Validity of an ultrasonographic joint-specific scoring system in juvenile idiopathic arthritis: a cross-sectional study comparing ultrasound findings of synovitis with whole-body magnetic resonance imaging and clinical assessment.

OBJECTIVE: To assess the validity of an ultrasonographic scoring system in juvenile idiopathic arthritis (JIA) by comparing ultrasound detected synovitis with whole-body MRI and clinical assessment of disease activity. METHODS: In a cross-sectional study, 27 patients with active JIA underwent clinical 71-joints examination, non-contrast enhanced whole-body MRI and ultrasound evaluation of 28 joints (elbow, radiocarpal, midcarpal, metacarpophalangeal 2-3, proximal interphalangeal 2-3, hip, knee, tibiotalar, talonavicular, subtalar and metatarsophalangeal 2-3). One rheumatologist, blinded to clinical findings, performed ultrasound and scored synovitis (B-mode and power Doppler) findings using a semiquantitative joint-specific scoring system for synovitis in JIA. A radiologist scored effusion/synovial thickening on whole-body MRI using a scoring system for whole-body MRI in JIA. At patient level, associations between ultrasound synovitis sum scores, whole-body MRI effusion/synovial thickening sum scores, clinical arthritis sum scores, and the 71-joints Juvenile Arthritis Disease Activity Score (JADAS71) were calculated using Spearman's correlation coefficients (rs). To explore associations at joint level, sensitivity and specificity were calculated for ultrasound using whole-body MRI or clinical joint examination as reference. RESULTS: Ultrasound synovitis sum scores strongly correlated with whole-body MRI effusion/synovial thickening sum scores (rs=0.74,p<0.01) and the JADAS71 (rs=0.71,p<0.01), and moderately with clinical arthritis sum scores (rs=0.57,p<0.01). Sensitivity/specificity of ultrasound in detecting synovitis were 0.57/0.96 and 0.55/0.96 using whole-body MRI or clinical joint examination as reference, respectively. CONCLUSION: Our findings suggest that ultrasound is a valid instrument to detect synovitis, and that ultrasound synovitis sum scores can reflect disease activity and may be an outcome measure in JIA.

Certolizumab pegol, abatacept, tocilizumab or active conventional treatment in early rheumatoid arthritis: 48-week clinical and radiographic results of the investigator-initiated randomised controlled NORD-STAR trial.

BACKGROUND: The optimal first-line treatment in early rheumatoid arthritis (RA) is debated. We compared clinical and radiographic outcomes of active conventional therapy with each of three biological treatments with different modes of action. METHODS: Investigator-initiated, randomised, blinded-assessor study. Patients with treatment-naïve early RA with moderate-severe disease activity were randomised 1:1:1:1 to methotrexate combined with (1) active conventional therapy: oral prednisolone (tapered quickly, discontinued at week 36) or sulfasalazine, hydroxychloroquine and intra-articular glucocorticoid injections in swollen joints; (2) certolizumab pegol; (3) abatacept or (4) tocilizumab. Coprimary endpoints were week 48 Clinical Disease Activity Index (CDAI) remission (CDAI ≤2.8) and change in radiographic van der Heijde-modified Sharp Score, estimated using logistic regression and analysis of covariance, adjusted for sex, anticitrullinated protein antibody status and country. Bonferroni's and Dunnet's procedures adjusted for multiple testing (significance level: 0.025). RESULTS: Eight hundred and twelve patients were randomised. Adjusted CDAI remission rates at week 48 were: 59.3% (abatacept), 52.3% (certolizumab), 51.9% (tocilizumab) and 39.2% (active conventional therapy). Compared with active conventional therapy, CDAI remission rates were significantly higher for abatacept (adjusted difference +20.1%, p<0.001) and certolizumab (+13.1%, p=0.021), but not for tocilizumab (+12.7%, p=0.030). Key secondary clinical outcomes were consistently better in biological groups. Radiographic progression was low, without group differences.The proportions of patients with serious adverse events were abatacept, 8.3%; certolizumab, 12.4%; tocilizumab, 9.2%; and active conventional therapy, 10.7%. CONCLUSIONS: Compared with active conventional therapy, clinical remission rates were superior for abatacept and certolizumab pegol, but not for tocilizumab. Radiographic progression was low and similar between treatments. TRIAL REGISTRATION NUMBER: NCT01491815.

Associations between power Doppler ultrasound findings and B-mode synovitis and clinical arthritis in juvenile idiopathic arthritis using a standardised scanning approach and scoring system.

