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Aims To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP). Methods and results The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014–19. The treatment goal for BP was Conclusion We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.

Objective To perform region-based development of whole-body MRI through validation of knee region scoring systems in spondyloarthritis (SpA). Methods Assessment of knee inflammatory pathologies using 2 systems, OMERACT MRI Whole-body score for Inflammation in Peripheral joints and Entheses (MRI-WIPE) and Knee Inflammation MRI Scoring System (KIMRISS), in 4 iterative multi-reader exercises. Results In the final exercise, reliability was mostly good for readers with highest agreement in previous exercise. Median pairwise single-measure ICCs for osteitis and synovitis/effusion status/change were 0.71/0.48 (WIPE-osteitis), 0.48/0.77 (WIPE-synovitis/effusion), 0.59/0.91 (KIMRISS-osteitis) and 0.92/0.97 (KIMRISS-synovitis/effusion). SRMs were 0.74 (WIPE-synovitis/effusion) and 0.78 (KIMRISS-synovitis/effusion). Conclusion MRI-WIPE and KIMRISS may both be useful in SpA whole-body evaluation studies.

Purpose To assess the agreement between readers using contrast-enhanced T1-weighted Dixon water- and fat-only images and OMERACT-recommended sequences for the scoring of osteitis and erosions according to the rheumatoid arthritis (RA) MRI scoring system (RAMRIS) in hands of patients with early RA. Materials and methods Both hands of 24 patients (16 women, 8 men; mean age, 45.7 ± 14.5 [SD] years; age range: 25–70 years) with early RA were prospectively imaged with fat-saturated T2-weighted sequences, non-Dixon T1-weighted imaging prior to contrast material injection and T1-weighted Dixon imaging after contrast material injection at 1.5 T. There were Two radiologists separately quantified osteitis and erosions according to RAMRIS using contrast-enhanced T1-weighted Dixon water-only and fat-saturated T2-weighted images for osteitis and contrast-enhanced T1-weighted Dixon fat-only and T1-weighted images prior to contrast material injection for erosions. Intraclass correlation coefficients (ICC) were calculated to assess inter-technique, intra-observer and inter-observer agreement. Results Mean ICC for the agreement between Dixon and non-Dixon images ranged from 0.68 (95%CI: 0.20–0.90) to 0.99 (95%CI: 0.95–1.00) for the scoring of osteitis and from 0.77 (95%CI: 0.38–0.93) to 0.99 (95%CI: 0.95–1.00) for the scoring of erosions. Mean ICC for the agreement between first and second readings ranged from 0.94 (95%CI: 0.81–0.98) to 0.97 (95%CI: 0.91–0.99) for the scoring of osteitis using Dixon and 0.91 (95%CI: 0.72–0.97) to 0.98 (95%CI: 0.92–0.99) using non-Dixon images and from 0.80 (95%CI: 0.45–0.94) to 0.97 (95%CI: 0.91–0.99) for the scoring of erosions using Dixon and 0.72 (95%CI: 0.29–0.91) to 0.98 (95%CI: 0.92–0.99) using non-Dixon images. Conclusion Contrast-enhanced T1-weighted Dixon water- and fat-only images can serve as an alternative to fat-saturated T2-weighted and T1-weighted MRI sequences for the assessment of osteitis and erosions according to the RAMRIS scoring system in hands of patients with early RA.

Purpose To investigate the diagnostic performance of sacroiliac joint (SIJ) magnetic resonance imaging (MRI) and the incremental value of spine MRI to “predict” clinical disease activity in patients with axial spondyloarthritis (axSpA). Materials and methods This cross-sectional study included adult patients with known axSpA according to the SpondyloArthritis International Society (ASAS) classification criteria, radiological arm. MRI disease activity was scored semi-quantitatively for SIJ and total spine MRI in each patient. Two cut-off levels (≥ 1.3 and ≥ 2.1) for ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP) were considered for clinical disease activity categorization. MRI scores were first evaluated individually. Then, SIJ score was combined with the score from a spine segment (lumbar, cervical, thoracic or total spine) to build a bi-parametric model using a classification tree. Receiver operating characteristic (ROC) curves were constructed to evaluate the classification performance according to disease activity category of these models. Results Forty-four patients (30 men, 14 women; mean age, 37 years ± 10 [SD] [range: 17–64 years]) with a mean disease duration of 5 years ± 8 (SD) (range: 0–35 years) were included. Thirty-six patients (36/44; 82%) had ASDAS-CRP ≥ 1.3 and 27 patients (27/44; 61%) had ASDAS-CRP ≥ 2.1. The most frequently involved spinal segment was mid-thoracic (T7-T8). The SIJ MRI score was an informative model to identify active axSpA (AUC ≥ 0.7, regardless of the cut-off level on ASDAS-CRP). Performance of bi-parametric models based on “SIJ + thoracic spine” (for detecting patients with ASDAS-CRP ≥ 1.3) or “SIJ + total spine” (for detecting patients with ASDAS-CRP ≥ 2.1) outperformed that of the individual SIJ score (P Conclusion The combination of MRI of the SIJ and spine allows to accurately discriminate between active and inactive axSpA, outperforming SIJ MRI alone.

ObjectivesThis study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range.MethodsAdult HS (age 18–80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1–5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort.Results939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA pConclusionsUltrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA.

Purpose The purpose of this study was to test the feasibility of joint space width (JSW) measurement on Dixon MR images with the “India ink” artifact between cartilage and bone marrow as a landmark for the subchondral plate and to correlate it with radiographic JSW. Materials and methods Both hands of six volunteers (three women, three men; mean age, 36.7 ± 10.4 [SD] years) and 24 patients with early rheumatoid arthritis (16 women, 8 men; mean age, 45.7 ± 14.5 [SD] years) were imaged with MRI Dixon sequences and radiographs. Two radiologists (R1, R2) separately measured JSW in 11 joints per hand on all Dixon images in volunteers, on contrast-enhanced T1-weighted out-of-phase images in patients and on radiographs in both groups. Inter-technique, intra-observer and inter-observer agreements were assessed using intraclass correlation coefficient (ICC) and Bland Altman analysis. Results In volunteers, agreement between JSW measurements on MRI and radiographs was the highest with T1-weighted Dixon out-of-phase images (mean ICC ranging from 0.69 to 0.76 for R1 and 0.65 to 0.74 for R2). In patients, median bias between JSW measurements at first and second readings was not statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of 0.00 and + 0.01 mm) and radiographs (mean bias of 0.00 and +0.01 mm). Median bias of the difference between measurements of R1 and R2 was statistically significantly different from 0 on T1-weighted Dixon out-of-phase images (mean bias of -0.11 and -0.09 mm; P Conclusion Measurement of hand JSW on T1-weighted Dixon out-of-phase images using India ink artifact as a landmark for the subchondral plate is repeatable and reproducible.

The use of efficient treatment with a treat-to-target strategy combined with early detection of the disease completely changed the imaging presentation and outcome of newly diagnosed rheumatoid arthritis (RA) patients. Magnetic Resonance Imaging (MRI) has become the reference technique in clinical research to detect and quantify inflammatory involvement of the soft tissues (synovitis and tenosynovitis) and bone marrow (osteitis) along with structural damages of the bone (erosions) in hands of patients with RA. Three-point Dixon MRI may be a valuable alternative to the currently recommended sequences as it yields effective fat signal suppression, high imaging quality and reproducible assessment of disease activity.

The purpose of this study was to test the hypothesis that Jaccoud arthropathy (JA) in patients with systemic lupus erythematosus (SLE) is associated with instability of the extensor digitorum (ED) tendons during flexion of the metacarpophalangeal (MCP) joints by comparing the position of the ED tendons between SLE patients with JA and control subjects on hand MRI obtained with flexed and extended MCP joints.Thirty-two hands of SLE patients with JA (13 women and 3 men; mean age, 50.0±12.2 [SD] years; age range: 26-68years) and 24 hands of sex- and age-matched control subjects (20 women and 4 men; mean age, 50.1±13.0 [SD] years; age range: 24-68years) were included in the study. Axial spin echo T1-weighted MRI images of the second to fifth MCP joints in flexion and in extension were obtained. Two radiologists (R1 and R2) separately measured the amplitude and assessed the direction of the displacement of the ED tendons with respect to the midline at the level of each MCP joint. Statistical analysis included two-way ANOVA with random effects to assess differences in amplitude and Fisher-Freeman-Halton exact test to assess differences in direction with P-values0.0083 and0.0063 considered as statistically significant respectively.Amplitude of the displacement of the ED tendons was statistically significantly greater in SLE patients with JA than in control subjects in flexion for both readers (median 58°, 95% confidence interval [CI]: 50°-65° vs. 20°, 95% CI: 16°-24°; P0.0001 for R1 and 54°, 95% CI: 47°-61° vs. 25°, 95% CI: 22°-28°; P0.0001 for R2) and in extension for one reader (17°, 95% CI: 15°-20° vs. 14°, 95% CI: 11°-16°; P=0.0048 for R1 and 20°, 95% CI: 15°-25° vs. 16°, 95% CI: 12°-18°; P=0.0292 for R2). Ulnar deviation of the ED tendons was statistically significantly more frequent in SLE patients with JA than in control subjects in flexion and in extension for both readers (P0.0001).JA is associated with instability of the ED tendons in patients with SLE best depicted when MCP joints are flexed.

