Synovial Power Doppler Signal Research Articles

Clinical, Patient-Reported, and Ultrasound Outcomes from an Open-Label, 12-week Observational Study of Certolizumab Pegol in Spanish Patients with Rheumatoid Arthritis with or without Prior Anti-TNF Exposure.

To assess the effectiveness and safety of certolizumab pegol (CZP) in Spanish patients with RA. SONAR (NCT01526434), a 12-week, open-label, prospective, observational, multicenter study. Patients with active RA for ≥3 months, according to ACR criteria, were treated with CZP (400mg at Weeks 0, 2 and 4, then 200mg every 2 weeks). The primary effectiveness endpoint was change from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12. Other assessments included DAS28(ESR), patient's assessment of arthritis pain (PtAAP-VAS) and Short Form 36-item Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS). Joint inflammation was investigated using Power Doppler (PD) ultrasound (US), to detect effusion, synovial hypertrophy and synovial PD signal. PDUS outcomes assessed CFB to Week 12 in synovial hypertrophy, effusion and PD signal indices. A total of 77/80 enrolled patients received ≥1 dose of CZP. The 12-week mean reduction from baseline (SD) was -0.6 (0.6) for HAQ-DI and -2.2 (1.5) for DAS28(ESR). PtAAP-VAS was reduced from baseline (mean [SD]: -36.8 [26.8]) and improvements in SF-36 PCS and SF-36 MCS were reported. Synovial hypertrophy, effusion and PD signal indices were reduced from baseline to Week 12. One death was reported during the study. Spanish patients with RA demonstrated improvements in clinical, PDUS and patient-reported outcomes over 12 weeks of CZP treatment. No new safety signals were identified, and the safety profile was in line with previous CZP studies. These results support previous clinical trial findings investigating CZP treatment for active RA.

Clinical, Patient-Reported, and Ultrasound Outcomes from an Open-Label, 12-week Observational Study of Certolizumab Pegol in Spanish Patients with Rheumatoid Arthritis with or without Prior Anti-TNF Exposure

ObjectivesTo assess the effectiveness and safety of certolizumab pegol (CZP) in Spanish patients with RA. Materials and methodsSONAR (NCT01526434), a 12-week, open-label, prospective, observational, multicenter study. Patients with active RA for ≥3 months, according to ACR criteria, were treated with CZP (400mg at Weeks 0, 2 and 4, then 200mg every 2 weeks). The primary effectiveness endpoint was change from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12. Other assessments included DAS28(ESR), patient's assessment of arthritis pain (PtAAP-VAS) and Short Form 36-item Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS). Joint inflammation was investigated using Power Doppler (PD) ultrasound (US), to detect effusion, synovial hypertrophy and synovial PD signal. PDUS outcomes assessed CFB to Week 12 in synovial hypertrophy, effusion and PD signal indices. ResultsA total of 77/80 enrolled patients received ≥1 dose of CZP. The 12-week mean reduction from baseline (SD) was −0.6 (0.6) for HAQ-DI and −2.2 (1.5) for DAS28(ESR). PtAAP-VAS was reduced from baseline (mean [SD]: −36.8 [26.8]) and improvements in SF-36 PCS and SF-36 MCS were reported. Synovial hypertrophy, effusion and PD signal indices were reduced from baseline to Week 12. One death was reported during the study. ConclusionsSpanish patients with RA demonstrated improvements in clinical, PDUS and patient-reported outcomes over 12 weeks of CZP treatment. No new safety signals were identified, and the safety profile was in line with previous CZP studies. These results support previous clinical trial findings investigating CZP treatment for active RA.