OBJECTIVES: To describe power Doppler (PD) ultrasound findings in joint regions with B-mode (BM) synovitis using a standardised scanning protocol and scoring system in patients with juvenile idiopathic arthritis (JIA). Further, to examine associations between PD findings and BM synovitis, clinical arthritis, patient characteristics and disease activity. METHODS: In this cross-sectional study, one experienced ultrasonographer, blinded to clinical findings, performed ultrasound examinations in 27 JIA patients with suspected clinical arthritis. The elbow, wrist, metacarpophalangeal 2-3, proximal interphalangeal 2-3, knee, ankle and metatarsophalangeal 2-3 joints were assessed bilaterally and scored semiquantitatively (grades 0-3) for BM and PD findings using a joint-specific scoring system with reference atlas. Multilevel mixed-effects ordered regression models were used to explore associations between PD findings and BM synovitis, clinical arthritis, age, sex, JIA subgroups, disease duration and 10-joint Juvenile Arthritis Disease Activity Score (JADAS10). RESULTS: Twenty-one girls and six boys, median age (IQR) 8 years (6-12 years) were included. Overall, 971 joint regions were evaluated by ultrasound, 129 had BM synovitis and were assessed for PD. PD findings were detected in 45 joint regions (34.9%), most frequently in the parapatellar recess of the knee (24.4%). Increasing PD grades were associated with higher BM grades (OR=5.0,p<0.001) and with clinical arthritis (OR=7.4,p<0.001) but not with age, sex, JIA subgroups, disease duration or JADAS10. CONCLUSION: Increasing severity of PD findings were significantly associated with BM synovitis and with clinical arthritis. This suggests that PD signals detected using a standardised ultrasound examination and scoring system can reflect active disease in JIA patients.

Do tender joints in active psoriatic arthritis reflect inflammation assessed by ultrasound and magnetic resonance imaging?

OBJECTIVE: To investigate the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and MRI in patients with active PsA and to explore if the associations differ according to patient-reported outcomes (PROs) and structural damage. METHODS: Forty-one patients with active PsA and hand involvement had 76/78 joints examined for swelling/tenderness and ultrasound and MRI of 24 and 12 finger joints, respectively. Synovitis, tenosynovitis, periarticular inflammation and erosions were assessed using OMERACT definitions and scoring systems. Correlation between imaging inflammation sum-scores (intra-and periarticular) and tender/swollen joint counts were calculated using Spearman's rho, agreement at joint level was examined using prevalence and bias adjusted kappa (PABAK). Subgroup analyses explored the influence of PROs and radiographic erosive disease on these associations. RESULTS: No significant correlations were found between tender or swollen joint counts and imaging inflammation sum-scores (rho = -0.31-0.38). In patients with higher level of overall pain, disability and lower self-reported mental health, a tendency towards negative correlations were found. At joint level, intra- and periarticular imaging inflammatory lesions had slight agreement with joint tenderness (PABAK = 0.02-0.19) and slight to moderate with swelling (PABAK = 0.16-0.54). For tender joints, agreement with imaging inflammation was even weaker in patients with either high overall pain scores, high disability scores, and/or non-erosive disease. CONCLUSION: Joint tenderness had low association with imaging signs of inflammation in PsA patients, particularly in patients with high self-reported pain, disability and low mental health, indicating that tenderness is influenced by other parameters than local inflammation.

Development and reliability of a novel ultrasonographic joint-specific scoring system for synovitis with reference atlas for patients with juvenile idiopathic arthritis.

