Gray-scale Score Research Articles

Ultrasonographic Synovitis Is Associated with the Development of Joint Destruction in Patients with Psoriatic Arthritis.

Psoriatic arthritis (PsA) is characterized by enthesitis. As persistent inflammation around joints results in bone and cartilage destruction and physical impairment, a detailed assessment of inflammation is essential. We previously reported the difference between clinical assessment (tenderness) and ultrasound (US) assessment (inflammation) of entheses. Herein, we investigated whether clinical or US assessment of joints and entheses can predict the progression of joint destruction in Japanese patients with PsA. Thirty joints and 14 entheses in 47 patients were assessed using US and clinical examination. The US greyscale (GS) and power Doppler (PD) scores at the ultrasonographic synovitis, the US active enthesitis count, and the clinical tender joint/entheses count were assessed. Additionally, the yearly radiographic progression of the Sharp-van der Heijde scoring method for PsA was assessed. Their correlations were investigated. About half of the patients with PsA experienced joint destruction during a follow-up period of 20.4 months. Progression of joint destruction in patients with PsA only correlated with joint GS and PD scores, reflecting the severity of ultrasonographic synovitis, not with the tender joint/entheses count. US examinations are essential for preventing joint destruction and physical impairment in patients with PsA.

The double shared epitope: Its impact on clinical features and ultrasound findings in rheumatoid arthritis.

The link between the HLA-DRB1 locus and the risk of rheumatoid arthritis (RA) shown in genome-wide association studies strengthens the shared epitope (SE) hypothesis. We aimed to assess the impact of the double dose of the SE (double SE) on RA and explore its clinical associations, including the response to abatacept. We evaluated RA patients treated with csDMARDs or abatacept for HLA-DRB1 typing, clinical characteristics at baseline, and disease activity and ultrasound findings over 12 months. Patients with the double SE (n = 12) had significantly higher anti-citrullinated protein antibody (ACPA) titers, higher total grayscale (GS) score, and power Doppler (PD) score at baseline than patients without the double SE. Patients with the double SE exhibited reduced rates of SDAI remission and pronounced improvements in multiple disease activity between baseline and 12 months, including SDAI, CDAI, total GS score, and total PD score. When focusing on abatacept-treated patients, the decreases in SDAI, CDAI, and total PD score between baseline and 12 months were significantly larger in patients with the double SE. Patients with the double SE exhibited distinct characteristics, increased disease activity, and improved response to abatacept treatment.

Clinical and ultrasound features of difficult-to-treat rheumatoid arthritis: A multicenter RA ultrasound cohort study

Objective: The optimal strategy for difficult-to-treat (D2T) rheumatoid arthritis (RA) has not been identified, and the ultrasound characteristics of D2T RA have not been reported. We investigated the clinical characteristics and factors contributing to the outcome in D2T RA in a multicentre RA ultrasound observational cohort. Method: We reviewed 307 Japanese patients diagnosed with RA who underwent treatment with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). We compared the differences in patient characteristics between the D2T RA and non-D2T RA groups. We examined the factors contributing to a good response [defined as b/tsDMARD continuation and Clinical Disease Activity Index (CDAI) ≤ 10 at 12 months] in the D2T RA patient group. Results: Forty-three patients (14%) were categorized as D2T RA and the remaining 264 (86%) as non-D2T RA at baseline. The grey-scale (GS) score, disease duration, and CDAI at the initiation of treatment were significantly higher in the D2T RA group than in the non-D2T RA group. In contrast, the power Doppler (PD) score was not significantly different between the two groups. Of the 43 D2T RA patients, 20 achieved a good response. The introduction of CTLA4-Ig (n = 5) was significantly associated with a good response in analysis based on inverse probability weighting with propensity score. GS and PD scores at baseline were not significantly associated with therapeutic response at 12 months in D2T RA patients. Conclusions: Patients with D2T RA had high clinical and ultrasound activity and poor responses to treatment with b/tsDMARDs. CTLA4-Ig was associated with a good response at 12 months in D2T RA patients.

Novel Scoring Systems and Age-Based Hepatic Shear Wave Stiffness Cut-Offs for Improving Sonographic Diagnosis of Biliary Atresia.

To make sonographic evaluation for biliary atresia (BA) more objective and reproducible using scoring systems, and evaluate hepatic shear wave elastography (SWE) as an adjunct in sonographic diagnosis of BA. Sixty-four infants with cholestatic jaundice were enrolled between June 2016 and March 2018 in this prospective observational cohort study. Sonography and SWE was performed with SuperSonic Aixplorer system. Novel scoring systems were developed incorporating established sonographic parameters and hepatic stiffness values and analysed using SPSS software. Of the 18 patients confirmed as BA, 3 were misdiagnosed on conventional sonography (16.7%) as non-BA. Gall bladder (GB) wall irregularity and fasting GB length were the most accurate (93.8%) and most specific (97.8%) individual parameters, respectively. A significant difference was noted in the triangular cord (TC) thickness of BA and non-BA infants (p <0.001), with a high specificity of 95.6% for a 4 mm cut-off value for a positive TC sign. Comparison of hepatic SWE stiffness among age-matched groups of BA and non-BA showed significant differences (≤60d: p=0.003; >60d: p <0.001) but with a reduced accuracy (93.8%). Diagnostic accuracy of greyscale scoring system (96.9%), greyscale + elastography scoring system in ≤60 d (94.4%) and >60 d (97.8%) were better than that of conventional sonographic diagnosis (93.8%). Grey scale scoring system improves the accuracy of sonographic diagnosis of BA without any additional cost or time penalty along with making it universally reproducible. SWE has only an adjunctive role, if any, in the sonographic diagnosis of BA.

