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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.

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.

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.

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

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 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.

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 Synovitis is the common feature of patients suffering from inflammatory arthropathies (IA). The development of ultrasound (US)-guided synovial biopsy will enable synovial tissue collection from small joints and will facilitate molecular studies, thus improving the understanding of mechanisms of IA as small joints are frequently involved in these diseases. Objectives To assess the safety, tolerability and feasibility to perform synovial biopsies from wrist and metacarpophalangeal (MCP) joints, using a minimally invasive US-guided technique in patients suffering from rheumatoid arthritis (RA), spondylarthropathies (SA) or undifferentiated arthritis (UA). Methods Two target joints (TJ) were biopsied: wrist and MCP. Patients with at least one clinically swollen joint at these levels, suffering from RA, SA, or UA underwent a US examination. The TJ chosen for the biopsy was the joint with the most important inflammatory changes on gray-scale (GS) US. GS synovitis and power-Doppler (PD) activity were assessed by OMERACT scores, on the day of the biopsy, as well as 2 weeks (w), 6w and 6 months (m) after the biopsy. In addition, tendon tears, hematoma, paratenonitis and tenosynovitis were searched by US. Patient-reported outcomes (PRO) included a standard questionnaire given to all patients on the day of the biopsy as well as 1w, 2w, and 6w after the biopsy. Tolerability and the patient-reported willingness to repeat the procedure was assessed using the 5-point Likert scale. Results Forty-one patients suffering from RA (27), SA (7) and UA (7) underwent US-guided biopsy of the wrists (20) and MCP (21) joints. A non-significant increase in pain was reported 24 h after the procedure. No difference in PRO of the biopsied joints was reported 2w and 6w after the biopsy, as compared to assessment before the biopsy. No infection or haemorrhage was observed after the biopsy. PRO did not differ significantly among patients suffering from RA, SA or UA. At the TJ, US scores tended to decrease 2w after the procedure. At 6w and 6m follow-up, no safety concerns were reported. Treatment response at the TJ was similar to the response of non-biopsied joints matched for the baseline US parameters. Conclusions With the exception of study of Kelly et al (Ann Rheum Dis. 2015;74:611–6117), data on safety, tolerability, feasibility and PRO using the minimally invasive US-guided biopsy technique are lacking. In this work, we confirm that US-guided biopsy of wrist and MCP joints is feasible, safe and well tolerated by RA patients. At 2w, 6w and 6m follow-up, no safety concerns were reported. Furthermore, no differences in PRO between RA, SA and UA were observed. This technique is therefore a promising approach to assess the presence and persistency of synovial inflammatory processes in patients with early and refractory IA, and to facilitate patients stratification according to transcriptomic profiles. Acknowledgement We acknowledge Pr C. Pitzalis and S. Kelly for giving us the opportunity to learn and further disseminate minimally invasive ultrasound-guided technique, and for fruitful discussions. Disclosure of Interest None declared

Objective. To assess the tendon and joint involvement at wrists and ankles of patients suffering from diffuse SSc and to identify the morphological substrate of tendon friction rubs (TFRs).Methods. Fifteen consecutive patients suffering from diffuse SSc were included. All patients had two musculoskeletal US (MSUS) examinations of the wrists and ankles. MRI was performed at the most affected joints as detected by MSUS and in all sites in which TFRs were present.Results. No clinically overt arthritis or tenosynovitis was detected in the wrists and/or ankles prior to MSUS. Synovitis, tenosynovitis and tendon tear were identified in 8, 4 and 2 of 15 patients, respectively, by both MSUS and MRI. At entry, 5 patients had palpable TFRs (4 bilateral and 1 unilateral) and 10 patients did not. Tenosynovitis was more frequently found in ankles with TFRs (3/9) than in those without TFRs (3/21), although the difference was not statistically different (P = 0.3). Using MRI, deep connective tissue infiltrates surrounding tendons were present in all sites with TFRs but in only one patient without TFRs.Conclusion. Both MSUS and MRI are effective in detecting synovitis and tenosynovitis in diffuse SSc patients. Tenosynovitis, synovitis and thickened retinacula are not infrequently seen in these patients. Our data suggest that juxta-tendinous connective tissue infiltrates might be the morphological substrate of tendon friction rubs, which may thus be a misnomer for tissue friction rubs.