Purpose To compare fat suppression effectiveness, image quality and disease activity scores between MRI protocols based on the Dixon method and the Chemical Shift Selective (CHESS) technique in hands of patients with suspicion of early rheumatoid arthritis (RA). Method Both hands of 28 patients (19 women; mean age 45.2 years old) with suspicion of early RA were prospectively imaged with Dixon- and CHESS-based OMERACT recommended protocols at 1.5 T including fat-suppressed T2-weighted and contrast-enhanced T1-weighted imaging. Two radiologists (R1/R2) separately assessed effectiveness of fat suppression and determined RAMRIS scores woth the Dixon- and CHESS-based protocols. R1 repeated the RAMRIS scoring and measured contrast-to-noise ratios (CNRs) on Dixon and CHESS images. Statistics included 2-way ANOVA test for the comparison of CNRs and Bland-Altman methodology for inter-technique and intra-observer agreement (p Results Fat suppression failure occurred in up to 1 patient with the Dixon- and 25 patients with the CHESS-based protocols. CNRs were significantly higher on T1-weighted and lower on T2-weighted Dixon images than on the corresponding CHESS images (p ≤ 0.042). Median bias of the difference between Dixon- and CHESS-based RAMRIS scores was not significantly different from 0 (−0.8 to +1.0 and −1.1 to +1.4 for R1/R2). Median bias of the difference between RAMRIS scores at first and second readings was significantly different from 0 with the CHESS-based protocols (−0.8 to +1.7) but not with the Dixon-based protocols (+0.0 to +1.0). Conclusions Dixon sequences yield more effective fat suppression and more reproducible RAMRIS scoring than CHESS sequences in hands with suspicion of early RA.

IntroductionUltrasound (US)-guided radiofrequency ablation (RFA) of genicular nerves (GNs) is increasingly performed to manage chronic knee pain. The anatomical foundations supporting the choice of original targets for US-guided GN-RFA have been thoroughly improved by recent anatomical studies. Therefore, this study aimed to provide a new protocol with revised anatomical targets for US-guided GN-RFA and to assess their accuracy in a cadaveric model.Materials and methodsFourteen fresh-frozen cadaveric knees were used. After a pilot study with 4 knees, five consistent nerves were targeted in the other 10 knees with revised anatomical landmarks: superior medial genicular nerve (SMGN), superior lateral genicular nerve (SLGN), inferior medial genicular nerve (IMGN), recurrent fibular nerve (RFN) and the infrapatellar branch of the saphenous nerve (IPBSN). For each nerve, the lumen of radiofrequency (RF) cannula was prefilled with non-diffusible black paint, and then the cannula was inserted at the target site under US guidance. After US verification of correct placement, the stylet was introduced in the cannula to create a limited black mark on the tissues at the top of the active tip. Anatomical dissection was performed to assess for accuracy.ResultsThe proportion of nerves directly found in contact with the black mark was 7/10, 8/10, 10/10 and 9/10 for the SMGN, SLGN, IMGN and RFN, respectively. The proportions of nerve captured by the theoretical largest monopolar RF lesions were 100% for the SMGN, IMGN and RFN, and IPBSN and 95% for SLGN. The mean distances from the center of the black mark to the targeted nerve were 2.1±2.2 mm, 1.0±1.4 mm, 0.75±1.1 mm and 2.4±4.5 mm for the SMGN, SLGN, IMGN and RFN, respectively.ConclusionUS-guided GN-RFA with revised anatomical targets resulted in accurate capture of the five targeted nerves. This protocol provides precise sensory denervation of a larger panel of nerves, targeting those whose constancy regarding anatomical location has been clearly demonstrated. It is expected to improve the clinical outcomes.

Background/purpose Studies have demonstrated that rheumatoid arthritis (RA) patients who achieve low disease activity or remission are able to taper biological disease-modifying antirheumatic drugs (bDMARDs). The aim of this study was to evaluate the proportion of patients in whom bDMARDs can be tapered in daily practice and to analyse the characteristics of these patients. Other objectives were to analyse which bDMARDs are more suitable for dose reduction and the cost savings. Results Data from 332 eligible RA patients from our Brussels UCLouvain cohort were retrospectively analysed; 140 patients (42.1%) received a tapered regimen, and 192 received stable doses of bDMARDs. The age at diagnosis (43.1 vs 38.7 years, p = 0.04), health assessment questionnaire (HAQ) score (1.3 vs 1.5, p = 0.048), RF positivity rate (83.3 vs 72.9%, p = 0.04) and disease duration at the time of bDMARD introduction (9.7 vs 12.1 years, p = 0.034) were significantly different between the reduced-dose and stable-dose groups. Interestingly, relatively more patients receiving a tapered dose were treated with a combination of bDMARDs and methotrexate (MTX) (86.7% vs 73.8%, p = 0.005). In our cohort, anti-TNF agents were the most commonly prescribed medications (68%). Only 15 patients experienced a flare during follow-up. Adalimumab, etanercept and rituximab were the most common bDMARDs in the reduced-dose group and were associated with the most important reductions in annual cost. Conclusion In daily practice, tapering bDMARDs in RA patients who have achieved low disease activity or remission is an achievable goal in a large proportion of patients, thereby reducing potential side effects and annual drug-associated costs. The combination of bDMARDs with MTX could improve the success of dose reduction attempts. Trial registration This retrospective non-interventional study was retrospectively registered with local ethics approval.

Whole-body magnetic resonance (MR) imaging techniques and protocols have been evolving continuously for the last 20 years, resulting in a powerful and mature tool for the detection, staging, and treatment monitoring of many oncologic and musculoskeletal disorders. The unique contrast resolution of MR imaging makes this imaging modality highly sensitive to pathologic alterations in bones, muscles, entheses, joints, and soft tissues, enabling this method to be expanded to the whole musculoskeletal system. Whole-body MR imaging is now used in numerous rheumatic, bone, and muscle disorders, and a full range of developing applications for this method have been emerging.

To compare the diagnostic accuracy of DWI and STIR sequences in Whole body (WB) MRI of SpA patients. Twenty consecutive patients with confirmed active SpA and 20 controls were investigated with identical WB MRI protocols, including DWI and STIR images. Two observers recorded 'lesions' (high signal intensity foci on STIR and high b-value DWI) in 17 anatomical areas, making a 17-point 'area score' and a 40-point 'lesion score'. ROC performance, inter-observer agreement, correlation with clinical parameters and spine and sacro-iliac joints (SIJ) MRI scores were assessed. SpA patients had significantly higher lesion scores on DWI than on STIR (p

Background:Inflammation in peripheral joints and entheses is common in spondyloarthritis (SpA). Whole-body magnetic resonance imaging (WB-MRI) allows assessment of the overall inflammatory status of arthritis patients including joints and entheses. The OMERACT MRI Whole-body scoring system for Inflammation in Peripheral joints and Entheses (MRI-WIPE) [1] has been developed and validated for the entire body assessment, including the knee, but not separately validated for the knee joint region. Detailed MRI scoring systems exist for heels, hands and feet, but although knee arthritis is a key cause of functional impairment, no detailed scoring system has been validated for inflammatory arthritides. The Knee Inflammation MRI Scoring System (KIMRISS) [2] was developed and validated in osteoarthritis and demonstrated good reliability.Objectives:To perform region-based development of whole-body MRI through validation of two knee region scoring systems in SpA.Methods:Assessment of inflammation was performed in the knee region on sagittal WB-MRIs using 2 scoring systems, MRI-WIPE and KIMRISS (Figure 1), in 4 iterative multi-reader exercises. In the final exercise, images (psoriatic arthritis, axial and peripheral SpA) were obtained before and after TNF-inhibitor.Results:In the final exercise (exercise 4), reliability was mostly good for experienced readers with the overall highest interreader agreement in the previous exercise (exercise 3). Median pairwise single measure intraclass correlation coefficients for osteitis and synovitis/effusion for status/change were 0.71/0.48 (WIPE osteitis), 0.48/0.77 (WIPE synovitis/effusion), 0.59/0.91 (KIMRISS osteitis) and 0.92/0.97 (KIMRISS synovitis/effusion) (Table 1). Wilcoxon signed-rank test showed significant change in synovitis/effusion for both methods and they correlated significantly regarding status in osteitis (0.92, pTable 1.MRI-WIPE knee and KIMRISS interreader reliability for OMERACT exercises 3 and 4MRI-WIPE KneeKIMRISSOsteitisSynovitis/effusionOsteitisSynovitis/effusionVariablesNo. patientsType of scoreMean scoreICCMean scoreICCMean scoreICCMean scoreICCExercise 39 readers11Status3.6 (0-16)0.57 (-0.06-0.98)1.8 (0-4)0.47 (0.05-0.85)32.3 (1-224)0.87 (0.66-0.99)29.9 (11-60)0.34 (-0.62-0.87)11Change1.1 (-2-6)0.53 (0.03-0.90)0 (-2-1)0.32 (-0.13-0.76)27.7 (-9-131)0.58 (-0.30-0.96)-1.6 (-33-11)0.48 (-0.32-0.95)Exercise 33 readers11Status3.1 (0-16)0.83 (0.71-0.97)2.5 (0-5)0.59 (0.51-0.71)34.4 (0-233)0.89 (0.83-0.99)36.5 (16-78)0.59 (0.08-0.86)11Change0.9 (-3-6)0.72 (0.57-0.83)0 (-2-1)0.63 (0.49-0.76)19.3 (-23-86)0.46 (0.18-0.83)-1.8 (-45-17)0.89 (0.82-0.95)Exercise 49 readers10Change-0.25 (-4-5)0.38 (-0.35-0.94)-1.0 (-3-1)0.30 (-0.43-0.89)-0.45 (-37-65)0.26 (-0.86-0.97)-14.7 (-48-0.20)0.48 (-0.39-0.99)20Status2.9 (0-7)0.50 (-0.01-0.84)2.1 (0-4)0.44 (-0.21-0.79)15.2 (0-66)0.35 (-0.04-0.89)55.6 (1-122)0.54 (0.01-0.96)Exercise 43 readers10Change0.2 (-2-6)0.48 (0.16-0.66)-1.4 (-5-0)0.77 (0.70-0.82)5.8 (-27-111)0.92 (0.90-0.94)-20.7 (-65-28)0.97 (0.96-0.98)20Status2.3 (0-6)0.71 (0.60-0.80)2.7 (0-5)0.48 (0.42-0.57)11.4 (0-36)0.59 (0.39-0.71)69.4 (1-153)0.91 (0.87-0.93)Sum scores are mean (range) of the patients scores. ICC values are mean (range). ICC is 2-way mixed model, single measure, by absolute agreement.Conclusion:MRI-WIPE and KIMRISS may both be useful as part of modular whole-body evaluation in clinical studies.References:[1]Krabbe S et al. J Rheum. 2019;46(9):1215-21[2]Jaremko JL et al. RMD Open. 2017;3(1):e000355Acknowledgements:We thank CARE Aarthritis Limited (carearthritis.com) for help with setting up the web-based scoring interface, the scoring exercises, and the web-based meetings. We thank all who participated in the SIG (Special Interest Group) virtual OMERACT meeting 29 October 2020. HMO, GDM and PGC are supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, United Kingdom. The views expressed in this study are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.Disclosure of Interests:Marie Wetterslev: None declared, Walter P Maksymowych Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Novartis, Pfizer and UCB, Robert G Lambert Consultant of: Parexel and Pfizer, Iris Eshed: None declared, Susanne Juhl Pedersen Speakers bureau: MSD, Pfizer, AbbVie, Novartis and UCB, Consultant of: AbbVie and Novartis, Grant/research support from: AbbVie, MSD, and Novartis, Maria Stoenoiu: None declared, Simon Krabbe: None declared, Paul Bird Speakers bureau: Janssen, Abbvie, UCB, Celgene, BMS, Novartis, Pfizer, Gilead, Eli-Lilly, Consultant of: Janssen, Abbvie, UCB, Celgene, BMS, Novartis, Pfizer, Gilead, Eli-Lilly, Violaine Foltz: None declared, Ashish Jacob Mathew: None declared, Frederique Gandjbakhch: None declared, Joel Paschke: None declared, 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, Gabriele De Marco: None declared, Helena Marzo-Ortega Speakers bureau: AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB, Grant/research support from: Janssen and Novartis, Anna Enevold Fløistrup Poulsen: None declared, Jacob L Jaremko: None declared, Philip G Conaghan Speakers bureau: AbbVie, AstraZeneca, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer and Stryker, Consultant of: AbbVie, AstraZeneca, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer and Stryker, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB

Background: Several studies have demonstrated that Rheumatoid Arthritis (RA) patients achieving low disease activity or remission are able to taper biological disease-modifying antirheumatic drugs (bDMARDs). Objectives: The aim of this study is to evaluate the proportion of patients in whom the bDMARD can be tapered in daily practice and to analyse the characteristics of these patients e. Another objective is to determine which bDMARDs are more adapted to dose reduction and the cost saving. Methods: Inclusion criteria were RA patients from our Brussels UCL cohort treated with a bDMARD for at least one year. A dose reduction was proposed by the senior physician when sustained low disease activity or remission was achieved. Patient characteristics and baseline features before the introduction of the current bDMARD were collected as well as flares if happened. We also calculated, for each bDMARD, the proportion of patients who received a decreased dose and the annual cost. Results: Data from 332 eligible RA patients were collected, 140 patients (42,1%) had a tapered regimen and 192 received a full dose of bDMARD. In the decreased dose group, age at diagnosis (43.1 vs 38.7 years, p=0.004), HAQ (1.3 vs 1.5, p=0.048), RF (83.3 vs 72.9%, p=0.026) and disease duration at the bDMARDs introduction (9.7 vs 12.1 years, p=0.034) were statistically different. As expected, the current DAS28-CRP was lower (2.26 vs 2.64, p=0.001) in the decreased dose group and interestingly, more patients receiving a decreased dose were treated with a combination of methotrexate when the bDMARD was introduced (86.7% vs 73.8%, p=0.005). No difference between groups was observed for gender, ACPA, erosion, number of previous bDMARDs, time to first conventional synthetic DMARD and biological DMARD, baseline DAS28-CRP and use of glucocorticoids. In our cohort, anti-TNF agents were the most commonly prescribed medications (anti-TNF 68%, tocilizumab 15%, rituximab 10%, abatacept 7%). Only 15 patients experienced a flare during the follow-up. Adalimumab, etanercept and rituximab were the most frequent decreased bDMARD and were associated with the most important reduction of annual cost. ABA : abatacept, ADA : adalimumab, CZP : certolizumab, ETN : etanercept, GOL : golimumab, IFX : infliximab, RTX : rituximab, TOC : tocilizumab Conclusion: In daily practice, tapering of bDMARDs in RA patients with low disease activity or remission is an achievable goal in a large proportion of patients, thereby reducing annual drug cost. The combination with methotrexate could be a positive predictive factor for the success of bDMARD tapering but further prospective research in daily practice are needed to confirm this result. Disclosure of Interests: Stephanie Dierckx: None declared, Bernard Lauwerys: None declared, Tatiana Sokolova: None declared, Laurent Meric de Bellefon: None declared, Maria Stoenoiu Grant/research support from: Abbvie, Roche, Wyeth, Adrien Nzeusseu: None declared, Frederic Houssiau: None declared, Aleksandra Avramovska: None declared, Patrick Durez Speakers bureau: Bristol-Myers Squibb, Eli Lilly, Sanofi, Celltrion

Background: Tenosynovitis (TS) is a common, often clinically undetectable finding in Rheumatoid Arthritis (RA). Recent data showed TS on ultrasound (US) has a role in predicting outcome in early disease and flare in clinical remission. However data is limited on US measured TS in healthy subjects (HS), none specifically encompassing the older age range when RA commonly presents. Objectives: This OMERACT study aimed to determine prevalence of US measured tendon abnormalities in HS throughout the age range. Methods: Adult HS without: joint pain (VAS A comparison cohort of DMARD-naive patients with RA (ACR-EULAR 2010 and/or 1987 criteria) at presentation was taken from the Birmingham Early Arthritis (BEACON) inception cohort, who underwent identical tendon US assessment. They were grouped into ≤12 and > 12 weeks from symptom onset. Results: Data from 899 HS and 144 RA patients were included. Prevalence of TSH and particularly PD abnormalities in HS was very low at all ages, and was all grade 1 except in one individual ECU tendon. ECU TSH grade≥1 was more common than DF grade≥1 in the older HS groups, and less common in the 18-39 age group (p=0.011). TSH and PD of grade ≥1 were common in RA patients, with DF PD abnormalities more common in early disease (p=0.02). Conclusion: Low prevalence of TSH or PD abnormalities in tendons of HS even in old age suggests US determined TS will be a robust tool in clinically managing RA. References: [1] Naredo E, D’Agostino MA, et al. Reliability consensus-based US score TS RA. ARD.2013;72(8):1328-34 Disclosure of Interests: Jeanette Trickey: None declared, Ilfita Sahbudin: None declared, Alessandra Bortoluzzi: None declared, Annamaria Iagnocco: None declared, Carlos Pineda: None declared, Cesar Sifuentes-Cantu: None declared, Coziana Ciurtin: None declared, Cristina Reategui Sokolova: None declared, Daniela Fodor: None declared, Ellen-Margrethe Hauge: None declared, Esperanza Naredo Consultant for: Abbvie, Speakers bureau: AbbVie, Roche, Bristol-Myers Squibb, Pfizer, UCB, Lilly, Novartis, Janssen, and Celgene GmbH, Florentin Ananu Vreju Consultant for: abbvie and novartis, Speakers bureau: abbvie, novartis, pfizer, sandoz, eli lilly, ucb pharma, Garifallia Sakellariou: None declared, George Bruyn : None declared, Georgios Filippou Speakers bureau: Laborest, Abbvie, BMS, Sanofi, Giuliana M.C. La Paglia : None declared, Gustavo Leon: None declared, Helen Keen: None declared, Hilde Berner Hammer Grant/research support from: AbbVie, Pfizer and Roche, Paid instructor for: AbbVie, Pfizer, UCB, Novartis, Roche, Speakers bureau: AbbVie, Pfizer, UCB, Novartis, Roche, Ilaria Tinazzi: None declared, Irene Azzolin: None declared, Jacek Flicinski: None declared, James Wilton: None declared, Kei Ikeda: None declared, Lene Terslev Speakers bureau: Speakers fee from : Roche, Novartis, Pfizer, MSD, BMS, Celgene, Mads Ammitzboll-Danielsen: None declared, Mads Nyhuus Bendix Rasch: None declared, Marcin Milchert: None declared, Maria Stoenoiu Grant/research support from: Abbvie, Roche, Wyeth, Marion Kortekaas: None declared, Marwin Gutierrez: None declared, Mihaela Maruseac: None declared, Mohammed A Mortada: None declared, Philippe Carron: None declared, Rositsa Karalilova: None declared, Ruth Wittoek: None declared, Sarah Ohrndorf: None declared, Takeshi Suzuki: None declared, Teodora Serban: None declared, Maria-Antonietta d’Agostino: None declared, Andrew Filer: None declared