P132 A late and rapid increase in ultrasound joint inflammation occurs when anti-CCP positive at-risk individuals with subclinical synovitis progress to inflammatory arthritis

Abstract Background/Aims Anti-CCP positive individuals with musculoskeletal (MSK) symptoms and subclinical synovitis on ultrasound (US) are at high risk of developing inflammatory arthritis (IA). Treatment initiation in these individuals is not accepted practice as they do not have clinical synovitis. We aimed to determine whether imaging characteristics change when individuals with pre-RA progress to IA in order to inform the optimal window of opportunity for therapeutic interventions. Methods Anti-CCP+ at-risk individuals with MSK symptoms from the Leeds CCP cohort were selected for having US subclinical synovitis [Grey scale (GS)≥1 and Power Doppler (PD)≥1] prior to IA development and an US scan performed at clinical synovitis onset. The US protocol included the metacarpophalangeal joints (MCPJs), proximal interphalangeal joints (PIPJs), wrists, elbows, knees, second-fifth metatarsophalangeal joints (MTPJs), extensor carpi ulnaris (ECU) and finger flexor tendons (FFTs). US PD and GS synovitis were scored semi-quantitatively (0-3) according to EULAR/OMERACT. At patient level, total GS and PD scores were compared between scans. Change on US in the joints that became clinically swollen was also assessed. Wilcoxon signed-rank tests were conducted for comparisons. Results Forty-six CCP2+ at-risk individuals were identified (Table). The median US scan interval was 3.5 months (IQR 1.25-8.75). At patient level the overall burden of PD in the joints increased at IA progression, trending towards significance [3 (IQR 1.25-5) vs 4 (IQR 2-7.25) p = 0.063]. Overall burden of GS did not increase. There was an increase in PD in the MCPJs [0 (IQR 0-2) vs 1.5 (IQR0-3) p = 0.008] and MCP and wrist joints combined [1 (IQR 0.25-3) vs 2 (IQR 1.25-4.75) p = 0.002]. GS at the elbows also significantly increased. At joint level PD [1 (IQR(0-2) vs 2 (IQR 0-3) p = 0.036] increased in joints swollen at progression and GS increased with a trend towards significance. Non-swollen joints did not change. Conclusion A marked increase in US joint inflammation is seen when CCP+ at-risk individuals with subclinical synovitis on US progress from pre-RA to clinical arthritis. This is particularly evident in the MCPJs, wrist joints and joints that become clinically swollen. Intervening when at-risk individuals have subclinical synovitis may represent a window of opportunity to prevent the rapid increase in joint inflammation which accompanies the onset of joint swelling. Disclosure K. Harnden: None. A. Di Matteo: None. D. Esperança Almeida: None. E. De Lorenzis: None. L. Duquenne: None. L. Garcia-Montoya: None. J. Nam: None. P. Emery: None. K. Mankia: None.

The role of ultrasound synovitis scores for patients who are at risk of rheumatoid arthritis.

The development of rheumatoid arthritis (RA) has been classified into 6 phases A-F according to the present risk factors in sequence of genes, environments, autoimmunity, arthralgia and joint swelling. To clarify the ultrasound synovitis scores in at-risk patients (phases C-E) and RA (phase F). Patients who had been experiencing hand joint symptoms for at least 6 weeks and asymptomatic patients with positive rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies were enrolled. A 40-joint ultrasonography with semiquantitative synovitis scoring for gray scale (GS) and power Doppler (PD) images was performed. A total of 139 patients were enrolled and classified into non-RA, phase C, phase D, phase E and phase F. Total GS scores in phases C (17.4 ± 7.0), D (16.0 ± 5.4), E (18.5 ± 7.7) and F (21.8 ± 9.1) were higher than those in non-RA (9.8 ± 4.0, P < 0.001). The total PD score in phase F (3.1 ± 4.6) was higher than that in phases C (0.2 ± 0.5), D (0.1 ± 0.4), and E (0.1 ± 0.3), as well as in non-RA (0.0 ± 0.0, P < 0.01). A total GS score ≥14 differentiated patients at risk for RA from patients with non-RA (area under curve [AUC] 0.82), while a total PD score ≥2 differentiated patients with RA from patients at risk for RA (AUC 0.71). Total GS score may differentiate patients at risk for RA from non-RA patients, while total PD score may differentiate patients with RA from those who are at risk for RA.

High-frequency ultrasound in patients with seronegative rheumatoid arthritis.

