Improvements in the control of inflammation in rheumatoid arthritis (RA) by conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) have led to a substantial change in the ...clinical outcomes of patients during the last 30 years. Current treatment can lead to sustained remission in some patients raising questions about the optimal management strategies in this subgroup of patients. Today, tapering of DMARDs and even their discontinuation appears as an interesting concept for achieving a more tailored and dynamic treatment approach of RA, especially in patients, who achieved full disease control by DMARD treatment. In this review article, current developments of DMARD tapering are discussed. The article provides an overview of existing studies on this topic and addresses new strategies to reach drug-free remission. Furthermore, concepts for defining patients eligible for DMARD tapering are described and potential future strategies in using biomarkers in predicting the risk for disease relapse after initiation of DMARD tapering are addressed. These findings are finally considered in light of the vision to achieve cure as an ultimate goal in patients with RA achieving full control of inflammation.
ObjectiveTo develop ultrasound (US) definitions and a US novel scoring system for major salivary gland (SG) lesions in patients with primary Sjögren’s syndrome (pSS) and to test their intrareader and ...inter-reader reliability using US video clips.MethodsTwenty-five rheumatologists were subjected to a three-round, web-based Delphi process in order to agree on (1) definitions and scanning procedure of salivary gland ultrasonography (SGUS): parotid, submandibular and sublingual glands (PG, SMG and SLG); (2) definitions for the elementary SGUS lesions in patients with Sjögren’s syndrome; (3) scoring system for grading changes. The experts rated the statements on a 1–5 Likert scale. In the second step, SGUS video clips of patients with pSS and non-pSS sicca cases were collected containing various spectrums of disease severity followed by an intrareader and inter-reader reliability exercise. Each video clip was evaluated according to the agreed definitions.ResultsConsensual definitions were developed after three Delphi rounds. Among the three selected SGs, US assessment of PGs and SMGs was agreed on. Agreement was reached to score only greyscale lesions and to focus on anechoic/hypoechoic foci in a semiquantitative matter or, if not possible on a qualitatively (present/absent) evaluation of fatty or fibrous lesions. Intrareader reliability for detecting and scoring these lesions was excellent (Cohen’s kappa 0.81) and inter-reader reliability was good (Light’s kappa 0.66).ConclusionNew definitions for developing a novel semiquantitative US score in patients with pSS were developed and tested on video clips. Inter-reader and intrareader reliabilities were good and excellent, respectively.
Objective To develop evidence-based recommendations on the use of imaging of the joints in the clinical management of rheumatoid arthritis (RA). Methods The task force comprised an expert group of ...rheumatologists, radiologists, methodologists and experienced rheumatology practitioners from 13 countries. Thirteen key questions on the role of imaging in RA were generated using a process of discussion and consensus. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, dual-emission x-ray absorptiometry, digital x-ray radiogrammetry, scintigraphy and positron emission tomography. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. The experts used the evidence obtained from the relevant studies to develop a set of 10 recommendations. The strength of recommendation was assessed using a visual analogue scale. Results A total of 6888 references was identified from the search process, from which 199 studies were included in the systematic review. Ten recommendations were produced encompassing the role of imaging in making a diagnosis of RA, detecting inflammation and damage, predicting outcome and response to treatment, monitoring disease activity, progression and remission. The strength of recommendation for each proposition varied according to both the research evidence and expert opinion. Conclusions Ten key recommendations for the role of imaging in the management of RA were developed using research-based evidence and expert opinion.
Objective To produce consensus-based scoring systems for ultrasound (US) tenosynovitis and to assess the intraobserver and interobserver reliability of these scoring systems in rheumatoid arthritis ...(RA). Methods We undertook a Delphi process on US-defined tenosynovitis and US scoring system of tenosynovitis in RA among 35 rheumatologists, experts in musculoskeletal US (MSUS), from 16 countries. Then, we assessed the intraobserver and interobserver reliability of US in scoring tenosynovitis on B-mode and with a power Doppler (PD) technique. Ten patients with RA with symptoms in the hands or feet were recruited. Ten rheumatologists expert in MSUS blindly, independently and consecutively scored for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two finger flexor tendons and two ankle tendons of each patient in two rounds in a blinded fashion. Intraobserver reliability was assessed by Cohen's κ. Interobserver reliability was assessed by Light's κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. Results Four-grade semiquantitative scoring systems were agreed upon for scoring tenosynovitis in B-mode and for scoring pathological peritendinous Doppler signal within the synovial sheath. The intraobserver reliability for tenosynovitis scoring on B-mode and PD mode was good (κ value 0.72 for B-mode; κ value 0.78 for PD mode). Interobserver reliability assessment showed good κ values for PD tenosynovitis scoring (first round, 0.64; second round, 0.65) and moderate κ values for B-mode tenosynovitis scoring (first round, 0.47; second round, 0.45). Conclusions US appears to be a reproducible tool for evaluating and monitoring tenosynovitis in RA.
