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IntroductionPersistent, knee pain is a common cause of disability. Education and exercise treatment are advocated in all clinical guidelines; however, the increasing prevalence of persistent knee pain presents challenges for health services regarding appropriate and scalable delivery of these treatments. Digital technologies may help address this, and this trial will evaluate the feasibility and acceptability of two electronic-rehabilitation interventions: ‘My Knee UK’ and ‘Group E-Rehab’.Methods and analysisThis protocol describes a non-blinded, randomised feasibility trial with three parallel groups. The trial aims to recruit 90 participants (45 years or older) with a history of persistent knee pain consistent with a clinical diagnosis of knee osteoarthritis. Participants will be randomly assigned in a 1:1:1 allocation ratio. The ‘My Knee UK’ intervention arm will receive a self-directed unsupervised internet-based home exercise programme plus short message service support (targeting exercise behaviour change) for 12 weeks; the ‘Group E-Rehab’ intervention arm will receive group-based physiotherapist-prescribed home exercises delivered via videoconferencing accompanied by internet-interactive educational sessions for 12 weeks; the control arm will receive usual physiotherapy care or continue with their usual self-management (depending on their recruitment path). Feasibility variables, patient-reported outcomes and clinical findings measured at baseline, 3 and 9 months will be assessed and integrated with qualitative interview data from a subset of Group E-Rehab and My Knee UK participants. If considered feasible and acceptable, a definitive randomised controlled trial can be conducted to investigate the clinical effectiveness and cost-effectiveness of one or both interventions with a view to implementation in routine care.Ethics and disseminationThe trial was approved by the West of Scotland Research Ethics Committee 5 (Reference: 20/WS/0006). The results of the study will be disseminated to study participants, the study grant funder and will be submitted for publication in peer-reviewed journals.Trial registration numberISRCTN15564385.

Background The VEDERA (Very Early vs. Delayed Etanercept in Rheumatoid Arthritis) randomised controlled trial compared the effect of conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy with biologic DMARD (bDMARD) therapy using the tumour necrosis factor inhibitor etanercept in treatment-naive, early rheumatoid arthritis patients. The CADERA (Coronary Artery Disease Evaluation in Rheumatoid Arthritis) trial was a bolt-on study in which VEDERA patients underwent cardiovascular magnetic resonance imaging to detect preclinical cardiovascular disease at baseline and following treatment. Objectives To evaluate whether or not patients with treatment-naive early rheumatoid arthritis have evidence of cardiovascular disease compared with matched control subjects; whether or not this is modifiable with DMARD therapy; and whether or not bDMARDs confer advantages over csDMARDs. Design The VEDERA patients underwent cardiovascular magnetic resonance imaging at baseline and at 1 and 2 years after treatment. Setting The setting was a tertiary centre rheumatology outpatient clinic and specialist cardiovascular magnetic resonance imaging unit. Participants Eighty-one patients completed all assessments at baseline, 71 completed all assessments at 1 year and 56 completed all assessments at 2 years. Patients had no history of cardiovascular disease, had had rheumatoid arthritis symptoms for ≤ 1 year, were DMARD treatment-naive and had a minimum Disease Activity Score-28 of 3.2. Thirty control subjects without cardiovascular disease were approximately individually matched by age and sex to the first 30 CADERA patients. Patients with a Disease Activity Score-28 of ≥ 2.6 at 48 weeks were considered non-responders. Interventions In the VEDERA trial patients were randomised to group 1, immediate etanercept and methotrexate, or group 2, methotrexate ± additional csDMARD therapy in a treat-to-target approach, with a switch to delayed etanercept and methotrexate in the event of failure to achieve clinical remission at 6 months. Main outcome measures The primary outcome measure was difference in baseline aortic distensibility between control subjects and the early rheumatoid arthritis group and the baseline to year 1 change in aortic distensibility in the early rheumatoid arthritis group. Secondary outcome measures were myocardial perfusion reserve, left ventricular strain and twist, left ventricular ejection fraction and left ventricular mass. Results Baseline aortic distensibility [geometric mean (95% confidence interval)] was significantly reduced in patients (n = 81) compared with control subjects (n = 30) [3.0 × 10–3/mmHg (2.7 × 10–3/mmHg to 3.3 × 10–3/mmHg) vs. 4.4 × 10–3/mmHg (3.7 × 10–3/mmHg to 5.2 × 10–3/mmHg), respectively; p n = 81, with imputation for missing values) [3.0 × 10–3/mmHg (2.7 × 10–3/mmHg to 3.4 × 10–3/mmHg) vs. 3.6 × 10–3/mmHg (3.1 × 10–3/mmHg to 4.1 × 10–3/mmHg), respectively; p n = 40 at baseline) versus group 2 (n = 41 at baseline): 3.8 × 10–3/mmHg versus 3.4 × 10–3/mmHg, p = 0.49; combined groups 1 and 2 non-responders (n = 38) versus combined groups 1 and 2 responders (n = 43): 3.5 × 10–3/mmHg versus 3.6 × 10–3/mmHg, p = 0.87; group 1 non-responders (n = 17) versus group 1 responders (n = 23): 3.6 × 10–3/mmHg versus 3.9 × 10–3/mmHg, p = 0.73. There was a trend towards a 10–30% difference in aortic distensibility between (group 1) responders who received first-line etanercept (n = 23) and (group 2) responders who never received etanercept (n = 13): 3.9 × 10–3/mmHg versus 2.8 × 10–3/mmHg, p = 0.19; ratio 0.7 (95% confidence interval 0.4 to 1.2), p = 0.19; ratio adjusted for baseline aortic distensibility 0.8 (95% confidence interval 0.5 to 1.2), p = 0.29; ratio fully adjusted for baseline characteristics 0.9 (95% confidence interval 0.6 to 1.4), p = 0.56. Conclusions The CADERA establishes evidence of the vascular changes in early rheumatoid arthritis compared with controls and shows improvement of vascular changes with rheumatoid arthritis DMARD therapy. Response to rheumatoid arthritis therapy does not add further to modification of cardiovascular disease but, within the response to either strategy, etanercept/methotrexate may confer greater benefits over standard methotrexate/csDMARD therapy. Trial registration Current Controlled Trials ISRCTN89222125 and ClinicalTrials.gov NCT01295151. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 4. See the NIHR Journals Library website for further project information. Pfizer Inc. (New York, NY, USA) supported the parent study, VEDERA, through an investigator-sponsored research grant reference WS1092499.