This study aimed to investigate the value of high-frequency ultrasound (HFUS) in differentiation of the seronegative rheumatoid arthritis (SNRA) and osteoarthritis (OA) and in the diagnosis of SNRA. 83 patients diagnosed with SNRA (SNRA group) and 40 diagnosed with OA (OA group) who received HFUS were retrospectively analyzed. The grayscale (GS) scores, power Doppler (PD) scores, and bone erosion (BE)scores were recorded, and added up to calculate the total scores of US variables. The correlations of the total scores of US variables with the 28-joint diseaseactivityscore (DAS28), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were analyzed. The diagnostic efficacy of the total scores of US variables for SNRA was assessed. In the SNRA group, the detection rate of abnormal US findings in the joints and tendons by GS and PD as well as BE was higher than those in the OA group. There were significant differences between the two groups in GS scores and PD scores of joints and tendons, and BE scores of joints (P < 0.05). In the SNRA group, the total scores of most US variables were positively correlated with CRP, ESR, and DAS28 (P < 0.05), while such correlations were not observed in the OA group (P > 0.05). Among different US variables, the diagnostic value of total PD scores of the joints was the highest for SNRA. HFUS could be used to differentiate SNRA from OA and make a diagnosis of SNRA based on joint and tendon synovial sheath assessment.

Evaluation of tenosynovitis in patients with seronegative rheumatoid arthritis using microvascular flow imaging.

The purpose of this research was investigate the potential use of MVFI (microvascular flow imaging) in the assessment of tenosynovitis in cases with SNRA (seronegative rheumatoid arthritis). Fifty-six SNRA cases and 20 HCs (healthy controls) were enrolled, and all of them were subjected to ultrasonographic examination of the compartments I-VI of the extensor tendons of the wrist, flexor carpi radialis and flexor tendons of the five digits. Each tendon synovial sheath was semi-quantitatively scored by GS (gray-scale) ultrasound, PD (power Doppler) ultrasound, and MVFI. The PD and MVFI scores for each tendon synovial sheath were added up for each patient to get the total scores. GS scores, PD scores, and MVFI scores of tendon synovial sheaths were compared between the two groups. The correlations of total PD scores and total MVFI scores with DAS28 (disease activity scores in 28 joints), ESR (erythrocyte sedimentation rate), and CRP (C-reactive protein) were analyzed. (1) In the HC group (480 tendons), GS revealed abnormalities in 29 (6.04%) tendon synovial sheaths. The GS score was 1.03±0.18 with the predominance of GS grade 1 (96.55%). In the SNRA group (1,344 tendons), GS detected abnormalities in 418 tendon synovial sheaths (31.10%). The GS score was 1.97±0.53 with the predominance of GS grade 2 (71.77%). There were significant differences in the GS examination rate and grade for tenosynovitis between the two groups (P<0.05). (2) In the SNRA group, involvement of the extensor carpi ulnaris in the 6th dorsal compartment was the most common among all extensor tendons; the flexor tendon of the third digit was the most commonly affected among all flexor tendons. (3) In the HC group, the MVFI and PD scores were 0 for tendon synovial sheaths upon GS examination. In the SNRA group, the blood flow display rate of abnormal tendon synovial sheaths indicated by GS was 83.49% and 64.59% upon MVFI and PD, respectively. The results of the two imaging techniques were significantly different (P<0.05). The blood flow grade of abnormal tendon synovial sheaths indicated by GS was significantly different between MVFI and PD (P<0.05), which was higher upon MVFI than PD. (4) The total MVFI score and the total PD score in the SNRA group were correlated positively with CRP, ESR and DAS28 (P<0.05). MVFI is a more sensitive way in detection of blood flow in the tendon synovial sheaths of SNRA cases, which may be used in clinic to evaluate disease activity and tenosynovitis in SNRA cases.

Compass Fundus-Guided Perimetry in Geographic Atrophy.

Purpose To evaluate compass (CMP), a recently introduced device that combines scanning ophthalmoscopy, automated perimetry, and eye tracking, for fundus-guided perimetry (microperimetry) with the purpose of correlating perimetric retinal sensitivity (PRS) and retinal geographic atrophy (GA) features. Materials and Methods A retrospective, cross-sectional study was performed in 56 eyes of 43 patients affected by GA. All patients underwent compass 10-2 perimetry, consisting of a full-threshold visual field on fundus photography and an infrared (IR) image of the central 30° of the retina. Data were exported to an Excel sheet. Binarization with black/white (B/W) variables was applied on the compass photo fundus and matched with visual field scores. Patients underwent autofluorescence (AF) and IR images (Heidelberg, Germany): CMP and Heidelberg IR images were homologated by using GIMP software (https://www.gimp.org), and then atrophic areas were manually measured with the ImageJ program. CMP perimetric grid was overlapped with AF and IR pictures by using GIMP, obtaining composite TIFF images, which were then analyzed with the ImageJ greyscale score (GSS) tool. A hyperautofluorescent halo was identified on the GA edges of some patients. Pearson's correlation between GA size on IR compass and IR Heidelberg and between GSS and PRS values has been calculated; the independent t-test was realized to calculate the correlation between GSS and B/W variables identified on the CMP photo fundus. The Spearman correlation between total deviation and pattern deviation was calculated. Results The AUC-ROC score between CMP scores and B/W variables was 93,4%. The Spearman correlation between total deviation and pattern deviation was highly significant (p = 0,00). The correlation between AF GSS values and PRS was significant (p value = 0,00), the correlation between GSS of hyperautofluorescent points and PRS was significant (p value = 0,00), and the correlation between IR GSS and PRS was significant (p value = 0,00). The correlation between AF GSS and B/W variables was significant (p value = 0,002), the correlation between hyperautofluorescent points and B/W was not significant (p value = 0,40), and the correlation between IR GSS and B/W was significant (p = 0,00). Conclusions Based on our preliminary results, compass seems to be a reliable, quick, and safe device for the anatomical and functional study of GA. The direct visualization of the visual field on the fundus photography as a background allows a precise assessment and clinical monitoring of this disease.

