Publications by authors named "Jane E Freeston"

24 Publications

  • Page 1 of 1

Receptor activator of nuclear factor kappa-Β ligand (RANKL) serum levels are associated with progression to seropositive/negative rheumatoid arthritis.

Clin Exp Rheumatol 2020 Jul 21. Epub 2020 Jul 21.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and Leeds Teaching Hospitals NHS Trust, Chapel Allerton Hospital, Leeds, UK.

Objectives: The aim of this study was to establish whether serum RANKL levels in early inflammatory arthritis (IA) were associated with rheumatoid arthritis (RA) diagnosis at follow-up, and to evaluate the added value of RANKL for RA diagnosis.

Methods: Serum from 298 patients was collected. Demographic and clinical (swollen/tender joint counts, CRP, DAS28-CRP, RF, ACPA and shared-epitope data were recorded. Baseline ultrasound of 26 joints was performed, including total power Doppler (PD). An ELISA was used to measure RANKL. Predictors of progression were identified using multivariable logistic regression analysis. Area under the receiver operating characteristics (AUROC) was used to assess the performance of the prediction models and quantify the added value of RANKL in RA diagnosis.

Results: 151 patients developed RA and 147 were non-RA (undifferentiated IA, other inflammatory diagnoses or non-persistent inflammation). RANKL levels were significantly higher in RA (median [IQR]: 474.1 [270.8-1430.6]) than in non-RA (median [IQR]: 301.0 [174.1-477.5]. Three clinical factors (age, SJC and PD) were identified by multivariable logistic regression with model performance AUROC of 77.9% (95% CI 72.1-83.8%). Adding RANKL resulted in a relative increase of 6.5% in the model classification performance of an AUROC of 83.0% (95% CI 77.9-88.1%). In ACPA-negative patients, the model performance increased from 77.6% (95% CI 69.5-85.7%) with clinical data only to 81.9% (95% CI 73.7-89.8%) with added value of RANKL and imaging.

Conclusions: RANKL levels can predict RA diagnosis over clinical biomarkers alone, both seropositive and particularly in seronegative IA patients.
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July 2020

Comparing Psoriatic Arthritis Low-field Magnetic Resonance Imaging, Ultrasound, and Clinical Outcomes: Data from the TICOPA Trial.

J Rheumatol 2020 09 1;47(9):1338-1343. Epub 2019 Nov 1.

From the Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds; National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds; Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford; Bradford Teaching Hospitals Foundation Trust, Bradford; York Teaching Hospitals NHS Foundation Trust, Scarborough General Hospital, Department of Rheumatology, Scarborough, UK.

Objective: The Tight Control of inflammation in Psoriatic arthritis (TICOPA; isrctn.com: ISRCTN30147736) trial compared standard care (StdC) and tight control (TC) in early psoriatic arthritis (PsA), demonstrating better outcomes for TC. This substudy evaluated the performance metrics of modern imaging outcomes and compared them to the clinical data.

Methods: Non-contrast 0.2T magnetic resonance imaging (MRI; single hand) was assessed using the Outcomes in Rheumatology (OMERACT) PsA MRI Scoring System (PsAMRIS) with an additional global inflammation score. Ultrasound (US; same hand) was scored for greyscale, power Doppler, and erosions at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints and scores summated.

Results: Seventy-eight patients had paired (baseline and 48 weeks) US data and 61 paired MRI data; 50 had matched clinical, MR, and US data. Significant within-group changes were seen for the inflammatory PsAMRIS components at MCP level: MRI global inflammation [median difference (range), standardized response mean (SRM)]: 3.25 (-5.0 to 12.0), 0.68; 1.0 (-4.5 to 17.5), 0.45 for TC and StdC, respectively. Similar within-group differences were obtained for US: 1.0 (-13.0 to 23.0), 0.45; 3.0 (-6.0 to 21.0), 0.77 for TC and StdC, respectively. No differences were seen between treatment groups. Significant correlations were found between baseline and change MRI and US scores. A significant correlation was found between baseline PsA disease activity scores and MRI global inflammation scores (Spearman ρ for MCP, PIP: 0.46, 0.63, respectively). No differences in erosion progression were observed.