Background Skeletal muscles undergo changes with ageing which can cause sarcopenia that can result in frailty. Quantitative MRI may detect the muscle-deficit component of frailty which could help improve the understanding of ageing muscles. Aims To investigate whether quantitative MRI measures of T2, fat fraction (FF), diffusion tensor imaging and muscle volume can detect differences within the muscles between three age groups, and to assess how these measures compare with frailty index, gait speed and muscle power. Methods 18 ‘young’ (18–30 years), 18 ‘middle-aged’ (31–68 years) and 18 ‘older’ (> 69 years) healthy participants were recruited. Participants had an MRI of their dominant thigh. Knee extension and flexion power and handgrip strength were measured. Frailty (English Longitudinal Study of Ageing frailty index) and gait speed were measured in the older participants. Results Young participants had a lower muscle MRI T2, FF and mean diffusivity than middle-aged and older participants; middle-aged participants had lower values than older participants. Young participants had greater muscle flexion and extension power, muscle volume and stronger hand grip than middle-aged and older participants; middle-aged participants had greater values than the older participants. Quantitative MRI measurements correlated with frailty index, gait speed, grip strength and muscle power. Discussion Quantitative MRI and strength measurements can detect muscle differences due to ageing. Older participants had raised T2, FF and mean diffusivity and lower muscle volume, grip strength and muscle power. Conclusions Quantitative MRI measurements correlate with frailty and muscle function and could be used for identifying differences across age groups within muscle.

ObjectivesWe 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.MethodsPragmatic, 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.ResultsWe 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.ConclusionsCompared 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 numberNCT02433184

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.

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.

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.