The correlation of ultrasound-detected synovitis in an individual small joint with overall clinical disease activity in patients with rheumatoid arthritis.

To explore the correlation between the ultrasound-detected synovitis in each individual joint at metacarpophalangeal (MCP), proximal interphalangeal (PIP), and metatarsophalangeal (MTP) regions and the clinical disease activity in patients with rheumatoid arthritis (RA). Clinical disease activity was assessed by disease activity score (DAS) based on 28-joint count and erythrocyte sedimentation rate (DAS28-ESR), C-reactive protein (DAS28-CRP), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI). Gray scale (GS) and power Doppler (PD) synovitis was assessed by ultrasound semi-quantitatively. The correlation between clinical disease activity indices and synovitis score in each joint was assessed using Spearman's rank correlation test. 211 RA patients were included in this study. The whole GS scores of all MCP joints showed the highest correlation with each Clinical Disease Activity Index (r = 0.403-0.452, p < 0.01). Likewise, the whole PD scores of all MCP joints also showed the highest correlation with clinical disease activity (r = 0.332-0.396, p < 0.01). At individual joint level,the highest correlation of GS score with DAS28-ESR (r = 0.411, p < 0.01), DAS28-CRP (r = 0.459, p < 0.01), and SDAI (r = 0.444, p < 0.01) was observed in MCP3 joint while with CDAI (r = 0.421, p < 0.01) in MCP2 joint. The highest correlation of PD score with DAS28-ESR (r = 0.353, p < 0.01), DAS28-CRP (r = 0.399, p < 0.01), CDAI (r = 0.368, p < 0.01), and SDAI (r = 0.377, p < 0.01) was observed in MCP5 joint. The ultrasound-detected synovitis at MCP joints, especially MCP2, MCP3, and MCP5 joints, was best correlated with clinical disease activity in most RA cases, in contrast to PIP and MTP joints. Key Points • The correlation of ultrasound-detected synovitis in each individual joint with the clinical disease activity in RA patients is diverse among joint regions. MCP joints showed the best, in contrast to PIP and MTP joints.

Sonographic Evaluation of Muscle Echogenicity for the Detection of Intensive Care Unit-Acquired Weakness: A Pilot Single-Center Prospective Cohort Study.

Qualitative assessment by the Heckmatt scale (HS) and quantitative greyscale analysis of muscle echogenicity were compared for their value in detecting intensive care unit-acquired weakness (ICU-AW). We performed muscle ultrasound (MUS) of eight skeletal muscles on day 3 and day 10 after ICU admission. We calculated the global mean greyscale score (MGS), the global mean z-score (MZS) and the global mean Heckmatt score (MHS). Longitudinal outcome was defined by the modified Rankin scale (mRS) and Barthel index (BI) after 100 days. In total, 652 ultrasound pictures from 38 critically ill patients (18 with and 20 without ICU-AW) and 10 controls were analyzed. Patients with ICU-AW had a higher MHS on day 10 compared to patients without ICU-AW (2.6 (0.4) vs. 2.2 (0.4), p = 0.006). The MHS was superior to ROC analysis (cut-off: 2.2, AUC: 0.79, p = 0.003, sensitivity 86%, specificity 60%) in detecting ICU-AW compared to MGS and MZS on day 10. The MHS correlated with the Medical Research Council sum score (MRC-SS) (r = −0.45, p = 0.004), the mRS (r = 0.45; p = 0.007) and BI (r = −0.38, p = 0.04) on day 100. Qualitative MUS analysis seems superior to quantitative greyscale analysis of muscle echogenicity for the detection of ICU-AW.

Assessment of serum interleukin-20 level in rheumatoid arthritis patients: Relation to disease activity and ultrasound measures