Abstract
Objectives
To investigate the dynamics of response of synovitis to IL-17A inhibition with secukinumab in patients with active PsA using Power Doppler ultrasound.
Methods
The randomized, ...placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis and clinical synovitis and enthesitis having an inadequate response to conventional DMARDs and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global EULAR and OMERACT Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included ACR 20 and 50 responses.
Results
Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo −9 (0.9) vs −6 (0.9), difference (95% CI): −3 (−6, −1); one-sided P=0.004 at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported.
Conclusion
This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients.
Trial registration
ClinicalTrials.gov; NCT02662985.
Video Abstract
10.1093/rheumatology/keab628_video1
Video Abstract
keab628media1
6284681081001
Objective
Musculoskeletal ultrasonography (US) has potential in the assessment of disease activity and structural damage in childhood arthritides. In order to assess pathology, the US characteristics ...of joints in healthy children need to be defined first. The aim of this study was to develop definitions for the various components of the normal pediatric joint.
Methods
The definitions were developed by an expert group and applicability was assessed on a collection of standardized scans of the knee and ankle joints by scoring the scans on a Likert scale. The definitions were then modified and applicability was reassessed before sending the definitions for approval to a larger panel of experts. A final scoring on stored images of all relevant joints at different ages followed.
Results
Five definitions were developed addressing the articular bone, cartilage, joint capsule, epiphyseal ossification center, and synovial membrane. In total, 224 US images of knees and ankles were acquired, of which 172 were selected for scoring. An agreement of ≥80% was not met for any of the definitions, but after modifications, 81–97% agreement was reached. This version of the definitions was approved by 15 US experts. In the final validation exercise, all definitions reached an agreement of ≥80% for the shoulder, elbow, wrist, metacarpophalangeal hip, knee, ankle and metatarsophalangeal joint.
Conclusion
US definitions for the normal pediatric joint were successfully developed through a Delphi process and validated in a practical exercise. These results provide the basis to develop definitions for pathology and to support the standardized use of US in pediatric rheumatology.
Abstract
Objective
The aim of this exercise from the OMERACT Ultrasound subgroup on Sjögren’s syndrome was to develop and assess the reliability of a consensus-based semiquantitative colour Doppler ...US scoring system for pathologic salivary gland vascularization in patients with primary Sjögren's syndrome (pSS).
Methods
Using the Delphi method, a colour Doppler semiquantitative scoring system for vascularization of bilateral parotid and submandibular glands was developed and tested in static images and on patients (9 pSS patients and 9 sonographers). Intra-reader and inter-reader reliability of grading the salivary glands were computed by weighted Cohen and Light’s kappa analysis, respectively.
Results
The consensus-based semiquantitative score was: grade 0, no visible vascular signals; grade 1, focal, dispersed vascular signals; grade 2, diffuse vascular signals detected in <50% of the gland; grade 3, diffuse vascular signals in >50% of the gland. In static images, the intra- and inter-reader reliability showed excellent kappa values (95% CI) of 0.90 (0.87, 0.93) and 0.80 (0.74, 0.84), respectively, for all four salivary glands together. In patients, the intra- and inter-reader reliability for all four salivary glands together was kappa = 0.84 (0.73, 0.92) and 0.70 (0.64, 0.76), respectively.
Conclusion
The consensus-based colour Doppler US scoring for the evaluation of salivary gland vascularization in pSS showed a good inter-reader reliability and excellent intra-reader reliability in static images and in patients. The clinical application of the developed scoring system should be tested in clinical settings.