ObjectivesThe objectives of this study were to assess the reliability of a novel objective outcome measure, laser Doppler imaging (LDI), its validity against skin biopsy histology and other clinical instruments, including localized cutaneous lupus disease area and severity index (L-CLASI) and visual analogue scale (VAS) score of photographs, and its responsiveness to clinical change with therapy.MethodsA prospective observational cohort study was conducted in 30 patients with active cutaneous lupus erythematosus (CLE). At baseline and 3 months, disease activity was assessed using L-CLASI and a high resolution LDI system by two assessors. Skin biopsy was scored as 0 = non-active, 1 = mild activity and 2 = active. Photographs were assessed by two clinicians using 100 mm VAS. Inter-rater reliability was analyzed using Bland–Altman limits of agreement. Correlation between histology and LDI, L-CLASI and VAS and sensitivity to change of LDI with physician subjective assessment of change (PSAC) at 3 months were analyzed using Kendall’s tau-a.ResultsOf 30 patients with CLE, 28 (93%) were female, mean (SD) age 48.4 (11.5) y, 25 (83%) were Caucasians, 25 (83%) had concurrent systemic lupus erythematosus and 16 (53%) were smokers. CLE subtypes were acute = 9, subacute = 8 and chronic = 13. Inter-rater agreement for LDI was fair but for VAS score of photographs was poor. In 20 patients with biopsy, correlation with histology was better for LDI (tau-a = 0.53) than L-CLASI (tau-a = 0.26) (difference = 0.27; 90% CI 0.05–0.49) or VAS score of photographs (tau-a = 0.17) (difference = 0.36; 90% CI 0.04–0.68). There was a moderate correlation between PSAC score and change in LDI (tau-a = 0.56; 90% CI 0.38–0.74; p ConclusionLDI provides a reliable, valid and responsive quantitative measure of inflammation in CLE. It has a better correlation with histology compared to clinical instruments. LDI provides an objective outcome measure for clinical trials.

Objective To investigate whether sonographically determined subclinical enthesopathy in patients with moderate‐to‐severe psoriasis regresses with the use of ustekinumab therapy for skin disease. Methods Seventy‐three patients with moderate‐to‐severe psoriasis, who were not treated with systemic therapy and did not have symptoms of psoriatic arthritis (PsA), and 23 healthy volunteers were screened by ultrasound for subclinical enthesitis. Subsequently, 23 patients with psoriasis whose ultrasound results showed inflammatory changes were treated with ustekinumab for 52 weeks. The evolution of sonographic abnormalities of the upper and lower limb entheses was assessed using an extensive gray‐scale and power Doppler (PD) ultrasound protocol at weeks 0, 12, 24, and 52. For each parameter, a gray‐scale or PD ultrasound score of >0 was determined to be abnormal, and a summative score based on the Glasgow Ultrasound Enthesitis Scoring System was calculated. Results Of all the patients with psoriasis screened using ultrasound, 49.3% had at least 1 inflammatory entheseal abnormality. Mean ± SD inflammation scores were higher in the patients with psoriasis compared with the healthy volunteers (9.9 ± 6.6 versus 1.0 ± 1.4). With treatment, the mean inflammation scores decreased significantly by 42.2% from week 0 to week 24 (–4.2 [95% confidence interval –6.3, –2.1]; P < 0.001) and by 47.5% by week 42 (–4.7 [95% confidence interval –7.1, –2.3]; P = 0.001). Entheseal structural abnormalities did not change significantly during treatment. Conclusion Within 12 weeks of treatment, interleukin‐12 (IL‐12)/IL‐23 inhibition for psoriasis appears to suppress subclinical enthesopathy, and the suppression is maintained through week 52. Further longitudinal studies are needed to determine whether therapy initiated for skin disease may prevent the development of PsA.

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

Objective To assess the responsiveness of clinical outcome measures in musculoskeletal SLE compared with US. Methods A prospective pilot study was conducted in consecutive SLE patients with inflammatory musculoskeletal symptoms. Clinical assessments including SLEDAI, BILAG, 28 tender and swollen joint counts, physician and patient visual analogue scales (VAS), and US were performed at 0, 2 and 4 weeks following 120 mg i.m. methylprednisolone acetate. Responsiveness was analysed using changes and effect sizes using Cohen’s criteria. Results Twenty patients were recruited. Fifteen out of 20 had clinical swelling at baseline. All clinical and US parameters were significantly improved at week 4 (all P ⩽ 0.01). Musculoskeletal-BILAG score improved in 16/20. Musculoskeletal-SLEDAI improved in 7/20. SLE responder index 4 criteria were assessed in 19 patients with SLEDAI ⩾4 at baseline and were met in 9/19 at 4 weeks. Effect sizes at 4 weeks were large (>0.5) for US, physician VAS and BILAG, and medium (>0.3) for joint counts and SLEDAI. Large effect sizes for improvement in US grey-scale and power Doppler were observed in both SLE responder index 4 responders (r = −0.51 and −0.56, respectively) and non-responders (r = −0.62 and −0.59, respectively) at 4 weeks. Conclusion This is the first study to measure the responsiveness of clinical outcome measures in musculoskeletal SLE against an objective inflammation measure. BILAG and physician VAS were the most responsive clinical instruments. US was highly responsive in musculoskeletal SLE, while SLEDAI and joint counts appeared suboptimal for detection of improvement. These results suggest that clinical trials based on the SLEDAI and SLE responder index 4 may underestimate the efficacy of therapy in SLE.