Aim of the workTo investigate the serum interleukin-20 (IL-20) level in rheumatoid arthritis (RA) patients and to elucidate its relationship with disease activity and ultrasonographic (US) findings. Patients and methods45 RA patients and 45 matched controls were enrolled. Modified health assessment questionnaire (mHAQ) and disease activity score(DAS-28) were determined. Power Doppler (PD) and Gray-scale (GS) US evaluation was made using German US7 score. Serum IL-20 level was analyzed using an enzyme-linked immunosorbent assay. ResultsMean age of patients was 34.5 ± 11 years; 39 females and 6 males and disease duration 15.8 ± 8.3 years. Their mean DAS-28 was 4.1 ± 1.1. The serum IL-20 levels were highly significant in patients (30.2; 19.1–58.5 ng/l) than in controls 13.1; 11–15.1 ng/l; p < 0.001). Serum IL-20 significantly correlated with DAS-28 (r = 0.32, p = 0.03), mHAQ (r = 0.87, p < 0.001), erythrocyte sedimentation rate (r = 0.82, p < 0.001), C-reactive protein (r = 0.32, p = 0.03), and disease duration (r = 0.87, p < 0.001). Significant correlations were found between IL-20 level and German US7 variables including synovitis (PD: p = 0.02 and GS: p = 0.01), tenosynovitis (PD: p = 0.01 and GS: p = 0.01) and erosion (p = 0.02) scores. Only morning stiffness, tenosynovitis GS score, tender joint count and mHAQ were significant predictors of IL- 20 serum level (p = 0.045, p = 0.04, p = 0.03 and p = 0.001 respectively). Serum IL-20 at cut-off point of 15.4 ng/l could significantly distinguish patients from controls (AUC = 0.89; sensitivity 82.2%, specificity 77.8% and accuracy of 80%; p < 0.001). ConclusionPatients with RA exhibited a significant elevation in IL-20. Serum IL-20 level significantly correlated with disease activity and ultrasound variables and may serve as a potentially effective biomarker in the evaluation of disease activity in RA.

Association between ultrasound images and patient-reported outcomes in the treatment of rheumatoid arthritis: a retrospective study

BackgroundImprovements in the treatment of rheumatoid arthritis (RA) have made it possible to achieve treatment goals. It has been reported that both residual synovitis caused by RA and the patients’ subjective symptoms remain even after achieving the treatment goals; however, there are limited reports showing a relationship between them. Furthermore, no studies have evaluated the relationship between patient-reported outcomes (PROs) and subclinical synovitis measured by musculoskeletal ultrasonography (MSUS) in the treatment of RA. This study aimed to investigate residual symptoms and residual synovitis due to remission (REM) or low disease activity (LDA).MethodsWe performed MSUS on 300 patients with RA who attended our hospital for routine care, and we analysed them cross-sectionally by disease activity. Grayscale (GS) and power Doppler (PD) synovitis was evaluated in 22 bilateral hand joints using MSUS. We first performed univariate and multivariate analysis by dividing the data by disease activity. Next, we analysed each PRO in the obtained MSUS results.ResultsA multivariate analysis of high disease activity (HDA)/moderate disease activity (MDA) vs. LDA/ REM group identified tender joint count (TJC), pain visual analog scale (VAS) score, and presence or absence of GS score ≥ 2. The one-way analysis of the relationship between the presence or absence of GS score ≥ 2 and each PRO showed a significant difference. In contrast, a multivariate analysis of LDA vs. REM group identified TJC and fatigue VAS score. In REM, PROs alone were relevant, and there was no correlation with MSUS.ConclusionWe found that the residual inflammation in the ultrasound images was associated with PROs in the LDA group, but not in the REM group.Trial registration Retrospectively registered.

The association between disease duration and mood disorders in rheumatoid arthritis patients.

The mood disorders have been recognized as common comorbidities of rheumatoid arthritis (RA), however unknown in patients with different RA courses. Therefore, we aimed to investigate the status of mood disorders in early RA and non-early RA patients and further identify the associated factors for mood disorders. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were assessed in all enrolled RA patients. Besides clinical assessments, power Doppler and greyscale (GS) ultrasound of 28 joints was performed. The frequency of mood disorders was compared between early RA and non-early RA patients. Multivariate regression was used to identify the associated factors for mood disorders. Tow hundred one RA patients were enrolled, with 76 early RA (disease duration ≤ 2years) and 125 non-early RA (disease duration > 2years). Mood disorders (depression and/or anxiety) were found in 42 (20.9%) patients. Depression was more frequently observed in early RA than non-early RA patients (26.3% vs. 14.4%, P = 0.036). A similar trend for anxiety was also observed in early RA compared to non-early RA patients, although the difference was insignificant (13.2% vs. 5.6%, P = 0.062). Disease duration (OR = 0.991, 95% CI 0.985-0.998, P = 0.009), health assessment questionnaire disability index (HAQ-DI) (OR = 1.045, 95% CI 1.005-1.086, P = 0.029) and GS synovitis score (OR = 1.065, 95% CI 1.017-1.115, P = 0.007) were identified as factors associated with depression. Disease duration (OR = 0.981, 95% CI 0.967-0.995, P = 0.009), HAQ-DI (OR = 1.071, 95% CI 1.013-1.133, P = 0.017) and GS synovitis score (OR = 1.072, 95% CI 1.012-1.136, P = 0.019) were identified to be associated with anxiety. Depression and anxiety were almost doubled in frequency in early RA than in long-standing RA patients. RA patients with short disease duration, high HAQ-DI and GS score were more likely to be in depression and anxiety. Key Points • Mood disorders were more frequent in early RA than non-early RA patients. • More attention to psychological status is needed in RA patients. • RA patients with short disease duration, poor physical function and severe synovitis were more likely to have depression and/or anxiety.