OBJECTIVE: To develop an ultrasonographic image acquisition protocol and a joint-specific scoring system for synovitis with reference atlas in patients with juvenile idiopathic arthritis (JIA) and to assess the reliability of the system. METHODS: Seven rheumatologists with extensive ultrasound experience developed a scanning protocol and a semiquantitative joint-specific scoring system for B-mode (BM) synovitis for the elbow, wrist, metacarpophalangeal 2-3, proximal interphalangeal 2-3, hip, knee, ankle and metatarsophalangeal 2-3 joints. An ultrasonographic reference atlas for BM synovitis, divided in four age groups (2-4, 5-8, 9-12, 13-18 years), and power Doppler (PD) activity was then developed. Reliability was assessed for all joints on still images and in a live exercise including 10 patients with JIA, calculated by intraclass correlation coefficient (ICC) and weighted kappa. RESULTS: A scanning protocol and scoring system for multiple joints with reference atlas composed of images with four different score levels for BM and PD were developed. Still image scoring for BM synovitis on joint level showed good to excellent intra-reader reliability (ICC/kappa ranges: 0.75-0.95/0.63-0.91) and moderate to excellent inter-reader reliability (ICC/kappa ranges: 0.89-0.99/0.50-0.91). Still image scoring for PD activity showed excellent intra-reader and inter-reader reliability (ICC/kappa: 0.96/0.91 and ICC/kappa: 0.97/0.80, respectively). In the live scoring, inter-reader reliability (ICC/kappa) was moderate to excellent for BM synovitis (0.94/0.51) and PD activity (0.91/0.60). CONCLUSION: An ultrasonographic image acquisition protocol and joint-specific scoring system with reference atlas were developed and demonstrated moderate to excellent reliability for scoring of synovitis in patients with JIA. This can be a valuable tool in clinical practice and future research.

Role of erosions typical of rheumatoid arthritis in the 2010 ACR/EULAR rheumatoid arthritis classification criteria: results from a very early arthritis cohort.

OBJECTIVE: To determine how the European League Against Rheumatism (EULAR) definition of erosive disease (erosion criterion) contributes to the number of patients classified as rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/EULAR RA classification criteria (2010 RA criteria) in an early arthritis cohort. METHODS: Patients from the observational study Norwegian Very Early Arthritis Clinic with joint swelling ≤16 weeks, a clinical diagnosis of RA or undifferentiated arthritis, and radiographs of hands and feet were included. Erosive disease was defined according to the EULAR definition accompanying the 2010 RA criteria. We calculated the additional number of patients being classified as RA based on the erosion criteria at baseline and during follow-up. RESULTS: Of the 289 included patients, 120 (41.5%) fulfilled the 2010 RA criteria, whereas 15 (5.2%) fulfilled only the erosion criterion at baseline. 118 patients had radiographic follow-up at 2 years, of whom 6.8% fulfilled the 2010 RA criteria and only one patient fulfilled solely the erosion criterion during follow-up. CONCLUSION: Few patients with early arthritis were classified as RA based on solely the erosion criteria, and of those who did almost all did so at baseline.

The OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging (MRI) Scoring System: Updated Recommendations by the OMERACT MRI in Arthritis Working Group.

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis (RA) Magnetic Resonance Imaging (MRI) scoring system (RAMRIS), evaluating bone erosion, bone marrow edema/osteitis, and synovitis, was introduced in 2002, and is now the standard method of objectively quantifying inflammation and damage by MRI in RA trials. The objective of this paper was to identify subsequent advances and based on them, to provide updated recommendations for the RAMRIS. METHODS: MRI studies relevant for RAMRIS and technical and scientific advances were analyzed by the OMERACT MRI in Arthritis Working Group, which used these data to provide updated considerations on image acquisition, RAMRIS definitions, and scoring systems for the original and new RA pathologies. Further, a research agenda was outlined. RESULTS: Since 2002, longitudinal studies and clinical trials have documented RAMRIS variables to have face, construct, and criterion validity; high reliability and sensitivity to change; and the ability to discriminate between therapies. This has enabled RAMRIS to demonstrate inhibition of structural damage progression with fewer patients and shorter followup times than has been possible with conventional radiography. Technical improvements, including higher field strengths and improved pulse sequences, allow higher image resolution and contrast-to-noise ratio. These have facilitated development and validation of scoring methods of new pathologies: joint space narrowing and tenosynovitis. These have high reproducibility and moderate sensitivity to change, and can be added to RAMRIS. Combined scores of inflammation or joint damage may increase sensitivity to change and discriminative power. However, this requires further research. CONCLUSION: Updated 2016 RAMRIS recommendations and a research agenda were developed.

EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis.

