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Background/Aims The combined use of Power Doppler and B-mode ultrasound (PDUS) allows visualisation of morphological and pathophysiological changes of the synovium. ULTIMATE (NCT02662985) was the first large, randomised, double-blind, placebo-controlled PDUS phase IIIb study in psoriatic arthritis (PsA) to demonstrate that the validated Global OMERACT EULAR Synovitis Score (GLOESS), an ultrasound score at patient level, could detect the early and continuous decrease in synovitis in a multicentre setting using different ultrasound devices and examiners. Since the ultrasound assessment for GLOESS is time-consuming owing to the number of joints assessed, we investigated the ability of various reduced joint sets to predict GLOESS. Methods ULTIMATE was a 52-week study of secukinumab with a 12-week, double-blind, placebo-controlled period followed by a 12-week, open-label treatment period and 6-month open-label extension period. GLOESS for 24 paired joints was calculated, with a resultant potential score ranging from 0 to 144. Based on their composite PDUS scores, highly correlated joint clusters were identified with a Spearman’s rank correlation matrix and a Clustered Image Map. Representative joints were then selected from each group by various approaches (best correlation, model optimisation, etc.) yielding several joint combinations. For these reduced joint sets, GLOESS was predicted with linear models based on data from 60% of randomly selected patients from ULTIMATE. The remaining 40% of patient data were used for model validation and diagnostics. Results Five models were established with reduced pairs of joint sets (9-13 pairs) for PDUS-detected synovitis. The joints included in each linear model are summarised in the Table. All five reduced joint set models demonstrated scores very close to full 48 joint GLOESS (R2 ∼0.95); models 1-3 (based on 9 joint pairs) were less accurate at predicting GLOESS than models 4 and 5 (based on 13 and 12 joint pairs, respectively) for the secukinumab cohort in the open-label part (data to be shown in poster). Conclusion All models of reduced joint sets for PDUS-detected synovitis predicted GLOESS well. The next steps will be to document responsiveness and ability to discriminate between active and placebo treatment. Disclosure P.G. Conaghan: Consultancies; P.G.C. has received consultancy fees from AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Janssen, Merck, Novartis and Pfizer, Stryker and UCB. Member of speakers’ bureau; P.G.C. has received speakers bureau fees from AbbVie, Novartis and Pfizer. M. D'agostino: Consultancies; M.A.D'A. has received consultancy fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Roche, Sanofi, and UCB. Member of speakers’ bureau; M.A.D'A. has received speakers bureau fees from AbbVie, BMS, Celgene, Eli Lilly, Janssen, Novartis, Roche, Sanofi and UCB. M. Boers: Consultancies; M.B. has received consultancy fees from Novartis. E. Naredo: Honoraria; E.N. has received honoraria for clinical trials from AbbVie, BMS and Novartis. Member of speakers’ bureau; E.N. has received speakers bureau fees from AbbVie, BMS, Celgene GmbH, Janssen, Lilly, Novartis, Pfizer, Roche and UCB. Grants/research support; E.N. has received research grants from Eli Lilly. P. Mandl: Member of speakers’ bureau; P.M. has received speakers bureau fees from AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche and UCB. Grants/research support; P.M. has received grant/research support from AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Roche and UCB. P. Carron: Consultancies; P.C. has received consultancy fees from AbbVie, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Gilead, Merck Sharp Dohme, Novartis, Pfizer and UCB. Member of speakers’ bureau; P.C. has received speakers bureau fees from AbbVie, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Gilead, Merck Sharp Dohme, Novartis, Pfizer and UCB. Grants/research support; P.C. has received grant/research support from Merck Sharp Dohme, Pfizer and UCB. M. Backhaus: Consultancies; M.B. has received consultancy fees from BMS, Galapagos, Jonsson, MSD, Novartis, Pfizer, Roche and UCB. Member of speakers’ bureau; M.B. has received speakers bureau fees from BMS, Galapagos, Jonsson, MSD, Novartis, Pfizer, Roche and UCB. Grants/research support; M.B. has received grant/research support from BMS, Galapagos, Jonsson, MSD, Novartis, Pfizer, Roche and UCB. A. López-Rodríguez: Consultancies; A.L.R. has received consultancy fees from Eli Lilly, GSK, Janssen, Novartis, Roche and UCB. Member of speakers’ bureau; A.L.R. has received speakers bureau fees from Eli Lilly, GSK, Janssen, Novartis, Roche and UCB. P. Hanova: Consultancies; P.H. has received consultancy fees from Novartis. P. Goyanka: Other; P.G. is an employee of Novartis. B.G. Sahoo: Other; B.G.S. is an employee of Novartis. C. Gaillez: Shareholder/stock ownership; C.G. is a shareholder of Novartis and BMS. Other; C.G. is an employee of Novartis. W. Bao: Shareholder/stock ownership; W.B. is a shareholder of Novartis. Other; W.B. is an employee of Novartis.

Objectives To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. Methods A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. Results The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. Conclusion The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.

Individuals carrying anti-citrullinated protein antibodies (ACPA) are considered at high risk of developing rheumatoid arthritis (RA). The altered expression of miRNAs contributes to the pathogenesis of RA. We aimed to identify differentially expressed miRNAs in the peripheral blood of ACPA-positive individuals with arthralgia at risk of RA compared to healthy controls (HC) and to determine their implications in the preclinical phase of RA. A comprehensive analysis of miRNAs revealed the dysregulation of miR-451 in peripheral blood mononuclear cells (PBMC) and plasma from RA-risk individuals. Higher miR-451 expression in PBMC from RA-risk individuals was further validated. Notably, miR-451 was previously shown to regulate CXCL16, a protein involved in RA pathogenesis. The expression of miR-451 in PBMC positively correlated with the CXCL16 mRNA, which could be secondary to the inflammation-induced expression of miR-451. Transfection of monocytes with pre-miR-451 in vitro resulted in the downregulation of CXCL16. Moreover, flow cytometry revealed a lower count of CXCL16-positive monocytes in RA-risk individuals. We propose that the constitutive or inflammation-induced upregulation of miR-451 in PBMC downregulates the expression of CXCL16, reduces the inflammatory milieu and thereby strives to delay the shift from the preclinical phase to the clinical manifestation of RA. This hypothesis warrants further investigation.

Background: There is no international consensus on an optimal ultrasound score for monitoring of rheumatoid arthritis (RA) on patient-level yet. Our aim was to reassess the US7 score for the identification of the most frequently pathologic and responsive joint/tendon regions to optimize it and contribute to an international consensus. Furthermore, we aimed to evaluate the impact of disease duration on the performance of the score.Methods: RA patients were assessed at baseline and after 3 and 6 months of starting/changing DMARD therapy by the US7 score in greyscale (GS) and power Doppler (PD). The frequency of pathologic joint/tendon regions and their responsiveness to therapy were analyzed by Friedman test including the comparison of palmar vs. dorsal regions (Chi-square test). The responsiveness of different reduced scores and the amount of information retained from the original US7 score were assessed by standardized response mean/linear regression. Analyses were also performed separately for early and established RA.Results: A total of 435 patients (N=138 early RA) were included (56.5 (SD 13.1) years old, 8.2 (9.1) years disease duration, 80% female). The dorsal wrist, palmar MCP2, extensor digitorum communis (EDC) and carpi ulnaris (ECU) tendons were most frequently affected by GS/PD synovitis/tenosynovitis (wrist: 45%/43%; MCP2: 35%/28%; EDC: 30%/11% and ECU: 25%/11%) and significantly changed within 6 months of therapy (all p≤0.003 by GS/PD). The dorsal vs. palmar side of the wrist by GS/PD (pConclusions: The wrist, MCP2, EDC and ECU tendons were most frequently pathologic and responsive to therapy in both early and established RA and should therefore be included in a comprehensive score for monitoring RA patients on patient-level.