EP31 Musculoskeletal ultrasound of rheumatoid arthritis pregnancy: a single centre experience

Abstract Background The utility of musculoskeletal ultrasound (MSK-US) in the measurement of disease activity of rheumatoid arthritis (RA) is well established. However, it has not been formally studied in pregnancy, with the literature limited to a single case report. Standard disease activity assessment in RA pregnancy comprises measurement of the DAS28(3) CRP score, which removes the visual analogue score (VAS) and replaces ESR with CRP, as both of these components may be confounded by pregnancy. Use of this modified score remains problematic as the tender joint count may be affected by non-specific musculoskeletal pain in pregnancy, and the swollen joint count may be obscured by peripheral oedema, especially late in pregnancy. No study of RA in pregnancy has used MSK-US to measure disease activity. Our objective was to conduct a pilot study of MSK-US in RA pregnancy, and compare findings with clinical assessment using the DAS28(3)CRP score. Methods We offered MSK-US to pregnant RA patients attending the UCLH obstetric rheumatology clinic from September 2018 to September 2019. Patients were assessed longitudinally through pregnancy/post-partum where possible. Examination was undertaken using a Logiq S8 US machine. The standard protocol comprised 22-joint assessment of hands (dorsal longitudinal and transverse views of wrists, metacarpophalangeal and proximal interphalangeal joints). In the feet, bilateral MTP joints were scanned with longitudinal views. Quantification of Power Doppler (PD) signal and grey scale (GS) synovitis was made as per the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) US definitions. PD and GS scores were calculated as mean scores of all joints scanned. Results To date, 17 pregnant RA patients have undergone a total of 35 MSK-US studies. Disease activity assessments showed 10/17 patients with persistent low activity through pregnancy, 5/17 with moderate or good response, 1/17 with no response and 1/17 with a moderate flare. Overall, PD scores correlated well with DAS28(3) CRP assessment (R2 = 0.68). All patients at moderate or high disease activity by DAS28(3) CRP had ≥1 joint with detectable PD signal, but 2/21 patients clinically in ‘remission’ and 3/7 patients in ‘low disease activity’ had detectable PD. One patient with only 2 tender and 1 swollen joints (and normal CRP; DAS28 3.17) had very extensive PD signal and contributed to the decision to recommence anti-TNF treatment in the 3rd trimester. It was noted that increased vascularity in pregnancy can complicate the assessment of synovial PD signal. MSK-US was particularly helpful in distinguishing true joint synovitis from subcutaneous oedema in the feet. Conclusion This is the first series of MSK-US in pregnant RA patients. The detection of active joint synovitis (by PD signal) in clinical remission/low disease activity states suggests a potential role for MSK-US in confirming apparent low disease activity in pregnancy, and thus guiding stratification of treatment. Disclosures C. Raine None. J. Manson None. C. Ciurtin None. I. Giles None.

Ultrasound remission can predict future good structural outcome in collagen-induced arthritis rats

Regarding the persistence of subclinical synovitis, the concept of ultrasound remission has been proposed in addition to clinical remission. The present study aims to explore whether ultrasound remission has predictive value and ultrasound remission at which time point has predictive value for good structural outcome. Collagen-induced arthritis (CIA) was induced in 32 rats by immunizing with bovine type II collagen. Twenty-four CIA rats were treated with rhTNFR:Fc, and 8 rats were left untreated. Ultrasonography was performed to assess synovial hypertrophy, power Doppler (PD) signal, and bone erosion of the ankle joints of both hindpaws every week following the booster immunization. In the treated group, the scores for synovial hypertrophy, PD signal and bone erosions decreased from baseline to the end. Synovial hypertrophy, PD signal, and bone erosion at baseline were not significantly associated with good structural outcome. Ultrasound remission from 4 to 6 weeks after treatment was significantly associated with good outcome and had the highest area under the curve, sensitivity, specificity, and positive and negative predictive values. Therefore, we conclude that ultrasound remission from 4 to 6 weeks after treatment has a high value for predicting good structural outcome in CIA rats.