The increased information provided by modern imaging has led to its more extensive use. Our aim was to develop evidence-based recommendations for the use of imaging in the clinical management of the most common arthropathy, osteoarthritis (OA). A task force (including rheumatologists, radiologists, methodologists, primary care doctors and patients) from nine countries defined 10 questions on the role of imaging in OA to support a systematic literature review (SLR). Joints of interest were the knee, hip, hand and foot; imaging modalities included conventional radiography (CR), MRI, ultrasonography, CT and nuclear medicine. PubMed and EMBASE were searched. The evidence was presented to the task force who subsequently developed the recommendations. The strength of agreement for each recommendation was assessed. 17 011 references were identified from which 390 studies were included in the SLR. Seven recommendations were produced, covering the lack of need for diagnostic imaging in patients with typical symptoms; the role of imaging in differential diagnosis; the lack of benefit in monitoring when no therapeutic modification is related, though consideration is required when unexpected clinical deterioration occurs; CR as the first-choice imaging modality; consideration of how to correctly acquire images and the role of imaging in guiding local injections. Recommendations for future research were also developed based on gaps in evidence, such as the use of imaging in identifying therapeutic targets, and demonstrating the added value of imaging. These evidence-based recommendations and related research agenda provide the basis for sensible use of imaging in routine clinical assessment of people with OA.

Establishment of age- and sex-adjusted reference data for hand bone mass and investigation of hand bone loss in patients with rheumatoid arthritis treated in clinical practice: an observational study from the DANBIO registry and the Copenhagen Osteoarthritis Study.

BACKGROUND: Rheumatoid arthritis is characterised by progressive joint destruction and loss of periarticular bone mass. Hand bone loss (HBL) has therefore been proposed as an outcome measure for treatment efficacy. A definition of increased HBL adjusted for age- and sex-related bone loss is lacking. In this study, we aimed to: 1) establish reference values for normal hand bone mass (bone mineral density measured by digital x-ray radiogrammetry (DXR-BMD)); and 2) examine whether HBL is normalised in rheumatoid arthritis patients during treatment with tumour necrosis factor alpha inhibitors (TNFI). METHODS: DXR-BMD was measured from hand x-rays in a reference cohort (1485 men/2541 women) without arthritis randomly selected from an urban Danish population. Sex- and age-related HBL/year was estimated. DXR-BMD was measured in rheumatoid arthritis patients (n = 350: at start of TNFI, and ~2 years after TNFI start), of which 135 patients had three x-rays (~2 years prior to TNFI, at start of TNFI, and ~2 years after TNFI start). Individual HBL/year prior to and during TNFI was calculated and compared to reference values. RESULTS: Estimated HBL/year varied strongly with age and sex. Compared to the reference values, 75 % of 135 patients had increased HBL prior to TNFI treatment and 59 % had increased HBL during TNFI treatment (p = 0.17, Chi-squared). In 38 % (38/101) of patients with increased HBL, HBL was normalised during TNFI treatment, whereas 47 % (16/34) of patients with normal HBL prior to TNFI had increased HBL during TNFI treatment. In the 350 patients, increased HBL during TNFI was associated with time-averaged 28-joint disease activity score (odds ratio 1.69 (95 % Confidence Interval 1.34-2.15)/unit increase, p < 0.001), and patients in time-averaged remission had lower HBL than patients without remission (0.0032 vs. 0.0058 g/cm(2)/year; p < 0.001, Mann-Whitney). CONCLUSIONS: We established age- and sex-specific reference values for DXR-BMD in a large cohort without arthritis. HBL was increased in the majority of rheumatoid arthritis patients initiating TNFI in clinical practice, and only normalised in a minority during TNFI.

MRI findings predict radiographic progression and development of erosions in hand osteoarthritis.

OBJECTIVES: To examine whether MRI features predict radiographic progression including erosive evolution in patients from the Oslo hand osteoarthritis (OA) cohort, which is the first longitudinal hand OA study with available MRI. METHODS: We included 74 patients (91% female, mean (SD) age of 67.9 (5.3) years) with MRI of the dominant hand and conventional radiographs taken at baseline and 5-year follow-up. Baseline MRIs were read according to the Oslo hand OA MRI score. We used three definitions of radiographic progression: Progression of joint space narrowing (JSN, grades 0-3), increased Kellgren-Lawrence score (grades 0-4) or incident erosions (absent/present). For each definition, we examined whether MRI features predicted radiographic progression in the same joint using Generalised Estimating Equations. We adjusted for age, sex, Body Mass Index, follow-up time and other erosive joints (the latter for analyses on incident erosions only). RESULTS: MRI-defined moderate/severe synovitis (OR=3.52, 95% CI 1.29 to 9.59), bone marrow lesions (BML) (OR=2.73, 95% CI 1.29 to 5.78) and JSN (severe JSN: OR=11.05, 95% CI 3.22 to 37.90) at baseline predicted progression of radiographic JSN. Similar results were found for increasing Kellgren-Lawrence score, except for weaker association for JSN. Baseline synovitis, BMLs, JSN, bone damage, osteophytes and malalignment were significantly associated with development of radiographic erosions, of which malalignment showed the strongest association (OR=10.18, 95% CI 2.01 to 51.64). CONCLUSIONS: BMLs, synovitis and JSN were the strongest predictors for radiographic progression. Malalignment was associated with incident erosions only. Future studies should explore whether reducing BMLs and inflammation can decrease the risk of structural progression.