Background/Aims Power Doppler ultrasound (PDUS) is a sensitive non-invasive imaging tool to visualize a wide range of articular and periarticular inflammation in psoriatic arthritis (PsA). ULTIMATE (NCT02662985) is the first large RCT that used ultrasound with Global OMERACT ultrasound synovitis score (GLOESS) as the primary endpoint, to demonstrate early benefits of secukinumab on synovitis in patients with PsA through 12 weeks. Here we report the responsiveness of ultrasound on synovitis and enthesitis, clinical efficacy, and safety of secukinumab up to 52 weeks. Methods This was a 52-week study with 12-week double-blind placebo-controlled treatment followed by 12-week open-label treatment and 6-month open-label extension treatment in all patients. Synovitis and ultrasound enthesitis response were measured by GLOESS and Global OMERACT enthesitis score (definitions 1 and 2) at patient level, respectively. Other assessments across key PsA manifestations of joints (ACR responses), enthesitis, (SPARCC), skin (PASI responses), dactylitis (LDI) and physical function (HAQ-DI) were also evaluated. Data are presented as observed. Results A total of 166 patients were enrolled, of which 90% (75/83) of secukinumab and 83% (69/83) of placebo-secukinumab participants completed 52 weeks. A continued improvement in GLOESS was observed in both secukinumab and placebo-secukinumab groups after switching to active therapy at Week 12 through Week 52 and a similar trend of improvement in Global OMERACT enthesitis score (definition 1 and 2) was observed up to 52 weeks in both groups (Table). At 52 weeks, sustained clinical response rates were observed in secukinumab (ACR20, 89%; ACR50, 68%; ACR70, 48%; PASI 90, 59%; PASI 100, 55%) and placebo-secukinumab groups (ACR20, 84%; ACR50, 72%; ACR70, 47%; PASI 90, 74%; PASI 100, 48%). Mean changes from baseline at Week 52 in HAQ-DI and SPARCC were -3.0 and -0.8 and -3.6 and -0.7 for secukinumab and placebo-secukinumab, respectively. There were no new or unexpected safety findings. Conclusion ULTIMATE demonstrated the responsiveness of ultrasound on both synovitis and enthesitis outcomes in PsA supporting its use in clinical trials, and confirmed the rapid and continued benefits of secukinumab through 52 weeks. Sustained efficacy was also observed across key clinical PsA manifestations with a safety profile consistent with previous reports. Disclosure P.G. Conaghan: Consultancies; AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer. Member of speakers’ bureau; AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer. M.A. D’Agostino: Consultancies; Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, Eli Lilly. Member of speakers’ bureau; Sanofi, Novartis, BMS, Janssen, Celgene, Roche, AbbVie, UCB, Eli Lilly. G. Schett: Member of speakers’ bureau; AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche, UCB. C. Guerrero: None. P. Hanova: None. T. Cazenave: None. M.S. Stoenoiu: Honoraria; Roche, AbbVie, BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; Roche, AbbVie, UCB. Grants/research support; Roche, AbbVie, UCB. M. Backhaus: Honoraria; Roche, AbbVie, BMS, Gilead, Jonsson, MSD, Novartis, Pfizer, UCB. Member of speakers’ bureau; Roche, AbbVie, UCB. Grants/research support; Roche, AbbVie, UCB. G. Mouterde: Consultancies; AbbVie, Lilly. Honoraria; AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, Chugai, UCB. Grants/research support; Celgene, Pfizer. M. Boers: Consultancies; BMS, Novartis, Pfizer, GSK. A. Duggan: Other; Employee of Novartis. P. Goyanka: Other; Employee of Novartis MSD. C. Gaillez: Shareholder/stock ownership; Novartis, BMS. Other; Employee of Novartis.

ObjectivesTo develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.MethodsThe OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima–media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24.ResultsAgreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72–0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from −1.19 to −2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff0.37–0.48).ConclusionWe developed a provisional OGUS for potential use in clinical trials.

Two-hundred patients were assessed for the presence of genetic allelic variants using PCR amplification and direct sequencing.In 19 patients, we detected genetic allelic variants affecting TPMT activity; in 1 case, it was an unpublished heterozygous variant c.85TC (p.W29R); of those, 15 patients were switched from AZA to a different medication, and 1 patient was prescribed a reduced dose of AZA.Our findings show the importance of testing for variants of the TPMT gene before the administration of AZA in clinical rheumatology practice. Patients with documented episodes of leukopenia or elevated liver biochemical tests while on AZA should undergo TPMT genotype testing and/or TPMT enzyme activity testing.

Background To assess the reliability of the consensually agreed US definitions of major salivary gland lesions and the US scoring system for salivary gland assessment in patients with SS. Methods Nine experienced sonographers scanned and read the US images of both parotid glands (PGs) and submandibular glands (SMGs) in eight patients with primary and secondary SS in two rounds. A consensually agreed four-grade semi-quantitative scoring was applied in B-mode for morphological lesions: grade 0, normal; grade 1, mild inhomogeneity without anechoic or hypoechoic areas; grade 2, moderate inhomogeneity with focal anechoic or hypoechoic areas; grade 3, severe inhomogeneity with diffuse an- or hypoechoic areas occupying the entire gland or fibrous gland. The presence or absence of typical SS lesions, i.e. the Sjögren’s signature, was scored binary. Intra- and interreader reliabilities were computed using weighted and unweighted Cohen’s and Light’s κ coefficients. Results The mean prevalence of grades 0–3 in PG were 43, 17, 23 and 31% and 28, 14, 33 and 32% for the SMGs, respectively. The weighted κ for intrareader reliability ranged from 0.44 to 1 for grading and 0.64 to 1 for the Sjögren’s signature of PG and 0.59 to 1 and −0.09 to 0.6 for SMGs, respectively. The interreader reliability κ for grading in PG was 0.62 (95% CI 0.47, 0.74) and for Sjögren’s signature it was 0.36 (95% CI 0, 0.43); in SMG it was 0.62 (95% CI 0.47, 0.72) and 0.03 (95% CI 0, 0.07) respectively. Conclusions The consensually agreed novel US scoring system for major salivary gland lesions showed substantial intra- and interreader reliability in patients with SS. The reliability of the Sjögren’s signature was moderate.

Objectives Individuals carrying antibodies against citrullinated proteins (ACPA) are at high risk of developing RA. EULAR provided a clinical definition of individuals with arthralgia suspicious for progression to RA (clinically suspect arthralgia, CSA). The alteration of monocyte subpopulations in patients with established RA has been previously described. We analysed peripheral blood monocyte subpopulations in individuals with arthralgia at risk of RA. Methods We included 70 at-risk individuals, defined as having arthralgia without arthritis and being either ACPA+ or meeting the clinical CSA definition, 23 patients with early RA (ERA) and 19 healthy controls (HCs). Monocytes classified as classical (CD14++CD16−), intermediate (CD14++CD16+/++) and nonclassical (CD14−/+CD16++) were analysed by flow cytometry. Results Of the 70 at-risk individuals, 46 were ACPA+ and 45 met the CSA definition. The at-risk individuals and, especially, ERA patients had a lower percentage of classical monocytes and a higher percentage of nonclassical monocytes than the HCs. ACPA positivity had no effect on the difference in the distribution of the monocyte subsets between at-risk individuals and ERA patients, but a difference was determined in those reaching the ERA phase. However, when compared with HCs, the shift of monocyte subsets was more significant in ACPA+ than in ACPA− individuals with arthralgia. This trend was observed in individuals who did not meet the CSA definition. This finding was, however, determined by a selection bias, as these individuals were solely ACPA+. Conclusion The shift from classical to nonclassical monocyte subpopulations was observed already in individuals at risk of developing RA.

Background:Enthesitis is a key clinical domain and imaging hallmark of psoriatic arthritis (PsA). Ultrasound (US) is a highly sensitive tool for detecting synovitis and enthesitis in PsA. The Outcome Measures in Rheumatology Initiative (OMERACT) has developed an US definition and scoring system of enthesitis for clinical studies.1 The ULTIMATE study (NCT02662985) is the first large double-blind (DB), placebo-controlled phase IIIb study designed to demonstrate a rapid and significant benefit of subcutaneous secukinumab vs. placebo on US detected synovitis in patients with PsA.2Objectives:To report the enthesitis response to secukinumab over 24 weeks using two novel US composite enthesitis scores.Methods:This was a 52-week study consisting of a 12-week DB, a 12-week open-label (OL) and a 6-month extension period.2 Inclusion criteria required ≥1 clinical enthesitis as per SPARCC enthesitis index, but not US-assessed enthesitis.2 Patients were randomised (1:1) to either weekly secukinumab (300 or 150 mg according to severity of skin psoriasis) or placebo followed by 4-weekly dosing thereafter. All placebo patients switched to OL secukinumab (placebo-secukinumab) at Week 12. Throughout the study, enthesitis was assessed with SPARCC and US. Six anatomical sites were assessed bilaterally with US: insertions of lateral epicondyle tendons, quadriceps, patellar ligaments (distal and proximal insertions), Achilles tendons and plantar fascia. Two exploratory global OMERACT-US enthesitis scores were tested: Definition 1 combining power Doppler (PD; 0–3) and Grey Scale (0–1) inflammation and Definition 2 rating PD only (0–3) across the six anatomical sites. Data were analysed with mixed-effect model repeated measures (MMRM) up to Week 12 and as observed from Week 12 to 24. The comparison of OMERACT-US enthesitis score within treatment groups was tested with paired and between treatment groups with unpaired t-tests.Results:Of 166 patients enrolled, 93% completed 24 weeks of treatment (secukinumab, 95%; placebo-secukinumab, 92%). The average clinical enthesitis count at baseline was 4. Since the presence of PD was not a mandatory inclusion criterion, a higher proportion of patients met Global OMERACT-US enthesitis score with Definition 1 vs. Definition 2 (81% vs. 33%) at baseline (Table). Mean reduction from baseline to Week 24 in SPARCC enthesitis index was 3 each for initial secukinumab and placebo-secukinumab groups. Resolution of enthesitis (SPARCC) was 46% for initial secukinumab and 54% for placebo-secukinumab groups at Week 24. A comparable decrease in OMERACT-US enthesitis (Definition 1 and 2) score was observed from baseline to Week 24 for initial secukinumab and placebo-secukinumab groups (Figure).Table 1.Distribution of US detected enthesitis at baseline according to OMERACT enthesitis score Definition 1 and 2SecukinumabPlaceboDef 1 >0Def 2 >0Def 1 >0Def 2 >0N=73346120Anatomical sites, %Achilles tendon4912452Lateral epicondyle49214621Patellar ligament distal insertion348294Patellar ligament proximal insertion3410184Plantar fascia360280Quadriceps insertion5512402Proportion of patients is irrespective of the enthesitis site left or right side. N, total number of patientsConclusion:A consistent clinical and US response on enthesitis was shown through 24 weeks across initial secukinumab and placebo switcher groups. While ULTIMATE has demonstrated the responsiveness of these global OMERACT-US enthesitis scores, further work is required to test these scores in PsA cohorts with inclusion criteria for both clinical and US enthesitis.References:[1]Balint PV, et al. Ann Rheum Dis. 2018;77:1730-5.[2]D’Agostino MA, et al. Arthritis Rheumatol. 2020;72(suppl 10).Disclosure of Interests:Maria-Antonietta D’Agostino Speakers bureau: Sanofi, Novartis, BMS, Janssen, Celgene, AbbVie, UCB pharma and Eli Lilly, Consultant of: Sanofi, Novartis, BMS, Janssen, Celgene, AbbVie, UCB pharma and Eli Lilly, Philip G Conaghan Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis and Pfizer, Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, Galapagos, Gilead, Novartis and Pfizer, Corine Gaillez Shareholder of: Novartis and BMS, Employee of: Novartis, Maarten Boers Consultant of: BMS, Novartis, Pfizer, and GSK, Esperanza Naredo Speakers bureau: AbbVie, Roche, BMS, Pfizer, UCB, Eli Lilly, Novartis, Janssen and Celgene, Consultant of: AbbVie, Novartis and BMS, Grant/research support from: Eli Lilly, Philippe Carron Speakers bureau: Pfizer, MSD, Novartis, BMS, AbbVie, UCB, Eli Lilly, Gilead and Celgene, Consultant of: Pfizer, MSD, Novartis, BMS, AbbVie, UCB, Eli Lilly, Gilead and Celgene, Grant/research support from: UCB, MSD and Pfizer, Petra Hanova: None declared, Tomás Cazenave: None declared, Catherine Bakewell Speakers bureau: AbbVie, Novartis, Sanofi Genzyme, and consulting honoraria from Pfizer, UCB, and Janssen, Consultant of: AbbVie, Novartis, Sanofi Genzyme, and consulting honoraria from Pfizer, UCB, and Janssen, Anne-Marie Duggan Employee of: Novartis, Punit Goyanka Employee of: Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Roche and UCB pharma