From A Formal Training Program In Musculoskeletal Ultrasound (MSUS) To A High Reproducibility for MSUS Ultrasound In Rheumatoid Arthritis

To assess the intra- and inter-observer reliability of Ultrasound (US) in scoring B-mode, Doppler synovitis and combined B-mode and Doppler synovitis scores in different peripheral joints of Rheumatoid Arthritis (RA) patients. Four rheumatologists with a formal training in Musculoskeletal US (MSKUS) particularly focus on definitions and scoring synovitis on B-mode and Doppler mode participated in a patient- based reliability exercise on 16 active RA patients. The four rheumatologists independently and consecutively performed a B-mode and Power Doppler (PD) US assessment of 7 joints of each patient in two rounds in a blinded fashion. Each joint was semi quantitatively scored from 0 to 3 for B-mode Synovitis (BS), Doppler Synovitis (DS), and combined B-mode/Doppler synovitis (CS). Intraobserver reliability was assessed by Cohen's κ. Interobserver reliability was assessed by unweight Light's κ. The mean prevalence of synovitis on B-mode was 83% of joints; scores ranging from grade 1 in 18% of joints, to grade 3 in 33%. In 55% of joints synovial PD signal was detected and the distribution of scores range from 14% of joints for grade 3, to 26% for grade 2. After a total of 448 joints scanned with 896 adquired images our intraobserver and interobserver reliability was good to excellent for most of the joints. Formal, structured and continuous training in musculoskeletal ultrasound would bring a good to excellent reproducibility in rheumatological hands with a high reliability in real time acquisition BS, DS and CS modalities for scoring synovitis in patients with active rheumatoid arthritis.

Identifying markers of sustained remission in rheumatoid arthritis patients on long-term tapered biological disease-modifying antirheumatic drugs.

To identify features associated with long-term persistent remission in rheumatoid arthritis (RA) patients on tapered biological disease-modifying antirheumatic drugs (bDMARD) (tap-bDMARD) therapy. We carried out a 40-month (m) extension follow-up study of 77 RA patients from a previous 12m tap-bDMARD study. Disease activity was assessed at baseline and every 3 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy (SH) and synovial power Doppler signal (i.e., Doppler synovitis) was performed before starting the tap-bDMARD strategy by a rheumatologist blinded to clinical and laboratory data. At the 40m mark, 44 (57.1%) patients failed the tap-bDMARD strategy, while 33 (42.9%) succeeded. Patients who presented a failed tap-bDMARD had significantly longer disease duration, a longer time from symptom onset to synthetic (s) DMARD start, longer duration of sDMARD treatment, a greater number of sDMARDs, and a higher baseline DAS28 and SDAI than patients with successful tap-bDMARD at 40 months. In logistic regression analysis, the presence of baseline Doppler synovitis, a DAS28 ≥ 2.2, and the presence of rheumatoid factor were identified as predictors of tap-bDMARD failure at 40m. In those patients who succeed tap-bDMARD at 12m, a smoking habit was significantly more frequently found in tap-bDMARD failures at 40m. Our results showed that DAS28 and the presence of Doppler synovitis, RF and a smoking habit predicted long-term tap-bDMARD failure.

What does power Doppler signal indicate in rheumatoid synovitis? A point of view from synovial histopathology

To clarify the nature of power Doppler (PD) signals in rheumatoid synovium and to establish the connection between PD signals and active inflammation using synovial histopathology. Ten adult patients (median age 57.0 years, 9 women and one man) with rheumatoid arthritis (RA) were enrolled and received ultrasound (US) examinations. US-guided synovial biopsies using core needle were performed in 7 knees, 2 wrists and one elbow. Each patient had one joint biopsied. In total, 11 synovial specimens were obtained for hematoxylin and eosin staining and histopathologic examinations. The US examinations revealed prominent synovial hypertrophy in all biopsied joints. Six synovial specimens were PD-positive (from 3 knees, 2 wrists and 1 elbow) while 5 synovial specimens were PD-negative (from 5 knees). In comparison with the PD-negative synovial specimens, the PD-positive synovial specimens had significantly more lymphocyte infiltration, vessel proliferation and lining hyperplasia on histologic examination. There was no significant difference in fibrin exudate and stromal fibrosis between the PD-positive and the PD-negative synovial specimens. PD signals in rheumatoid synovium indicate active inflammation and vascularization supported by synovial histopathology. Our study establishes the connection between synovial PD signals and active synovitis in RA.

