The usefulness of ultrasound in predicting outcomes in patients with shoulder pain: a prospective observational study.

OBJECTIVES: Shoulder pain is common but current clinical classification has limited utility. We aimed to determine whether groups of ultrasound-based shoulder pathologies exist and to evaluate outcomes according to identified groups and individual pathologies. METHODS: Prospective study of a community-based cohort with shoulder pain referred for their first ultrasound scan at a single radiology unit, with subsequent routine clinical care. Patient-reported outcomes were collected at baseline, 2 weeks and 6 months; standardised ultrasound reporting was employed. Latent class analysis (LCA) identified ultrasound pathology-based groups. Multiple linear regression analysis explored associations between baseline pathologies, subsequent treatment and shoulder pain and disability index (SPADI). Short-term response to corticosteroid injections was investigated. RESULTS: Of 500 participants (mean age 53.6; 52% female), 330 completed follow-up. LCA identified 4 groups: bursitis with (33%) or without (27%) acromioclavicular joint degeneration, rotator cuff tear (21%), no bursitis/tear (19%). Total SPADI was higher at baseline for cuff tears (mean 55.1 vs 49.7-51.3; overall p= 0.005), but accounting for this, groups did not differ at 6 months (43.5 vs 38.5-40.5; p= 0.379). Baseline SPADI was the only predictor of 6-month SPADI retained by penalised modelling; neither LCA-derived US groups nor individual pathologies were selected. Response to baseline injection at week 2 did not differ between groups (mean SPADI 40.1-43.8; p= 0.423). CONCLUSION: Ultrasound-based classification (groups or individual pathologies) of shoulder pain did not predict medium-term outcomes using current treatments. The role of routine diagnostic ultrasound for shoulder pain needs consideration; it may be useful if evidence-based therapies for specific pathologies are established.

Muscle deterioration due to rheumatoid arthritis: assessment by quantitative MRI and strength testing.

OBJECTIVES: RA patients often present with low muscle mass and decreased strength. Quantitative MRI offers a non-invasive measurement of muscle status. This study assessed whether MRI-based measurements of T2, fat fraction, diffusion tensor imaging and muscle volume can detect differences between the thigh muscles of RA patients and healthy controls, and assessed the muscle phenotype of different disease stages. METHODS: Thirty-nine RA patients (13 'new RA'-newly diagnosed, treatment naïve, 13 'active RA'-persistent DAS28 >3.2 for >1 year, 13 'remission RA'-persistent DAS28 <2.6 for >1 year) and 13 age and gender directly matched healthy controls had an MRI scan of their dominant thigh. All participants had knee extension and flexion torque and grip strength measured. RESULTS: MRI T2 and fat fraction were higher in the three groups of RA patients compared with healthy controls in the thigh muscles. There were no clinically meaningful differences in the mean diffusivity. The muscle volume, handgrip strength, knee extension and flexion were lower in all three groups of RA patients compared with healthy controls. CONCLUSION: Quantitative MRI and muscle strength measurements can potentially detect differences within the muscles between RA patients and healthy controls. These differences may be seen in RA patients who are yet to start treatment, those with persistent active disease, and those who were in clinical remission. This suggests that the muscles in RA patients are affected in the early stages of the disease and that signs of muscle pathology and muscle weakness are still observed in clinical remission.

Ultrasound to identify systemic lupus erythematosus patients with musculoskeletal symptoms who respond best to therapy: the US Evaluation For mUsculoskeletal Lupus longitudinal multicentre study.