Homer’s Iliad tells the epic story of the Trojan War, a 10-year siege of the city of Troy, conducted by an alliance of Greek kings1. According to Homer, the reason for the Trojan war was the abduction of the most beautiful of women, Helen, by the Trojan prince Paris. Since the excavation works of the German archeologist Heinrich Schliemann, we know that the city indeed existed on the northwestern coast of Turkey. The Iliad gives an account of only the 10th year of the siege, in which the Greek warrior Achilles slays Hector, the commander of the Trojan army, and drags him for 9 days behind his chariot around the city. According to Greek mythology, Achilles was unbeatable, yet vulnerable for a single spot of his body where his mother held him as a baby while dipping him in the river Styx. Following the death of Hector, Paris shot an arrow guided by the god Apollo at Achilles. The arrow struck Achilles right at the enthesis of the tendon in the heel, presumably leaving him defenseless on the battlefield and leading to his death. Homer’s poems clearly illustrate the mechanical vulnerability of the entheses, although the poet could not be aware of the mechanoinflammatory entheseal concepts 2800 years ago. In their report entitled “Entheseal changes in response to age, body mass index, and physical activity: an ultrasound study in healthy … Address correspondence to Dr. G. Bruyn, MC Groep Hospitals, Department of Rheumatology, Lelystad 8333 AA, the Netherlands. E-mail: gawbruyn{at}wxs.nl

Background:During the transition to rheumatoid arthritis (RA) patients pass through several phases. In the preclinical phase, the presence of anti citrullinated protein antibodies (ACPA) can be detected [1]. A set of clinical characteristics for patients with arthralgia who are at risk of progression to RA was established (clinically suspected arthralgia; CSA) [2]. Ultrasound (US) is more sensitive diagnostic tool in detecting synovitis than clinical assessment and was recommended to use in diagnostics of RA.Objectives:To test if ultrasound-detected synovitis among patients at risk of progression to RA increases the risk of developing clinical arthritis (CA) in the future.Methods:ACPA+ individuals with arthralgia and/or those fulfilling CSA criteria were enrolled into the study and were assessed in 3 months interval (routine clinical investigation with laboratory tests, 68-joint count, US assessment). Tender and swollen joint counts were provided by an independent investigator. Sonographer was blinded to all clinical and laboratory data. CA was defined as clinically swollen and tender joint. All US assessments were provided by a single experienced investigator. Thirty joints US score was assessed bilaterally in wrist, MCP I-V, PIP II-V (dorsal and palmar approach), MTP II-V (dorsal approach), ankle (dorsal, medial and lateral approach). US synovitis was defined according the EULAR-OMERACT and scored separately in gray-scale (GS) 0-3 (zero to severe synovitis) and Power Doppler (PD) 0-3 (zero to high activity). Scores were calculated as sum scores. For the statistical analysis, we used GraphPad Prism 8.0.0 software (Wilcoxon-Mann-Whitney test), and relative risk ratio (RR).Results:93 patients were enrolled into the study (95% female). 58 patients were ACPA+ (all of them RF+), 35 were ACPA- (10 of them RF+). Of ACPA+ individuals, 100% fulfilled the CSA criteria, all seronegative individuals met the CSA criteria. At baseline, GS≥1 was detected in 69 patients (74%), PD≥1 was in 26 (28 %) patients. Single erosion was found by US in 1 patient (0,9%) at baseline. 14 patients (15%) developed CA within 30 months, 77% of them till month 10 from the baseline. No statistical difference in US synovitis score was found between ACPA+ vs. ACPA- and CSA+ vs. CSA- groups at baseline. RR to develop CA at the joint level in patients with GS≥1 at baseline was 1.37 (95% CI 0.99-1.89; pConclusion:US-detected synovitis in patients at risk of RA further increases the risk of developing clinical arthritis in the future. US detected synovitis in joints appear about 3 months prior synovitis detected by routine clinical assessment.References:[1]Bos, W. H., Wolbink, G. J., Boers, et al. Arthritis development in patients with arthralgia is strongly associated with anti- citrullinated protein antibody status: a prospective cohort study. Annals of the Rheumatic Diseases, 2010;69(3):490-4.[2]van Steenbergen HW, Aletaha D, Beaart-van de Voorde LJJ, et al. EULAR definition of arthralgia suspicious for progression to rheumatoid arthritis. Annals of the Rheumatic Diseases 2017;76:491-6.Acknowledgments:Project AZV-17-32612ADisclosure of Interests:Petra Hanova: None declared, Klára Prajzlerová: None declared, Nora Petrovská: None declared, Monika Gregová Consultant of: Novartis, Abbvie, Paid instructor for: Novartis, Speakers bureau: Novartis, Abbvie, MSD, Heřman Mann: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiří Vencovský: None declared, Ladislav Šenolt: None declared, Mária Filková: None declared

ObjectiveTo develop ultrasound (US) definitions and a US novel scoring system for major salivary gland (SG) lesions in patients with primary Sjögren’s syndrome (pSS) and to test their intrareader and inter-reader reliability using US video clips.MethodsTwenty-five rheumatologists were subjected to a three-round, web-based Delphi process in order to agree on (1) definitions and scanning procedure of salivary gland ultrasonography (SGUS): parotid, submandibular and sublingual glands (PG, SMG and SLG); (2) definitions for the elementary SGUS lesions in patients with Sjögren’s syndrome; (3) scoring system for grading changes. The experts rated the statements on a 1–5 Likert scale. In the second step, SGUS video clips of patients with pSS and non-pSS sicca cases were collected containing various spectrums of disease severity followed by an intrareader and inter-reader reliability exercise. Each video clip was evaluated according to the agreed definitions.ResultsConsensual definitions were developed after three Delphi rounds. Among the three selected SGs, US assessment of PGs and SMGs was agreed on. Agreement was reached to score only greyscale lesions and to focus on anechoic/hypoechoic foci in a semiquantitative matter or, if not possible on a qualitatively (present/absent) evaluation of fatty or fibrous lesions. Intrareader reliability for detecting and scoring these lesions was excellent (Cohen’s kappa 0.81) and inter-reader reliability was good (Light’s kappa 0.66).ConclusionNew definitions for developing a novel semiquantitative US score in patients with pSS were developed and tested on video clips. Inter-reader and intrareader reliabilities were good and excellent, respectively.