Objectives To evaluate synovitis (clinical vs ultrasound (US)) to predict structural progression in rheumatoid arthritis (RA). Methods Patients with RA. Study design Prospective, 2-year follow-up. ...Data collected Synovitis (32 joints (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal, 10 metatarsophalangeal)) at baseline and after 4 months of therapy by clinical, US grey scale (GS-US) and power doppler (PD-US); x-rays at baseline and at year 2. Analysis Measures of association (OR) were tested between structural deterioration and the presence of baseline synovitis, or its persistence, after 4 months of therapy using generalised estimating equation analysis. Results Structural deterioration was observed in 9% of the 1888 evaluated joints in 59 patients. Baseline synovitis increased the risk of structural progression: OR=2.01 (1.36–2.98) p<0.001 versus 1.61 (1.06–2.45) p=0.026 versus 1.75 (1.18–2.58) p=0.005 for the clinical versus US-GS versus US-PD evaluation, respectively. In the joints with normal baseline examination (clinical or US), an increased probability for structural progression in the presence of synovitis for the other modality was also observed (OR=2.16 (1.16–4.02) p=0.015 and 3.50 (1.77–6.95) p<0.001 for US-GS and US-PD and 2.79 (1.35–5.76) p=0.002) for clinical examination. Persistent (vs disappearance) synovitis after 4 months of therapy was also predictive of subsequent structural progression. Conclusions This study confirms the validity of synovitis for predicting subsequent structural deterioration irrespective of the modality of examination of joints, but also suggests that both clinical and ultrasonographic examinations may be relevant to optimally evaluate the risk of subsequent structural deterioration.
This study aims to investigate ultrasound (US) findings on salivary glands (SG) in patients with Sjögren syndrome (SS) vs. other connective tissue diseases (CTDs) and to assess the relationship of ...SGUS abnormalities with autoantibody profile in both groups. We enrolled 81 patients, 45 diagnosed with SS (39 with primary SS, 6 with secondary SS) and 36 diagnosed with other CTDs. All patients underwent a prospective evaluation of sicca symptoms, a Schirmer’s test, and a B-mode US assessment of the parotid and submandibular glands, all blinded to the diagnosis. Each SG was semi-quantitatively scored 0–3; a grade ≥ 2 was considered pathological. SGUS involvement was classified as normal or pathological at the patient level and for each pair at the gland level. In addition, a total SGUS score of 0–12 and a parotid/submandibular score of 0–6 were calculated for each patient. Autoimmunity laboratory data were also obtained. All SGUS scores were higher in SS patients than in those with CTD (
p
< 0.001) and significantly more SS patients showed a pathological global (
p
< 0.001), parotid (
p
< 0.001), or submandibular (
p
= 0.001) US score compared with CTD patients. In SS patients, the presence of autoantibodies was significantly associated with pathological SGUS and higher scores, particularly at the parotid level, while in CTD patients, xerostomia and a pathological Schirmer’s test were associated with pathological US and higher scores at the submandibular level (
p
< 0.05). SGUS showed a different grade of abnormality, site involvement, and associated autoantibody profile in SS patients as compared with other CTD.
Key Points
•
Patients with SS and other CTDs showed different grades of SGUS abnormality
.
•
Patients with SS and other CTDs showed different gland involvement and associated autoantibody profiles
.
•
Anti-Ro60 and anti-Ro52 Ro60 positivity were associated with the severity of parotid involvement in SS patients.
Bone erosions in rheumatoid arthritis (RA) have been studied in an increasing amount of research. Both earlier and present classification criteria of RA contain erosions as a significant ...classification component. Ultrasound (US) can detect bone changes in accessible surfaces. Therefore, the study group performed a systematic literature review of assessment of RA bone erosions with US.
A systematic search of PubMed and Embase was performed. Data on the definitions of RA bone erosions, their size, scoring, relation to synovitis, comparators, and elements of the OMERACT (Outcome Measures in Rheumatology Clinical Trials) filter were collected and analyzed.
The selection process identified 58 original research papers. The assessed joints were most frequently metacarpophalangeal (MCP; 41 papers), proximal interphalangeal (19 papers), and metatarsophalangeal joints (MTP; 18 papers). The OMERACT definition of RA bone erosion on US was used most often (17 papers). Second and fifth MCP and fifth MTP were recommended as target joints. Conventional radiography was the most frequently used comparator (27 papers), then magnetic resonance imaging (17 papers) and computed tomography (5 papers). Reliability of assessment was presented in 20 papers and sensitivity to change in 11 papers.
This paper presents results of a systematic literature review of bone erosion assessment in RA with US. The survey suggests that US can be a helpful adjunct to the existing methods of imaging bone erosions in RA. It analyzes definitions, scoring systems, used comparators, and elements of the OMERACT filter. It also presents recommendations for a future research agenda based on the results of the review.
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