Conclusion: The PsAMRIS and US inflammation scores demonstrated good responsiveness. No between-group differences were demonstrated, but this substudy was likely underpowered to determine differences between the 2 treatment strategies.
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http://dx.doi.org/10.3899/jrheum.181385DOI Listing
September 2020

MRI inflammation of the hand interosseous tendons occurs in anti-CCP-positive at-risk individuals and may precede the development of clinical synovitis.

Ann Rheum Dis 2019 06 23;78(6):781-786. Epub 2019 Mar 23.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK

Interosseous tendon inflammation (ITI) has been described in rheumatoid arthritis (RA). Whether ITI occurs in at-risk individuals before the onset of clinical synovitis is unknown.

Objectives: To investigate, by MRI, ITI in anti-cyclic citrullinated peptide (CCP)-positive at-risk individuals (CCP +at risk) and to describe the anatomy, prevalence and clinical associations across the RA continuum.

Methods: Hand MRI was performed in 93 CCP + at risk, 47 early RA (ERA), 28 established 'late' RA (LRA) and 20 healthy controls (HC) and scored for ITI, flexor tenosynovitis (TSV) and RA MRI scoring at the metacarpophalangeal joints (MCPJs). Cadaveric and histological studies were performed to explore the anatomical basis for MRI ITI.

Results: The proportion of subjects with ITI and the number of inflamed interosseous tendons (ITs) increased along the disease continuum (p<0.001): 19% of CCP +at risk, 49% of ERA and 57% of LRA had ≥1 IT inflamed . ITI was not found in any HC. ITI was more frequently identified in tender MCPJs compared with nontender MCPJs (28% vs 12%, respectively). No IT tenosynovial sheath was identified in cadavers on dissection or histological studies suggesting MRI findings represent peritendonitis. Dye studies indicated no communication between the IT and the joint.

Conclusions: ITI occurs in CCP + at-risk individuals and can precede the onset of clinical synovitis. The ITs may be important nonsynovial extracapsular targets in the development and progression of RA.
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http://dx.doi.org/10.1136/annrheumdis-2018-214331DOI Listing
June 2019

Assessing arthritis in the context of cystic fibrosis.

Pediatr Pulmonol 2019 06 5;54(6):770-777. Epub 2019 Mar 5.

Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

Inflammatory arthritis in the context of cystic fibrosis (CF) can represent a diagnostic and therapeutic challenge. Poor recognition and under-treatment of musculoskeletal conditions increases symptom burden, affects quality of life, and may lead to changes to an individual's ability to carry out activities of daily living and to exercise. A careful assessment and multidisciplinary approach is essential when considering a diagnosis of CF-associated arthritis (CFA), both in terms of identifying other treatable conditions, such as rheumatoid arthritis, and effectively addressing symptoms. In this collaboration between CF specialists and Rheumatologists, we consider joint symptoms in patients with CF, with a focus on CFA. We offer a differential diagnosis list and consider steps to assess and manage CF patients presenting with arthralgia including appropriate up-to-date rheumatological assessment.
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http://dx.doi.org/10.1002/ppul.24290DOI Listing
June 2019

Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

Pharmacogenomics J 2018 07 25;18(4):528-538. Epub 2018 May 25.

Leeds Institute of Cancer and Pathology, University of Leeds, and NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.
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http://dx.doi.org/10.1038/s41397-018-0025-5DOI Listing
July 2018

Comorbidities in Anti-Cyclic Citrullinated Peptide Positive At-Risk Individuals Do Not Differ from Those Patients with Early Inflammatory Arthritis.

Front Med (Lausanne) 2018 19;5:35. Epub 2018 Feb 19.

Leeds Institute for Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom.

Objectives: To compare comorbidities in a cohort of cyclic citrullinated peptide (CCP) antibody positive patients without or prior to onset of inflammatory arthritis (IA) to those in patients with early IA.