Background: Antibodies against citrullinated proteins (ACPA) are present months to years before the clinical manifestation of rheumatoid arthritis (RA). ACPA+ individuals are at 8-10x higher risk of developing RA compared to seronegative individuals. EULAR characterised individuals with arthralgia suspicious for progression to RA based on their clinical features (clinically suspect arthralgia, CSA). Objectives: The alteration of natural killer (NK) cells and monocyte subpopulations in patients with established RA has been previously described. We therefore aimed to study the lymphocyte and monocyte subpopulations in individuals in the preclinical phase of RA. Methods: Our study included 49 individuals with arthralgia (mean age 45.97±11.95 years; 92% females) and 80 age and gender matched healthy controls (HC). Leukocytes from peripheral blood were analysed by flow cytometry. Lymphocyte subpopulations were defined as B (CD19+CD3-), T (CD3+CD4+, CD3+CD8+) and NK (CD16/56+CD3-) cells. Monocytes were further classified to classical (CD14++CD16-), intermediate (CD14++CD16+/++) and non-classical (CD14-/+CD16++) subsets. Data were analysed using Mann Whitney test and expressed as median and interquartile range [IQR]. Results: Out of 49 individuals with arthralgia, 36 were ACPA+ and 28 met CSA definition (15 of them were ACPA+), with symptoms duration 21 months [IQR=53], CRP 3.18 mg/L [IQR=3.6], DAS28 score 2.28 [IQR=1.31]. As per definition, there was no evidence of clinical arthritis on examination of 66 joints at baseline. Ten individuals developed RA within a median of 4 months of follow up. Individuals with arthralgia had higher%CD3+ T cells (78.10 [8.10] vs. 75.04 [9.26], p=0.001) and lower%NK (11.20 [7.20] vs. 12.89 [6.62], p≤0.001) as well as absolute count of NK cells (0.18 [0.13] vs. 0.24 [0.17], p≤0.001) compared to HC. Similarly, higher%CD3+ T cells (77.95 [8.65] vs. 75.04 [9.26], p=0.003) and lower%NK (10.85 [7.81] vs. 12.89 [6.62], p=0.003) and absolute count of NK cells (0.20 [0.14] vs. 0.24 [0.17], p=0.003) was confirmed in a subgroup of ACPA+ individuals compared to HC. Moreover, individuals who developed RA during follow up, had a lower baseline absolute count of NK cells (0.14 [0.10] vs. 0.19 [0.15], p=0.039). Analysis of monocyte subpopulations revealed higher count of non-classical (5.99 [4.87] vs. 4.03; IQR [3.28], p=0.022) and intermediate (5.82 [2.93] vs. 4.31 [2.08], p=0.034) monocytes and lower count of classical monocytes (86.06 [7.69] vs. 89.41 [3.52], p=0.005) in individuals with arthralgia compared to HC. Specifically, also ACPA+ patients had higher count of non-classical (6.07 [5.84 vs. 4.03 [3.28, p=0.020) and intermediate (5.86 [3.05] vs. 4.31 [2.08], p=0.036) and lower count of classical (85.43 [8.34] vs. 89.41 [3.59], p=0.005) monocytes compared to HC. There was no difference in% or absolute count of lymphocytes and monocytes subpopulations at the time of manifestation of RA and between ACPA+ and ACPA- individuals. Conclusion: We show lower numbers of NK cells and classical monocytes and expansion of intermediate and non-classical monocytes in individuals in the preclinical phase of RA, especially in ACPA+ individuals. Such disproportion or pro-inflammatory potential of these cells was previously shown in the pathogenesis of established RA. We hypothesize that the dysregulation observed in at-risk individuals may be a prognostic marker and a predisposition leading to further development of RA. Acknowledgement: Projects AZV-17-32612A and MHCR 023728 Disclosure of Interests: Klara Prajzlerova: None declared, Olga Krystfkova: None declared, Petra Hanova: None declared, Hana Hulejova: None declared, Monika Gregova: None declared, Karel Pavelka: None declared, Jiři Vencovský Consultant for: Samsung, Speakers bureau: AbbVie, Novartis, Pfizer, Sanofi, Eli Lilly, Biogen, UCB, MSD, Werfen, Roche, Ladislav Senolt Grant/research support from: AbbVie, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene Corporation, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Amgen, Takeda, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Maria Filkova: None declared

Background:Natural killer (NK) cells and non-conventional T cells (NK-T and γδ-T cells) are involved in the regulation of immune system and their alteration was previously described in patients with established rheumatoid arthritis (RA). The positivity of antibodies against citrullinated proteins (ACPA) significantly increases the risk of progression to RA. The clinical characteristics of individuals at risk of progression to RA (clinically suspect arthralgia, CSA) has recently been established by EULAR irrespective of the ACPA status.Objectives:We aimed to study lymphocyte subpopulations in individuals at risk of developing RA.Methods:Our study included 95 individuals with arthralgia at risk of developing RA based on ACPA positivity and/or meeting CSA definition and 70 age and gender matched healthy controls (HC). Whole blood samples were analysed by flow cytometry. The percentage and absolute count of CD3+ T cells, CD3-CD16/56+ NK cells, CD3+CD16/56+ NK-T cells and CD3bright γδ-T cells were evaluated in CD45+CD14- lymphocyte populations.Results:Out of 95 individuals with arthralgia (median age 47 years [IQR=16], 92% females), 58 were ACPA+ and 62 met CSA definition (26 of them were ACPA+). Median symptom duration was 12 months [IQR=53], CRP 2.43 [IQR=3.32]. As per definition, there was no evidence of clinical arthritis on examination of 66 joints at baseline. Fourteen individuals developed RA within a median of 3 months of follow up with CRP 4.34 [IQR=17.46] and DAS28(CRP) score 4.84 [IQR=2.43].Analysis of lymphocyte subpopulations showed higher %CD3+ T cells (p=0.001) and lower %NK (p=0.002) as well as absolute count of NK (p≤0.001), NK-T (p=0.016) and γδ-T cells (p=0.025) and trend to lower %NK-T (p=0.054) in all individuals with arthralgia compared to HC. Similarly, higher %CD3+ T cells (p=0.005) and lower %NK (p=0.004), %NK-T (p=0.027), %γδ-T cells (p=0.050) and absolute count of NK (p=0.002), NK-T (p=0.016) and γδ-T cells (p=0.019) were confirmed in a subgroup of ACPA+ individuals compared to HC. In addition, individuals who met CSA criteria irrespective of ACPA status had higher %CD3 T cells (p=0.004) and lower %NK cells (p=0.002) and absolute count of NK (p≤0.001), NK-T (p=0.019) and γδ-T cells (p=0.042) compared to HC. We observed no differences either between ACPA- or CSA- and HC or between ACPA+ and ACPA- or CSA+ and CSA- individuals with arthralgia. In addition, there were no differences in lymphocyte subsets in individuals who have developed RA so far and patients with arthralgia or at the time of RA manifestation.Conclusion:We identified lower number of NK cells as well as NK-T and γδ-T cells in individuals at risk of developing of RA. The decrease in non-conventional T cells was observed despite the increased percentage of the classical T cells. We hypothesize that the disproportion of these lymphocyte subpopulations, described previously in established RA, observed here in at-risk individuals may reflect their predisposition for further development of RA.Acknowledgments:Projects AZV-17-32612A and MHCR 023728Disclosure of Interests:Klára Prajzlerová: None declared, Olga Kryštůfková: None declared, Nora Petrovská: None declared, Petra Hánová: None declared, Hana Hulejova: None declared, Monika Gregová Consultant of: Novartis, Abbvie, Paid instructor for: Novartis, Speakers bureau: Novartis, Abbvie, MSD, Heřman Mann: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiří Vencovský: None declared, Ladislav Šenolt: None declared, Mária Filková: None declared

Objective.To evaluate the intraobserver and interobserver reliability of the ultrasonographic (US) assessment of subtalar joint (STJ) synovitis in patients with rheumatoid arthritis (RA).Methods.Following a Delphi process, 12 sonographers conducted an US reliability exercise on 10 RA patients with hindfoot pain. The anteromedial, posteromedial, and posterolateral STJ was assessed using B-mode and power Doppler (PD) techniques according to an agreed US protocol and using a 4-grade semiquantitative grading score for synovitis [synovial hypertrophy (SH) and signal] and a dichotomous score for the presence of joint effusion (JE). Intraobserver and interobserver reliability were computed by Cohen’s and Light’s κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal.Results.Mean weighted Cohen’s κ for SH, PD, and JE were 0.80 (95% CI 0.62–0.98), 0.61 (95% CI 0.48–0.73), and 0.52 (95% CI 0.36–0.67), respectively. Weighted Cohen’s κ for SH, PD, and JE in the anteromedial, posteromedial, and posterolateral STJ were −0.04 to 0.79, 0.42–0.95, and 0.28–0.77; 0.31–1, −0.05 to 0.65, and −0.2 to 0.69; 0.66–1, 0.52–1, and 0.42–0.88, respectively. Weighted Light’s κ for SH was 0.67 (95% CI 0.58–0.74), 0.46 (95% CI 0.35–0.59) for PD, and 0.16 (95% CI 0.08–0.27) for JE. Weighted Light’s κ for SH, PD, and JE were 0.63 (95% CI 0.45–0.82), 0.33 (95% CI 0.19–0.42), and 0.09 (95% CI −0.01 to 0.19), for the anteromedial; 0.49 (95% CI 0.27–0.64), 0.35 (95% CI 0.27–0.4), and 0.04 (95% CI −0.06 to 0.1) for posteromedial; and 0.82 (95% CI 0.75–0.89), 0.66 (95% CI 0.56–0.8), and 0.18 (95% CI 0.04–0.34) for posterolateral STJ, respectively.Conclusion.Using a multisite assessment, US appears to be a reliable tool for assessing synovitis of STJ in RA.

Objective.To identify and synthesize the best available evidence on the application of musculoskeletal (MSK) ultrasound (US) in patients with systemic lupus erythematosus (SLE) and to present the measurement properties of US in different elementary lesions and pathologies.Methods.A systematic literature search of PubMed, Embase, and the Cochrane Library was performed. Original articles were included that were published in English between August 1, 2014, and December 31, 2018, reporting US, Doppler, synovitis, joint effusion, bone erosion, tenosynovitis, and enthesitis in patients with SLE. Data extraction focused on the definition and quantification of US-detected synovitis, joint effusion, bone erosion, tenosynovitis, enthesitis, and the measurement properties of US according to the OMERACT Filter 2.1 instruments selection.Results.Of the 143 identified articles, 15 were included. Most articles were cross-sectional studies (14/15, 93%). The majority of the studies used the OMERACT definitions for ultrasonographic pathology. Regarding the measurement properties of US in different elementary lesions and pathologies, all studies dealt with face validity, content validity, and feasibility. Most studies achieved construct validity. Concerning the reliability of image reading, 1 study (1/15, 7%) assessed both intraobserver and interobserver reliability. For image acquisition, 4 studies (4/15, 27%) evaluated interobserver reliability and none had evaluated intraobserver reliability. Criterion validity was assessed in 1 study (1/15, 7%). Responsiveness was not considered in any of the studies.Conclusion.This literature review demonstrates the need for further research and validation work to define the involvement of US as an outcome measurement instrument for the MSK manifestations in patients with SLE.