Background Previous studies have shown an increased prevalence of synovitis and tenosynovitis in systemic sclerosis (SSc) as detected by magnetic resonance imaging (MRI) or musculo-skeletal ultrasound (US). It was assumed that MRI and US can accurately describe synovitis and tenosynovitis in these patients. However, histological examination was not available in these studies. Objectives To assess the histologic pattern of synovium in SSc patients suffering from synovitis detected by MRI or US. Methods Seven synovial biopsies from 4 different SSc patients were analyzed by immunohistochemistry (IC). Three patients underwent a second synovial biopsy one year later. Imaging studies (US, MRI, radiographs) were performed prior to biopsies. The histologic pattern in synovium from SSc patients was compared with that observed in patients suffering from lupus arthritis (LA, n:5), rheumatoid arthritis (RA, n:7), spondylarthritis (SPA, n:10) and osteoarthritis (OA, n:6). Results In all SSc patients, imaging studies confirmed the presence of joint effusion and active synovitis with increased vascularisation (Figure). In addition, in one SSc patient, intra-articular calcifications were observed by US. Microscopic examination of the SSc synovium revealed altered global architecture with marked angiogenesis, inflammatory cell infiltrates, increased collagen density and extracellular deposits (Figure). The increased thickness of the synovium was due both to increased deposition of extracellular matrix (collagen) and infiltrates of inflammatory cells. These changes paralleled those observed by imaging and were more severe in patients with longer duration of the disease. Furthermore, IC revealed an increased density of T lymphocytes and macrophages (Figure), with low density of B-cells and plasmocytes. Perivascular T-cell infiltrates and T-cell aggregates were present around inflammatory nodules, the latter being associated with marked deposits of extracellular, amorphous material. Angiogenesis consisted mainly in increased density of immature vessels, as detected by WT1 immunostaining. Arteriolar onion-skin like lesions were present in biopsies from two patients with more severe patients. Paired synovial biopsies confirmed the persistence of abnormal synovial findings at one year. This histologic pattern was distinct from that observed in LA, RA, SPA and OA. One SSc patient had joint infection and delayed wound healing after biopsy, leading us to stop recruiting SSc patients. Conclusions SSc-related synovitis is characterized by the presence of both inflammatory and non-inflammatory changes, including increased vascularity, inflammatory cells infiltrates, fibrosis and collagen deposits within the synovium. Furthermore, we present here the first histologic data suggesting that US and MRI can accurately describe synovitis and tenosynovitis in SSc patients. Larger studies including more synovial biopsies are ethically difficult to justify in view of the increased probability of infections and delayed wound healing in SSc patients. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) is a chronic, inflammatory disease with joint destruction and permanent disability. Biologic agents offer a better outcome when disease is not adequately controlled by DMARDs. Nevertheless, many concerns still exist about the safety of biologics compared to classical DMARDs treatment. Objectives The purpose of the study was to test the hypothesis that adverse events (AEs), including severe infections and malignancies, are more common in patients receiving biologics than in those treated with DMARDs. Methods This study included data from 1143 patients followed in our outpatient academic clinic for whom each severe infection and malignancy was identified. Relative risks were then calculated by comparing the rates of these events. Sub-categories of adverse events were created to clarify what type of infection and/or cancer were observed. Finally, an estimate of survival by Kaplan-Meier method was calculated for these two major adverse events. The experimental group, including patients who were treated with biological agent at any time and the control group, patients who have never taken any biological agent, were compared across these survival curves. Results We included 1143 patients (74% female, mean age of 51.3 (14.2) years, 75% treated with corticosteroids and 7% with diabetes), 604 (53%) were exposed to biologics and 539 (47%) controls. There were 226 severe infection in the biological group with an IR of 4.89 events/100 patient years (IRR=2.1 95% CI 1.7 to 2.5) as compared with 168 and 2.35 events/100 PY with DMARDs only. In the biological group, increase risk was observed for skin, musculoskeletal, pulmonary, urinary, mycobacterial and herpes zoster infection. The relative risk associated with the use of biological agents in the treatment of rheumatoid arthritis for the development of malignancy was 1.0 (confidence interval 95%: 0.7-1.4) without any significant differences among type of cancer. Survival rates are presented in the figure. Conclusions This study showed a significant increase in the incidence of severe infections in patients exposed to bioiogical agent. During a mean follow-up of 11 years, no significant risk to develop a cancer was observed. Further longterm observation of severe infection and malignancy in severe RA patients treated with biologics are still needed. Disclosure of Interest None declared