Background: Finger extensor tendon (FET) involvement at ultrasound examination (US) was previously described in patients suffering from early and established psoriatic arthritis1. The reliability of the US measure of FET was as least as good as for synovitis2. The involvement of the FET in patients suffering from rheumatoid arthritis remains controversial. Objectives: To assess the involvement of FET in early rheumatoid arthritis (ERA) patients and in asymptomatic subjects (CTR). Methods: Inclusion criteria for ERA patients were: less than 6 months since the ERA diagnosis; age >18 years; without DMARD treatment or oral glucorticoid treatment. Inclusion criteria for CTRL subjects were : age >18 years; no pain in hands and fingers (VAS pain =0/100); no known rheumatic disease such a systemic diseases, rheumatoid, psoriatic arthritis, spondyloarthritis, hand osteoarthritis, gout, chondrocalcinosis; no psoriasis, no inflammatory bowel diseases. US assessments were performed blindly to the clinical and laboratory data. FET were assessed in longitudinal and in transverse view at the metacarpo phalangeal joint (MCP) and proximal phalangeal joint (PIP) level both in grey-scale (GS), power Doppler (PD) and in color Doppler (CD) mode. In addition the following joints were assessed for the presence and grade (0-3 according to OMERACT definitions) for both GS and PD synovitis: wrists, ankles, metatarsophalangeal (MTP) (2-5) and MCP (1-5) joints. Results: Sixty-two consecutive ERA patients and 34 CTR were included in this study. Mean age and gender distribution were comparable between ERA and CTR (47,3±14,5 vs. 43,4±12,5). ACPA were present in 61%, rheumatoid factor in 54%, and bone erosions in 27% of ERA patients. 57% of ERA patients presented with FET and 0% of CTR (p Conclusion: FET is relatively frequent in ERA patients and it is not present in asymptomatic subjects. Our results show that FET involvement is associated with the presence of ACPA, rheumatoid factor and bone erosions, thus identifying patients with possibly more aggressive or severe disease at baseline. References: [1] Wiell C, Szkudlarek M, Hasselquist M, Moller JM, Vestergaard A, Norregaard J, Terslev L, Ostergaard. Ultrasonography, magnetic resonance imaging, radiography, and clinical assessment of inflammatory and destructive changes in fingers and toes of patients with psoriatic arthritis Arthritis Res Ther. 2007;9(6):R119. [2] Macia-Villa C, Falcao S, Gutierrez M, Medina J, Hammer HB, De Miguel E. What is metacarpophalangeal joint swelling in psoriatic arthritis? Ultrasound findings and reliability assessment. Clin Exp Rheumatol. 2018;36(5):896-899. Disclosure of Interests: Mihaela Maruseac: None declared, Adrien Nzeusseu: None declared, Maria Stoenoiu Grant/research support from: Abbvie, Roche, Wyeth

Background Interstitial lung disease (ILD) evaluation is challenging, given the low sensitivity of X-ray and pulmonary function tests, and limited accessibility and radiation linked to repetitive HRCT. Lung Ultrasound (US) has shown potential in the evaluation of ILD of autoimmune diseases including systemic sclerosis. Objectives To define and asses the reliability of definitions of US-detected findings in ILD. Methods A taskforce (TF) within the OMERACT US WG performed a literature review (LR) to identify US lesions in ILD, a Delphi exercise to define these lesions and a web-based exercise to test the reliability of these definitions by using either intraclass correlation coefficient (ICC) or kappa statistics. Prior to the Delphi exercise all participants received training files and were subsequently asked to provide clips on BL, PLI and normal findings. Based on the results of the LR, which identified B-lines (BL) and pleural line irregularity (PLI) as main US findings in ILD, the Delphi exercise contained statements on US definitions on BL and PLI. After reaching agreement (> 75%) on the above mentioned items, a set of 80 high-quality clips (30 for PLI, 50 for BL), was selected and distributed to the TF members in order to score them (semiquantitatively, 0-2 for PLI and total number for BL) Results The 3 Delphi rounds and the web-based exercise were completed by 24 and 22 sonographers, respectively. Final definitions are reported in Table I. The web-based exercise showed moderate inter-reader reliability for both BL (ICC=0.61) and PLI (kappa=0.69). Table I: definitions of PLI and BL Pleural line irregularity (PLI): a loss of regularity that may be associated with an increase in thickness, focal, diffuse, or nodular B-line (BL): a vertical hyperechoic reverberation artifacts that arise from the pleural line, extend to the bottom of the screen without fading, and move synchronously with lung sliding Conclusion US is a candidate imaging modality to identify and monitor ILD in rheumatic diseases; US consensus based definitions of main US findings were defined and endorsed. Further development is planned for validating US as an outcome measurement instrument for ILD. Disclosure of Interests Andrea Delle Sedie Speakers bureau: Abbvie, UCB, Celgene, MSD, Lene Terslev Speakers bureau: Speakers fee from : Roche, Novartis, Pfizer, MSD, BMS, Celgene, George Bruyn : None declared, Tomas Cazenave: None declared, stavros chrysidis: None declared, Mario Diaz: None declared, Marco Di Carlo: None declared, Marilena Frigato: None declared, Luna Gargani: None declared, Marwin Gutierrez: None declared, ALOJZIJA HOCEVAR: None declared, Annamaria Iagnocco: None declared, Aaron Juche: None declared, Peter Mandl: None declared, Esperanza Naredo Consultant for: Abbvie, Speakers bureau: AbbVie, Roche, Bristol-Myers Squibb, Pfizer, UCB, Lilly, Novartis, Janssen, and Celgene GmbH, Mohammed A Mortada: None declared, Carlos Pineda: None declared, Francesco Porta: None declared, Viviana Ravagnani: None declared, Carlo Alberto Scire: None declared, Teodora Serban: None declared, Kate Smith: None declared, Maria Stoenoiu Grant/research support from: Abbvie, Roche, Wyeth, Marika Tardella: None declared, Karina Torralba: None declared, Richard Wakefield: None declared, Maria-Antonietta d’Agostino: None declared

Objective Ubiquitination of proteins leads to their degradation by the proteasome, and is regulated by ubiquitin ligases and substrate-specific ubiquitin-specific peptidases (USPs). The ubiquitination process also plays important roles in the regulation of cell metabolism and cell cycle. Here, we found that the expression of several USPs is increased in SSc tenosynovial and skin biopsies, and we demonstrated that USP inhibition decreases TGF-β signalling in primary fibroblast cell lines. Methods High-density transcriptomic studies were performed using total RNA obtained from SSc tenosynovial samples. Confirmatory immunostaining experiments were performed on tenosynovial and skin samples. In vitro experiments were conducted in order to study the influence of USP modulation on responses to TGF-β stimulation. Results Tenosynovial biopsies from SSc patients overexpressed known disease-associated gene pathways: fibrosis, cytokines and chemokines, and Wnt/TGF-β signalling, but also several USPs. Immunohistochemistry experiments confirmed the detection of USPs in the same samples, and in SSc skin biopsies. Exposure of primary fibroblast cell lines to TGF-β induced USP gene expression. The use of a pan-USP inhibitor decreased SMAD3 phosphorylation, and expression of COL1A1, COL3A1 and fibronectin gene expression in TGF-β-stimulated fibroblasts. The effect of the USP inhibitor resulted in increased SMAD3 ubiquitination, and was blocked by a proteasome inhibitor, thereby confirming the specificity of its action. Conclusion Overexpression of several USPs, including USP15, amplifies fibrotic responses induced by TGF-β, and is a potential therapeutic target in SSc.

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.

Background:The combination of methotrexate (MTX) and tocilizumab (TCZ) has been proven to be superior to MTX alone in early rheumatoid arthritis (RA)1 and was able to prevent radiographic progression. Ultrasound (US) has become a valid imaging modality in managing RA. Together with clinical examination, US may allow a comprehensive monitoring of response to therapy. So far, few data are available concerning the early response to TCZ plus MTX in very early RA (VERA).Objectives:In this study we aimed to assess the early US response to TCZ plus MTX in VERA, DMARD-naïve patients.Methods:In this open-label, single-arm study, VERA patients received TCZ (162 mg/week, subcutaneously) and MTX (15-20 mg/week, per os) for 24 weeks as induction therapy, followed by MTX as maintenance therapy. RA was diagnosed according to the 2010 ACR/European league against rheumatism (EULAR) criteria. All patients who fulfilled the inclusion criteria (ClinicalTrials.gov: NCT02837146) underwent blood tests, clinical and ultrasound examinations at the predefined time-points: 0,2,4,8,12,24,32,48,54 weeks (w). Ultrasound examination of 34 joints (elbows, wrists, MCP [1-5, bilateral], PIP ([2-5, bilateral], knees, ankles and MTP [2-5, bilateral]) was performed blindly to clinical data. Gray-scale (GS), power-Doppler (PD) scores, and the global OMERACT-EULAR synovitis score (GLOESS) were assessed in each joint. The sum of individual scores was calculated for 17-joint score (JS) (whole joint set), 10-JS (wrists, MCP, ankles and MTP joints), 12-JS2, and 7-JS3.Results:Forty-four patients (77% women), aged 46.7 ± 12.4 years, completed the 24-week period. Two-thirds (72.7%) were positive for anti-citrullinated protein antibody (ACPA) and 18.2% had bone erosions. At baseline, the mean 28 swollen joints count (28-SJC) was 7.55± 4.5, mean disease activity score (DAS28)-CRP score was 5.2 ± 0.15, mean simplified clinical activity score (SDAI) was 31.4 ± 1.9, mean clinical activity score (CDAI) was 29.1 ± 1.8 and mean health assessments questionnaire (HAQ) score was 1.3 ± 0.1. The C-reactive protein (CRP) decreased significantly at 2w (pThe GLOESS and GS scores allowed us detecting the earliest significant treatment response at 2w and PD scores at 4w (pConclusion:US scores were able to detect therapeutic response to TCZ plus MTX earlier than clinical scores and may therefore be a promising imaging biomarker.References:[1]Burmester GR et al. Ann Rheum Dis 2017; 76; 1279-1284.[2]Naredo E et al. Arthritis Rheum 2008; 59(4): 515-522.[3]Backhaus M et al. Arthritis Rheum 2009; 61: 1194-1201.Disclosure of Interests:Maria Stoenoiu Grant/research support from: UCB, Roche, Abbvie, MSD, Sanofi, Celgene, Mihaela Maruseac: None declared, Mouna Messaoudi: None declared, Adrien Nzeusseu Toukap Grant/research support from: AbbVie, Eli Lilly, Janssen, UCB, Novartis, Celgene Corporation, Pfizer, Esperanza Naredo Grant/research support from: AbbVie, Roche, BMS, Pfizer, UCB, Eli Lilly, Novartis, Janssen, Celgene