Ultrasound-detected activity in rheumatoid arthritis on methotrexate therapy: Which joints and tendons should be assessed to predict unstable remission?

The aim of the study was to investigate the predictive value of different reduced joint ultrasound (US) assessments of synovitis and tenosynovitis in relation to unstable remission in a cohort of rheumatoid arthritis (RA) patients on methotrexate therapy. Forty-seven RA patients (38 women, 9 men), being treated with methotrexate (MTX), in clinical remission as judged by their consultant rheumatologist were evaluated for disease activity according to the Disease Activity Score (DAS) 28 at baseline and 6months. Sustained remission and unstable remission were defined according to the baseline and 6-month DAS28 and changes in RA therapy during the follow-up. Each patient underwent at baseline a B-mode and power Doppler (PD) assessment of 44 joints and 20 tendons/tendon compartments by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH), synovial PD signal, B-mode tenosynovitis, and Doppler tenosynovitis were scored 0-3. The presence and index of synovial PD signal in 44 joints [odds ratio (OR) 8.21 (p=0.016) and OR 2.20 (p=0.049), respectively] and in 12 joints [OR 5.82 (p=0.041) and OR 4.19 (p=0.020), respectively], the presence of SH in wrist and MCP joints [OR 4.79 (p=0.045)], and the presence of synovial PD signal in wrist-MCP-ankle-MTP joints [OR 4.62 (p=0.046)] were predictors of unstable remission. The 12-joint or wrist-hand-ankle-MTP US assessments can predict unstable remission in RA patients in apparent clinical remission being treated with MTX.

Does ultrasound-scored synovitis depend on the pharmacokinetics of subcutaneous anti-TNF agents in patients with rheumatoid arthritis?

The aim of this study was to investigate the influence of the pharmacokinetics of s.c. anti-TNF agents on the grade of US-detected synovitis in RA patients. Fifty RA patients were prospectively recruited from the Biologic Therapy Unit of our hospital. Inclusion criteria were being in treatment with s.c. anti-TNF agents and having had neither changes in therapy nor local corticosteroid injections in the previous 3 months. Patients underwent clinical, laboratory [28-joint DAS (DAS28) and Simplified Disease Activity Index (SDAI)] and US assessment at two time points, i.e. at peak plasma drug concentration and at trough plasma drug concentration. US assessments were performed blindly to the anti-TNF agent, the administration time and the clinical and laboratory data. Twenty-eight joints were investigated for the presence and grade (0-3) of B-mode synovitis and synovial power Doppler signal. Global indices for B-mode synovitis (BSI) and Doppler synovitis (DSI) were calculated for 12 joints and for wrist-hand-ankle-foot joints. B-mode US remission was defined as a BSI <1 and Doppler US remission as a DSI <1. There were no significant differences between the clinical, laboratory and B-mode and Doppler US parameters at peak time and trough time (P = 0.132-0.986). There were no significant differences between the proportion of patients with active disease and those in remission according to DAS28, SDAI, B-mode US and Doppler US at peak time and trough time assessments (P = 0.070-1). Our results suggested that s.c. anti-TNF pharmacokinetics do not significantly influence US-scored synovitis in RA patients.

AB0434 Relation of Subclinical Ultrasound Detected Synovitis and Peripheral B-Cell Counts in Rheumatoid Arthritis Patients Treated with Rituximab

BackgroundThe clinical response in patients with Rheumatoid Arthritis (RA) to rituximab (RTX) has been shown to be related with the presence of B-cells in the synovi. To date this has...