OBJECTIVES: To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of clinical features predicting US synovitis/tenosynovitis. METHODS: In a longitudinal multicentre study, SLE patients with physician-diagnosed inflammatory joint pain received intramuscular methylprednisolone 120 mg once. Clinical assessments, patient-reported outcomes and bilateral hand/wrist USs were collected at 0, 2 and 6 weeks. The primary outcome (determined via internal pilot) was the early morning stiffness visual analogue scale (EMS-VAS) at 2 weeks, adjusted for baseline, comparing patients with positive (greyscale ≥2 and/or power Doppler ≥1) and negative US. Post hoc analyses excluded FM. RESULTS: Of 133 patients, 78 had a positive US. Only 53 (68%) of these had one or more swollen joint. Of 66 patients with one or more swollen joint, 20% had a negative US. A positive US was associated with joint swelling, symmetrical small joint distribution and serology. The primary endpoint was not met: in the full analysis set (N = 133) there was no difference in baseline-adjusted EMS-VAS at week 2 [-7.7 mm (95% CI -19.0, 3.5); P = 0.178]. After excluding 32 patients with FM, response was significantly better in patients with a positive US at baseline [baseline-adjusted EMS-VAS at 2 weeks -12.1 mm (95% CI -22.2, -0.1); P = 0.049]. This difference was greater when adjusted for treatment [-12.8 mm (95% CI -22, -3); P = 0.007]. BILAG and SLEDAI responses were higher in US-positive patients. CONCLUSION: In SLE patients without FM, those with a positive US had a better clinical response to therapy. Imaging-detected synovitis/tenosynovitis may be considered to decide on therapy and enrich clinical trials.

Pragmatic randomised controlled trial of very early etanercept and MTX versus MTX with delayed etanercept in RA: the VEDERA trial.

OBJECTIVES: We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX. METHODS: Pragmatic, open-label, randomised controlled trial of treatment-naïve ERA (≤12 months symptom), Disease Activity Score 28 joint (DAS28)-erythrocyte sedimentation rate (ESR) ≥3.2, rheumatoid factor (RF)+/-anticitrullinated peptide antibody (ACPA) positive or ultrasound power Doppler (PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR ≥2.6 and intramuscular corticosteroid at protocolised time points. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints. RESULTS: We randomised 120 patients, 60 to each arm (71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3 (13.1, 30.8) weeks; mean (SD) DAS28 5.1 (1.1)). Remission rates with ETN+MTX and MTX-TT, respectively, were 38% vs 33% at week 24; 52% vs 38% at week 48 (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211). Greater, sustained DAS28-ESR remission observed with ETN+MTX versus MTX-TT (42% and 27%, respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR 2.84, 95% CI 0.8 to 9.6) of achieving remission after 24 weeks of ETN administered first line compared with administered post-MTX. CONCLUSIONS: Compared with remission rates typically reported with first-line tumour necrosis factor inhabitor+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested. Trial registration number NCT02433184.

Investigating the patient acceptable symptom state cut-offs: longitudinal data from a community cohort using the shoulder pain and disability index.

This prospective study aimed to determine the patient acceptable symptom state (PASS) cut-off for the patient reported outcome measure shoulder pain and disability index (SPADI), and evaluate predictors of PASS achievement following standard shoulder care. Patients with shoulder pain, referred for shoulder ultrasound were recruited from a community cohort. Patients completed both SPADI (scored 0-130) and a question on symptom state and followed-up at 6 months. PASS was calculated from Rasch-transformed scores using 2 methods: the 75th percentile of the cumulative response curve and the receiver operating characteristic curve (ROC). Logistic regression was used to identify factors associated with PASS. 304 participants (169 females, mean age 57.2 years) were included. At 6 months, 193 (63%) reported PASS. The association between SPADI at 6 months and PASS depended on baseline SPADI (interaction p = 0.036). Those with higher baseline scores had higher 6 months PASS cut-offs. Using the 75th percentile method, the 6 months total SPADI cut-off was 49.2 in those starting in the highest tertile at baseline compared to 39.4 in the lowest tertile: 46.4 vs. 36.7 for pain, 46.8 vs. 25.1 for disability. The ROC method yielded similar results. We have shown for the first time that the PASS cut-off for SPADI is dependent on baseline severity scores. Understanding the SPADI PASS threshold is important for clinical research to allow standardised reporting of shoulder intervention success at the patient level.

Inter- and intra-reader reproducibility of shear wave elastography measurements for musculoskeletal soft tissue masses.