Biomechanical stress in the context of competitive sports training triggers enthesitis

ObjectiveTo evaluate the influence of mechanical stress on the development of immediate enthesitis.MethodsThe BEAT study is an interventional study that assessed entheses in competitive badminton players before and immediately after a 60-min intensive training session. Power Doppler (PD) signal and Gray scale (GS) changes were assessed in the insertion sites of both Achilles tendon, patellar tendons, and lateral humeral epicondyles and quantified using a validated scoring system.ResultsThirty-two badminton players were included. One hundred ninety-two entheseal sites were examined twice. The respective empirical total scores for PD examination were 0.1 (0.3) before and 0.5 (0.9) after training. Mean total GS scores were 2.9 (2.5) and 3.1 (2.5) before and after training, respectively. The mean total PD score difference of 0.4 between pre- and post-training was significant (p = 0.0014), whereas no significant difference for the mean total GS score was observed. Overall, seven participants (22%) showed an increased empirical total PD score. A mixed effects model showed a significant increase of PD scores after training, with a mean increase per site of 0.06 (95% CI 0.01 to 0.12, p = 0.017).ConclusionsMechanical stress leads to rapid inflammatory responses in the entheseal structures of humans. These data support the concept of mechanoinflammation in diseases associated with enthesitis.

POS0635 COMPARING THE ULTRASONOGRAPHIC EVALUATION IN PATIENTS WITH JAPANESE RHEUMATOID ARTHRITIS BETWEEN BARICITINIB AND TNF ANTAGONIST THERAPY

Background:Baricitinib (BAR) and TNF antagonist are the important therapeutic agent for the treatment of rheumatoid arthritis.However there is still few studies of improvement of ultrasonographic findings in RA treated comparison with BAR and TNF.Objectives:To evaluate the clinical efficacy of BAR and TNF therapy patients with rheumatoid arthritis (RA) using ultrasonography (US).Methods:Participants comprised 16 and 45 Japanese RA patients who had recently received BAR and TNF. All patients with a diagnosis of RA according to the 2010 ACR/EULAR criteria. Patients underwent clinical and laboratory assessments every 4 weeks from baseline to 24 weeks, and US assessments at baseline, 4, 12 and 24 weeks. Gray scale (GS) and power doppler (PD) signals were scored using a semi-quantitative scale from 0 to 3 at 26 (0-78) synovial sites (22 joints) in the following joints: bilateral first to fifth metacarpopharangeal (MCP) joints (dorsal recess); first interphalangeal (IP) and second to fifth proximal interphalangeal (PIP) (dorsal recess) joints; and the wrists (dorsal radial, median and ulnar). We evaluated the improvement of GS and PD score from baseline to week 24.Results:In the patients receiving BAR (n=16) and TNF (n=45), the mean age was 55.9 vs 54.6 years old (p=0.682), disease duration was 10.2 vs 6.1 years (p=0.094), the rate of MTX use was 75% vs 89% (p=346), the mean MTX dose was 9.3 vs 10.2 mg/w (p=0.443), the rate of ACPA positive was 94% vs 82% (p=0.476), DAS28-ESR was 4.25 vs 4.61 (p=0.289), CDAI was 15.8 vs 18.5 (p=0.210), GS score was 21.6 vs 16.3 (p=0.436) and PD score was 15.0 vs 9.5 (p=0.260). The degree of improvement respective changes in GS and PD score after 4, 12 and 24 weeks were as follows: GS: -7.2 vs -3.7 (p=0.268) and PD: -7.6 vs -2.3 (p=0.158) after 4 weeks, GS: -10.9 vs -5.0 (p=0.161) and PD: -9.2 vs -3.8 (p=0.049) after 12 weeks, GS: -12.9 vs -6.1 (p=0.485) and PD: -11.3 vs -5.7 (p=0.062) after 24 weeks between BAR and TNF (Fig.1, 2). Next, The improvement rate of respective changes in GS and PD score after 4, 12 and 24 weeks were as follows: GS: -23.8% vs -11.6% (p=0.580) and PD: -30.3% vs -16.5% (p=0.343) after 4 weeks, GS: -39.6% vs -15.6% (p=0.129) and PD: -47.1% vs -30.8% (p=0.210) after 12 weeks, GS: -52.2% vs -22.2% (p=0.248) and PD: -77.1% vs -50.1% (p=0.048) after 24 weeks between BAR and TNF.Conclusion:The present study provides evidence supporting both the BAR and TNF therapy showed improvement effect over time, but in a comparison between BAR and TNF, the PD score of BAR showed a siginificant improvement effect compared to TNF at 12 and 24 weeks. It was suggeted that BAR may improve inflammatory synovitis earlier compared to TNF.Disclosure of Interests:None declared

POS0259 ULTRASOUND AS AN IMAGING BIOMARKER OF EARLY RESPONSE TO TOCILIZUMAB AND METHOTREXATE IN VERY EARLY RHEUMATOID ARTHRITIS, TOVERA – A LONGITUDINAL STUDY

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 (p&lt;0.05) and, accordingly DAS28-CRP score decreased significantly at 4w (p&lt;0.05). The 28-SJC and CDAI scores decreased significantly at 8w (p&lt;0.05). The HAQ and visual analogue scale (VAS) disease activity reported by patients decreased significantly at 8w (p&lt;0.05) and VAS fatigue at 12w (p&lt;0.05).The GLOESS and GS scores allowed us detecting the earliest significant treatment response at 2w and PD scores at 4w (p&lt;0.05). Among US joint subsets, 17-JS (p&lt;0.01), 12-JS (p&lt;0.05) and 10-JS (p&lt;0.05) were able to detect the earliest treatment response at 2w. The 7-joint score detected the earliest response at 4w, both in GS and PD (p&lt;0.05).Conclusion:US scores were able to detect therapeutic response to TCZ plus MTX earlier than clinical scores and may therefore be a promising imaging biomarker.