Increasing synovitis and bone marrow lesions are associated with incident joint tenderness in hand osteoarthritis.

OBJECTIVES: To explore whether changes of MRI-defined synovitis and bone marrow lesions (BMLs) are related to changes in joint tenderness in a 5-year longitudinal study of the Oslo hand osteoarthritis (OA) cohort. METHODS: We included 70 patients (63 women, mean (SD) age 67.9 (5.5) years). BMLs and contrast-enhanced synovitis in the distal and proximal interphalangeal joints were evaluated on 0-3 scales in n=69 and n=48 patients, respectively. Among joints without tenderness at baseline, we explored whether increasing/incident synovitis and BMLs were associated with incident joint tenderness using generalised estimating equations. Among joints with tenderness at baseline, we explored whether decreasing or resolution of synovitis and BMLs were associated with loss of joint tenderness. We adjusted for age, sex, body mass index, follow-up time and changes in radiographic OA. RESULTS: Among joints without tenderness at baseline, increasing/incident synovitis and BMLs were seen in 45 of 220 (20.5%) and 47 of 312 (15.1%) joints, respectively. Statistically significant associations to incident joint tenderness were found for increasing/incident synovitis (OR=2.66, 95% CI 1.38 to 5.11) and BMLs (OR=2.85, 95% CI 1.23 to 6.58) independent of structural progression. We found a trend that resolution of synovitis (OR=1.72, 95% CI 0.80 to 3.68) and moderate/large decreases of BMLs (OR=1.90, 95% CI 0.57 to 6.33) were associated with loss of joint tenderness, but these associations were non-significant. CONCLUSIONS: The Oslo hand OA cohort is the first study with longitudinal hand MRIs. Increasing synovitis and BMLs were significantly associated with incident joint tenderness, whereas no significant associations were found for decreasing or loss of synovitis and BMLs.

Clinical and Radiographic Outcomes in Patients Diagnosed with Early Rheumatoid Arthritis in the First Years of the Biologic Treatment Era: A 10-year Prospective Observational Study.

OBJECTIVE: To study short-term and longterm clinical and radiographic outcomes in patients with early rheumatoid arthritis (RA) in the first decade of the biologic treatment era. METHODS: Patients with early RA diagnosed at a rheumatology outpatient clinic were consecutively enrolled between 1999 and 2001. Data were collected on demographic characteristics, disease activity, patient-reported outcomes, and treatments. Radiographs of hands and feet were performed at baseline and after 2, 5, and 10 years and scored according to the Sharp/van der Heijde method, yielding a modified total Sharp score (mTSS). RESULTS: Mean baseline age for the 94 included patients (36 men and 58 women) was 50.4 years and symptom duration 12.3 months; 67.8% were rheumatoid factor-positive. The proportion of patients in remission and in low, moderate, and high disease activity status was at baseline 4.3%, 1.1%, 35.1%, and 59.6% and at 10 years 52.1%, 20.5%, 27.4%, and 0.0%, respectively. For the period 0-2 years, 62.8% had used prednisolone, 91.5% synthetic disease-modifying antirheumatic drug (DMARD), and 18.1% biologic DMARD, and for the period 2-10 years the numbers were 50.6%, 89.3%, and 62.7%, respectively. At baseline, 70% of the patients had erosions on radiographs. Mean annual change in mTSS was for 0-2 years 3.4, 2-5 years 1.7, and 5-10 years 1.2. CONCLUSION: A large proportion of our patients with RA diagnosed and treated in the new biologic treatment era achieved a status of clinical remission or low disease activity and had only a minor increase in radiographic joint damage after the first years of followup.

Validation of the OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) for the Hand and Foot in a Randomized Placebo-controlled Trial.