OBJECTIVE: To determine inter- and intra-reader reproducibility of shear wave elastography measurements for musculoskeletal soft tissue masses. MATERIALS AND METHODS: In all, 64 patients with musculoskeletal soft tissue masses were scanned by two readers prior to biopsy; each taking five measurements of shear wave velocity (m/s) and stiffness (kPa). A single lesion per patient was scanned in transverse and cranio-caudal planes. Depth measurements (cm) and volume (cm3) were recorded for each lesion, for each reader. Linear mixed modelling was performed to assess limits of agreement (LOA), inter- and intra-reader repeatability, including analyses for measured depth and volume. RESULTS: Of the 64 lesions scanned, 24 (38%) were malignant. Bland-Altman plots demonstrated negligible bias with wide LOA for all measurements. Transverse velocity was the most reliable measure-intraclass correlation (95% CI) = 0.917 (0.886, 1)-though reader 1 measures could be between 38% lower and 57% higher than reader 2 [ratio-scale bias (95% LOA) = 0.99 (0.64, 1.55)]. Repeatability coefficients indicated most disagreement resulted from poor within-reader reproducibility. LOA between readers calculated from means of five repeated measurements were narrower-transverse velocity ratio-scale bias (95% LOA) = 1.00 (0.74, 1.35). Depth affected both estimated velocity and repeatability; volume also affected repeatability. CONCLUSION: This study found poor repeatability of measurements with wide LOA due mostly to intra-reader variability. Transverse velocity was the most reliable measure; variability may be affected by lesion depth. At least five measurements should be reported with LOA to assist future comparability between shear wave elastography systems in evaluating soft tissue masses.

Shear-Wave Elastography of Benign versus Malignant Musculoskeletal Soft-Tissue Masses: Comparison with Conventional US and MRI.

Purpose To examine if shear-wave elastography (SWE) improves the accuracy of diagnosing soft-tissue masses as benign or malignant compared with US alone or in combination with MRI. Materials and Methods Two hundred six consecutive adult participants (mean age, 57.7 years; range, 18-91 years), including 89 men (median age, 56.0 years; range, 21-91 years) and 117 women (median age, 59.1 years; range, 18-88 years), who were referred for biopsy of a soft-tissue mass were prospectively recruited from December 2015 through March 2017. Participants underwent B-mode US, MRI, and SWE prior to biopsy. Three musculoskeletal radiologists independently reviewed US images alone, followed by US and MRI images together, and classified lesions as benign, probably benign, probably malignant, or malignant. For SWE, the area under the receiver operating characteristic (ROC) curve (AUC) was calculated for transverse shear-wave velocity (SWV). Multivariable logistic regression was used to investigate the association between SWE and malignancy alongside individual demographic and imaging variables. Results At histologic examination, 79 of 206 (38%) participants had malignant lesions. SWV showed good diagnostic accuracy for lesions classified as benign or probably benign by US alone (AUC = 0.87 [95% confidence interval {CI}: 0.79, 0.95]). SWV did not provide substantive diagnostic information for lesions classified as probably malignant or malignant, whether the classification was made with or without MRI. However, multivariable modeling indicated that diagnostic accuracy may vary by lesion position (interaction P = .02; superficial, odds ratio [OR] = 17.7 [95% CI: 1.50, 207], P = .02; deep/mixed, OR = 0.24 [95% CI: 0.07, 0.86], P = .03) and participant age (interaction P = .01; eg, age 43 years, OR = 0.72 [95% CI: 0.15, 3.5], P = .69; age 72 years, OR = 0.08 [95% CI: 0.02, 0.37], P = .001). Conclusion Shear-wave elastography can increase accuracy of soft-tissue lesion diagnosis in conjunction with US. However, a single cut-off may not be universally applicable with diagnostic accuracy that is affected by lesion position and patient age. © RSNA, 2018 Online supplemental material is available for this article.

Defining inflammatory musculoskeletal manifestations in systemic lupus erythematosus.

