Jane Freeston

Should imaging be a component of rheumatoid arthritis remission criteria? A comparison between traditional and modified composite remission scores and imaging assessments

Objectives Patients can fulfil clinical criteria for remission, yet still have evidence of synovitis detectable clinically and by ultrasound, and this is associated with structural damage. Stricter remission criteria may more accurately reflect true remission (no synovitis). This hypothesis was examined by studying patients using more stringent thresholds for clinical remission and determining their levels of ultrasound synovitis. Methods Rheumatoid arthritis patients with a disease activity score in 28 joints (DAS28) ≤2.6 for at least 6 months were classified using standard and more stringent DAS28 and simplified disease activity index (SDAI) remission thresholds and the corresponding clinical and ultrasound imaging measures of synovitis recorded. Results 128 patients (all DAS28 <2.6, median DAS28 1.70) receiving either disease-modifying antirheumatic drugs alone (n=66) or with a tumour necrosis factor blocker (n=62) were recruited. Of the 640 imaged joints, 5% had moderate or severe power Doppler (PD) activity, 8% were clinically swollen and 1% tender. In patients fulfilling DAS28, American College of Rheumatology or SDAI remission criteria, moderate or severe PD activity was present in 21%, 15% and 19%, respectively. More stringent DAS28 and SDAI criteria reduced the mean number of swollen and tender joints (p<0.001) but not the percentage of patients with PD activity: 32 patients had a DAS28 <1.17 but eight (25%) had significant PD activity. Conclusion Using more stringent remission criteria resulted in reduced signs and symptoms of inflammation, but the percentage of joints with PD activity was not reduced, even in those without signs or symptoms. These data suggest that clinical criteria are sufficiently insensitive to detect low but clinically relevant levels of inflammation accurately.

A diagnostic algorithm for persistence of very early inflammatory arthritis: the utility of power doppler ultrasound when added to conventional assessment tools

Objectives: The aim of this study was to assess the value of power Doppler ultrasound (PDUS) in combination with routine management in a cohort of patients with very early inflammatory arthritis (IA). Methods: 50 patients with ⩽12 weeks of inflammatory symptoms with or without signs had clinical, laboratory and imaging assessments. Diagnosis was recorded at 12 months. Assuming a 15% pre-test probability of IA, post-test probabilities for various assessments were calculated and used to develop a diagnostic algorithm. Results: All patients positive for rheumatoid factor (RF) and/or cyclic citrullinated peptide (CCP) developed persistent IA, so the added value of PDUS was assessed in the seronegative (RF and CCP negative) group. The probability of IA in a seronegative patient was 6%. The addition of clinical and radiographic features raised the probability of IA to 30% and, with certain ultrasound features, this rose to 94%. Conclusions: In seronegative patients with early IA, combining PDUS with routine assessment can have a major impact on the certainty of diagnosis.

Disease remission state in patients treated with the combination of tumor necrosis factor blockade and methotrexate or with disease-modifying antirheumatic drugs: A clinical and imaging comparative study.

OBJECTIVE For patients with rheumatoid arthritis (RA) in remission who are receiving disease-modifying antirheumatic drugs (DMARDs), radiographic progression correlates with imaging-detected synovitis as measured by power Doppler activity. In contrast, patients with disease in remission who are receiving the combination of tumor necrosis factor (TNF) blockade with methotrexate (MTX) (combination treatment) have reduced radiographic damage for the equivalent clinical state. We undertook this study to determine whether the difference in radiographic outcome is a result of more complete suppression of imaging-detected synovitis. METHODS One hundred patients with RA in remission (Disease Activity Score in 28 joints [DAS28] <2.6) for at least 6 months while receiving either combination treatment (n = 50) or DMARDs (n = 50) were matched for clinical variables. Ultrasound of metacarpophalangeal joints 1-5 and the wrist joints was performed. Remission according to imaging results was defined as a score of 0 for both grey scale synovitis and power Doppler activity. RESULTS In patients receiving combination treatment or DMARDs (median DAS28 1.65 versus 1.78, median disease duration 120 months versus 90 months, and median duration of remission 13 months versus 18 months), the proportion with remission according to imaging results was not significantly different (10% versus 16%, respectively). The combination treatment group had more grey scale synovitis (P < 0.001) but similar power Doppler activity (48% versus 60%, respectively; P = 0.229) in any joint as compared with the DMARD group. Results were not affected by stratification for duration of disease or remission. CONCLUSION In RA patients with disease in remission, imaging-detected synovitis persists, with power Doppler activity seen in >or=48% of the patients regardless of therapy. These results suggest that superior radiographic outcomes in patients treated with the combination of TNF blockade and MTX may not be due to complete suppression of imaging-detected synovitis.