OBJECTIVE: To assess changes following treatment and the reliability and responsiveness to change of the Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) in a randomized controlled trial. METHODS: Forty patients with PsA randomized to either placebo or abatacept (ABA) had MRI of either 1 hand (n = 20) or 1 foot (n = 20) at baseline and after 6 months. Images were scored blindly twice by 3 independent readers according to the PsAMRIS (for synovitis, tenosynovitis, periarticular inflammation, bone edema, bone erosion, and bone proliferation). RESULTS: Inflammatory features improved numerically but statistically nonsignificantly in the ABA group but not the placebo group. Baseline intrareader intraclass correlation coefficients (ICC) were good (≥ 0.50) to very good (≥ 0.80) for all features in both hand and foot. Baseline interreader ICC were good (ICC 0.72-0.96) for all features, except periarticular inflammation and bone proliferation in the hand and tenosynovitis in the foot (ICC 0.25-0.44). Intrareader and interreader ICC for change scores varied. Guyatt's responsiveness index (GRI) was high for inflammatory features in the hand and metatarsophalangeal joints (GRI -0.67 to -3.13; bone edema not calculable). Minimal change and low prevalence resulted in low ICC and GRI for bone damage. CONCLUSION: PsAMRIS showed overall good intrareader agreement in the hand and foot, and inflammatory feature scores were responsive to change, suggesting that PsAMRIS may be a valid tool for MRI assessment of hands and feet in PsA clinical trials.

Instruments Measuring Pain, Physical Function, or Patient's Global Assessment in Hand Osteoarthritis: A Systematic Literature Search.

OBJECTIVE: Description of use and metric properties of instruments measuring pain, physical function, or patient's global assessment (PtGA) in hand osteoarthritis (OA). METHODS: Medical literature databases up to January 2014 were systematically reviewed for studies reporting on instruments measuring pain, physical function, or PtGA in hand OA. The frequency of the use of these instruments were described, as well as their metric properties, including discrimination (reliability, sensitivity to change), feasibility, and validity. RESULTS: In 66 included studies, various questionnaires and performance- or assessor-based instruments were applied for evaluation of pain, physical function, or PtGA. No major differences regarding metric properties were observed between the instruments, although the amount of supporting evidence varied. The most frequently evaluated questionnaires were the Australian/Canadian Hand OA Index (AUSCAN) pain subscale and visual analog scale (VAS) pain for pain assessment, and the AUSCAN function subscale and Functional Index for Hand OA (FIHOA) for physical function assessment. Excellent reliability was shown for the AUSCAN and FIHOA, and good sensitivity to change for all mentioned instruments; additionally, the FIHOA had good feasibility. Good construct validity was suggested for all mentioned questionnaires. The most commonly applied performance- or assessor-based instruments were the grip and pinch strength for the assessment of physical function, and the assessment of pain by palpation. For these measures, good sensitivity to change and construct validity were established. CONCLUSION: The AUSCAN, FIHOA, VAS pain, grip and pinch strength, and pain on palpation were most frequently used and provided most supporting evidence for good metric properties. More research has to be performed to compare the different instruments with each other.

The Longitudinal Reliability and Responsiveness of the OMERACT Hand Osteoarthritis Magnetic Resonance Imaging Scoring System (HOAMRIS).

OBJECTIVE: To evaluate the interreader reliability of change scores and the responsiveness of the OMERACT Hand Osteoarthritis (OA) Magnetic Resonance Image (MRI) Scoring System (HOAMRIS). METHODS: Paired MRI (baseline and 5-yr followup) from 20 patients with hand OA were scored with known time sequence by 3 readers according to the HOAMRIS: Synovitis, erosive damage, cysts, osteophytes, cartilage space loss, malalignment, and bone marrow lesions (BML; 0-3 scales with 0.5 increments for synovitis, erosive damage, and BML). Interreader reliability for status and change scores were assessed by intraclass correlation coefficients (ICC), percentage exact agreement and percentage close agreement (PEA/PCA), and smallest detectable change (SDC). Responsiveness was assessed by standardized response means (SRM). RESULTS: Cross-sectional interreader ICC were good to very good (≥ 0.74) for all features except synovitis, cysts, and malalignment (ICC 0.50-0.58). The range of change values was small, leading to low ICC for change scores. The SDC values for sum scores (total range 0-24) varied between 1.97-3.05 (except 1.08 for malalignment). For status scores, PEA/PCA on scores in individual joints across the readers were 8.1-50.0 and 43.8-78.1, respectively. Similarly, PEA/PCA for change scores were 20.6-63.8 and 66.3-93.1, respectively. All features except cysts and BML demonstrated good responsiveness with higher SRM for sum scores (range 0.46-1.62) than for scores in individual joints (range 0.24-0.73). CONCLUSION: Good to very good interreader ICC values were found for cross-sectional readings, whereas the longitudinal reliability was lower because of a smaller range of change scores. All features, except cysts and BML, showed good responsiveness.