Objective: To define the prevalence and clinical associations of clinical and imaging definitions of synovitis in unselected SLE patients with musculoskeletal (MSK) symptoms. Methods: 112 patients with SLE (excluding RF and CCP positive patients); 88 consecutive with inflammatory MSK symptoms and 24 asymptomatic SLE controls were recruited. Patients had clinical assessment (BILAG, SLEDAI, joint counts, patient and physician visual analogue score), routine laboratory tests and US of two hands and wrists (synovitis and tenosynovitis, OMERACT definitions). Results: Overall, 68% (60/88) of symptomatic patients had US inflammation (grey scale ⩾ 2 and/or PD ⩾ 1 or tenosynovitis) compared with 17% (4/23) of asymptomatic patients. In symptomatic patients, clinical inflammation was seen defined by BILAG A or B in 38% (34/88) or defined by the SLEDAI-MSK criterion in 32% (28/88). BILAG A/B had sensitivity (95% CI) of 56% (41, 69%) and specificity of 89% (72, 96%) for US-confirmed inflammation. SLEDAI-MSK criterion had sensitivity of 44% (31, 59%) and specificity of 89% (72, 96%). In patients with inflammatory symptoms, 27% (24/88) had subclinical inflammation (abnormal US but no clinically swollen joints) and 35% (31/88) had no clinical or US inflammation. Subclinical tenosynovitis and PD were associated with significantly higher IgG, physician visual analogue score, tender joint count. Conclusion: In SLE patients with MSK symptoms, a large proportion of objective, clinically meaningful inflammation is only identifiable by US. The existing classification of MSK SLE using disease activity instruments based on joint swelling is inaccurate to guide patient selection for clinical trials, biologic therapy, or treat-to-target protocols.

Validity of a two-component imaging-derived disease activity score for improved assessment of synovitis in early rheumatoid arthritis.

OBJECTIVES: Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis. METHODS: Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients). RESULTS: Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood <-2.6, P < 0.01), Larsen score and presence of erosions. CONCLUSION: A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.

Muscle shear wave elastography in idiopathic inflammatory myopathies: a case-control study with MRI correlation.

OBJECTIVE: To investigate muscle stiffness in patients with idiopathic inflammatory myopathies (IIM) using shear wave elastography (SWE) and to correlate the results with muscle strength and MRI features of myositis. MATERIALS AND METHODS: Muscle shear wave velocity (SWV) was measured in 23 active IIM patients (13 females, mean age 50.4 ± 16.1 years) and 23 matched healthy controls (13 females, mean age 50.7 ± 16.2 years). The investigated muscles included the vastus lateralis (VL), rectus femoris (RF), vastus medialis (VM) vastus intermedius (VI), biceps femoris (BF), semitendinosus (ST), semimembranosus (SM) and the biceps brachii (BB) scanned during relaxed resting and passive stretching positions. Participants performed multiple tests to evaluate their muscle strength. IIM patients had a thigh MRI to assess degrees of oedema, fatty infiltration and atrophy. RESULTS: In the resting position, IIM patients had a 12.9-22.2% significantly lower SWV (p < 0.05) for the quadriceps and hamstrings, but not BB. There was no difference during passive stretching. The SWV for VL, VI and BF showed moderate correlations with the muscle strength tests ranging from r = 0.47 to r = 0.70 (all p < 0.05). Lower SWV was associated with greater MRI scores of oedema (p = 0.001) and atrophy (p = 0.006). However, SWV did not correlate with fatty infiltration (r < 0.3; p = 0.28), creatine kinase (r = 0.28; p = 0.19) or disease duration (r = 0.26; p = 0.24). CONCLUSION: Shear wave elastography may detect abnormal reduced thigh stiffness in IIM patients. SWE measurements were significantly associated with muscle weakness and MRI signs of oedema and atrophy. Future research should investigate this new technology for monitoring disease activity.

Prediction of autoimmune connective tissue disease in an at-risk cohort: prognostic value of a novel two-score system for interferon status.