Objective: Type I interferon (IFN ) responses are broadly associated with autoimmune diseases, including systemic lupus erythematosus (SLE ). Given the cardinal role of autoantibodies in SLE , this study was undertaken to investigate whether the findings of a B cell–specific IFN assay correlate with SLE activity. Methods: B cells and peripheral blood mononuclear cells (PBMC s) were stimulated with type I IFN and type II IFN . Gene expression was analyzed, and the expression of pathway‐related membrane proteins was determined. A flow cytometry assay for tetherin (CD 317), an IFN ‐induced protein ubiquitously expressed on leukocytes, was validated in vitro and then clinically against SLE diagnosis, plasmablast expansion, and the British Isles Lupus Assessment Group (BILAG ) 2004 score in a discovery cohort (n = 156 SLE patients, 30 rheumatoid arthritis [RA ] patients, and 25 healthy controls). A second, longitudinal validation cohort of 80 SLE patients was also evaluated for flare prediction. Results: In vitro, a close cell‐specific and dose‐response relationship between type I IFN –responsive genes and cell surface tetherin was observed in all immune cell subsets. Tetherin expression on multiple cell subsets was selectively responsive to stimulation with type I IFN compared to types II and III IFN s. In patient samples from the discovery cohort, memory B cell tetherin showed the strongest associations with diagnosis (SLE :healthy control effect size 0.11 [P = 0.003]; SLE :RA effect size 0.17 [P < 0.001]), plasmablast numbers in rituximab‐treated patients (R = 0.38, P = 0.047), and BILAG 2004. These associations were equivalent to or stronger than those for IFN score or monocyte tetherin. Memory B cell tetherin was found to be predictive of future clinical flares in the validation cohort (hazard ratio 2.29 [95% confidence interval 1.01–4.64]; P = 0.022). Conclusion: Our findings indicate that memory B cell surface tetherin, a B cell–specific IFN assay, is associated with SLE diagnosis and disease activity, and predicts flares better than tetherin on other cell subsets or whole blood assays, as determined in an independent validation cohort.