Report from the OMERACT Hand Osteoarthritis Working Group: Set of Core Domains and Preliminary Set of Instruments for Use in Clinical Trials and Observational Studies.

OBJECTIVE: During OMERACT 12, a workshop was held with the aim to endorse a core set of domains for 3 settings: clinical trials of symptom and structure modification and observational studies. Additional goals were to endorse a core set of contextual factors for these settings, and to define preliminary instruments for each core domain. Finally, an agenda for future research in hand osteoarthritis (OA) was to be proposed. METHODS: Literature reviews of preliminary instruments for each core domain of the proposed core set for hand OA in the settings described above. Literature review of radiographic scoring methods and modern imaging in hand OA were also performed. Proposed contextual factors for a core set were identified through 2 Delphi exercises with participation of hand OA experts, patient partners, and OMERACT participants. RESULTS: Results from Delphi exercises and systematic literature reviews were presented and discussed. It was agreed that a preliminary core domain set for the setting clinical trials of symptom modification should contain at least "pain, physical function, patient global assessment, joint activity and hand strength." The settings clinical trial of structure modification and observational studies would in addition include structural damage. Preliminary instruments for the proposed domains were agreed on. A list of prioritized contextual factors was defined and endorsed for further research. A research agenda was proposed for domain instrument validation according to the OMERACT Filter 2.0. CONCLUSION: Preliminary core sets for clinical trials of symptom and structure modification and observational studies in hand osteoarthritis, including preliminary instruments and contextual factors, were agreed upon during OMERACT 12.

Magnetic Resonance Imaging in Hand Osteoarthritis: Intraobserver Reliability and Criterion Validity for Clinical and Structural Characteristics.

OBJECTIVE: To investigate criterion validity and intraobserver reliability of magnetic resonance imaging (MRI) in hand osteoarthritis (HOA). METHODS: In 16 patients with HOA (median age 57 yrs, 62% women, 13 with erosive OA), 3 Tesla MRI scans with gadolinium-chelate administration of right second to fifth distal interphalangeal/proximal interphalangeal joints were scored according to the Oslo HOA scoring method for synovial thickening, bone marrow lesions (BML), osteophytes, joint space narrowing (JSN), and erosions (grade 0-3). Ultrasound (US) was scored for synovial thickening and osteophytes, radiographs for osteophytes and JSN (Osteoarthritis Research Society International score), and anatomical phases (Verbruggen-Veys score). Pain was assessed during physical examination. Correlations of MRI with US and radiographic features were assessed with generalizability theory. With generalized estimating equations analyses, MRI features were associated with pain, adjusting for confounding. RESULTS: Forty-three percent, 27%, 77%, and 61% of joints had synovial thickening (moderate/severe), BML, osteophytes, and erosions on MRI, respectively. Intraobserver reliability, assessed in 6 patients, was good (ICC 0.77-1.00). Correlations between osteophytes, JSN, and erosions on radiographs and MRI were moderate, substantial, and fair (ICC 0.53, 0.68, and 0.32, respectively); MRI showed more lesions than radiography. Correlation between synovial thickening and osteophytes on MRI and US was moderate (ICC 0.43 and 0.49, respectively). MRI was more sensitive for synovial thickening, US for osteophytes. Pain was associated with moderate/severe synovial thickening (adjusted OR 2.4, 95% CI 1.06-5.5), collateral ligaments (4.2, 2.2-8.3), BML (3.5, 1.6-7.7), erosions (4.5, 1.7-12.2), and osteophytes (2.4, 1.1-5.2). CONCLUSION: MRI is a reliable and valid method to assess inflammatory and structural features in HOA. It gives additional information over radiographs and US.

The OMERACT MRI in Arthritis Working Group - Update on Status and Future Research Priorities.