Methods: Baseline data from two established cohorts were used. The first recruited people at risk of IA: CCP antibody positive cases without IA (CCP Cohort,  = 296). The second cohort [the Inflammatory Arthritis CONtinuum study (IACON)] recruited patients with early IA ( = 725). Proportions of patients with given comorbidities were compared between cohorts and then logistic regression was used to determine odds ratios (OR) for the CCP cohort having specific comorbidities, compared to IACON patients. Analyses adjusted for gender, age, smoking status, and body mass index.

Results: Patients from the CCP cohort were younger (mean age 50, compared to 53 years). The proportion of patients with at least one comorbidity was higher in the IACON than the CCP cohort: (40% compared to 24%, respectively). Results of logistic regression analyses suggested the odds of hypertension, taking a lipid-lowering agent, ischemic heart disease, cerebrovascular disease, lung disease, and diabetes were not increased in either cohort. However, patients in the CCP cohort were more likely to be taking an antidepressant (OR = 1.62, 95% CI 1.03, 2.56,  = 0.037).

Conclusion: There was no significant difference in comorbidities among people with CCP antibodies but without IA, compared to those of patients with established IA.
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http://dx.doi.org/10.3389/fmed.2018.00035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825886PMC
February 2018

Ultrasound-detectable grey scale synovitis predicts future fulfilment of the 2010 ACR/EULAR RA classification criteria in patients with new-onset undifferentiated arthritis.

RMD Open 2017 30;3(1):e000394. Epub 2017 Mar 30.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.

Objective: To determine the clinical outcomes for patients with new-onset undifferentiated arthritis (UA), not fulfilling the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) classification criteria, and the clinical and imaging predictors of disease progression in these patients.

Methods: A prospective observational study was conducted in treatment-naïve UA patients. Baseline ultrasound involved semiquantitative assessment of grey scale (GS) synovitis and power Doppler activity (PD) at 26 joints. Outcomes were fulfilment of 2010 RA criteria (joint involvement determined clinically) and initiation of methotrexate over 12 months. Cox proportional hazards analysis was used to investigate predictors of outcome.

Results: Of 60 patients, 13(22%) progressed to RA and 32(53%) ever received methotrexate. Analyses of predictors of outcome were conducted in the subgroup (n=41) of patients with complete baseline data. The presence of GS was associated with progression to RA and methotrexate use: HRs (95% CI) were 1.25(1.07 to 1.45) and 1.16(1.02 to 1.32), respectively, for the number of joints with GS≥ grade 2 after adjustment for swollen joints. PD was not predictive in the low levels at which it was observed. Progression to RA was also associated with fulfilment of the 2010 criteria using ultrasound synovitis for enumerating joint involvement, higher baseline disability and radiographic erosion.

Conclusions: This is the first report of ultrasound findings in early UA (defined by presence of clinical synovitis and non-fulfilment of 2010 RA criteria). A significant proportion of patients with UA progressed to RA and/or required methotrexate. GS synovitis was predictive of disease progression.
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http://dx.doi.org/10.1136/rmdopen-2016-000394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5387989PMC
March 2017

Abatacept reduces disease activity and ultrasound power Doppler in ACPA-negative undifferentiated arthritis: a proof-of-concept clinical and imaging study.

Rheumatology (Oxford) 2017 01 22;56(1):58-67. Epub 2016 Oct 22.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds.

Objectives: No proven treatment exists for ACPA-negative undifferentiated arthritis (UA). The aim of this study was to evaluate whether abatacept is effective in treating poor prognosis, ACPA-negative UA, including its effect on power Doppler on US (PDUS).

Methods: A proof-of-concept, open-label, prospective study of 20 patients with DMARD-naïve, ACPA-negative UA (⩾2 joint synovitis) and PDUS ⩾ 1 with clinical and 20-joint US (grey scale/PDUS) assessments at baseline, 6, 12, 18 and 24 months. All patients received 12 months of abatacept (monotherapy for minimum first 6 months). The primary end point was a composite of the proportion of patients that at 6 months achieved DAS44 remission, a maximum of one swollen joint for at least 3 consecutive months and no radiographic progression (over 0-12 months).