Background:Whole-body MRI (WB-MRI) allows assessment of the overall inflammation in arthritis patients, including joint and entheses. To enhance the use of WB-MRI in clinical trials, the OMERACT MRI in Arthritis Working Group developed the OMERACT MRI Whole-body score for Inflammation in Peripheral joints and Entheses in inflammatory arthritis (MRI-WIPE) [1]. This has been validated for the entire body, including the hip/pelvis region, but not for each individual region. More detailed scoring systems exist for heels, hands and feet but although hip arthritis is a key cause of functional impairment in spondyloarthritis (SpA), no detailed scoring system has been published for use in SpA. The Hip Inflammation Magnetic Resonance Imaging Scoring System (HIMRISS) was developed and validated in osteoarthritis showing good reliability.Objectives:To validate reliability, correlation and responsiveness of two WB-MRI scores for the hip/pelvis region in SpA.Methods:Inflammation in the hip/pelvis region was assessed on coronal WB-MRIs in 4 iterative multi-reader exercises using MRI-WIPE for the hip/pelvis region and HIMRISS (Figure 1). In final exercises, images (axial/peripheral SpA and psoriatic arthritis) were obtained before and after TNF-inhibitor.Results:In final exercises reliability was mostly good for the best calibrated readers. Median single-measure intraclass correlation coefficients were 0.58-0.65 (WIPE osteitis), 0.10-0.88 (HIMRISS osteitis), 0.38-0.72/0.52-0.60 (WIPE synovitis/effusion) and 0.68-0.89/0.78-0.85 (HIMRISS synovitis/effusion) (Table 1). The methods correlated significantly for status in osteitis (0.72, p=0.019) and for synovitis/effusion status (0.83, p=0.003) and change (0.73, p=0.017) (Table 1). In exercise 4 Wilcoxon signed-rank test showed significant change in osteitis between timepoints using WIPE hip/pelvis and SRM was large (1.23), while lower for WIPE synovitis/effusion and HIMRISS.Table 1.MRI-WIPE hip/pelvis and HIMRISS interreader reliability for OMERACT exercises 3-4MRI-WIPE hip/pelvisHIMRISSOsteitisSynovitis/effusionOsteitisSynovitis/effusionVariablesNo. patients(cases)Type of scoreMeanscoreICCMeanscoreICCMeanscoreICCMeanscoreICCExercise 39 readers11Status2.3 (0-10)0.69 (0.23-0.93)1.4 (0-4)0.58 (-0.06-0.96)8.2 (1-60)0.84 (0.56-0.99)12.8 (3-25)0.52 (0.00-.91)11Change-0.2 (-1-1)NA-0.2 (-3-1)0.50 (0.10-0.87)-0.35 (-3-1)NA-1.8 (-17-10)0.50 (-0.05-0.89)Exercise 33 readers11Status1.8 (0-10)0.63 (0.46-0.93)1.7 (0-5)0.60 (0.34-0.80)6.6 (0-65)0.88 (0.77-0.94)12.8 (2-28)0.89 (0.87-0.91)11Change-0.12 (-1-1)NA-0.12 (-3-2)0.60 (0.48-0.83)-0.7 (-7-0)NA-1.6 (-21-8)0.78 (0.70-0.87)Exercise 49 readers10 (1-10)Status1.2 (0-4)0.21 (-0.39-0.91)1.1 (0-2)0.19 (-0.31-0.69)1.8 (0-6)0.07 (-0.17-0.83)16.4 (9-23)0.31 (0.00-0.89)10 (11-20)Status1.6 (0-6)0.51 (-0.08-0.99)1 (0-3)0.40 (-0.17-0.88)3.5 (1-8)0,08 (-0.21-0.95)11.2 (5-24)0.49 (0.00-0.94)10 11-20)Change-0.4 (-2-0)NA-0.39 (-2-0)0.22 (-0.68-0.83)-2.2 (-7-2)NA-5.2 (-18-0)0.57 (0.02-0.92)20 (1-20)Status1.4 (0-6)0.41 (-0.35-0.92)1.0 (0-3)0.27 (-0.07-0.75)2.7 (0-9)0.09 (-0.17-0.85)13.8 (5-25)0.45 (0.01-0.90)Exercise 43 readers10 (1-10)Status0.8 (0-4)0.29 (0.01-0.78)1.3 (0-2)-0.02 (-0.29-0.12)0.4 (0-2)-0.04 (-0.04-0.04)15.8 (5-26)0.73 (0.59-0.89)10 (11-20)Status1.8 (0-9)0.65 (0.52-0.76)1.2 (0-4)0.72 (0.62-0.81)1.7 (0-5)0.06 (-0.17-0.35)9.2 (2-26)0.68 (0.53-0.88)10 (11-20)Change-0.6 (-2-0)NA-0.5 (-3-1)0.52 (0.49-0.55)-0.2 (-2-1)NA-2.8 (-19-6)0.85 (0.82-0.88)20 (1-20)Status1.3 (0-9)0.58 (0.43-0.69)1.2 (0-4)0.38 (0.31-0.44)1.0 (0-5)0.10 (-0.09-0.33)12.5 (2-26)0.73 (0.69-0.77)Sum scores and ICCs are mean (range). ICC is 2-way mixed, single measure, by absolute agreement.Conclusion:MRI-WIPE and HIMRISS may be useful tools in modular WB-MRI evaluation of hip/pelvis inflammation in clinical trials in SpA.References:[1]Krabbe S et al. J Rheum. 2019;46(9):1215-21[2]Jaremko JL et al. J Rheum. 2019;46(9)1239-42Acknowledgements:We thank CARE Arthritis Limited (carearthritis.com) for help with setting up the web-based scoring interface, scoring exercises, and the web-based meetings. We acknowledge the contribution of SIG (Special Interest Group) participants at the virtual OMERACT meeting October 29, 2020. HMO, GDM and PGC are supported in part by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, United Kingdom. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.Disclosure of Interests:Marie Wetterslev: None declared, Robert G Lambert Consultant of: Parexel and Pfizer, Walter P Maksymowych Speakers bureau: AbbVie, Janssen, Novartis, Pfizer and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Novartis, Pfizer and UCB, Iris Eshed: None declared, Susanne Juhl Pedersen Speakers bureau: MSD, Pfizer, AbbVie, Novartis and UCB, Consultant of: AbbVie and Novartis, Grant/research support from: AbbVie, MSD, and Novartis, Paul Bird Speakers bureau: Janssen, Abbvie, UCB, Celgene, BMS, Novartis, Pfizer, Gilead, Eli-Lilly, Consultant of: Janssen, Abbvie, UCB, Celgene, BMS, Novartis, Pfizer, Gilead, Eli-Lilly, Maria Stoenoiu: None declared, Simon Krabbe: None declared, Ashish Jacob Mathew: None declared, Violaine Foltz: None declared, Frederique Gandjbakhch: None declared, Joel Paschke: None declared, Gabriele De Marco: None declared, Helena Marzo-Ortega Speakers bureau: AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, Takeda and UCB, Grant/research support from: Janssen and Novartis, 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, Anna Enevold Fløistrup Poulsen: None declared, Jacob L Jaremko: None declared, Philip G Conaghan Speakers bureau: AbbVie, BMS, Eli Lilly, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer, Regeneron, Stryker, Consultant of: AbbVie, BMS, Eli Lilly, Flexion Therapeutics, Galapagos, Gilead, Novartis, Pfizer, Regeneron, Stryker, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB

Background:OMERACT recommends three “core set” MRI sequences with an optional cartilage-dedicated sequence to perform Rheumatoid Arthritis (RA) MRI scoring (RAMRIS) (1). Dixon method allows the production of four different images from a single MRI sequence.Objectives:To test a short MRI protocol based on a single Dixon sequence to assess disease activity and cartilage in hands of patients with early RA.Methods:Twenty-four patients (16 women, mean age 45.7 years old) with early DMARD-naive RA meeting the ACR/EULAR 2010 criteria were prospectively included. Both hands of each patient were imaged with MRI including contrast-enhanced T1-weighted Dixon and OMERACT “core set” MRI sequences and with conventional radiography.Two musculoskeletal radiologists (R1 and R2) separately assessed disease activity according to RAMRIS scoring system based on the Dixon images (contrast-enhanced T1-weighted Dixon water-only images to score synovitis, tenosynovitis and osteitis and contrast-enhanced T1-weighted Dixon fat-only images to score erosions) and the three OMERACT “core set” MRI sequences (contrast-enhanced fat-saturated T1-weighted images to score synovitis and tenosynovitis, fat-saturated T2-weighted images to score osteitis and T1-weighted images without contrast-material injection to score erosions).One radiologist (R1) separately measured the thickness of the cartilage in the joints corresponding to those assessed by the Sharp/van der Heijde modified scoring method on contrast-enhanced T1-weighted Dixon out-of-phase images and radiographs (2).RAMRIS scoring and measurement of the cartilage thickness were repeated by R1 to assess intra-observer agreement. Statistical analysis was based on intra-class correlation coefficients (ICC) with 95% confidence interval to assess inter-technique, intra-observer and inter-observer agreement. The strength of agreement was interpreted as follows: ≤0, poor; 0.01-0.20, slight; 0.21-0.40, fair; 0.41-0.60, moderate; 0.61-0.80, substantial and ≥0.81, excellent.Results:Agreement between total RAMRIS scores obtained with the Dixon water- and fat-only images and total RAMRIS scores obtained with the OMERACT sequences was excellent for R1 (0.94; 0.86-0.97) and R2 (0.91; 0.81-0.96). Intra-observer agreement was excellent with Dixon images (0.97; 0.92-0.98) and OMERACT sequences (0.96; 0.90-0.98). Inter-observer agreement was excellent with Dixon images (0.92; 0.82-0.96) and OMERACT sequences (0.93; 0.85-0.97).Agreement between the measures of cartilage thickness on the Dixon out-of-phase images and the measures of cartilage thickness on radiographs was substantial (0.71; 0.66-0.75). Intra-observer agreement was excellent with Dixon out-of-phase images (0.94; 0.93-0.95) and radiographs (0.93; 0.92-0.94).Conclusion:An MRI protocol based on a single contrast-enhanced T1-weighted Dixon sequence allows reproducible RAMRIS scoring and measurement of the cartilage thickness. Further studies should be performed to evaluate the value of a short MRI protocol based on the Dixon method to monitor disease activity including cartilage loss in treated RA patients.References:[1]Ostergaard M, Peterfy CG, Bird P, Gandjbakhch F, Glinatsi D, Eshed I, et al. The OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging (MRI) Scoring System: Updated Recommendations by the OMERACT MRI in Arthritis Working Group. J Rheumatol. 2017;44(11):1706-12.[2]van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol. 1999;26(3):743-5.Disclosure of Interests:Thomas Kirchgesner: None declared, Maria Stoenoiu: None declared, Nicolas Michoux: None declared, Patrick Durez Speakers bureau: AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Pfizer, Sanofi, Bruno Vande Berg: None declared