Background: The incidence of subtalar joint (STJ) disease in patients with rheumatoid arthritis (RA) is greatly increased between five and ten years of disease duration and regularly precedes changes in the tibiotalar joint [1]. The joint is notoriously difficult to assess clinically and frequently overlooked in favour of the more accessible tibiotalar joint. We hypothesized that US might be used as a reliable outcome measure to evaluate synovitis of the STJ in patients with RA. The objectives of this study were first, to develop an expert consensus derived definition of synovitis and scanning protocol for the STJ and second, to test the reliability of the definitions and protocol. Objectives: To evaluate the intra- and interobserver reliability of the US assessment of STJ synovitis in patients with RA. Methods: Following a Delphi process, twelve sonographers conducted an US reliability exercise on 10 RA patients with hindfoot pain. The anteromedial, posteromedial, and posterolateral STJ was assessed using B-mode and power Doppler (PD) techniques according to an agreed US protocol and using a 4-grade semiquantitative grading score for synovitis (synovial hypertrophy (SH) and power Doppler (PD) signal) and a dichotomous score for the presence of joint effusion (JE). Intraobserver and interobserver reliability were computed by Cohen and Light kappa (k). Weighted k coefficients with absolute weighting were computed for B-mode and PD signal. Results: Mean weighted Cohen’s kappa for SH, PD, and JE, was 0.80 (0.62–0.98), 0.61 (0.48–0.73), and 0.52 (0.36–0.67), respectively. Weighted Cohen’s kappa for SH, PD, and JE in the anteromedial, posteromedial and posterolateral STJ was -0.04–0.79, 0.42–0.95, and 0.28–0.77; 0.31–1, -0.05–0.65, and -0.2–0.69; 0.66–1, 0.52–1, and 0.42–0.88, respectively. Weigthed Light kappa for SH was 0.67 (95%CI 0.58–0.74), 0.46 (0.35–0.59) for PD, and 0.16 (0.08–0.27) for JE. Weighted Light kappa for SH, PD, and JE was 0.63 (0.45–0.82),0.33 (0.19–0.42) and 0.09 (-0.01–0.19), for the anteromedial; 0.49 (0.27–0.64), 0.35 (0.27–0.4), and 0.04 (-0.06–0.1) for posteromedial, and 0.82 (0.75–0.89), 0.66 (0.56–0.8), and 0.18 (0.04–0.34) for posterolateral STJ, respectively. Conclusions: Ultrasound is a feasible and reliable tool for assessing synovitis of the posterolateral STJ in RA, but not for the anteromedial and posteromedial STJ. SH can be reliably detected in B-mode and PD mode, but this is not true for JE. Reference 1. Van der Leeden M, Steultjens MP, Van Ursem J, et al. Prevalence and course of forefoot impairments and walking disability in the first eight years of rheumatoid arthritis. Arthritis Rheum2008;59:1596–1602. Disclosure of Interest: None declared

Background Accurate disease activity measurement is a key component of rheumatoid arthritis (RA) management. In 2012, multi-biomarker disease activity (MBDA) test using 12 serum proteins was presented 1 . Objectives To develop a novel test for measuring inflammatory activity in RA. Methods Serum samples were obtained from 82 patients with RA (60 females, median disease duration 4.2 years, median age 55.2 years, RF positivity 60.3%, ACPA positivity 69.7%). A detailed stepwise analysis of 20 candidate biomarkers selected from the literature search (IL1β, IL-6, IL-7, IL-8, IL-12p70, IL-17A, IL-22, IL-33, IL-34, IFNγ, VEGF, YKL-40, CXCL-13, MMP-3, resistin, visfatin, leptin, adiponectin, calprotectin and CRP) was performed. Methods of factor analysis (a statistical method used to describe variability among observed, correlated variables in terms of a potentially lower number of unobserved variables called factors) were used in order to develop a tool composed of different serum markers that would optimally reflect disease activity in RA. Spearman correlation index was used to explore associations between newly designed tool and clinical as well ultrasound parameters (German US7 score) of disease activity. Results We have developed a “Molecular Disease Activity” test covering underlying pathophysiological processes composed of 8 serum markers: calprotectin, CRP, IL-6, MMP-3, VEGF, resistin, IL-22 and IL-7 that optimally reflected inflammatory activity in RA. This model was significantly associated with clinical (DAS28-ESR, DAS29-CRP, CDAI, SDAI) and ultrasound variables (PD syn score, GS syn score) of disease activity in RA, as shown in table 1. Conclusions We believe that this newly designed test based on 8 serum markers may contribute to more accurate measurement of inflammatory activity in RA and improvement of patients‘ outcomes. Further evaluation of this tool in a larger cohort is needed. Reference [1] Centola M, Cavet G, Shen Y, et al. Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis. Plos One2013Apr 9;8(4). Acknowledgements Supported by the project of Ministry of Health, Czech Rep. No. 0 23 728 and SVV No. 260 373. Disclosure of Interest None declared

Objectives: To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise.Methods: Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise.Results: Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The 'halo' and 'compression' signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the 'halo' sign and the 'compression' sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts.Conclusions: The 'halo' and the 'compression' signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent.

Background Ultrasonography (US) of salivary glands (USSG) may support diagnosis and evaluation of disease activity in primary Sjogren9s syndrome pSS. In order to extent the use of USSG in daily practice, consensus definitions of normal and abnormal USSG findings are needed. Objectives To obtain consensual definitions of normal and abnormal USSG findings using a Delphi process. Methods Twenty-seven experts participated in the Delphi process. A Likert scale from 1–5 was used in which 1 indicated complete disagreement and 5 complete agreement. Three core items were proposed: 1. Consensus of assessment of SG (parotid gland (PG), submandibular glands (SMG), sublingual glands SLG)). 2. Consensus for elementary lesions of PG, SMG, and SLG changes in PSS patients. 3. Consensus on grading of PG, SM, and SLG in pSS. Results The consensus of definitions between experts was reached after three rounds.The results (table 1) showed agreement with more than 75% of agreement in normal and abnormal definitions in SG and concluded to not evaluate SLG in pSS patients as well as to score pSS SG patients with at least two abnormal glands out of 4 (2 PG and 2 SMG) with a scoring system >2 for each abnormal gland. Conclusions We developed a consensual US definition of normal and abnormal USGS findings through a Delphi exercise process. This finding will be used as a basis to further proceed with the validation of USGS for clinical application. Disclosure of Interest None declared

Background Individuals with clinically suspect arthralgia (CSA) with positivity of anti-citrullinated protein antibodies (ACPA) are considered at high risk of developing rheumatoid arthritis (RA). The altered expression of miRNAs is involved in the development and maintenance of autoimmune diseases. We aimed to investigate differentially expressed miRNAs in peripheral blood mononuclear cells (PBMC) in CSA and healthy controls (HC). Material and methods The study included 19 CSA and 20 HC. Disease activity assessments and ultrasound of 28 small joints was performed in CSA. Total RNA from PBMC was isolated. A comprehensive analysis of miRNAs was performed using TaqMan Low Density Array (TLDA) in 5 samples per group. Single assay analysis of miR-451a, CXCL16 and IL-8 was performed in remaining samples and normalised to RNU44 or ACTB, respectively. dCt was used for relative quantification. Results TLDA analysis revealed 2.43x higher levels of miR-451a in CSA compared to HC. Further validation next confirmed 3.19x higher expression of miR-451a in CSA (p≤0.001). CXCL16 and IL-8 were predicted as miR-451a targets. Expression of miR-451 positively correlated with CXCL16 (r=0.497; p=0.030) in CSA and IL-8 in both CSA (r=0.485; p=0.035) and HC (r=0.617; p=0.004). This is suggestive of an indirect regulation by miR-451 and a specific role of CXCL16 in CSA. Moreover, the expression of both CXCL16 (1.51x; p=0.013) and IL-8 (3.17x; p=0.032) was higher in CSA compared to HC. By definition, all CSA individuals had swollen joint count 0. Ten CSA had some degree of subclinical activity on ultrasound (GC>1/PD>0). Levels of miR-451 significantly correlated with DAS28-CRP (r=0.575; p=0.010), SDAI (r=0.676; p=0.004) and VAS (r=0.484; p=0.036). CXCL16 correlated with tender joint count (r=0.576; p=0.010). Subclinical activity as per US had no effect on the levels of miR-451a, CXCL16 or IL-8 in PBMC. Conclusions Although CSA cannot be considered a disease itself, and is rather a clinical suspicion of a disease, high levels of miR-451a in PBMC distinguish these individuals at high risk of developing RA. Moreover, miR-451 in PBMC reflects the activity at this pre-clinical phase and correlates with CXCL16 with a role in angiogenesis and chemotaxis. Acknowledgement Projects MHCR 023728, SVV 2 60 263.