OBJECTIVE: To evaluate clinical, interferon and imaging predictors of progression from 'At Risk' to autoimmune connective tissue diseases (AI-CTDs). METHODS: A prospective observational study was conducted in At-Risk of AI-CTD (defined as antinuclear antibody (ANA) positive; ≤1 clinical systemic lupus erythematosus (SLE) criterion; symptom duration <12 months and treatment-naïve). Bloods and skin biopsy (non-lesional) were analysed for two interferon-stimulated gene expression scores previously described (IFN-Score-A and IFN-Score-B). Forty-nine healthy controls (HCs) and 114 SLE were used as negative and positive controls. Musculoskeletal ultrasound was performed. Progression was defined by meeting classification criteria for AI-CTDs at 12 months. RESULTS: 118 individuals with 12-month follow-up were included. Of these, 19/118 (16%) progressed to AI-CTD (SLE=14, primary Sjogren's=5). At baseline, both IFN scores differed among At-Risk, HCs and SLE groups (p<0.001) and both were elevated in At-Risk who progressed to AI-CTD at 12 months versus non-progressors, to a greater extent for IFN-Score-B (fold difference (95% CI) 3.22 (1.74 to 5.95), p<0.001) than IFN-Score-A (2.94 (1.14 to 7.54); p=0.018). Progressors did not have significantly greater baseline clinical characteristics or ultrasound findings. Fold difference between At-Risk and HCs for IFN-Score-A was markedly greater in skin than blood. In multivariable logistic regression, only family history of autoimmune rheumatic disease, OR 8.2 (95% CI 1.58 to 42.53) and IFN-Score-B, 3.79 (1.50-9.58) increased the odds of progression. CONCLUSION: A two-factor interferon score and family history predict progression from ANA positivity to AI-CTD. These interferon scores may allow stratification of individuals At-Risk of AI-CTD permitting early intervention for disease prevention and avoid irreversible organ damage.

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

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.

The GOLMePsA study protocol: an investigator-initiated, double-blind, parallel-group, randomised, controlled trial of GOLimumab and methotrexate versus methotrexate in early diagnosed psoriatic arthritis using clinical and whole body MRI outcomes.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis which impacts significantly on the quality of life and work capacity of affected individuals. Recent evidence has shown that early control of inflammation in PsA leads to improved long-term outcomes. It is postulated that prompt intervention after diagnosis using a remission-induction treatment strategy will lead to improved outcomes and optimal disease control of PsA. The aim of the present study was to compare the clinical efficacy of a treatment strategy in newly diagnosed, treatment naïve PsA subjects, using the combination of golimumab (GOL), methotrexate (MTX) and steroids versus standard care (MTX monotherapy plus steroids). METHODS/DESIGN: GOLMePsA is an investigator initiated, phase IIIb, single-centre, randomised, double-blind, placebo-controlled, two-armed, parallel-group, imaging-supplemented study. Eighty-eight PsA patients, diagnosed within 24 months prior to screening and treatment naïve, will be randomised at baseline to receive: (arm 1) the combination of intramuscular/intra-articular prednisolone, MTX and GOL or (arm 2) the combination of intramuscular/intra-articular prednisolone, MTX and placebo for 24 weeks (interventional period). Primary outcome measure is clinical improvement (at least 1 unit difference) in the Psoriatic ArthritiS Disease Activity Score (PASDAS) composite index. Reflecting a "step down" therapeutic approach, all participants successfully completing the interventional period will be followed up for a further 28 weeks. During this observational period, stable maintenance MTX monotherapy will continue for both arms, unless in case of intolerance or PsA relapse. In the latter case, additional treatment will be provided. Overall, the GOLMePsA study length is planned to be 52 weeks. DISCUSSION: The hypothesis underlining this study is that very early treatment with first-line GOL reduces disease activity in PsA, in comparison to conventional therapy. TRIAL REGISTRATION: EudraCT 2013-004122-28 . 24/09/2013.

Plantar plate pathology is associated with erosive disease in the painful forefoot of patients with rheumatoid arthritis.