Background:Jaccoud arthropathy (JA) is a rare joint deformity mostly associated with systemic lupus erythematosus (SLE) (1). JA may be defined as a reversible deformity of the hands during flexion with ulnar deviation and swan neck deformities of the fingers. The physiopathology and the mechanisms leading to JA still remain to be elucidated.Objectives:To test the hypothesis that Jaccoud arthropathy (JA) in systemic lupus erythematosus (SLE) patients is associated with abnormal extensor digitorum (ED) tendons displacement during flexion of the metacarpophalangeal (MCP) joints.Methods:16 SLE patients with JA (JA+), 12 SLE patients without JA (JA-) and 24 control subjects were included in the study. Transverse spin echo T1-weighted MR sequences of the MCP joints in flexion and in extension were obtained in each hand of SLE patients and in one randomly-selected hand of control subjects. Two radiologists separately measured the amplitude and the direction of the displacement of the ED tendons with respect to the midline at the level of the MCP joints. Statistical analysis included two-way ANOVA with random effects to assess differences in amplitude (pResults:Amplitude of the displacement of the ED tendons was statistically significantly higher in JA+ patients than in JA- patients and controls in flexion for both readers (pConclusion:JA is associated with abnormal displacement of the ED tendons in flexion and extension. Abnormal displacement of the ED tendons is absent in patients without JA.References:[1]Santiago MB. Miscellaneous non-inflammatory musculoskeletal conditions. Jaccoud’s arthropathy. Best Pract Res Clin Rheumatol. 2011;25(5):715-25.Figure 1.Axial spin echo T1-weighted images of a 49-year-old woman with SLE and JA (a) in flexion and (b) extension. In flexion, the extensor digitorum (ED) tendons of the 3rdand 4thfingers are completely displaced on the ulnar aspect of the metacarpal heads (white arrows) with no tendon visible on the dorsal aspect (arrowheads). In extension, the ED tendons of the 3rdand 4thfingers are slightly displaced on the ulnar side of the dorsal aspect of the metacarpal heads (black arrows).Figure 2.Axial spin echo T1-weighted images of the sex- and age-matched control subject of the patient from Figure 1 (a) in flexion and (b) extension. The extensor digitorum tendons of the 3rdand 4thfingers are normally positioned on the dorsal aspect of the metacarpal heads in flexion (white arrows) and extension (black arrows).Disclosure of Interests:Thomas Kirchgesner: None declared, Maria Stoenoiu: None declared, Nicolas Michoux: None declared, Xavier Libouton: None declared, Frederic Houssiau Grant/research support from: UCB, Consultant of: GSK, Bruno Vande Berg: None declared

Key messages #### What is already known about this subject? #### What does this study add? #### How might this impact on clinical practice? Entheses are sites where tendons, fascia, ligament or joint capsule attach to bones of the appendicular or axial skeleton.1 2 Inflammation at these sites, enthesitis, involves both soft tissue and bone, and is considered as a core pathological process in spondyloarthritis (SpA), including psoriatic arthritis (PsA).3 4 The prevalence of enthesitis in SpA, including PsA, has been reported to be 13.6%–35%, with Achilles tendon and plantar fascia insertion being the most common sites.5 6 Assessing enthesitis as primary or secondary outcome in clinical trials requires a comprehensive, sensitive and validated assessment method. Clinical examination using different enthesitis indices has been shown to have low sensitivity and specificity, with suboptimal reproducibility.7 8 MRI allows sensitive assessment of enthesitis,9–11 and the OMERACT MRI in Arthritis Working Group has recently developed and validated the OMERACT Heel Enthesitis MRI Scoring System (HEMRIS), along with consensus-based definitions of the MRI features to be scored.12 Thus, this method may facilitate a more reliable assessment of enthesitis in clinical trials. The exact area of assessment and the individual grades of HEMRIS may be difficult for new readers to conceptualise. Furthermore, the applicability and reproducibility of …

Background: The aim of this global collaboration was to develop a consensual set of items for the analysis of synovial biopsies in clinical practice and translational research through the EULAR Synovitis Study Group (ESSG) and OMERACT Synovial Tissue Biopsy Group. Methods: Participants were consulted through a modified Delphi method. Three sequential rounds occurred over 12 months. Members were sent a written questionnaire containing items divided into two parts. Items were identified and formulated based on a scoping review. The first part of the questionnaire referred to synovial biopsies in clinical practice including five subsections, and the second part to translational research with six subsections. Every participant was asked to score each item on a 5-point Likert scale. Items with a median score above 3.5 and a ≥ 70% agreement were selected for the next round. The last round was conducted orally at EULAR in June 2017. Results: Twenty-seven participants from 19 centers were contacted by email. Twenty participants from 17 centers answered. Response rates for next rounds were 100%. For the first part relating to clinical practice, 20/44 items (45.5%) were selected. For the second part relating to translational research, 18/43 items (41.9%) were selected for the final set. Conclusions: We herein propose a consensual set of analysis items to be used for synovial biopsies conducted in clinical practice and translational research.

Background We present a European multicenter study, comparing safety data and patient-reported outcomes (PRO) from patients undergoing synovial biopsy using ultrasound-guided needle biopsy (US-NB), ultrasound-guided portal and forceps (US-P&F) or arthroscopic-guided (AG) procedures. Objectives To describe safety and PRO data on joint indices of pain, stiffness and swelling before and after biopsy, procedural discomfort, joint status compared with before biopsy and willingness to undergo a second biopsy for each technique and compare the three techniques. To evaluate the impact on PRO and safety data of corticosteroid therapy as part of the biopsy procedure and sequential biopsy procedures. Methods Data were collected on the day of biopsy and 7-14 days postprocedure. Joint pain, swelling and stiffness indices were recorded as 0-100mm Visual Analogue Scale; qualitative outcome variables on five-point Likert scales. Groups were compared with linear regression, adjusting for disease activity, corticosteroid therapy and prebiopsy PRO value and accounting for repeated measurements. Results A total of 524 synovial biopsy procedures were documented (402 US-NB, 65 US-P&F and 57 AGSB). There were eight adverse events (1.5%) with no difference between biopsy methods (p=0.55). All PROs were improved 2weeks postprocedure, and there were no differences in postbiopsy change in PROs between biopsy methods. Corticosteroid administration, whether intramuscular (n=62) or intra-Articular (n=38), did not result in more adverse events (p=0.81) and was associated with reduction in postbiopsy swelling (p, SCOPUS: ar.j, info:eu-repo/semantics/published

Whole-body magnetic resonance (MR) imaging techniques and protocols have been evolving continuously for the last 20 years, resulting in a powerful and mature tool for the detection, staging, and treatment monitoring of many oncologic and musculoskeletal disorders. The unique contrast resolution of MR imaging makes this imaging modality highly sensitive to pathologic alterations in bones, muscles, entheses, joints, and soft tissues, enabling this method to be expanded to the whole musculoskeletal system. Whole-body MR imaging is now used in numerous rheumatic, bone, and muscle disorders, and a full range of developing applications for this method have been emerging.

Whole-body MRI is an emerging imaging technique on continuous evolution, used in many oncologic indications and introduced more recently in rheumatologic and systemic disorders. In this article, we review the recent musculoskeletal applications of this technique outside the field of cancer. Whole-body MRI, with its high sensitivity to bone marrow and soft-tissue alterations, and ability of extensive body coverage, is progressively regarded as an effective and powerful imaging tool for the detection, staging, and monitoring under treatment of many rheumatic diseases and systemic pathologies affecting the musculoskeletal system. Disease specific imaging protocols have been designed. Whole-body MRI is an appealing, non-irradiating tool emerging in musculoskeletal imaging. It is becoming the imaging of choice in several non-oncologic indications, and its application field is on continuous expansion.

Background Musculoskeletal ultrasound (US) was developed more than four decades ago and gradually made its way to daily rheumatological practice. This dynamic, non-irradiating and relatively inexpensive technique allows detection of synovitis/tenosynovitis as well as quantification of joint inflammation. However, several external factors, such as, joint position, machine settings, sonographer expertise and certain medications can influence the results of the US examination. Objectives The aim of this study was to investigate whether the pharmacokinetics of intravenous ( i.v. ) infliximab (IFX) influences the grade of US detected synovitis, measured by gray-scale (GS) and colour Doppler (CD) in rheumatoid arthritis (RA) patients. Methods Inclusion criteria were RA patients with at least one swollen joint, being treated with i.v. IFX, who had neither, changes in DMARD therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory and US assessment at three time points: at trough, peak plasma drug concentration and at mid-cycle. US assessments were performed blindly to the clinical and laboratory data. Twenty-four joints were assessed for the presence and grade (0–3) of GS synovitis and synovial CD signal: elbows, wrists, 2nd-5th metacarpophalangeal (MCP) joints, knees, ankles, 2nd-5th metatarsophalangeal (MTP) joints. A global OMERACT-EULAR synovitis score (GLOESS) as well as the sum of GS and CD scores were calculated for the 24-joint set, for the 12-joint set (Naredo score) and for wrists-MCP-ankles-MTP joints. Several disease activity scores (DAS) [28-joint DAS (DAS28-CRP), Simplified Disease Activity Index (SDAI)] and health assessment questionnaire (HAQ) were assessed in all patients. Trough plasma IFX concentrations were available in 20 patients. Results Twenty-two RA patients were prospectively recruited from the biologic therapy unit of our hospital. Two thirds of patients were female and mean age was 61 years. The majority of them had long-standing seropositive RA and over 90% had radiographic damage. The median of IFX treatment duration was 9 years. There were no significant differences between the GS, CD and GLOESS scores at IFX peak time and trough time. US-joint count, GS, CD and GLOESS scores did not significantly differ between peak time and trough time. Patients with long-lasting RA treated with IFX had relatively stable US-detected synovitis and slightly lower clinical scores at 4 weeks after IFX administration as compared to baseline. The DAS28CRP, 28 and 44 swollen joint counts did not correlate with trough serum IFX concentrations. US scores (GS and GLOESS) significantly correlate with trough serum IFX concentrations (Spearman correlation coefficient, r=−0.55, p=0.01, n=20). Patients with low trough IFX levels, especially ≤1 µg/ml, had higher US joint count as well as US scores (p Reference [1] US-scored synovitis is not significantly influenced by pharmacokinetics of IFX in RA patients. US examination can be conducted independently of time of IFX administration i.e. before or after IFX administration in clinical trials. Although there was no correlation with clinical scores, low trough IFX concentration correlated with the degree of US-detected synovitis. Disclosure of Interest None declared