Musculoskeletal ultrasound (US) now thrives as an established imaging modality for the investigation and management of chronic inflammatory arthritis. We summarize here results of the Outcome Measures in Rheumatology (OMERACT) US working group (WG) projects of the last 2 years. These results were reported at the OMERACT 12 meeting at the plenary session and discussed during breakout sessions. Topics included standardization of US use in rheumatic disease over the last decade and its contribution to understanding musculoskeletal diseases. This is the first update report of WG activities in validating US as an outcome measure in musculoskeletal inflammatory and degenerative diseases, including pediatric arthritis, since the OMERACT 11 meeting.

When it comes to thinking about musculoskeletal imaging, traditionally beset with techniques as conventional radiography (CR) and computerized tomography (CT), the scenery has dramatically changed....

Background We have previously shown differential expression of some circulating miRNAs in patients with early RA (ERA) and their potential as markers of disease activity and treatment response. Objectives We aimed to investigate differentially expressed circulating miRNAs in clinically suspect arthralgia patients with positive antibodies to citrullinated peptide antigens (ACPA) who are at high risk of developing RA and compared them to ERA and established RA. Methods The study included 20 ACPA+ arthralgia patients, 25 treatment naive ERA patients who met the 2010 ACR/EULAR criteria (disease duration Results Patients with arthralgia showed no clinical and ultrasound evidence of arthritis (grey scale and power Doppler for single joint ≤1) Of these, all were ACPA+, CRP 7.4±19.2 mg/l. Treatment naive ERA patients had active disease (DAS28 5.7±1.3, CRP 20.7±23.2 mg/l), 60% were ACPA+. Patients with established RA all had high disease activity (DAS28 6.6±0.9, CRP 28.1±31.3 mg/l), 73% were ACPA+, had failed DMARDs therapy and were due to commence anti-TNF treatment. Out of the 380 miRNAs analysed by TLDA, 128 miRNAs were detected in HC, 129 in arthralgia, 44 in ERA and 25 in RA patients. TLDA analysis revealed 1.7x higher levels of miR-126 in ACPA+ arthralgia patients compared to HC, and 27x and 63x lower levels in ERA and RA compared to HC, respectively. These data were suggestive of significant dysregulation of miR-126 in patients with active polyarthritis compared to ACPA+ arthralgia. However, further validation showed no difference in miR-126 levels among HC, arthralgia and ERA patients but the levels were 2.6x lower in RA patients compared to HC (p=0.0037). The levels of miR-126 significantly negatively correlated with DAS28 (r=-0.460; p=0.047), SDAI (r=-0.535; p=0.018), SJC (r=-0.504; p=0.028), and TJC (r=-0.517; p=0.023) in treatment naive ERA patients, but not in those with established disease. There was no correlation with CRP in any patient group. Conclusions Higher miR-126 levels reflect lower disease activity in treatment naive ERA patients. We hypothesize that significant downregulation of miR-126 levels in RA patients may be modified by previous exposure to multiple treatments. Acknowledgement MHCR 023728 project Disclosure of Interest None declared

Objectives To estimate the time to reach reliable results in a larger group of rheumatologists at onset of their musculoskeletal ultrasound (MSUS) training in modified 7-joints scoring system (US7). Methods US7 has been shown a useful tool to estimate activity of rheumatoid arthritis (RA) in daily clinical practice. The system has been extensively described including an atlas. Targets of the US7 include synovitis (in B-mode and Power Doppler (BM+PD)), tenosynovitis (BM+PD) and erosive changes of 7 joints (wrist, MCP II+III, PIP II+III, MTP II+V) on the dominant site. We used a modification of the original US7 published, assessing both palmar and dorsal view of MCP and PIP joints. 9 rheumatologists with basic/intermed. level of MSUS underwent a training in general MSUS+US7. At month 1, reliability testing in scoring of static pictures was performed. At months 3 and 12, two reliability-testing sessions were organized. 4 patients with various stages of activity and disease progression of RA were repeatedly scanned, in 2 rounds per session. Sonographers were blind to all patients9 data. 2 US machines were used for each session and the setting was fixed before the start. Smoking or drinking alcohol was not allowed. Each patient was investigated by the same US machine in the same daytime in each round of a testing session. Inter-/intra-observer agreement was calculated for each modality of US7 (synovitis score in BM+PD, tenosynovitis score in BM+PD, erosion score) by using non-weighted Cohen kappa (intra-observer agreement) and Light9s kappa (inter-observer agreement). Results At month 1, mean intra- and inter-observer agreement in scoring of static images was reached; κ=0,61 and 0,60 respectively (good). At month 3, mean inter-observer reliability was low (κ Conclusions Ultrasound is an operator dependent technique. The level of experience necessary to obtain reliable results in modified US7 (as an example of easy and well determined US method) was achieved after 12 months of low intensity training with direct supervision of a specialist on demand. Low intensity training is in the authors9 experience the most frequently used method among beginners in MSUS. Scoring of static images was reliable already after 1 month. Although the probe positions in US7 are well defined, the inter-/intra-observer reliability in scoring of self-obtained images was none in month 3 and the difference leading to good results in month 12 must have been achieved in this later period of training. The difference between higher intra-observer and none inter-observer agreement in month 3 suggests that direct supervision of a specialist in MSUS in this stage of education would lead to quicker progress and better results in achieving reliability among the group members. Acknowledgement Supported by the project for conceptual development of research organization 023728 and by project no. NT12437. Disclosure of Interest None declared

Background Adipocytokines are soluble mediators secreted by adipose tissue and immune cells with potent immune regulatory functions. Some adipocytokines have been previously associated with disease activity and radiographic progression in patients with rheumatoid arthritis (RA) 1 . Objectives To investigate associations between adipocytokines, clinical and traditional laboratory markers as well as with ultrasound synovitis in patients with RA. Methods A total of 82 patients with RA (62 females, median disease duration 4.2 years) were enrolled into this study. All patients underwent clinical examination (swollen joint count - SJC, tender joint count – TJC, Disease activity score - DAS28-ESR and DAS28-CRP, Clinical disease activity index - CDAI, Simplified disease activity index - SDAI). Moreover, ultrasound examination of 7 selected joints mostly affected in RA (wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints) was performed to measure synovial hypertrophy in Grey Scale (GS) and pathological neovascularization in Power Doppler (PD) using semi-quantitative grading 0–3 3 . Blood samples were taken at the same day as clinical and ultrasound assessments. Serum concentrations of adiponectin, resistin, visfatin, leptin and CRP were measured. Clinical and laboratory measures were correlated with ultrasound findings using Spearman9s correlation coefficient. Results Serum visfatin and resistin levels were associated with the disease activity (Figure 1) and correlated significantly with DAS28-ESR (r=0.473, p Conclusions Our study supports circulating visfatin and resistin as promising serum pro-inflammatory biomarkers reflecting clinical, laboratory as well as ultrasound parameters of synovial inflammation in RA. References Senolt L, Krystufkova O, Hulejova H, Kuklova M, Filkova M, Cerezo LA, Belacek J, Haluzik M, Forejtova S, Gay S, Pavelka K, Vencovsky J: The level of serum visfatin (PBEF) is associated with total number of B cells in patients with rheumatoid arthritis and decreases following B cell depletion therapy. Cytokine 2011, 55: 116–121 Acknowledgement This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728, IGA grant No. NT12437 and GAUK grant No. 1010213. Disclosure of Interest None declared

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 US7S 1 . 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 R 2 of the model was improved by addition of US7 items from 43.6 to 46.9 (p 2 ). 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

Background and objectives Calprotectin (S100A8/S100A9 complex) is associated with disease activity, radiographic progression and may predict treatment response in patients with rheumatoid arthritis (RA). The aim of our study was to examine the serum levels of calprotectin in clinically suspect arthralgia patientswith positive antibodies to citrullinated peptide antigens (ACPA) who areat high risk of developing RA. Materials and methods This cross-sectional study included 20 ACPA+ arthralgiapatients, 55 patients with early RA (disease duration Results Patients with clinically suspect arthralgia showed no clinical and ultrasound evidence of arthritis (grey scale and power Doppler for single joint ≤ 1). Of these, all were ACPA+, 70%females; age 41.92 ± 11.72 years, CRP 7.39 ± 19.19 mg/l. Treatment naive patients with early RA had active disease (meanDAS28:5.54 ± 1.62), 65% were ACPA+, 71% were females; age 54.17 ± 16.77 years and CRP 20.46 ± 26.66 mg/l. Serum calprotectin in clinically suspect ACPA+ arthralgia patientswas not significantly different compared to HC (2980 ± 1610 vs. 3368 ± 1624 ng/ml, p = 0.35) but was significantly lower in both groups compared to early RA (5977 ± 5787 ng/ml, p = 0.01 and 0.02 respectively). There was no correlation between calprotectin and CRP in suspect arthralgia patients, however, in early RA, serum calprotectin significantly correlated with DAS28 (r = 0.432, p = 0.001) and CRP (r = 0.670, p Conclusions Calprotectin is not increased in ACPA positive patients who have normal ultrasound findings of small joints and thus may not help to predict RA development in this early stage of the disease. However, calprotectin is significantly elevated in patients with active early RA, where it serves as a reliable biomarker of disease activity. Acknowledgements IGA project no. NT 14498, project of MHCR 023728 and project SVV 260 155.