Results: Twenty of the 23 patients screened were enrolled [14 female; mean (sd) age 53.4 (11.2) years, symptom duration 7.5 (0.9) months]. Two (10%) achieved the composite primary end point. A reduction in the mean (sd) DAS44 was observed from a baseline value of 2.66 (0.77) to 2.01 (0.81) at 6 months and to 1.78 (0.95) at 12 months. The DAS44 remission rates were 6/20 (30%; 95% CI: 15, 51%) at 6 months and 8/20 (40%; 95% CI: 22, 62%) at 12 months. A striking decrease in the median (interquartile range; IQR) total PDUS score was noted from 10 (4-23) at baseline to 3 (2-12) and 3 (0-5) at 6 and 12 months, respectively.

Conclusion: This report is a first in potentially identifying an effective therapy, abatacept monotherapy, for poor-prognosis, ACPA-negative UA, supported by a clear reduction in PDUS. These data justify evaluation in a controlled study.
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http://dx.doi.org/10.1093/rheumatology/kew357DOI Listing
January 2017

Discordance between the predictors of clinical and imaging remission in patients with early rheumatoid arthritis in clinical practice: implications for the use of ultrasound within a treatment-to-target strategy.

Rheumatology (Oxford) 2016 07 19;55(7):1177-87. Epub 2016 Mar 19.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK

Objective: To assess the prevalence, relationship between and predictors of clinical and imaging remission in early RA, achieved with treat-to-target management in clinical practice.

Methods: A prospective observational study was conducted in patients with new-onset RA. The treatment target was remission by DAS28-CRP < 2.6. Twelve-month outcomes included DAS28-CRP remission, DAS44-CRP remission, ACR/EULAR Boolean remission (BR) and absent or absent/minimal power Doppler activity (PDA) on US of 26 joints (total PDA score = 0 or ⩽1, respectively). Logistic regression was conducted to identify baseline predictors of these outcomes.

Results: Of 105 patients with complete 12-month data, the rate of DAS28-CRP remission was 43%, DAS44-CRP remission was 39%, BR was 14%, absent PDA was 40% and absent/minimal PDA was 57%. Among patients achieving clinical remission defined by DAS28-CRP, DAS44-CRP or BR, absence of PDA was observed in 42, 44 and 40%, respectively; absent/minimal PDA was detected in 62, 66 and 67%, respectively. On multivariable analysis, shorter symptom duration, male gender, fewer tender joints and lower disability were associated with the clinical remission definitions. Lack of OA predicted absence of PDA, and lower total baseline PDA predicted absent/minimal PDA.

Conclusion: DAS28-CRP remission and absence of PDA were observed in almost half of the patients, but less than a quarter achieved both. Achievement of BR was rare. The low agreement between any of the clinical and imaging outcomes and differences in their predictors highlight the complex interaction between symptoms and synovitis, with implications for treat-to-target management. Long-term follow-up should determine the most appropriate target.
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http://dx.doi.org/10.1093/rheumatology/kew037DOI Listing
July 2016

The prevalence of tenosynovitis of the interosseous tendons of the hand in patients with rheumatoid arthritis.

Eur Radiol 2016 Feb 5;26(2):444-50. Epub 2015 Jun 5.

Musculoskeletal Radiology Department, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Aim: The aim of this study was to establish the prevalence of tenosynovitis affecting the interosseous tendons of the hand in a rheumatoid arthritis (RA) population and to assess for association with metacarpophalangeal (MCP) joint synovitis, flexor tendon tenosynovitis or ulnar drift.

Methods: Forty-four patients with RA underwent hand MRI along with 20 normal controls. Coronal 3D T1 VIBE sequences pre- and post-contrast were performed and reconstructed. The presence of interosseous tendon tenosynovitis was recorded alongside MCP joint synovitis, flexor tendon tenosynovitis and ulnar drift.

Results: Twenty-one (47.7%) patients with RA showed interosseous tendon tenosynovitis. Fifty-two (14.8%) interosseous tendons showed tenosynovitis amongst the RA patients. Interosseous tendon tenosynovitis was more commonly seen in association with adjacent MCP joint synovitis (p < 0.001), but nine MCP joints (5.1%) showed adjacent interosseous tenosynovitis in the absence of joint synovitis. Interosseous tendon tenosynovitis was more frequently seen in fingers which also showed flexor tendon tenosynovitis (p < 0.001) and in patients with ulnar drift of the fingers (p = 0.01).