SP0063 Imaging Biomarkers in Undifferentiated Arthritis. Are Mri/Us Useful Tools?

Ultrasonography (US)In a systematic literature search up to 2009 [1], no US publications on pure undifferentiated populations and only 2 publications in mixed populations (not optimal) [2,3] were available. In...

Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome

IntroductionArthritis is the most frequent manifestation of Blau syndrome, an autoinflammatory disorder caused by the genetic mutation of NOD2. However, detailed information on arthritis in Blau syndrome on which the therapeutic strategy should be based on is lacking. This multi-center study aimed to accurately characterize the articular manifestation of Blau syndrome and also to demonstrate the utility of musculoskeletal ultrasound in Blau syndrome.MethodsPatients who had been diagnosed with Blau syndrome by genetic analysis of NOD2 were recruited. A total of 102 synovial sites in 40 joints were assessed semiquantitatively by ultrasound for gray-scale synovitis and synovial power Doppler (PD) signal.ResultsIn total, 10 patients whose age ranged from 10 months to 37 years enrolled in this study. Although only 4 joints (0.8%) were tender on physical examination, 81 joints (16.9%) were clinically swollen. Moreover, 240 (50.0%), and 124 (25.8%) joints showed gray-scale (GS) synovitis and synovial PD signal on ultrasound, respectively. Importantly, GS synovitis was present in 168 out of 399 non-swollen joints, in which 61 also exhibited synovial PD signal. Among 40 joint regions, the ankle, the wrist, and the proximal interphalangeal joints were the most frequently and severely affected joints. Comparisons between different synovial tissues demonstrated a significantly higher proportion of the joints with tenosynovitis as compared with that with intra-articular synovitis (41.5% versus 27.9%, P < 0.0001). In respect of age and treatment, synovial PD signals were minimal in the youngest patient and in the oldest two patients, and were relatively mild in patients receiving treatment with methotrexate plus TNF antagonists. In two patients who underwent the second ultrasound examination, total PD scores markedly decreased after initiating the treatment with a tumor necrosis factor (TNF) antagonist.ConclusionsThe detailed information on synovial inflammation obtained by ultrasound confirms the dissociation between pain and inflammation and the frequently involved joint regions and synovial tissue in the arthritis of Blau syndrome. Our data also demonstrate that ultrasonography can be a potent tool in monitoring the activity of synovial inflammation and in investigating the pathophysiology of arthritis in this rare but archetypical autoinflammatory condition.

Analysis of the factors which influence the measurement of synovial power Doppler signals with semi-quantitative and quantitative measures – a pilot multicenter exercise in Japan

Objectives. This pilot multicenter exercise aimed to evaluate the inter-observer reproducibility of synovial power Doppler (PD) signals in rheumatoid arthritis (RA) patients and to determine the factors influencing the measurements.Methods. Two representative RA patients were assessed by four independent experienced sonographers. The influence of machine difference, deterioration of the transducer and pulse repetition frequency (PRF) on the assessment of synovial PD signals was investigated.Results. Intra-class correlation coefficient (ICC) for the scanner–reader reproducibility of semi-quantitative PD score was high (0.867). ICC for the inter-scanner reproducibility of synovial PD pixel count was higher than that of semi-quantitative PD score. The assessment of PD signals significantly differed between two machines with quantitative measurements but did not with semi-quantitative score. The assessment of PD signals with a deteriorated transducer was much less sensitive than that with an intact one. The semi-quantitative scores for PD signals were comparable between three different PRFs (500/800/1,300 Hz), whereas the pixel count was significantly lower with the highest one in the knee joint.Conclusions. Measurement of PD signal can be substantially affected by deteriorated quality of the transducer, whereas the differences are relatively modest between machines with similar specifications and also between PRF settings within a low range.