To estimate the annual incidence and prevalence of psoriatic arthritis (PsA), ankylosing spondylitis (AS), and reactive arthritis (ReA) in a sample of the Czech population.The population-based study was conducted in two regions of the Czech Republic (with a total population of 186000 inhabitants) in 2002-2003. Incident cases were registered on condition of confirming a definite diagnosis according to existing classification criteria during the study period (1 March 2002 to 1 March 2003). Prevalence was studied on the basis of identification of established diagnoses (before 1 March 2002) from registers of living patients of participating rheumatologists and other specialists. The age-standardized estimates of incidence and prevalence were calculated using the European standard population.The total annual incidence of PsA in adults agedor= 16 years was 3.6/100000 [95% confidence interval (CI) 1.4-7.6/100000] and the prevalence of PsA was 49.1/100000 (95% CI 39.5-60.4/100000). The annual incidence of AS in adults was 6.4/100000 (95% CI 3.3-11.3/100000) and the prevalence of AS was 94.2/100000 (95% CI 80.8-109.2/100 000). The annual incidence of ReA in adults was 9.3/100000 (95% CI 5.5-14.8/100000) and the prevalence of ReA was 91.3/100000 (95% CI 78.1-106.2/100000).The annual incidence and prevalence rates of PsA, AS, and ReA in the first population-based survey in the Czech Republic compared well with data reported from other countries.

Background Calprotectin (S100A8/9, MRP8/14) is a promising circulating biomarker reflecting disease activity in patients with rheumatoid arthritis (RA). In two small previous studies in RA patients 1,2 , serum calprotectin correlated with ultrasound synovial inflammation. Objectives To investigate associations between serum calprotectin, clinical and ultrasound-determined disease activity in a larger cohort of RA patients in a cross-sectional study. Methods A total of 167 patients with RA (134 females) were enrolled in this study. All patients underwent clinical assessment (SJC, TJC, DAS28-ESR) and ultrasound examination according to the US-7 score 3 to assess synovitis by gray-scale (GS) and power Doppler (PD) using semiquantitative grading (0-3). Serum calprotecin was measured by ELISA. Associations between serum calprotectin, C-reactive protein (CRP) and clinical as well as ultrasound findings were explored using Spearman9s correlation coefficient. A multiple regression analysis was used to determine the predictive value of calprotectin (mg/l), CRP (mg/l) and DAS28 for GS and PD synovitis score. Results Serum calprotectin significantly correlated with DAS28 (r=0.357, p Using a multivariate linear regression model with calprotectin, CRP and DAS28-FW as explanatory variables, calprotectin and DAS28, but not CRP, were significant predictors for GS (β=0.371, p Conclusions This study confirms in a large cohort of RA patients that serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of disease activity. Calprotectin is more closely associated with local joint inflammation than CRP and thus may represent a more specific circulating biomarker for monitoring synovial inflammation in RA patients. References Hammer HB, Fagerhol MK, Wien TN, Kvien TK. The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab. Arthritis Res Ther. 2011;13(5):R178. Hurnakova J, Hanova P, Hulejova H, et al. Serum calprotectin (S100A8/9) correlates with clinical and ultrasound outcomes in patients with early rheumatoid arthritis. In Ann Rheum Dis. 2014; Suppl (2):658–658. Backhaus M, Ohrndorf S, Kellner H, Strunk J, Backhaus TM, Hartung W, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009 Sep 15; 61(9):1194-1201. Acknowledgements This work was supported by the project (Ministry of Health, Czech Republic) for consensual development of research organization 023728, IGA grant No. NT12437 and GAUK grant No. 1010213. Disclosure of Interest None declared

Background Calprotectin, a heterodimeric complex of S100A8/9 (MRP8/14), has been demonstrated as an important biomarker of clinical and laboratory disease activity and structural joint damage in rheumatoid arthritis (RA). 1,2 Ultrasound is a sensitive and reliable tool for assessing synovial inflammation in RA. 3 Objectives To test the hypothesis that calprotectin is associated with clinical and ultrasound disease activity in patients with RA in a cross-sectional study and to investigate the contribution of various parameters to predict ultrasound findings. Methods A total of 37 patients with RA (24 females, median disease duration 18 months) underwent clinical examination (DAS28) and 7-joint ultrasound score (US-7) of clinically dominant wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints to assess synovitis and tenosynovitis by gray-scale (GS) and power Doppler (PD) ultrasound using semiquantitative grading 0-3. The levels of serum calprotectin and C-reactive protein were measured at the time of ultrasound assessment. Clinical and laboratory measures were correlated with ultrasound findings. Multiple regression analysis was used to determine the predictive value of calprotectin, CRP and DAS28 to determine PD synovitis. Results We found that DAS28 (r=0.605, p 2 =0.811). Conclusions This study confirms tight association between clinical, laboratory and ultrasound assessment and support circulating calprotectin as an important biomarker for monitoring synovial inflammation in RA. References Andres Cerezo L, Mann H, Pecha O, et al. Decreases in serum levels of S100A8/9 (calprotectin) correlate with improvements in total swollen joint count in patients with recent-onset rheumatoid arthritis. Arthritis Res Ther. 2011;13(4):R122. Hammer HB, Fagerhol MK, Wien TN, Kvien TK. The soluble biomarker calprotectin (an S100 protein) is associated to ultrasonographic synovitis scores and is sensitive to change in patients with rheumatoid arthritis treated with adalimumab. Arthritis Res Ther. 2011;13(5):R178. Backhaus TM, et al. The US7 score is sensitive to change in a large cohort of patients with rheumatoid arthritis over 12 months of therapy. Ann Rheum Dis. 2013 Jul;72(7):1163-9. Acknowledgements This work was supported by project of MHCR for conceptual development of research organization 023728, IGA grant No. NT12437 and GAUK grant No. 1010213. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5005

Background It has been shown that patients in remission of rheumatoid arthritis (RA) continue to have subclinical synovitis 1 . Objectives To evaluate the usefulness of the US7 scoring system in detecting synovitis in patients with RA who are in remission of disease. Methods 73 patients with remission of rheumatoid arthritis (RA) according to DAS 28 2 . Sonographers used the same US machine; settings were not allowed to be changed. Inter- and intraobserver reliability in using US7 scoring system were computed for all measurements. Spearmann coefficient was used to calculate statistical correlations. Results 212 patient visits were recorded and 1484 joints were investigated. Only 13 patients (17.3%) in clinical remission had no synovitis in US7 (GS0, PD0), regardless whether tenosynovitis was present or not. 50 patients (68%) continued to have subclinical synovitis in US7 at the baseline (GSUS/PDUS>1). Relapse rate during one-year observation (DAS28>2.6) was 17% at 3rd and 6th months, respectively, 11% in 9th month and 18% at 12th month, respectively. Total score of GSUS and PDUS synovitis at month 3 (p Conclusions With the US7 score, it was possible to find a high percentage of subclinical synovitis in patients in remission of RA according to previous studies published using other scoring systems. Therefore, US7 might be a simple and effective tool to monitor disease activity of RA even in the state of remission. There was a better correlation between US7 GSUS findings and ACR/EULAR remission criteria than remission assessed according to DAS28 criteria. Further studies are needed to confirm these findings with US7 scoring system. References Gartner M, et al. Sonographic joint assessment in rheumatoid arthritis: associations with clinical joint assessment during a state of remission. Arthritis Rheum. 2013 Aug;65(8):2005-14. Backhaus TM, et al. The US7 score is sensitive to change in a large cohort of patients with rheumatoid arthritis over 12 months of therapy. Ann Rheum Dis. 2013 Jul;72(7):1163-9. Acknowledgements Supported by project of MHCR for conceptual development of research organization 023728 and IGA grant No. NT12437. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3859

Background Arthritis is frequently observed symptom in patients with idiopathic inflammatory myopathies (IIM) in clinical practice, but there is a lack of systematic reports of prevalence and/or characteristics of arthritis in myositis patients. Objectives To determine prevalence of arthritis in IIM patients; it’s relation to the course of the muscle disease; characteristics of arthritis with respect to severity, distribution and extent as well as it’s relation to autoantibody profiles, HLA genes, and others disease’s characteristics. Methods 106 consecutive patients with definite diagnosis of IIM were included in this cross-sectional study. 68-joint index and clinical aspects of disease, history of arthritis and autoantibody profiles were obtained. Musculoskeletal ultrasonography using German Ultrasound Score 7 (US-7)[1] was performed in 55 IIM patients and in 60 control patients with rheumatoid arthritis (RA). High resolution genotyping in HLA-DRB1 locus was performed in 71 IIM patients. Results In 65 patients (61.3%) arthritis occurred at any time during the course of myositis; 42 had arthritis at the beginning of myositis (in 22 patients before and in 16 simultaneously with onset of muscle weakness). On clinical examination 52 (49.1%) patients had arthritis, with 25 having polyarthritis, 17 oligoarthritis and 10 monoarthritis. Wrists (21.7%) and shoulders, MCP, and PIP joints (each 20.8%) were the most frequently affected joints. Significant association of Anti-Jo-1 positivity with arthritis was found (28 patients with arthritis from 29 anti-Jo-1 positive; p ). Gray-Scale (GS) synovitis was observed in 39 out of 55 (70.9%) patients; Power-Doppler (PD) activity was present in 34 (61.8%). Only 4 (7.3%) patients had US tenosynovitis and 3 (5.5%) had bony erosions. 57/60 (95%) RA patients had GS-synovitis, which was PD-active in 54 (90%). In the control group of RA patients tenosynovitis was present in 25 (41.7%) patients and 25 (41.7%) patients had one or more joint erosions. Mean US-7 score as well as scores of individual joints or modality subscores were significantly lower in IIM than in RA. When only patients with positive findings were compared, significant differences were found in total US-7 score, and GS-synovitis and PD-tenosynovitis subscores, but not in PD-synovitis, GS-tenosynovitis as well as in scores of individual joints. No association of arthritis and HLA-DRB1 was found. Conclusions Our data suggest that arthritis is a common feature of myositis. It is often present at the beginning of muscular manifestation of disease, or it may even precede the onset of muscle weakness. Most common presentation is symmetrical, non erosive polyarthritis affecting particularly wrists, shoulders, MCP and PIP joints of the hands. We confirmed strong association of arthritis with anti-Jo-1 antibody. Ultrasound assessment of joint involvement shows less frequent involvement than in RA, but comparable activity of synovitis measured by PD in affected joints. Patients with IIM have less erosions and tenosynovitis than RA patients. References Backhaus M, Ohrndorf S, Kellner H et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009;61:1194-201. Acknowledgements Supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00023728 (Institute of Rheumatology) and Research grant (Ministry of Health, Czech Republic) NT 12437 Disclosure of Interest None Declared