Conclusion: Tenosynovitis of the hand interosseous tendons was found in 47.7% of patients with RA. In the majority of cases this was adjacent to MCP joint synovitis; however, interosseous tendon tenosynovitis was also seen in isolation.

Key Points: • Tenosynovitis of the interosseous tendons of the hand occurs in rheumatoid arthritis. • Interosseous tendon tenosynovitis has a prevalence of 47.7% in patients with RA. • Interosseous tendon tenosynovitis is related to MCP joint synovitis in the adjacent joints.
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http://dx.doi.org/10.1007/s00330-015-3859-0DOI Listing
February 2016

The specificity of ultrasound-detected bone erosions for rheumatoid arthritis.

Ann Rheum Dis 2015 May 20;74(5):897-903. Epub 2014 Jan 20.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds & NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.

Background: Bone erosion is one of the hallmarks of rheumatoid arthritis (RA), but also seen in other rheumatic diseases. The objective of this study was to determine the specificity of ultrasound (US)-detected bone erosions (including their size) in the classical 'target' joints for RA.

Methods: Patients fulfilling the diagnostic criteria for RA, psoriatic arthritis, osteoarthritis or gout in addition to healthy volunteers were included. The following areas were examined by US: distal radius and ulna, 2nd, 3rd and 5th metacarpophalangeal (MCP), 2nd and 3rd proximal interphalangeal (PIP) and 1st and 5th metatarsophalangeal (MTP) joints. All joints were scanned in four quadrants using both semiquantitative (0-3) and quantitative (erosion diameter) scoring systems.

Results: 310 subjects were recruited. The inter-reader and intrareader agreements were good to excellent. US-detected bone erosions were more frequent but not specific for RA (specificity 32.9% and sensitivity 91.4%). The presence of erosions with semiquantitative score ≥2 in four target joints (2nd, 5rd MCP, 5th MTP joints and distal ulna) was highly specific for RA (specificity 97.9% and sensitivity 41.4%). Size of erosion was found to be associated with RA. Erosions of any size in the 5th MTP joint were both specific and sensitive for RA (specificity 85.4% and sensitivity 68.6%).

Conclusions: The presence of US-detected erosions is not specific for RA. However, larger erosions in selected joints, especially 2nd and 5rd MCP, 5th MTP joints and distal ulna, were highly specific for and predictive of RA.
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http://dx.doi.org/10.1136/annrheumdis-2013-204864DOI Listing
May 2015

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.

J Rheumatol 2014 Feb 15;41(2):398-406. Epub 2013 Dec 15.

From the Department of Rheumatology, Pitie Salpetriere Hospital, APHP, Université Paris 6-UPMC, Paris, France; Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and UK National Institute for Health Research (NIHR) Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK; Department of Rheumatology, Slagelse Hospital, Slagelse, Denmark; Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway; Hull York Medical School, University of York, York, UK; Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Glostrup Hospital, Copenhagen, Denmark; and Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; St. George Hospital, University of NSW, Sydney, Australia; King Christian X's Hospital for Rheumatic Diseases, University of Southern Denmark, Odense, Denmark; and Department of Molecular Medicine and Pathology, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand.

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.
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http://dx.doi.org/10.3899/jrheum.131088DOI Listing
February 2014

Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with gray-scale and power Doppler ultrasound.

Arthritis Care Res (Hoboken) 2014 Mar;66(3):432-9

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds, UK.

Objective: 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.

Methods: Forty-nine disease-modifying antirheumatic drug-naive patients with recent-onset PsA (median disease duration 10 months) underwent gray-scale (GS) and power Doppler (PD) US of 40 joints plus tender and swollen joint counts of 68/66 joints. GS and PD were scored on a 0-3 semiquantitative scale for each joint. Clinically active joints were defined as tender and/or swollen and US active joints were defined as a GS score ≥2 and/or a PD score ≥1.