BACKGROUND: Disease-related foot pathology is recognised to have a significant impact on mobility and functional capacity in the majority of patients with rheumatoid arthritis (RA). The forefoot is widely affected and the metatarsophalangeal (MTP) joints are the most common site of symptoms. The plantar plates are the fibrocartilaginous distal attachments of the plantar fascia inserting into the five proximal phalanges. Together with the transverse metatarsal ligament they prevent splaying of the forefoot and subluxation of the MTP joints. Damage to the plantar plates is a plausible mechanism therefore, through which the forefoot presentation, commonly described as 'walking on pebbles', may develop in patients with RA. The aims of this study were to investigate the relationship between plantar plate pathology and clinical, biomechanical and plain radiography findings in the painful forefoot of patients with RA. Secondly, to compare plantar plate pathology at the symptomatic lesser (2nd-5th) MTP joints in patients with RA, with a group of healthy age and gender matched control subjects without foot pain. METHODS: In 41 patients with RA and ten control subjects the forefoot was imaged using 3T MRI. Intermediate weighted fat-suppressed sagittal and short axis sequences were acquired through the lesser MTP joints. Images were read prospectively by two radiologists and consensus reached. Plantar plate pathology in patients with RA was compared with control subjects. Multivariable multilevel modelling was used to assess the association between plantar plate pathology and the clinical, biomechanical and plain radiography findings. RESULTS: There were significant differences between control subjects and patients with RA in the presence of plantar plate pathology at the lesser MTP joints. No substantive or statistically significant associations were found between plantar plate pathology and clinical and biomechanical findings. The presence of plantar plate pathology was independently associated with an increase in the odds of erosion (OR = 52.50 [8.38-326.97], p < 0.001). CONCLUSION: The distribution of plantar plate pathology at the lesser MTP joints in healthy control subjects differs to that seen in patients with RA who have the consequence of inflammatory disease in the forefoot. Longitudinal follow-up is required to determine the mechanism and presentation of plantar plate pathology in the painful forefoot of patients with RA.

Enriching case selection for imminent RA: the use of anti-CCP antibodies in individuals with new non-specific musculoskeletal symptoms - a cohort study.

OBJECTIVES: Around 1% of the population test positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies. This biomarker predicts the progression to rheumatoid arthritis (RA) but over a variable time frame. To increase its clinical relevance, this study sought to determine (1) if the proportion of anti-CCP-positive individuals could be enriched by case selection of people attending primary care with new non-specific musculoskeletal (MSK) symptoms but without clinical synovitis (CS) and (2) whether these individuals progress rapidly to inflammatory arthritis (IA), in particular RA. METHODS: In this prospective cohort study, individuals aged ≥18 years with new non-specific MSK symptoms, without CS, were recruited from primary care in the UK. Anti-CCP-positive individuals were invited for follow-up in the rheumatology department, Leeds. Those who tested negative were sent questionnaires 12 months later. RESULTS: 2028 individuals were recruited. Of these, 2.8% (57/2028) were anti-CCP positive, of whom 47% (27/57) developed IA - 24 RA, 1 undifferentiated IA (UIA), 2 polymyositis; 92.6% (25/27) within 12 months, median 1.8 months (IQR 1.0-4.3, range 0.3-16.1). Of the anti-CCP-negative individuals, 1.3% (20/1559) developed IA (1 UIA, 13 RA, 6 psoriatic arthritis); 75% (15/20) within 12 months. The relative risk for developing RA within 12 months in the anti-CCP-positive group was 66.8 (95% CI 32.2 to 138.4, p<0.001); for IA, it was 45.5 (95% CI 25.4 to 81.6, p<0.001). CONCLUSIONS: Selecting individuals with new non-specific MSK symptoms without CS enriched the prevalence of anti-CCP positivity to 2.8%. Those who tested positive had a high risk of rapidly developing RA. The cost-effectiveness of this approach will need to be determined. TRIAL REGISTRATION NUMBER: NCT02012764.

Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis.