OP0182 IN RA PATIENTS IN REMISSION, WHICH BIOMARKERS PREDICT SUCCESSFUL TAPERING OF CSDMARDS?

Background:Recommendations for the management of patients with RA who achieve stable clinical remission ≥6 months with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) are to taper (with the aim of potentially stopping), although there are currently no validated biomarkers permitting prediction of sustained remission.Objectives:To assess the rate of sustained remission over 12 months In RA patients in remission, who received either (i) structured tapering of csDMARDs or (ii) continuation of current therapy, focusing on the value of imaging and immunological biomarkers as well as patient-reported outcome measures (PROs).Methods:RA patients (n=200) prospectively attending a remission clinic, fulfilling DAS28(3v)CRP&lt;2.6 for ≥6 months on stable csDMARD therapy (mono or combination therapy &amp; no corticosteroids) were included. Patients were offered the choice of structured cs-DMARD tapering according to a pre-defined protocol (Table 1) or remaining on stable therapy. Clinical, ultrasound (US), immunological (T-cell subsets) and PRO data were collected at inclusion. Loss of remission was defined as increase of DAS28(3v)CRP &gt;2.6. Mann-Whitney-U and Chi-square tests were used to compare outcomes. After imputing missing data, regressions for predicting sustained remission were performed. AUROCs were used to compare models.Table 1.csDMARD tapering scheduleDrugBaseline DoseTaper 1Taper 2Taper 3Taper 4Taper 5Hydroxychloroquine200mg bd200mg odStop---Hydroxychloroquine200mg odStop----Sulfasalazine1.5g bd1g bd1.5g od500mg bd500mg odStopSulfasalazine1g bd1.5g od500mg bd500mg odStop-Sulfasalazine500mg bd500mg odStop---Sulfasalazine500mg odStop----Methotrexate25mg/week15mg/week7.5mg/weekNo changeStop-Methotrexate15mg/week7.5mg/weekNo changeStop--Methotrexate7.5mg/weekNo changeStop---NB: Patients were seen 3-monthly. If they remained in remission following tapering, they proceeded to the next taper unless there is a significant clinical reason not to taper at the time of assessment (as per standard care). Order of cs-DMARD tapering applies to patients on dual/triple therapy. All but 5 (112) were on methotrexate.Results:The decision to taper treatment was associated with male gender, longer remission duration, normal CRP and lower grey scale scores (p&lt;0.05). Of those who tapered 64% (75/117) remained in clinical remission at 12 months, compared to 80% (66/83, p=0.018) of patients who remained on stable treatment. At 15 months 11/117 (10%) had successfully stopped therapy.In the tapering group, higher CRP, TJC and IRC were consistently associated with inability to sustain remission, as well as higher scores for several PROs (p&lt;0.05) with a trend for total PD (P=0.066). Predicting sustained remission was modelled and retained RAQoL, total PD and a T-cell subset (Figure 1, 85% accuracy, AUROC 0.872).Figure 1.AUROC Analysis of tapering cohort dataIn the non-tapering group, higher CRP/ESR, SJC and shorter disease duration (p&lt;0.05) were associated with flare. No parameter was able to predict sustained remission.Conclusion:In patients who chose to taper, the combination of clinical, PRO, US and T-cell parameters demonstrated added value for predicting sustained remission (85% accuracy) compared to clinical parameters alone. Different biomarkers were associated with sustained remission on continued therapy. These data may assist with informed tapering of csDMARDs.Disclosure of Interests:None declared

AB0787 RECEIVER OPERATING CHARACTERISTIC ANALYSIS OF JOINT INFLAMMATION IN RELATION TO DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS ASSESSED USING A NOVEL COMBINED THERMAL AND ULTRASOUND IMAGING