OBJECTIVE: To provide an update on the status and future research priorities of the Outcome Measures in Rheumatology (OMERACT) magnetic resonance imaging (MRI) in arthritis working group. METHODS: A summary is provided of the activities of the group within rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA), and its research priorities. RESULTS: The OMERACT RA MRI score (RAMRIS) evaluating bone erosion, bone edema (osteitis), and synovitis is now the standard method of quantifying articular pathology in RA trials. Cartilage loss is another important part of joint damage, and at the OMERACT 12 conference, we provided longitudinal data demonstrating reliability and sensitivity to change of the RAMRIS JSN component score, supporting its use in future clinical trials. The MRI group has previously developed a PsA MRI score (PsAMRIS). At OMERACT 12, PsAMRIS was evaluated in a randomized placebo-controlled trial of patients with PsA, demonstrating the responsiveness and discriminatory ability of applying the PsAMRIS to hands and feet. A hand OA MRI score (HOAMRIS) was introduced at OMERACT 11, and has subsequently been further validated. At OMERACT 12, good cross-sectional interreader reliability, but variable reliability of change scores, were reported. Potential future research areas were identified at the MRI session at OMERACT 12 including assessment of tenosynovitis in RA and enthesitis in PsA and focusing on alternative MRI techniques. CONCLUSION: MRI has been further developed and validated as an outcome measure in RA, PsA, and OA. The group will continue its efforts to optimize the value of MRI as a robust biomarker in rheumatology clinical trials.

Validation of the OMERACT Magnetic Resonance Imaging Joint Space Narrowing Score for the Wrist in a Multireader Longitudinal Trial.

OBJECTIVE: To assess the intrareader and interreader agreement and sensitivity to change of the Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis Magnetic Resonance Imaging Joint Space Narrowing (RAMRIS-JSN) score in the rheumatoid arthritis (RA) wrist in a longitudinal multireader exercise. METHODS: Coronal T1-weighted MR image sets of 1 wrist from 20 patients with early RA were assessed twice for JSN at 17 sites at baseline and after 36 or 60 months by 4 readers blinded to patient data but not time order. The joints were scored 0-4 according to the OMERACT RAMRIS-JSN score. Intraclass correlation coefficients (ICC), smallest detectable change (SDC), percentage exact/close agreement (PEA/PCA), and standardized response mean (SRM) were calculated. RESULTS: Median baseline and change score was 10.3 and 1.9, respectively. Intrareader ICC for baseline and change scores was good (≥ 0.50) to very good (≥ 0.80) for all and 3 of 4 readers, respectively. Interreader ICC was very good for change (0.93), while poor for baseline score if all 4 readers were included (0.36), but very good if 1 reader was excluded (0.87). Intrareader and interreader SDC was low (2.34-3.18), except for the intrareader SDC for 1 reader (6.75). The mean PEA/PCA was high for baseline and change scores both within and between the readers (51.5-99.2), except for interreader baseline PEA (14.4). SRM was moderate for all readers (0.55-0.77). CONCLUSION: The OMERACT RAMRIS-JSN score showed high overall intrareader and interreader reliability, and moderate sensitivity to change, supporting inclusion of the measure as part of the OMERACT RAMRIS system.

Influence of field strength, coil type and image resolution on assessment of synovitis by unenhanced MRI--a comparison with contrast-enhanced MRI.

OBJECTIVES: To explore if the reliability of synovitis assessment by unenhanced MRI is influenced by different MRI field-strengths, coil types and image resolutions in RA patients. METHODS: Forty-one RA patients and 12 healthy controls underwent hand MRI (wrist and 2(nd)--5(th) metacarpophalangeal joints) at 4 different field-strengths (0.23 T/0.6 T/1.5 T/3.0 T) on the same day. Seven protocols using a STIR sequence with different field-strengths, coils (flex coils/dedicated phased-array extremity coils) and resolution were applied and scored blindly for synovitis (OMERACT-RAMRIS method). A 1.5 T post-contrast T1-weighted sequence was used as gold standard reference. RESULTS: Fair-good agreement (ICC=0.38--0.72) between the standard reference and the different STIR protocols (best agreement with extremity coil and small voxel size at 1.5 T). The accuracy for presence/absence of synovitis was very high per person (0.80--1.0), and moderate-high per joint (0.63--0.85), whereas exact agreements on scores were moderate (0.50--0.66). The intrareader agreement (15 patients and 3 controls) on presence/absence of synovitis was very high (0.87--1.0). CONCLUSIONS: Unenhanced MRI using STIR sequence is only moderately reliable for assessing hand synovitis in RA, when contrast-enhanced MRI is considered the gold standard reference. Contrast injection, field strength and coil type influence synovitis assessment, and should be considered before performing MRI in clinical trials and practice. KEY POINTS: • STIR is only moderately reliable for synovitis assessment, compared with post-contrast-T1-w. • Contrast injection, field strength, and coil type influence synovitis assessment. • Contrast injection is recommended for reliable and reproducible hand synovitis assessment.