The OMERACT ultrasound task force - Status and perspectives

This article reports the most recent work of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Task Force, and highlights the future research priorities discussed at the OMERACT 10 meeting. Results of the following studies were presented: (1) intra- and interobserver reliability of ultrasound detecting and scoring synovitis in different joints of patients with rheumatoid arthritis (RA); (2) systematic review of previous ultrasound scoring systems of synovitis in RA; (3) enthesitis systematic review and Delphi definition exercise in spondyloarthritis enthesitis; (4) enthesitis intra- and interobserver reliability exercise; and (5) Delphi definition exercise in hand osteoarthritis, and reliability exercises. Study conclusions were discussed, and a future research agenda was approved, notably further validation of an OMERACT ultrasound global synovitis score (GLOSS) in RA, emphasizing the importance of testing feasibility, predictive value, and added value over standard clinical variables. Future research areas will include validating scoring systems for enthesitis and osteoarthritis, and testing the metric qualities of ultrasound for evaluating tenosynovitis and structural damage in RA.

Synovitis and osteitis are very frequent in rheumatoid arthritis clinical remission: results from an MRI study of 294 patients in clinical remission or low disease activity state.

Objective. In rheumatoid arthritis (RA), radiographic progression may occur despite clinical remission. This may be explained by subclinical inflammation. Magnetic resonance imaging (MRI) provides a greater sensitivity than clinical examination and radiography for assessing disease activity. Our objective was to determine the MRI characteristics of RA patients in clinical remission or low disease activity (LDA) state. Methods. Databases from 6 cohorts were collected from 5 international centers. RA patients in clinical remission according to Disease Activity Score28-C-reactive protein (DAS28-CRP < 2.6; n = 213) or LDA-state (2.6 ≤ DAS28-CRP < 3.2; n = 81) with available MRI data were included. MRI were assessed according to the OMERACT RA MRI scoring system (RAMRIS). Results. Patient characteristics: 70% women, median age 55 (interquartile range, IQR 43–63) years, disease duration 2.3 (IQR 0.7–5.1) years, DAS28-CRP 2.2 (IQR 1.8–2.6), Simplified Disease Activity Index, SDAI, 3.9 (IQR 1.9–6.5), Clinical Disease Activity Index, CDAI, 3.1 (IQR 1.5– 5.8), rheumatoid factor/anti-cyclic citrullinated peptide positivity 57%/54%, presence of radiographic erosions: 66%. Wrist and metacarpophalangeal MRI (MCP-MRI) data were available for 287 and 241 patients, respectively. MRI inflammatory activity in wrist and/or MCP joints was observed in the majority [synovitis: 95%, bone edema (osteitis): 35%] of patients. The median (IQR) RAMRIS score was 6 (3–9) for synovitis and 0 (0–2) for osteitis. Synovitis and osteitis were not less frequent in DAS28 clinical remission (synovitis/osteitis 96%/35%) than LDA (91/36). A trend towards lower frequencies of osteitis in patients in SDAI and CDAI remission was observed. Conclusion. Subclinical inflammation was identified by MRI in the majority of RA patients in clinical remission or LDA state. This may explain structural progression in such patients. Further work is required to understand the place of modern imaging in future remission criteria.

The OMERACT Ultrasound Task Force — Advances and Priorities

This article reports the most recent work of the OMERACT Ultrasound Task Force (post OMERACT 8) and highlights of future research priorities discussed at the OMERACT 9 meeting, Kananaskis, Canada, May 2008. Results of 3 studies were presented: (1) assessing intermachine reliability; (2) applying the scoring system developed in the hand to other joints most commonly affected in rheumatoid arthritis (RA); and (3) assessing interobserver reliability on a deep target joint (shoulder). Results demonstrated good intermachine reliability between multiple examiners, and good applicability of the scoring system for the hand on other joints (including shoulder). Study conclusions were discussed and a future research agenda was generated, notably the further development of a Global OMERACT Sonography Scoring (GLOSS) system in RA, emphasizing the importance of testing feasibility and added value over standard clinical variables. Future disease areas of importance to develop include a scoring system for enthesitis and osteoarthritis.

The optimal assessment of the rheumatoid arthritis hindfoot: a comparative study of clinical examination, ultrasound and high field MRI

Objectives: The aim of this pilot study was to compare clinical examination (CE) and ultrasound (US) with high field MRI (as the reference standard) for the detection of rearfoot and midtarsal joint synovitis and secondly tenosynovitis of the ankle tendons in patients with established rheumatoid arthritis (RA). Methods: Patients with RA (as determined by the modified American College of Rheumatology (ACR) criteria) with symptoms of midfoot and rearfoot disease were recruited. Demographic data were collected. All underwent CE, US and high field MRI (with intravenous gadolinium contrast) of their right foot. Percentage exact agreement (PEA), sensitivity and specificity were calculated for CE and US when compared to MRI. Inter-reader reliability for CE and US was also assessed. Results: Compared to the gold standard of MRI, for CE (joint synovitis) the ranges for sensitivity, specificity and PEA were 55–83%, 23–46% and 46–60%, and for US were 64–89%, 60–80% and 64–78%, respectively. Compared to the gold standard of MRI, for CE (tenosynovitis) the ranges for sensitivity, specificity and PEA were 0–100%, 20–91% and 55–91%, and for US were 0–67%, 86–100% and 59–86%, respectively. Conclusion: CE was sensitive but US more specific in identifying hindfoot pathology in RA when compared to the reference standard of MRI. There was poor interobserver variability between ultrasonographers suggesting a need for standardisation of acquisition and interpretation of US images of the hindfoot.