Background:A novel combined thermal and ultrasound (CTUS) imaging approach in rheumatoid arthritis (RA) was recently shown to be superior to either imaging modality alone in terms of correlation with the 28-joint disease activity score (DAS28).Objectives:To determine the performance of CTUS imaging in identifying RA patients with at least moderate disease activity (DAS28 &gt; 3.2).Methods:Bilateral hand (22 joints) thermal and ultrasound (US) imaging was performed. Thermal imaging provides the surface temperature readings at the joints with MAX, AVG and MIN derived per patient by summing the temperature differences with a control temperature, for the respective maximum (Tmax), average (Tavg) and minimum (Tmin) temperatures at each joint. US imaging assesses joint inflammation by summing up the power Doppler (PD) and grey-scale (GS) joint inflammation scores (graded 0-3 at each joint recess) at each joint to obtain the respective total PD and total GS scores per patient. CTUS imaging utilizes data from both thermal and US imaging to derive the MAX (PD), AVG (PD) and MIN (PD) by multiplying MAX, AVG and MIN by a factor of 2 when a patient’s Total PD &gt; median score, which otherwise remained the same as the MAX, AVG and MIN. The results of the imaging parameters were compared between patients with DAS28 ≤ 3.2 and those with DAS28 &gt; 3.2. Sensitivity (Sn), specificity (Sp) and receiver operating characteristic (ROC) curve analysis was performed to determine if the use of CTUS imaging can help identify patients with DAS28 &gt; 3.2.Results:In this cross-sectional study, 814 joints from 37 RA patients (75.7% female; 75.7% Chinese; baseline mean disease duration, 30.9 months; baseline mean DAS28, 4.43) were imaged. The mean (SD) values for the CTUS—but not single modality—imaging parameters (Table 1) were all significantly greater among patients with DAS28 &gt; 3.2 versus those with DAS28 ≤ 3.2 (P-values were all &lt;0.01). Based on cut-off levels of (a) MAX (PD) ≥ 94.5, (b) MIN (PD) ≥ 42.3 and (c) AVG (PD) ≥ 64.6 in identifying patients with DAS28 &gt; 3.2, the respective area under the ROC curves (AUCs) (95%CIs) were (a) 0.731 (0.541, 0.921) with Sn = 58.1%; Sp = 100.0%; negative predictive value (NPV) = 31.6%; positive predictive value (PPV) = 100.0%; accuracy = 64.9%, (b) 0.758 (0.591, 0.925) with Sn = 61.3%; Sp = 100.0%; NPV = 33.3%; PPV = 100.0%; accuracy = 67.6% and (c) 0.763 (0.596, 0.931) with Sn = 61.3%; Sp = 100.0%; NPV = 33.3%; PPV = 100.0%; accuracy = 67.6%.Conclusion:The severity of joint inflammation as detected by CTUS—but not single modality—imaging parameters were significantly greater among patients with DAS28 &gt; 3.2 versus those with DAS28 ≤ 3.2. For the first time ever, by applying ROC analysis, this has helped to determine cut-off MAX (PD), MIN (PD) and AVG (PD) levels for identifying patients with DAS28 &gt; 3.2; the usefulness of these cut-off levels will require further validation in independent RA cohorts.Table 1.Comparison of imaging parameters between patient groups.Imaging ParameterDAS28 Mean (95% CI)Difference (95% CI)P-valueDAS28 ≤ 3.2DAS28 &gt; 3.2MAX (PD)75.25 (58.8, 91.7)119.5 (101.12, 137.87)-44.25 (-70.49, -18.01)0.0022**MIN (PD)33.72 (25.82, 41.61)57.51 (47.63, 67.39)-23.79 (-37.13, -10.45)0.0012**AVG (PD)50.72 (39.45, 61.98)85.39 (71.89, 98.88)-34.67 (-53.27, -16.07)0.0008***MAX67.38 (50.75, 84.02)82.23 (74.71, 89.75)-14.85 (-34.11, 4.42)0.1268MIN30.27 (22.06, 38.47)40.02 (35.02, 45.03)-9.75 (-22.18, 2.66)0.1198AVG45.45 (33.94, 56.96)59.11 (52.99, 65.23)-13.66 (-29.04, 1.72)0.0801Total PD2.83 (-0.23, 5.9)3.65 (2.71, 4.58)-0.82 (-3.39, 1.77)0.5269Total GS6.67 (1.31, 12.02)6.58 (4.12, 9.04)0.09 (-6.21, 6.38)0.9780Statistically significant: **P&lt;0.01, ***P&lt;0.001.Disclosure of Interests:None declared

Ultrasound-aided diagnosis of preclinical phases of psoriatic arthritis in biologic-naïve psoriasis patients with or without arthralgia.

The evolution of psoriasis (PsO) to psoriatic arthritis (PsA) has been proposed recently. There are three phases that occur in sequence prior to classifiable PsA: PsO patients, PsO patients with a positive imaging, and PsO patients with arthralgia not explained by other diagnosis. The purpose of this study was to compare the differences among preclinical phases using ultrasound and clinical assessment. Patients with psoriasis were recruited. Patients who had been previously diagnosed with psoriatic arthritis or who had used biologics were excluded. A 52-joint ultrasound (52j US) assessment and clinical assessments including the swollen joint count, tender joint count, erythrocyte sediment rate, C-reactive protein, dactylitis score, enthesitis score, psoriasis severity, and nail psoriasis severity, were performed. A total of 188 eligible psoriasis patients were enrolled. Physical examination revealed 39 patients (20%) with at least one swollen joint. The 52j US assessment demonstrated 90 patients (47%) having at least one joint with grey-scale score 2-3. All patients were further stratified into PsO patients (n=58), PsO patients with a positive imaging, (n=59), PsO patients with arthralgia not explained by other diagnosis (n=27), and classifiable PsA (n=39). There were no differences in clinical characteristics other than tender joint count found among the three preclinical phases of PsA. Dactylitis score, swollen joint count and heatly assessment questionnaire score were significantly higher in classifiable PsA. Nearly half of the psoriasis patients without previously diagnosed psoriatic arthritis would be classified into the preclinical phases of psoriatic arthritis based on the 52j US and clinical assessments. Ultrasound assessment is helpful for identifying psoriasis patients who are in the preclinical phases of psoriatic arthritis, particularly for those without arthralgia.