Background Myositis is an autoimmune disease which can cause a decrease in quality of life and increased mortality, presenting with muscle weakness, raised muscle enzymes and myalgia. Diagnosis is reliant on subjective clinical examinations, blood tests, conventional MRI and invasive muscle biopsies. Quantitative T2 MRI offers a non-invasive measurement of muscle oedema which could help improve the understanding of muscle pathology and potentially inform diagnosis. The aim of this study was to evaluate whether quantitative T2 MRI of muscles is sensitive enough to detect differences in myositis patients compared to healthy controls, and how it compares with current radiologist scoring methods. Methods 16 myositis patients were recruited (10/16 female, 10 polymyositis, 6 dermatomyositis, mean age 50 ± 26), median CK 1000IU/L ± 3100IU/L, and 16 age and gender matched healthy controls were recruited. MRI of the dominant thigh were performed. Imaging was performed using a fat-suppressed turbo-spin echo sequence. Quantitative T2 measurements were obtained from regions of interest (ROI) drawn manually within the individual muscles that make up the quadriceps and hamstrings with no distinction made between affected and unaffected muscles. A mono-exponential fit was used to obtain an estimate of the T2 from each ROI. Two radiologists blinded to the diagnosis, semi-quantitatively scored by consensus the muscles on a 4-point visual scale as either no oedema (0), mild oedema (1), moderate oedema (2) or severe oedema (3). Muscle strength was assessed using an isokinetic dynamometer. Results T2 values were higher in myositis patients compared to healthy controls [mean (SD) hamstring myositis 47.8ms (7.7ms), healthy 39.9ms (1.5ms), p < 0.001; quadriceps myositis 53.8ms (12.1ms), healthy 42.1ms (2.1ms), p < 0.001]. Quantitative T2 correlated with the radiologists’ oedema scores with rs=0.7 in the hamstrings (p < 0.001) and rs=0.6 in the quadriceps (p < 0.001), with an upward trend in T2 as radiologist scored visible oedema increased. Patients who had been classified as normal by the radiologists were compared with matched healthy controls (n = 8), T2 values for patients with ‘normal muscle’ were still higher than those for healthy controls: mean T2 in the hamstrings (myositis 42.2ms, healthy controls 38.7ms, p = 0.004); mean T2 in the quadriceps (myositis 43.9ms, healthy controls 40.1ms, p = 0.001). T2 was inversely correlated with muscle strength in all participants. Conclusion Quantitative T2 measurements can detect muscle differences between myositis patients and healthy control groups, which suggests that this measurement could be used as an objective method to monitor muscles. They are also sensitive to differences that may not be detected by radiologists. This suggests that subtle systemic changes in muscle in myositis patients, which go undetected in semi-quantitative visual scoring, can be detected using quantitative T2 measurements. This shows the potential for T2 measurements to be a diagnostic measure in the diagnosis and management of myositis. Disclosures M. Farrow None. J. Biglands None. A. Grainger None. E. Hensor None. P. O'Connor None. A. Ladas None. S. Tanner None. A. Aslam None. P. Emery None. A. Tan None.

Background Rheumatoid arthritis (RA) can present with the loss of muscle mass and a decrease in strength and functional capability. Quantitative MRI offers a non-invasive measurement of muscle status which could improve the understanding of muscle pathology in RA. The purpose of this study was to assess whether MRI-based measurements of T2, fat fraction (FF), diffusion tensor imaging and muscle volume can detect differences between the muscles of RA patients and healthy controls in the thigh; and to assess how different stages of the disease present differently. Methods 39 RA patients were recruited, comprised of 3 groups: 13 newly diagnosed treatment naïve (Group 1 - New RA: 10/13 female, mean age 63 years, mean CRP 31.5, mean EMS 71 minutes), 13 in clinical remission DAS28 3.2 ± raised CRP/ESR ± DMARD/targeted therapy escalation ± requiring steroid therapy (Group 3 - Resistant RA: 10/13 female, mean age 65, mean CRP 17.4, mean disease 123 months, mean EMS 63 minutes). 13 healthy controls were also recruited. All 4 groups were age and gender matched. MRI of the dominant thigh was performed using a STEAM-EPI imaging sequence to assess diffusion: mean diffusivity (MD) and fractional anisotropy (FA), 2-point Dixon imaging to assess FF and a fat-suppressed turbo-spin echo sequence to measure T2. All participants had knee extension/flexion and grip strength torque measured using isokinetic dynamometer. Results A one-way ANOVA analysis demonstrated significant differences in T2, FF and muscle volume between RA patients and healthy controls, but no difference in MD or FA. There was no significant difference between the RA groups. T2 and FF were higher in RA patients whilst muscle volume was lower. Muscle volume was significantly correlated with early morning stiffness (rs = 0.4, p = 0.001), DAS28 (rs = 0.4, p = 0.001) and grip strength (rs = 0.5, p < 0.001). All RA patients showed weaker strength compared to the healthy controls. Although the patients in remission (group 2) had better results compared to New (group 1) and Resistant RA patients (group 3), they performed worse than the healthy controls in all strength assessments. Conclusion Quantitative MRI can detect changes in the muscles of RA patients, whether they are newly diagnosed, in remission or with persistently active disease. Difference in T2, FF and muscle volume were apparent even at diagnosis, suggesting muscle changes in RA occur early. Despite effective RA therapy, patients in remission show worse MRI parameters and strength compared to healthy individuals. These warrant attention in improving the muscle strength and quality throughout the spectrum of the RA continuum. Disclosures M. Farrow: None. J. Biglands: None. S. Tanner: None. E. Hensor: None. M. Buch: None. P. Emery: None. A. Tan: None.