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 Magnetic resonance imaging (MRI) allows objective assessment of inflammation in peripheral joints and entheses. MRI scoring systems have until now focused on assessing specific parts of the musculoskeletal system in detail, e.g. the Rheumatoid Arthritis MRI Scoring System (RAMRIS), which is applied to wrist and metacarpophalangeal joints and adjacent tendon sheaths. The interest in a whole-body MRI approach is growing as modern MRI scanners now permit whole-body scanning within an acceptable time frame, and future improvements in MRI hardware and pulse sequences are expected to improve scan time and image resolution further. Objectives To develop a whole-body MRI scoring system for inflammation of peripheral joints and entheses and to investigate its feasibility and reliability. Methods Definitions of the key pathologies and locations for assessment have been agreed upon in the OMERACT MRI Working Group1. In a first round in June 2017, 9 readers (AJM/DG/FG/IE/MO/PB/SJP/SK/WPM) scored MR images of 2 patients with spondyloarthritis using a draft web-based scoring system. Results were discussed and the scoring system was slightly modified. Hereafter, in a second round in October 2017, 14 MRI readers (3 musculoskeletal radiologist (IE/JLJ/RGL) and 11 rheumatologists with varying exposure to MRI (AJM/DG/FG/MS/MO/PB/RP/SJP/SK/VF/WPM), scored 5 similar patients by the modified scoring system. Using a semiquantitative scale 0–3 (none/mild/moderate/severe), synovitis and osteitis were scored separately for 83 joints, and soft tissue inflammation and osteitis were scored separately for 33 entheses. Discrepancies between readers were discussed during an online meeting to obtain consensus, to train inexperienced readers, and to identify potential pitfalls when applying the scoring system. Results Inter-reader reliability was overall moderate for joint scores and poor for enthesis scores; however, among the 3 musculoskeletal radiologists, enthesis scores were as reliable as joint scores (Table). Reliability did not improve between the first and second round, possibly because patients with several very conspicuous inflammatory lesions were selected as cases in the first round. Conclusions It is feasible to perform online multi-reader scoring exercises of whole-body MRI using a web-based scoring interface. MRI readers need to be further trained and calibrated in the semiquantitative scoring approach used to increase inter-reader reliability. Reference [1] Ostergaard M, et al. J Rheumatol2017;44:1699–1705. Disclosure of Interest None declared

Background Patients (Pts) with Undifferentiated Arthritis (UA), positive for ACPA antibodies are at high risk of progressing to Rheumatoid Arthritis (RA). TNF play a key role in the pathogenesis of RA. Very early treatment with the combination of Methotrexate and Infliximab (IFX) in a small cohort of UA showed a benefit in clinical symptoms and reduction of MRI evidence of synovitis and erosions. Objectives To assess whether IFX as a monotherapy is more effective than placebo (Pbo) in UA pts positive for ACPA. Here we evaluate the clinical response, the MRI RAMRIS score MRI and the risk to develop RA. Methods This was a randomised, double-blind, Pbo-controlled, two-arm parallel design study of 12 months to the primary endpoint (proportion of pts who developed RA by ARA 2007 criteria). Pts with UA and symptomatic clinical synovitis of ≥1 joints and ACPA positivity were randomised 1:1 to IFX (3 mg/kg) or Pbo at week 0, 2, 6, 14 and 22, after which treatment was terminated. NSAIDs/stable low-dose oral corticosteroid (≤5 mg/day prednisone or equivalent) were permitted but no DMARDs. Disease activity measures (DAS28-CRP) were evaluated at BL, Wks 2 and 4, and every 4 wks until Wk 52. OMERACT RAMRIS scores (components: erosion, osteitis, synovitis, tenosynovitis) and peritendinitis scores were evaluated at BL and Mth 4. Pts who developed RA at any time were discontinued and could receive standard of care. Results 28 pts were randomised (mean age: 48±12 years; mean duration of arthritis: 0.34±0.53 year; mean CRP level: 1.67±2.23 mg/dL). By 1 year, 11/15 (73%) pts treated with IFX developed RA vs 10/15 (67%) Pbo-treated pts (Kaplan Meier, log rank p=0.868). At wk 14, ACR 20, 50, 70 responses were observed respectively in 71.4%, 42.9%, 28.6% pts treated with IFX vs 21.4%, 0%, 0% treated with Pbo. Remission DAS28CRP rate was observed in 50% in the IFX group vs 21.4% in the Pbo group. Pts in the IFX arm experienced significantly greater improvements in RAMRIS score versus pbo at wk 16 (see graph). No severe safety issues was observed except one case of severe hepatotoxicity induced by Isoniazid. Conclusions In this small randomised cohort of UA ACPA positive pts, we noted a significant difference in the RAMRIS scoring after 4 months in the IFX group vs PBo. This is the first study to report a worsening of disease activity based on the RAMRIS scores in the PBo group but changes were minimal and not observed in all pts. IFX has higher efficacy but did not prevent the progression to definite RA. Further analyses are ongoing to determine MRI predictors for severity. Reference [1] Quinn MA, et al. Arthritis Rheum2005; 52(1):27–35. Disclosure of Interest None declared

Background: The development of ultrasound-guided synovial biopsy will enable synovial tissue collection from small joints and will facilitate histopathological studies, thus improving the understanding of early rheumatoid arthritis (ERA). The CAP48 cohort is an original multicentre prospective observational study of early Rheumatoid Arthritis (RA) patients up to 50 years old supported by a charity program of the Belgian French speaking radio-television (RTBF). Objectives: The objectives of this cohort are to observe if a tight control favour remission at 6 months and to define synovial markers for severy and response to therapy. Methods: RA patients fulfilling the ACR/EULAR 2010 criteria and naive to DMARDs therapy were recruited. Synovial biopsies before treatment were obtained using an ultrasound guided needle biopsy (US-NB) of the small joints or miniarthroscopy of the knee. RA disease activity measures including DAS28CRP domains were evaluated every 3 months and treatment was adapted by the treating physician. Tissues were assessed for quality. Retrieved tissue was fixed, stained and paraffin embedded for blinded tissue pathotype description. Results: A synovial biopsy was performed in 37 patients using US-NB in n patients. Patients were classified according 4 types of synovial histopathology findings. Baseline characteristics of the cohort is summarized in table 1. All patients in the diffuse lymphoid group were ACPA negative and the majority of the ACPA positive patients were classified in the pauci immune and fibrous group. As shown in figure 1, the pauci immune ERA group showed lower DAS28-CRP response than the other groups. Conclusions: Synovial tissue analysis could provide a step change towards personalized medicine in daily clinical practice for disease stratification and treatment selection of ERA. In the CAP48 cohort, a high number of these young and ERA patients achieved remission at 6 months but a lower response was observed in the pauci immune group. Further analyses are ongoing to define individual synovial markers of severity and response. Disclosure of Interest: None declared

Background None Objectives To compare the diagnostic value of DWI and STIR sequences as part of WB-MRI studies in AxSpA patients. Methods 20 consecutive patients (P) with confirmed diagnosis of active AxSpA and 20 controls (C) referred for metastatic cancer screening were investigated with identical WB-MRI protocols including DWI and STIR images. Two independent observers recorded the presence of “lesions” (high signal intensity foci on STIR and high b-value DWI images) in 17 anatomic areas; making a 17-point “area score”) and a calculated 40-point “lesion score”. Both were tested for correlation with clinical and biological parameters. Results In P, the “lesion score” was significantly higher with DWI than with STIR (p 4 had 100% sensitivity and 95% specificity. With STIR, a threshold of >3 had 85% sensitivity and 90% specificity. The area score AUC was significantly lower with STIR than with DWI (p=0.0233), but no satisfactory area score threshold was identified. The most frequently involved areas were the spine and hip entheses in C, the spine and SIJ in P. Manubrio- and chondro-sternal joint involvement was specific for AxSpA. The lesion score was positively correlated with ASDAS-CRP and (log) CRP. Conclusions DWI is a promising alternative to STIR in WB-MRI studies for the detection of active lesions in AxSpA. Training may be necessary. The involvement of specific anatomic areas could distinguish P from C. Acknowledgements None Disclosure of Interest None declared