Development and Preliminary Validation of a Magnetic Resonance Imaging Joint Space Narrowing Score for Use in Rheumatoid Arthritis: Potential Adjunct to the OMERACT RA MRI Scoring System

Objective. To develop and validate a magnetic resonance imaging (MRI) method of assessment of joint space narrowing (JSN) in rheumatoid arthritis (RA). Methods. Phase A: JSN was scored 0–4 on MR images of 5 RA patients and 3 controls at 15 wrist sites and 2nd–5th metacarpophalangeal (MCP) joints by 8 readers (7 once, one twice), using a preliminary scoring system. Phase B: Image review, discussion, and consensus on JSN definition, and revised scoring system. Phase C: MR images of 15 RA patients and 4 controls were scored using revised system by 5 readers (4 once, one twice), and results compared with radiographs [Sharp-van der Heijde (SvdH) method]. Results. Phase A: Intraobserver agreement: intraclass correlation coefficient (ICC) = 0.99; smallest detectable difference (SDD, for mean of readings) = 2.8 JSN units (4.9% of observed maximal score). Interobserver agreement: ICC = 0.93; SDD = 6.4 JSN units (9.9%). Phase B: Agreement was reached on JSN definition (reduced joint space width compared to normal, as assessed in a slice perpendicular to the joint surface), and revised scoring system (0–4 at 17 wrist sites and 2nd–5th MCP; 0: none; 1: 1–33%; 2: 34–66%; 3: 67–99%; 4: ankylosis). Phase C: Intraobserver agreement: ICC = 0.90; SDD = 6.8 JSN units (11.0%). Interobserver agreement: ICC = 0.92 and SDD = 6.2 JSN units (8.7%). The correlation (ICC) with the SvdH radiographic JSN score of the wrist/hand was 0.77. Simplified approaches evaluating fewer joint spaces demonstrated similar reliability and correlation with radiographic scores. Conclusion. An MRI scoring system of JSN in RA wrist and MCP joints was developed and showed construct validity and good intra- and interreader agreements. The system may, after further validation in longitudinal data sets, be useful as an outcome measure in RA.

Determining a Magnetic Resonance Imaging Inflammatory Activity Acceptable State Without Subsequent Radiographic Progression in Rheumatoid Arthritis: Results from a Followup MRI Study of 254 Patients in Clinical Remission or Low Disease Activity

Objective. To assess the predictive value of magnetic resonance imaging (MRI)-detected subclinical inflammation for subsequent radiographic progression in a longitudinal study of patients with rheumatoid arthritis (RA) in clinical remission or low disease activity (LDA), and to determine cutoffs for an MRI inflammatory activity acceptable state in RA in which radiographic progression rarely occurs. Methods. Patients with RA in clinical remission [28-joint Disease Activity Score-C-reactive protein (DAS28-CRP) < 2.6, n = 185] or LDA state (2.6 ≤ DAS28-CRP < 3.2, n = 69) with longitudinal MRI and radiographic data were included from 5 cohorts (4 international centers). MRI were assessed according to the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS). Statistical analyses included an underlying conditional logistic regression model stratified per cohort, with radiographic progression as dependent variable. Results. A total of 254 patients were included in the multivariate analyses. At baseline, synovitis was observed in 95% and osteitis in 49% of patients. Radiographic progression was observed in 60 patients (24%). RAMRIS synovitis was the only independent predictive factor in multivariate analysis. ROC analysis identified a cutoff value for baseline RAMRIS synovitis score of 5 (maximum possible score 21). Rheumatoid factor (RF) status yielded a significant interaction with synovitis (p value = 0.044). RF-positive patients with a RAMRIS synovitis score of > 5 vs ≤ 5, had an OR of 4.4 (95% CI 1.72–11.4) for radiographic progression. Conclusion. High MRI synovitis score predicts radiographic progression in patients in clinical remission/LDA. A cutoff point for determining an MRI inflammatory activity acceptable state based on the RAMRIS synovitis score was established. Incorporating MRI in future remission criteria should be considered.

Is There Subclinical Synovitis in Early Psoriatic Arthritis? A Clinical Comparison With Gray‐Scale and Power Doppler Ultrasound

Arthritis activity assessments in psoriatic arthritis (PsA) have traditionally relied on tender and swollen joint counts, but in rheumatoid arthritis, multiple studies have demonstrated subclinical inflammation using modern imaging. The aim of this study was to compare clinical examination and ultrasound (US) findings in an early PsA cohort.