Background In SLE, musculoskeletal manifestations have an impact on quality of life, disability and clinical trial outcomes, but are harder to assess than in RA and PsA. We previously showed that joint swelling lacks sensitivity, specificity and responsiveness compared to ultrasound. USEFUL was a multicentre longitudinal study to determine clinical features predicting ultrasound synovitis and whether patients with ultrasound synovitis respond better to therapy.\ud \ud Methods SLE patients were recruited if the referring physician deemed they had inflammatory pain warranting treatment. Swollen joints were not required. At baseline, physicians recorded the features that led them to diagnose inflammatory pain and features of concurrent fibromyalgia and osteoarthritis. Stable doses of prednisolone (≤5 mg/day), antimalarials or immunosuppressants were allowed. Participants received depomedrone 120 mg IM then were assessed at 0, 2 and 6 weeks for 66/68 swollen and tender joint counts, BILAG-2004, SLEDAI-2K, physician global and MSK-VAS, inflammatory markers, patient pain and disease activity-VAS, HAQ-DI, LupusQoL, ultrasound of hands and wrists (blinded to patient and clinical assessor). An internal pilot determined the primary endpoint: EMS-VAS at 2 weeks (adjusted for baseline) between patients with ultrasound-synovitis vs. normal ultrasound at baseline. Sensitivity analyses adjusted for prednisolone and immunosuppressants.\ud \ud Results 122/133 patients recruited completed all visits. There was significant disagreement between clinical examination and ultrasound. 78/133 had ultrasound synovitis; 68% of these had ≥1 swollen joint. Of 66/133 patients with ≥ 1 swollen joint, 20% had normal ultrasound.\ud \ud Ultrasound-synovitis was more likely with joint swelling, a symmetrical small joint distribution and active serology. Physician-determined EMS, other lupus features or prior response to therapy were not associated. Fibromyalgia or osteoarthritis did not reduce the probability of ultrasound synovitis.\ud \ud In the full analysis set (n=133) there was no difference in EMS VAS at 2 weeks according to ultrasound synovial status as baseline (difference -8 mm, 95% CI -19, 4 mm, p=0.178). 32 patients had fibromyalgia. After excluding these patients, we found a statistically and clinically significantly better clinical response to depomedrone in patients with ultrasound-synovitis at baseline (baseline-adjusted EMS VAS at 2 weeks -12 mm, 95% CI -24, 0 mm, p=0.049). This difference was greater in the treatment-adjusted sensitivity analysis (-12.8 (95% CI -22, -3 mm), p=0.007) and the per-protocol-adjusted sensitivity analysis (-14.8 mm (95% CI -20.8, -8.8 mm), p

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 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.

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.

ObjectiveTo evaluate clinical, interferon and imaging predictors of progression from ‘At Risk’ to autoimmune connective tissue diseases (AI-CTDs).MethodsA 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 Results118 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 (pConclusionA 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.

Background\ud Activity monitors provide objective measurements of physical activity, however, the accuracy of these devices in people with polymyalgia rheumatica (PMR) is unknown. Therefore, this study aimed to obtain preliminary evidence of the accuracy of two activity monitors and explore if clinical and gait-related factors altered device accuracy in people with PMR.\ud \ud Methods\ud The ActiGraph with low frequency extension (+LFE) and standard (-LFE) algorithms, Fitbit-Zip (waist) and Fitbit-Zip (shirt) were concurrently tested using a two-minute walk test (2MWT) and stairs test in 27 people with PMR currently treated with prednisolone. To determine accuracy, activity monitor step-count was compared to a gold-standard step-count (GSSC; calculated from video recording) using Bland-Altman plots.\ud \ud Results\ud The Fitbit-Zip (waist) achieved closest agreement to the GSSC for the 2MWT (mean bias (95%CI): 10 (-3, 23); 95%LOA: −55, 74). The ActiGraph (+LFE) achieved closest agreement to the GSSC for the stairs test (mean bias (95%CI): 0 (-1, 1); 95%LOA: −5, 5). The ActiGraph (-LFE) performed poorly in both tests. All devices demonstrated reduced accuracy in participants with lower gait velocity, reduced stride length, longer double-limb support phase and greater self-reported functional impairment.\ud \ud Conclusion\ud Our preliminary results suggest that in controlled conditions, the Fitbit-Zip fairly accurately measures step-count during walking in people with PMR receiving treatment. However, device error was greater than data published in healthy people. The ActiGraph may not be recommended without activation of the LFE. We identified clinical and gait-related factors associated with higher levels of functional impairment that reduced device accuracy. Further work is required to evaluate the validity of the activity monitors in field conditions.