SAT0021 Both Gray-Scale Synovial Hypertrophy and Synovial Power Doppler Signals on a Comprehensive Ultrasound Scan are the Predictive Factors of Relapse After Discontinuation of Biological Agents in Patients with Rheumatoid Arthritis

BackgroundClinical information does not accurately predict relapse after discontinuation of biological agents in patients with rheumatoid arthritis (RA). Although ultrasound is a sensitive tool to detect sub-clinical synovial inflammation in...

Ultrasound Joint Inflammation in Rheumatoid Arthritis in Clinical Remission: How Many and Which Joints Should Be Assessed?

To investigate the sensitivity for detecting subclinical synovitis of different reduced joint ultrasound (US) assessment models as compared with a comprehensive US assessment in rheumatoid arthritis (RA) patients in clinical remission. Sixty-seven RA patients (50 women, 17 men) in clinical remission as judged by their consultant rheumatologist and treated with methotrexate were prospectively recruited. Patients were evaluated for disease activity according to the Disease Activity Score in 28 joints (DAS28) and the Simplified Disease Activity Index (SDAI) by the same investigator. Each patient underwent a 44-joint B-mode and power Doppler (PD) assessment by a rheumatologist blinded to the clinical and laboratory data. B-mode synovial hypertrophy (SH) and synovial PD signal were scored from 0-3 at each joint. Global indices for SH and PD signal were calculated for the 44-joint and different joint combination models for each patient. SH was detected in 87.8% of patients with a DAS28 <2.6 and in 81.8% of patients with an SDAI <3.3. Synovial PD signal was detected in 46.3% of patients with a DAS28 <2.6 and in 36.4% of patients with an SDAI <3.3. Wrist, second through fifth metacarpophalangeal (MCP), ankle, and second through fifth metatarsophalangeal (MTP) joint and 12-joint US assessments showed the highest correlations with the comprehensive US assessment. The wrist, MCP, ankle, and MTP joint US assessment showed the highest sensitivity for detecting SH and synovial PD signal in patients in remission according to the DAS28 and SDAI as compared to the comprehensive US assessment. US assessment of the wrist, MCP, ankle, and MTP joints can be highly sensitive for detecting residual B-mode and Doppler joint inflammation in RA patients.

High prevalence of ultrasonographic synovitis and enthesopathy in patients with psoriasis without psoriatic arthritis: a prospective case-control study

To investigate the presence of synovitis, tenosynovitis and enthesitis with power Doppler (PD) ultrasonography (US) in patients with psoriasis without musculoskeletal diseases as compared with controls with other skin diseases without musculoskeletal disorders. A total of 162 patients with plaque psoriasis and 60 age-matched controls with other skin diseases, all without musculoskeletal diseases, were prospectively recruited at 14 centres. They underwent dermatological and rheumatological assessment and a blinded PDUS evaluation. Clinical assessment included demographics, comorbidities, severity of psoriasis, work and sport activities and musculoskeletal clinical examination. PDUS evaluation consisted of the detection of grey scale (GS) synovitis and synovial PD signal in 36 joints, GS tenosynovitis and tenosynovial PD signal at 22 sites, and GS enthesopathy and entheseal PD signal in 18 entheses. US synovitis and enthesopathy were significantly more frequent in psoriatic patients than in controls (P = 0.024 and 0.005, respectively). The percentage of joints with US synovitis was 3.2% in the psoriasis group and 1.3% in the control group (P < 0.0005). US enthesopathy was present in 11.6% of entheses in the psoriasis group and 5.3% of entheses in the control group (P < 0.0005). Entheseal PD signal was found in 10 (7.4%) psoriatic patients, whereas no controls showed this finding (P = 0.05). Among demographic and clinical data, having psoriasis was the only significant predictive variable of the presence of US synovitis [odds ratio (OR) 2.1; P = 0.007] and enthesopathy (OR 2.6; P = 0.027). Psoriatic patients showed a significant prevalence of asymptomatic US synovitis and enthesopathy, which may indicate a subclinical musculoskeletal involvement.