OBJECTIVES: To determine whether ultrasound can identify anti-cyclic citrullinated peptide (anti-CCP) antibody-positive patients without clinical synovitis (CS) who progress to inflammatory arthritis (IA). METHODS: In a prospective study, anti-CCP-positive patients without CS underwent ultrasound imaging of 32 joints (wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints (MTPs)) and were monitored for the development of IA. Associations between baseline ultrasound findings (grey scale (GS), power Doppler (PD) and erosions) and (1) progression to IA and (2) development of CS within an individual joint were measured. RESULTS: Consecutive anti-CCP-positive patients (n=136; mean age 51 years, 100 women) were followed up for median of 18.3 months (range 0.1-79.6). At baseline 96% had GS, 30% had PD and 21% had one or more erosions. IA developed in 57 patients (42%) after median of 8.6 months (range 0.1-52.4). Ultrasound abnormalities (GS ≥2, PD ≥1 or erosion ≥1) were found in 86% at baseline compared with 67% of non-progressors (χ2=6.3, p=0.012). Progression to IA was significantly higher in those with ultrasound findings in any joint (excluding MTPs for GS) (GS ≥2: 55% vs 24%, HR (95% CI) 2.3 (1.0 to 4.9), p=0.038; PD ≥2: 75% vs 32%, 3.7 (2.0 to 6.9), p<0.001 and erosion ≥1: 71% vs 34%, 2.9 (1.7 to 5.1), p<0.001). Furthermore, progression occurred earlier with PD ≥2 (median 7.1 vs 52.4 months) and erosion ≥1 (15.4 vs 46.5). At the individual joint level, the trend for progression to CS was more significant for GS and PD (GS ≥2: 26% vs 3%, 9.4 (5.1 to 17.5), p<0.001; PD ≥2: 55% vs 4%, 31.3 (15.6 to 62.9), p<0.001). CONCLUSION: Ultrasound features of joint inflammation may be detected in anti-CCP-positive patients without CS. Ultrasound findings predict progression (and rate of progression) to IA, with the risk of progression highest in those with PD signal. TRIAL REGISTRATION NUMBER: NCT02012764; Results.

The relationship between three-dimensional knee MRI bone shape and total knee replacement-a case control study: data from the Osteoarthritis Initiative.

OBJECTIVE: There is growing understanding of the importance of bone in OA. Our aim was to determine the relationship between 3D MRI bone shape and total knee replacement (TKR). METHODS: A nested case-control study within the Osteoarthritis Initiative cohort identified case knees with confirmed TKR for OA and controls that were matched using propensity scores. Active appearance modelling quantification of the bone shape of all knee bones identified vectors between knees having or not having OA. Vectors were scaled such that -1 and +1 represented the mean non-OA and mean OA shapes. RESULTS: Compared to controls (n = 310), TKR cases (n = 310) had a more positive mean baseline 3D bone shape vector, indicating more advanced structural OA, for the femur [mean 0.98 vs -0.11; difference (95% CI) 1.10 (0.88, 1.31)], tibia [mean 0.86 vs -0.07; difference (95% CI) 0.94 (0.72, 1.16)] and patella [mean 0.95 vs 0.03; difference (95% CI) 0.92 (0.65, 1.20)]. Odds ratios (95% CI) for TKR per normalized unit of 3D bone shape vector for the femur, tibia and patella were: 1.85 (1.59, 2.16), 1.64 (1.42, 1.89) and 1.36 (1.22, 1.50), respectively, all P < 0.001. After including Kellgren-Lawrence grade in a multivariable analysis, only the femur 3D shape vector remained significantly associated with TKR [odds ratio 1.24 (1.02, 1.51)]. CONCLUSION: 3D bone shape was associated with the endpoint of this study, TKR, with femoral shape being most associated. This study contributes to the validation of quantitative MRI bone biomarkers for OA structure-modification trials.

Improvement in insulin resistance is greater when infliximab is added to methotrexate during intensive treatment of early rheumatoid arthritis-results from the IDEA study.

OBJECTIVES: To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies. METHODS: Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy. Homeostasis model assessment-estimated IR (HOMA-IR) (glucose*insulin/405) was used to measure IR. Multiple imputation was employed, and linear regression analyses were adjusted for baseline values. RESULTS: Changes in DAS44-CRP did not differ between the treatment arms at weeks 26 and 78. Mean TC/HDL-C, HOMA-IR and NT-proBNP improved in both groups at weeks 26 and 78, although change in NT-proBNP was not statistically significant at week 78. Changes in TC/HDL-C and NT-proBNP were similar between treatment arms, but HOMA-IR values in the IFX + MTX arm were 42% lower than those treated with MTX + methylprednisolone at week 78 (P = 0.003); the difference remained significant after adjustment for baseline BMI, ACPA positivity, smoking status and intramuscular glucocorticoid use (P = 0.007). CONCLUSION: When implementing a treat-to-target approach, treatment of early RA was associated with improvement in TC/HDL-C, HOMA-IR and NT-proBNP, and a greater long-term improvement in HOMA-IR was seen in those treated with IFX. TRIAL REGISTRATION: EU Clinical Trials Register, http://www.clinicaltrialsregister.eu, Eudract-2005-005013-37; ISRTCNregisrty, http://www.isrctn.com, ISRCTN48638981.