Background Enthesitis is regarded the primary lesion in spondyloarthritis (SpA) and MRI allows sensitive visualisation of entheseal inflammation/damage, but no validated, internationally accepted scoring system exists. Objectives To develop and perform preliminary validation of a novel OMERACT MRI scoring system for assessing ankle enthesitis in SpA patients, and to improve this through iterative multi-reader scoring exercises and calibration sessions. Methods A systematic literature review of MRI studies on enthesitis in SpA identified key inflammatory and structural pathologies. Definitions were agreed by consensus within the OMERACT MRI in arthritis working group. Then, in a first internet-based multireader exercise the Achilles tendon and plantar fascia entheses in 10 ankle MRIs (sagittal T1W, sagittal and Axial T2W fat suppressed) were scored by 15 readers (3 radiologists and 12 rheumatologists), with varying expertise in ankle MRI, for tendon/fascia thickness/signal change, tendon/peritendon signal alteration, retrocalcaneal bursitis, bone spur, erosion and bone marrow oedema, using semi-quantitative scores (0–3: no/mild/moderate/severe pathology). After a subsequent calibration session leading to minor modifications of assessed parameters, 16 ankle MRIs (specifications as above), were scored by 15 readers in exercise 2 with a modified score sheet. Rules were agreed for scoring pathologies. In both exercises, scores for each reader for individual variables were compared and discussed, and mean scores for each variable were determined using descriptive statistics, as were sum scores. Inter-reader agreement was calculated using two-way consistency single measures intra-class correlation coefficient (ICC 3,1) for inflammatory and structural lesions. Results Exercise 1: Mean pairwise inter-reader ICC for combined score of inflammatory and structural variables was 0.65 (range 0.10–0.94), with 75% of values being good/very good (≥0.50). Discussion of results led to minor modifications of parameters to be assessed. Exercise 2: Inter-reader agreement (ICC) for all inflammatory variables combined ranged from 0.26–0.93 among reader pairs (mean 0.64; median 0.66; IQR 0.46–0.79). For structural variables combined ICC ranged from 0.05–0.91 among reader pairs (mean 0.45; median 0.45; IQR 0.2–0.6). Conclusions Initial steps in developing an OMERACT MRI heel enthesitis scoring system have demonstrated overall moderate reliability of the proposed variables. Further modification, refinement, calibration and validation (ongoing) are needed before this system is ready for use in SpA clinical trials. Disclosure of Interest None declared

The fascial system is a three-dimensional continuum of connective tissues present everywhere throughout the body, from the head to the toes and from the skin to the bone. The current article aims to review the normal anatomy of the fasciae of the musculoskeletal system with macroscopic and microscopic correlations and to describe their appearance at MRI in normal subjects and in patients with autoimmune diseases of the musculoskeletal system. Key Points • The fascial system is a three-dimensional continuum of connective tissues. • It is present everywhere throughout the body, from the head to the toes and from the skin to the bone. • The normal fascial system is barely visible at MRI. • MR patterns of fascial involvement in autoimmune diseases reflect the complex anatomy of the fasciae of the musculoskeletal system.

Whole-body coverage using MRI was developed almost 2 decades ago. The first applications focused on the investigation of the skeleton to detect neoplastic disease, mainly metastases from solid cancers, and involvement by multiple myeloma and lymphoma. But the extensive coverage of the whole musculoskeletal system, combined with the exquisite sensitivity of MRI to tissue alteration in relation to different pathologic conditions, mainly inflammation, has led to the identification of a growing number of indications outside oncology. Seronegative rheumatisms, systemic sclerosis, inflammatory diseases involving muscles or fascias, and multifocal osseous, vascular, or neurologic diseases represent currently validated or emerging indications of whole-body MRI (WB-MRI). We first illustrate the most valuable indications of WB-MRI in seronegative rheumatisms that include providing significant diagnostic information in patients with negative or ambiguous MRI of the sacroiliac joints and the lumbar spine, assessing disease activity in advanced (ankylosed) central disease, and evaluating the peripherally dominant forms of spondyloarthropathy. Then we review the increasing indications of WB-MRI in other rheumatologic and nonneoplastic disorders, underline the clinical needs, and illustrate the role of WB-MRI in the positive diagnosis and evaluation of disease burden, therapeutic decisions, and treatment monitoring.

Objective.To provide an update from the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group on the progress for defining ultrasound (US) minimal disease activity threshold at joint level in rheumatoid arthritis (RA) and for standardization of US application in juvenile idiopathic arthritis (JIA).Methods.For minimal disease activity, healthy controls (HC) and patients with early arthritis (EA) who were naive to disease-modifying antirheumatic drugs were recruited from 2 centers. US was performed of the hands and feet, and scored semiquantitatively (0–3) for synovial hypertrophy (SH) and power Doppler (PD). Synovial effusion (SE) was scored a binary variable. For JIA, a Delphi approach and subsequent validation in static images and patient-based exercises were used to developed preliminary definitions for synovitis and a scoring system.Results.For minimal disease activity, 7% HC had at least 1 joint abnormality versus 30% in the EA group. In HC, the findings of SH and PD were predominantly grade 1 whereas all grades were seen in the EA cohort, but SE was rare. In JIA, synovitis can be diagnosed based on B-mode findings alone because of the presence of physiological vascularization. A semiquantitative scoring system (0–3) for synovitis for both B-mode and Doppler were developed in which the cutoff between Doppler grade 2 and grade 3 was 30%.Conclusion.The first step has been taken to define the threshold for minimal disease activity in RA by US and to define and develop a scoring system for synovitis in JIA. Further steps are planned for the continuous validation of US in these areas.

BACKGROUND: Initial studies of adenovirus-mediated gene transfer to the peritoneum have shown transgene expression in the mesothelium from the parietal peritoneum. Using a replication-deficient adenovirus encoding beta-galactosidase (Ad beta Gal), we investigated the expression efficiency and the distribution of the transgene to different areas of both visceral and parietal peritoneum and to extra-peritoneal tissues. METHODS: Male Wistar rats received an intraperitoneal injection of 15 ml of 0.9% NaCl alone or containing 1 x 10(9) or 3 x 10(9) p.f.u. of Ad beta Gal. Evaluations of the histology of the peritoneum, the transgene expression and the safety of adenovirus-mediated gene transfer, using measurement of both beta Gal activity and staining, were performed 1, 3 and 5 days post-injection. RESULTS: At 1 day post-injection of 3 x 10(9) p.f.u. of Ad beta Gal, significant beta Gal activity and staining were detected in the omentum and mesenteric peritoneum. beta Gal staining was observed in endothelial cells, mesothelial cells and adipocytes. Focal mononuclear infiltrates restricted to the submesothelial area of the visceral peritoneum were also observed. No expression was detected in the mesocolon and parietal peritoneum, where the mesothelium was damaged. Significant beta Gal activity and staining were observed in lymph nodes, lungs, liver, heart and kidneys, in the absence of inflammatory changes. CONCLUSIONS: Intraperitoneal delivery of adenoviral vectors allows highly efficient transgene expression in mesothelial cells, but also in endothelial cells and adipocytes of the visceral peritoneum. Adverse focal mononuclear infiltrates, as well as spreading of the adenoviral vector from the abdominal cavity to the systemic circulation, were observed in parallel. Transgene expression in endothelial cells is potentially important since the latter play a key role in the alterations of the peritoneal membrane associated with long-term peritoneal dialysis. However, these data emphasize the need for less immunogenic adenoviral vectors, ideally containing an endothelial cell-specific promoter, to overcome immune response-related problems and spreading to extra-peritoneal tissues.

The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore responsible for transcellular water permeability during peritoneal dialysis (PD). This water permeability accounts for up to 50% of ultrafiltration (UF) during a hypertonic dwell, and its loss can be a major clinical problem for PD patients. By analogy with the lung, the hypothesis was tested that corticosteroids may increase AQP1 expression in the peritoneal membrane (PM) and improve water permeability and UF in rats. First, the expression and distribution of the glucocorticoid receptor (GR) in the PM and capillary endothelium was documented. Time-course and dose-response analyses showed that a daily IM injection of dexamethasone (1 or 4 mg/kg) for 5 d induced an approximately twofold increase in the expression of AQP1 at the mRNA and protein levels. The GR antagonist RU-486 completely inhibited the dexamethasone effect. The functional counterpart of the increased AQP1 expression was a significant increase in sodium sieving and net UF across the PM, contrasting with a lack of effect on the osmotic gradient and permeability for small solutes. The latter observation reflected the lack of effect of corticosteroids on nitric oxide synthase (NOS) activity and endothelial NOS isoform expression in the PM. In conclusion, corticosteroids induce AQP1 expression in the capillary endothelium of the PM, which is reflected by increased transcellular water permeability and UF. These data emphasize the critical role of AQP1 during PD and suggest that pharmacologic regulation of AQP1 may provide a target for manipulating water permeability across the PM.

Nitric oxide (NO) is a well-known mediator of autoimmune processes. In the thyroid gland, it is produced in response to interleukin 1 (IL-1) and may mediate cytokine action at an early stage of autoimmune thyroiditis. In this study, we have investigated whether NO is involved in cytokine-induced cytotoxic effects and epithelial barrier alterations in thyrocytes. Human thyroid epithelial cells were cultured as tight polarised monolayers on a permeable support and exposed or not to IL-1alpha (100 U/ml), alone or in combination with interferon-gamma (IFN-gamma; 100 U/ml) added to the basal compartment. NO production was not detected in control thyrocytes, but was significantly induced by the combination of IL-1alpha with IFN-gamma, in a time-dependent fashion. Similarly, expression of the inducible isoform of nitric oxide synthase (NOSII), determined by immunoblot and immunofluorescence confocal microscopy, was not detected in control cells, but was markedly induced after 48-h exposure to both cytokines. This treatment significantly increased the release of cytosolic lactate dehydrogenase (LDH) in the apical and basolateral media and decreased transepithelial electrical resistance. Although IFN-gamma was not sufficient to induce NO production, it could by itself decrease transepithelial resistance and synergised the IL-1alpha effect on LDH release. The NOS inhibitor, L-nitro-arginine-methyl ester, suppressed the cytokine-induced NO production and decreased the LDH release, but failed to prevent the loss of transepithelial resistance. These results indicated that human thyrocytes express NOSII and produce NO in response to IL-1alpha+IFN-gamma and suggest that NO acts as a mediator of cytokine-induced cytotoxicity in the thyroid gland and may promote the exposure of autoantigens to the immune system. In contrast, NO does not appear to mediate the cytokine-induced disruption of the thyroid epithelial barrier.