Results: The most common sites for subclinical synovitis were the wrist (30.6%), knee (21.4%), metatarsophalangeal (MTP) joints (26.5-33.7%), and metacarpophalangeal joints (10.2-19.4%). Excluding MTP joints and ankles, 37 (75.5%) of 49 patients had subclinical synovitis with a median of 3 (interquartile range [IQR] 1-4) joints involved. In contrast, clinical overestimation of synovitis occurred most commonly at the shoulder (38%) and ankle (28.6%). Twelve of 49 patients were classified clinically as having oligoarthritis; of these, subclinical synovitis identified 8 (75%) as having polyarthritis with an increase in their median joint count from 3 (IQR 1-4) to 6 (IQR 5-7).

Conclusion: This study has demonstrated that subclinical synovitis, as identified by US, is very common in early PsA and led to the majority of oligoarthritis patients being reclassified as having polyarthritis. Further research is required into the relationship of such subclinical synovitis to structural progression.
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http://dx.doi.org/10.1002/acr.22158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4282111PMC
March 2014

MRI and ultrasonography for diagnosis and monitoring of psoriatic arthritis.

Best Pract Res Clin Rheumatol 2012 Dec;26(6):805-22

Division of Rheumatic and Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, UK.

Imaging techniques such as magnetic resonance imaging (MRI) and ultrasound (US) have been increasingly used in psoriatic arthritis (PsA) providing additional clues to the pathogenesis of this peripheral, axial and dermatologic disease. This has improved our understanding of the disease and can be used to aid diagnosis and then to follow outcomes of treatment. Both imaging modalities have highlighted the differing involvement of PsA when compared with rheumatoid arthritis (RA) with a significant burden of entheseal disease, flexor tenosynovitis (occurring alone or as part of dactylitis) and other extra-capsular inflammatory changes. MRI scanning has also highlighted the link between the nail and the distal interphalangeal (DIP) joint confirming previous clinical observations. Imaging studies in psoriasis patients have discovered a high level of subclinical inflammatory change but the clinical importance of such findings has not yet been defined. The potential use of MRI and US to monitor treatment outcomes has encouraged research in this field. In MRI, the PsA MRI Score (PsAMRIS) has been developed with promising initial validation. In US, work is ongoing with the OMERACT group to define key pathologies and to develop scoring systems. A few scoring systems are available for enthesitis scoring using US which are further being developed and refined. Further improvements in technologies in both of these fields offer exciting possibilities for future research. New MRI techniques offer the chance to image previously 'dark' structures such as tendons which is key in spondyloarthritides (SpA). Sonoelastography may also improve our understanding of tendon involvement in SpA. Whole-body multi-joint MRI allows a 'snapshot' of inflammation in PsA including joints, entheses and spinal involvement. Three-dimensional US should improve reliability and comparability of US scoring reducing inter-operator variability. The latest machines offer real-time fusion imaging employing US machines with an in-built virtual navigator system linked to previous MRI acquisitions. All of these new techniques should aid our understanding of PsA and our ability to objectively measure response to therapy.
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http://dx.doi.org/10.1016/j.berh.2012.09.004DOI Listing
December 2012

Does joint position affect US findings in inflammatory arthritis?

Rheumatology (Oxford) 2012 May 16;51(5):921-5. Epub 2012 Jan 16.

Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine (LIMM), University of Leeds and NIHR Leeds Musculoskeletal Biomedical Research Unit, Second Floor, Chapel Allerton Hospital, Leeds LS7 4SA, UK.

Objective: Musculoskeletal US is being increasingly used for the assessment of synovitis, although questions remain about its reliability. One potential factor affecting reliability is the lack of consensus of image acquisition methods such as using different joint positions. This may have an implication on the reproducibility of studies that use US as an outcome measure. The aim of this study was to determine whether a change in joint position might significantly alter the quantification of US-detected synovitis in patients with inflammatory arthritis (IA).

Methods: IA patients with clinically swollen wrists, MCP and/or knee joints were recruited. These joints were assessed quantitatively for the presence of synovitis when they were placed in different positions.

