiovascular diseases. Acknowledgements This work was supported by the project MHCR No. 023728. Disclosure of Interest None declared

SAT0538 Progression of pain, number of clinically swollen joints and ultrasound detected synovitis and osteophyte formation in patients with hand osteoarthritis over two years

Background Hand osteoarthritis (HOA) is a common and frequent cause of pain. HOA is a heterogeneous group of disorders with two main subsets including non-erosive and erosive disease. Few studies demonstrated inflammatory ultrasound changes and more severe clinical symptoms in patients with erosive compared with non-erosive disease, however the results are inconsistent. Objectives he aim of this study was to evaluate progression of pain, stiffness, physical impairment and ultrasound features in patients with erosive and non-erosive HOA in a two years longitudinal study. Methods Consecutive patients with symptomatic HOA fulfilling the American College of Rheumatology (ACR) criteria were included in this study. Joint pain and swelling were assessed. Patients reported joint pain on 100 mm visual analogue scale (VAS). Pain, joint stiffness and disability were assessed by the Australian/Canadian OA hand index (AUSCAN). Radiographs of both hands were examined and erosive disease was defined by at least one erosive interphalangeal joint. Synovial hypertrophy and power Doppler signal (PDS) were scored with ultrasound. Synovitis was graded on a scale of 0–3 and osteophytes were defined as cortical protrusions seen in two planes. Patients were examined at baseline and at the two years follow-up. Results Altogether, 129 patients (12 male) with symptomatic nodal HOA were included in this study and followed between April 2012 and January 2017. Out of these patients, 72 had erosive disease. The disease duration (p<0.01) was significantly higher in patients with erosive compared with non-erosive disease. Pain (p<0.05) and the number of clinically swollen joints (p<0.05) were significantly higher in patients with erosive compared with non-erosive disease at baseline. There were significant progression of pain (p<0.05) and the number of clinically swollen joints (p<0.01) at the two years follow up. The progression in clinically swollen joint count was about 21% higher in patients with erosive disease. According to the AUSCAN, patients with erosive compared with non-erosive disease had more pain (p<0.05) and stiffness (p<0.01) at baseline. Pain and stiffness, but not function, got worse (p<0.01) in patients with erosive compared with non-erosive disease at the two years follow up. US-detected pathologies such as gray-scale synovitis total score (p<0.001), intensity of PDS (p<0.01) and number of osteophytes (p<0.01) were significantly higher in patients with erosive compared with non-erosive disease at baseline. There were improvements in gray-scale synovitis total score and intensity of PDS in patients with non-erosive disease while patients with erosive disease worsened at the two years follow up. On the other hand, the progression of US-determined osteophyte formation was observed in both groups. Conclusions The findings of this study show that pain and number of clinically swollen joints associated with US-detected synovial hypertrophy inflammatory signs and osteophyte formation is more severe in patients with erosive HOA than in patients with non-erosive disease. In addition, osteophyte formation is more likely to progress independent of synovial inflammation. Acknowledgements This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728. Disclosure of Interest None declared

FRI0532 Association between The 7-Joint Ultrasound Score (US7S) and Physical Function in Rheumatoid Arthritis

Objectives To investigate the longitudinal relationship between physical disability and US7S in a prospective cohort of patients with RA. Methods A cohort of 205 RA pts (49 incident/156 prevalent) (mean±SD age 55±14 years, 47% RF+, 63% ACPA+, DAS28-CRP 3.7±1.5, mHAQ 0.43±0.52, disease duration in incident vs. prevalent pts. 0.9±0.7 vs. 8.1± 8.3 resp.) was followed up longitudinally for 29±9 months. Assessments at baseline and at month 3 and 6, and then every 6 months comprised DAS28-CRP, functional evaluations using the modified Health Assessment Questionnaire (mHAQ) and an ultrasound assessment of the clinically dominant hand and foot by US7S1. US7S consists of 5 subscores for synovitis (syn) and tenosynovitis (ten) assessed by grey-scale (GS) and Power-Doppler (PD), and an erosions score (ES). A linear mixed model was used to assess the longitudinal relationship between US7 subscores and mHAQ. Univariate analyses with an interaction term for incident vs. prevalent disease, and a multivariate analysis (with age, sex, BMI, RF and ACPA status, and DAS28-CRP entered as covariates) were performed. Results In univariate analyses (table) mHAQ was longitudinally associated with GSsyn, PDsyn, PDten and GSten US7 subscores (with resp. β coefficients significantly higher in incident patients), while erosions score was a significant predictor of mHAQ only in prevalent pts. In a multivariate model the US7 subscores were individually no longer significant predictors of mHAQ, although the R2 of the model was improved by addition of US7 items from 43.6 to 46.9 (p<0.001 for improvement of R2).Table 1. Univariate analyses and interaction with incident (i)/prevalent (p) RA (predicted variable – mHAQ) Predictor RA β (95% CI) p-value* p-value** % variability explained – R2 DAS28-CRP all 0.112 (0.100; 0.123) <0.001 0.510 44.5 i 0.120 (0.093; 0.146) <0.001 p 0.110 (0.097; 0.123) <0.001 GSsynUS all 0.008 (0.004; 0.011) <0.001 0.038 3.2 i 0.014 (0.007; 0.021) <0.001 p 0.006 (0.002; 0.010) 0.002 PDsynUS all 0.012 (0.008; 0.016) <0.001 0.018 4.3 i 0.021 (0.012; 0.029) <0.001 p 0.009 (0.004; 0.014) <0.001 GStenUS all 0.018 (0.002; 0.035) 0.032 0.078 1.7 i 0.045 (0.011; 0.080) 0.010 p 0.010 (0.000; 0.020) 0.316 PDtenUS all 0.024 (0.012; 0.037) <0.001 0.032 2.0 i 0.053 (0.024; 0.083) <0.001 p 0.017 (0.010; 0.024) 0.013 ES all 0.009 (−0.003; 0.021) 0.145 0.062 0.3 i −0.021 (−0.055; 0.013) 0.216 p 0.013 (0.001; 0.026) 0.047 *p-value of significance of given β. **p-value of significance of difference between incident and prevalent RA. Conclusions This study provides evidence that RA related activity and damage reflected by US7S contribute to impaired physical function in RA, and their impact differs in early and established disease. When combined with conventional clinical parameters, the additional explanatory value of US7 for mHAQ was only minor. References Backhaus M. et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009 Sep 15;61(9):1194–201 Acknowledgement This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728, and IGA grant NT12437 Disclosure of Interest None declared