Sonoelastography of Musculoskeletal Soft Tissue Masses: A Pilot Study of Quantitative Evaluation.

OBJECTIVES: To evaluate quantitative sonoelastography of benign and malignant musculoskeletal soft tissue masses. METHODS: We conducted a prospective study of 50 patients from a specialist sarcoma center who had extremity soft tissue masses referred for biopsy. After consent, the quantitative shear wave velocity (meters per second) was measured in longitudinal and transverse planes (3 readings in each plane and mean calculated). All masses subsequently underwent biopsy, excision, or both, with the histologic diagnosis taken as the reference standard. At a subsequent sitting, all anonymized B-mode sonograms were scored independently by 2 radiologists as benign or malignant with agreement by consensus if necessary. RESULTS: Of the 50 masses, 15 were malignant and 35 benign. Nine masses had incomplete velocity readings. Intraclass correlation coefficients for intra-reader reliability of velocity measurements were highly repeatable. There was preliminary evidence that the longitudinal shear wave velocity of malignant masses was on average 30% slower than that of benign masses (P< .10). Longitudinal and transverse shear wave measurements were moderately associated with each other (P = .003). There was no evidence that shear wave velocity varied with patient age, sex, or mass volume. For B-mode assessment of malignancy, sensitivity (Wilson 90% confidence interval) was 73.3% (52.1%, 87.4%), and specificity was 77.1% (63.8%, 86.6%). Interobserver agreement was substantial (κ= 0.86). Four of 15 malignant masses (26.6%) were incorrectly classified as benign on B-mode assessment (all grade 1 liposarcomas). CONCLUSIONS: These data suggest that shear wave velocity measurement is reproducible and that malignant masses may have slower longitudinal shear wave velocities than benign masses. The sample size of this pilot study precludes adjusted analysis but should form the basis for larger study designs.

The clinical characteristics of older people with chronic multiple-site joint pains and their utilisation of therapeutic interventions: data from a prospective cohort study.

BACKGROUND: Chronic multiple-site joint pain (MSJP) is common in older people and associated with poor outcomes, yet under-researched. Our aim was to detail the clinical characteristics of people with MSJP and their utilisation of therapies. METHODS: MSJP was defined as pain in at least one large joint and one other joint for >6 weeks in the last three months. A mixed community, primary and secondary care cohort of people >50 years old underwent detailed history and examination by a single clinician. Treatment utilisation was recorded comprehensively. RESULTS: 201 adults were recruited, 82% women, mean age 63, BMI 31 kg/m(2). Median number of painful joints per patient was 6 (IQR 4-9; range 2-17); most common painful sites were knee (84%), lower back (62%) and shoulder (47%). 194/201 (96%) had an osteoarthritis (OA) diagnosis, 155/194 (80%) also had soft tissue pathology and 72% had back problems. 85% had OA at multiple sites. Upper and lower limb weakness was common (90 and 77% respectively). Lower limb weakness was significantly associated with obesity. Only 26% had received written information about their joints. Though 79% had attended physiotherapy, the majority (93%) had muscle weakness. Only 36 % of overweight participants had accessed weight-loss support. Half of those with foot pain had seen a podiatrist or used appliances. Multiple concurrent pharmacological therapies were used by 47%. CONCLUSION: MSJP represents a combination of OA, back pain and soft tissue disorders; muscle weakness is extremely common. Therapies appear underutilised in people with MJSP. Identifying the reasons for this should guide effective intervention research.