Results: Seventy-five patients with IA were assessed. The greatest grey scale (GS) and power Doppler (PD) scores for the MCP joints were found in the flat (0°) position (91 and 100% of cases, respectively) compared with other positions (P < 0.001). Similar results were found in the wrist joints. The greatest GS and PD scores for the knee joint were found in 30° flexion [100 and 95.6% of cases, respectively, compared with other positions (P < 0.001)]. The inter- and intra-reader reliability was good to excellent.

Conclusion: The position in which a joint is scanned for synovitis appears to significantly influence the US assessment of synovitis. Our study suggests that the standardized scanning of the hand joints in a flat position and the knees in a 30° position are associated with the highest GS and PD scores.
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http://dx.doi.org/10.1093/rheumatology/ker383DOI Listing
May 2012

The OMERACT ultrasound task force--status and perspectives.

J Rheumatol 2011 Sep;38(9):2063-7

Hospital Universitario Severo Ochoa, Madrid, Spain.

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.
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http://dx.doi.org/10.3899/jrheum.110425DOI Listing
September 2011

Do non-steroidal anti-inflammatory drugs have a significant effect on detection and grading of ultrasound-detected synovitis in patients with rheumatoid arthritis? Results from a randomised study.

Ann Rheum Dis 2011 Oct 28;70(10):1746-51. Epub 2011 Jul 28.

Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, LS7 4SA, UK.

Objectives: To determine whether non-steroidal anti-inflammatory drugs (NSAIDs) have a significant effect on ultrasonographic (US) grey scale (GS) and power Doppler (PD) assessment of synovitis in rheumatoid arthritis (RA).

Methods: Patients with RA taking NSAIDs were randomised to either stopping (for a minimum of 5 drug half-lives) or continuing the drug. All patients had a clinical assessment and US examination of both hands and wrists before and after stopping/continuing the NSAID. Changes at follow-up were compared between groups using Mann-Whitney U tests.

Results: A total of 58 patients with RA were recruited. All the clinical assessment parameters (including disease activity, pain, general state of health and physician global visual analogue score and tender and swollen joints count) showed an increase in the group who stopped their NSAID treatment. The total GS and PD score showed median (first to third quartiles) increase of 9.5 (5.75 to 19.0) and 4.0 (2.0 to 6.0) per patient, respectively, in the patients who stopped their NSAID in comparison with 1.0 (-1.0 to 2.25) and 0.0 (-2.0 to 3.0), respectively, in the patients who continued their NSAID (p<0.001). There was an increase in the number of joints scoring >0 for GS and PD in the patients who stopped the NSAID. The inter- and intrareader agreement was good to excellent for the US examination.

Conclusion: NSAID usage may mask the GS and PD signal and result in lower scoring despite continuing disease activity. Consideration should be given to the NSAID effect in designing clinical studies which use US to assess response to therapeutic.
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http://dx.doi.org/10.1136/annrheumdis-2011-200017DOI Listing
October 2011

The OMERACT ultrasound task force -- Advances and priorities.

J Rheumatol 2009 Aug;36(8):1829-32

Université Versailles Saint Quentin en Yvelines, Service de Rhumatologie, Hôpital Ambroise Paré, Boulogne-Billancourt, France.

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.
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http://dx.doi.org/10.3899/jrheum.090354DOI Listing
August 2009

The OMERACT MRI inflammatory arthritis group: advances and future research priorities.

J Rheumatol 2009 Aug;36(8):1803-5

Section of Musculoskeletal Disease, Chapel Allerton Hospital, Leeds, UK.

The OMERACT magnetic resonance imaging (MRI) in inflammatory arthritis group previously developed the rheumatoid arthritis MRI score (RAMRIS) for use in clinical studies, evaluated the use of extremity MRI, and initiated development of a psoriatic arthritis MRI score (PsAMRIS). At OMERACT 9 the group looked at clarifications of applying the RAMRIS, and presented data from a study examining how the contrast agent gadolinium affects RAMRIS outcomes. Much of the group's effort has been aimed at the iterative development of its PsA score, and reported exercises examining this score demonstrated encouraging results, allowing subsequent presentation of a preliminary PsAMRIS. The large amount of data presented were followed by discussions with the wider audience highlighting constructive suggestions for future research priorities, including further feasibility studies, understanding imaging remission, and further improvements to PsAMRIS.
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http://dx.doi.org/10.3899/jrheum.090349DOI Listing
August 2009

The role of MRI in rheumatoid arthritis: research and clinical issues.