Background Musculoskeletal ultrasound may be a useful method for monitoring activity in rheumatoid arthritis (RA). German US-7 score is a recently introduced scoring index to assess synovitis and erosions in patients with RA 1 . Objectives Our goal was to determine a feasibility of the German US-7 score among non-experts users in a pilot cohort study. Methods A group of 100 patients with RA (81 females, 19 males; 25 with early and 75 with long-standing arthritis) treated with conventional DMARDs (N=84 patients) and/or biologics (N=12 patients) underwent clinical examination (TJC, SJC, DAS28), laboratory tests (CRP, FW) and ultrasound assessment at baseline and after 3 and 6 months. Distinct pathologic lesions detected by ultrasound examination were assessed by eight physicians in seven joint areas (wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metacarpophalangeal joints) of the clinically dominant hand and foot according to the German US7 score. Synovitis and tenosynovial vascularity due to inflammation were scored semiquantitatively (0-3) in Grey Scale (GS) and Power Doppler (PD). Tenosynovitis (GS) and erosions were scored on a yes or no basis. All values are shown as mean±SD. Followed parameters and correlations were statistically analysed as a change from baseline to second follow-up using Spearman´s correlation coefficients. P values below 0.05 were considered as statistically significant. Results In this study, serum levels of CRP decreased from 7.13±8.69 at baseline to 5.71±6.6 mg/l after 6 months and DAS28 changed from 3.78±1.65 at baseline to 3.14±1.43 after 6 months. Similarly, synovitis sum score in GS decreased from 7.42±6.66 at baseline to 5.05±5.29 after 6 months, synovitis score in PD decreased from 4.16±5.14 at baseline to 2.74±3.10 after 6 months. There were significant correlations between DAS28 reduction and synovitis improvement in GS (R=0.371, p Conclusions Our results show, that the German US-7 scoring system correlates well with clinical disease activity assessment even in the hands of non-expert users and thus, is a well feasible method for use in daily practice. It may be suggested that the decrease in all investigated parameters during the study period might be due to the implementation of ultrasound as a part of disease activity control influencing the treatment strategy. References Backhaus M, Ohrndorf S, Kellner H, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum. 2009;61:1194-201. Acknowledgements Supported by IGA MZ CR No. NT/12437-5 and MZ CR No. MZO 00023728 grants. Disclosure of Interest None Declared

Background and Objectives Arthritis in idiopathic inflammatory myopathies (IIM) is frequently observed in clinical practise, but, to our knowledge, there is lack of systemic reports of prevalence and/or characteristics of arthritis in myositis patients. The aim of this study is to determine prevalence of arthritis in IIM patients; it’s relation to the course of the muscle disease; characteristics of arthritis with respect to seriousness, distribution and extent as well as it’s relation to autoantibody profiles and others disease’s characteristics. Materials and Methods In this cross-sectional study, clinical aspects of disease, history of arthritis and autoantibody profiles were obtained from 106 consecutive patients with definite diagnosis of IIM. In all of them the 68-joint index was investigated. In 55 IIM patients and in 60 control patients with rheumatoid arthritis (RA) German Ultrasound Score 7 (US-7) was performed. Results Arthritis at any time of course of myositis occurred in 65 patients (61.3%); 42 had arthritis at the beginning of myositis (in 22 patients before and in 16 together with onset of muscle weakness). 52 patients presented arthritis at clinical examination (25 poly-, 17 oligo-, and 10 with monoarthritis). Most frequently affected joints were wrists (21.7%) and shoulders, metacarpophalangeal, and proximal interphalangeal joints (20.8%). From 29 anti-Jo-1 positive patients 28 had arthritis and significant association between arthritis and anti-Jo-1 positivity was found (p ) . 39 out of 55 (70.9%) patients had Gray-Scale (GS) synovitis on ultrasound; in 34 of them also Power-Doppler (PD) positivity was found. Only 4 patients had ultrasonographic tenosynovitis and 3 had bony erosions. From 60 RA patients 57 (95%) had GS synovitis, which was PD-active in 54. Tenosynovitis was found in 25 patients. 25 RA patients had one or more joint erosions. Mean US-7 score as well as scores of individual joints or modality subscores were significantly lower in IIM than in RA, but, when compared only those patients with positive findings, the differences were found in total US-7 score, and GS-synovitis and PD-tenosynovitis subscores, but not in PD-synovitis, GS-tenosynovitis as well as in scores of individual joints. Conclusions Our data suggest that arthritis is common feature of myositis. It is often present at the beginning of muscular manifestation of disease, or it even precedes the onset of muscle weakness. Most common presentation is symmetrical, non erosive polyarthritis affecting particularly wrists, shoulders, metacarpophalangeal and proximal interphalangeal joints of the hands. We confirmed strong association of arthritis with anti-Jo-1 antibody. Ultrasound investigation of joint involvement in IIM shows less frequent involvement than in RA, but comparable activity of synovitis measured by PD in affected joints. IIMs have less erosions and tenosynovitis than RA.

Background Restoring normal physical functioning is a major therapeutic aim in the management of rheumatoid arthritis (RA). It is unknown, whether the extent of synovial inflammation quantified by musculoskeletal ultrasound (US) can predict current or future capacity for physical functioning. To answer this question we investigated the longitudinal relationship between physical function assessed by the health assessment questionnaire (HAQ) and the German 7-joint ultrasound score (US7S) in a prospective cohort of patients with RA. Methods Patients with RA (n = 185 (46 with incident and 139 with prevalent disease) were followed for 30.9 ± 9.1 months. Baseline and annual assessments comprised the disease activity score in 28 joints (DAS28), HAQ and US7S. The US7S includes semiquantitative measurements of synovitis assessed by greyscale (GS) and power Doppler (PD) in seven joints of the clinically dominant hand and foot, which are then aggregated in PD and GS synovitis sum-scores (PDsynSS and GSsynSS). A linear mixed-effect model was used to assess the longitudinal relationship between GSsynSS, PDsynSS and HAQ. We used standard and time-lag models to explore the association between HAQ, and GSsynSS, PDsynSS and DAS28 measured at the same time or at the previous visit 12 months ago, respectively. Results When the standard model was applied, in univariate analyses HAQ score was positively associated with GSsynSS and PDsynSS with β coefficients significantly higher in incident than in prevalent disease. In multivariate analysis both synSSs were individually no longer significant predictors of HAQ score. When using the time-lag model, after adjustment for the previous DAS28 or HAQ score, both PDsynSS and GSsynSS were significantly and negatively associated with the current HAQ. Conclusions US7 PD and GS synovitis sum-scores alone were positively associated with current functional status reflected by the HAQ in patients with RA, and this relationship was stronger in patients with early disease. When combined with the DAS28 or HAQ, US7 PD and GS synovitis sum-scores were predictive of the change in HAQ score over one year. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-1208-6) contains supplementary material, which is available to authorized users.

Introduction Calprotectin, 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. Methods A 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. Results The 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). Conclusions The 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.

To estimate the annual incidence and prevalence of rheumatoid arthritis (RA), juvenile arthritis (JIA) and gout in a population based study in two regions of the Czech Republic with total population of 186,000 inhabitants.The study was conducted in the Town of Ceske Budejovice and district of Cheb in the Czech Republic (with a total population of 186,000 inhabitants) in the years 2002 and 2003. Incident cases were registered on condition that the definite diagnosis was confirmed according to existing classification criteria during the study period. Prevalence was studied on the basis of identification of established diagnosis from registers of patients of participating rheumatologists and other specialists. They were asked to report all living patients who had been diagnosed before 1st March 2002. Patients were only included in the study if their permanent address was in the selected study area.Overall, we found 48 incident and 947 prevalent cases of RA among adults (16+ years), 4 incident and 43 prevalent cases of JIA among children (less than 16 years old), and 64 incident and 425 prevalent cases of gout among adults (16+ years). The total annual incidence of RA was 31/100,000 in the adult population aged 16 years and more (95% CI 20 to 42/100,000). The prevalence of RA was 610/100,000 (95% CI 561 to 658/100,000) in the adult population. An annual incidence of gout in adults was 41/100,000 (95% CI 28 to 53/100,000). The prevalence of gout was 300/100,000 (95% CI 266 to 334/100,000). The annual incidence of JIA was 13/100,000 in children less than 16 years old (95%CI 1 to 20/100,000). The prevalence of JIA in children was 140/100,000 (95% CI 117 to 280/100,000).This study estimates the annual incidence and prevalence rates of RA, gout and JIA in the first population-based survey in the Czech Republic. The rates of RA and JIA compare well with figures reported from other countries; figures in gout seem to be lower than reported elsewhere.