Curr Opin Rheumatol 2009 Mar;21(2):95-101

Chapel Allerton Hospital, University of Leeds, UK.

Purpose Of Review: This review describes the important role of MRI in rheumatoid arthritis (RA), exploring recent reliability and validity work, as well as the current use of MRI in clinical trials and practice.

Recent Findings: Both bone oedema and erosions on MRI have been confirmed as representing osteitis and cortical bone defects, respectively, adding to what was already known about the validity of contrast enhanced synovium representing synovitis. An increasing number of studies have used MRI as an outcome measure with interest moving from disease-modifying antirheumatic drugs (DMARDs) to biological therapies and a more technical focus on dynamic imaging. In addition, low-field extremity MRI has been developed as a well tolerated, comfortable and convenient method for imaging assessment in clinical practice.

Summary: This review has highlighted both recent research advances as well as the future potential for MRI in RA, with the aim that MRI will become part of standard measures for RA clinical trials. With respect to extremity imaging, further work is required to provide useful clinical algorithms.
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http://dx.doi.org/10.1097/BOR.0b013e32832498f0DOI Listing
March 2009

Using extremity magnetic resonance imaging to assess and monitor early rheumatoid arthritis: the optimal joint combination to be scanned in clinical practice.

J Rheumatol 2008 Apr 1;35(4):580-3. Epub 2008 Mar 1.

University of Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.

Objective: To identify the optimal combination for detecting erosions in early rheumatoid arthritis using extremity magnetic resonance imaging (eMRI).

Methods: In 44 patients, eMRI of 1 hand identified 77% who were erosive, 2 hands 89%, and 2 hands and feet 91%.

Results: eMRI identified 4 times as many erosions as radiography. At 6 months, eMRI of 1 hand identified an increase in erosions in 50% subjects, 2 hands in 55%, and 2 hands and feet in 55%. When only subjects with a change in erosion score above the smallest detectable difference were considered, these numbers were 30%, 25%, and 20%, respectively.

Conclusion: eMRI provides superior erosion identification compared to radiography. Imaging 2 hands can be used as a screening tool and 1 hand to monitor erosions over time.
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April 2008

A modification of the Omeract RA MRI score for erosions for use with an extremity MRI system with reduced field of view.

Ann Rheum Dis 2007 Dec 6;66(12):1669-71. Epub 2007 Jul 6.

Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK.

Objectives: To develop and test the reliability of a modified version of the OMERACT rheumatoid arthritis magnetic resonance imaging score (RAMRIS) for erosions using extremity MRI (eMRI) with reduced field of view (RAMRIS-RV).

Methods: Using a MagneVu 0.2 T machine, the preliminary RAMRIS-RV assessed erosions in metacarpophalangeal (MCP) joints 2-3, bases of metacarpal (MC) 2-5, and all wrist bones excluding base MC 1, pisiform and trapezium. T1 weighted images of >/=500 MCP and wrist bony sites from a mixed severity RA and control cohort were evaluated. An inter-reader reliability study evaluating 300 wrist and 160 MCP bony sites was then performed.

Results: Mean per cent exact (and close) agreement results were as follows: MCP proximal sites 83.5 (96.2), MCP distal 54.4 (77.2), bases MC 2-4 85.2 (96.7), carpal bones 79.0 (92.1), distal radius/ulna 66.4 (87.8). The base of MCP 5 was visualised in
Conclusions: The RAMRIS-RV is a practical tool that can be used with eMRI with a reduced field of view. This study shows excellent inter-reader reliability for erosion assessment, albeit in a reduced number of bony sites.
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http://dx.doi.org/10.1136/ard.2007.072561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095331PMC
December 2007

The future of imaging in monitoring biologic therapy.

Nat Clin Pract Rheumatol 2007 Jan;3(1):2-3

Leeds Teaching Hospital, Leeds, UK.

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http://dx.doi.org/10.1038/ncprheum0381DOI Listing
January 2007