Purpose There is currently no standardized method for muscle shear wave elastography (SWE). The objective of this study was to investigate the effect of unit of measurement, depth, and probe load on the reliability of muscle SWE. Methods The vastus lateralis, biceps femoris, biceps brachii, and abductor digiti minimi muscles were scanned on 20 healthy participants. The SWE readings were measured in shear wave velocity (m/s) and Young's modulus (kPa). Three acquisitions of varying depths were acquired from vastus lateralis. Minimal probe load was compared with the use of a standoff gel layer. Three repeated measurements were acquired to assess reliability using intraclass correlations (ICC). Results The mean elasticity varied across muscle groups and ranged from 1.54 m/s for biceps femoris to 2.55 m/s for abductor digiti minimi (difference = 1.01 m/s [95% confidence interval, CI = 0.92, 1.10]). Reporting readings in meters per second resulted in higher ICC of 0.83 (0.65, 0.93) in comparison to 0.77 (0.52, 0.90) for kilopascal for the vastus lateralis muscle only. Variance increased proportionally with depth reaching 0.17 (equivalent to ±0.82 m/s) at 6 cm. Using a standoff gel decreased ICC to 0.63 (0.20, 0.84) despite similar mean elasticity readings to minimal probe load. Conclusions Different acquisition and technical factors may significantly affect the reliability of SWE in skeletal muscles. Readings acquired in the unit of shear wave velocity (m/s) from depths less than 4 cm using a minimal probe load without a standoff gel yielded the best reliability.

Objective.To assess patient-reported variables as predictors of change in disease activity and disability in early rheumatoid arthritis (RA).Methods.Cases were recruited to the Yorkshire Early Arthritis Register (YEAR) between 1997 and 2009 (n = 1415). Predictors of the 28-joint Disease Activity Score (DAS28) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) at baseline and change over 12 months were identified using multilevel models. Baseline predictors were sex, age, symptom duration, autoantibody status, pain and fatigue visual analog scales (VAS), duration of early morning stiffness (EMS), DAS28, and HAQ-DI.Results.Rates of change were slower in women than men: DAS28 fell by 0.19 and 0.17 units/month, and HAQ-DI by 0.028 and 0.023 units/month in men and women, respectively. Baseline pain and EMS had small effects on rates of change, whereas fatigue VAS was only associated with DAS28 and HAQ-DI at baseline. In patients recruited up to 2002, DAS28 reduced more quickly in those with greater pain at baseline (by 0.01 units/mo of DAS28 per cm pain VAS, p = 0.024); in patients recruited after 2002, the effect for pain was stronger (by 0.01 units/mo, p = 0.087). DAS28 reduction was greater with longer EMS. In both cohorts, fall in HAQ-DI (p = 0.006) was greater in patients with longer EMS duration, but pain and fatigue were not significant predictors of change in HAQ-DI.Conclusion.Patient-reported fatigue, pain, and stiffness at baseline are of limited value for the prediction of RA change in disease activity (DAS28) and activity limitation (HAQ-DI).

OBJECTIVE: To evaluate predictors of serious infection events (SIEs) during rituximab (RTX) therapy and effects of hypogammaglobulinemia on SIE rates, and humoral response and its persistence after discontinuation of RTX in the treatment of rheumatic and musculoskeletal diseases (RMDs).METHODS: A retrospective longitudinal study of 700 RMD patients treated with RTX in a single center was conducted. Immunoglobulin levels were measured at baseline and at 4-6 months after each treatment cycle. Baseline predictors of SIEs were assessed using multivariable logistic regression; for RTX cycles 2-4, a mixed-effects logistic regression model was used.RESULTS: A total of 507 patients (72%) had rheumatoid arthritis, 94 (13%) had systemic lupus erythematosus, 49 (7%) had antineutrophil cytoplasmic antibody-associated vasculitis, and 50 (7%) had other RMDs. The number of SIEs recorded was 281 in 176 patients (9.8 per 100 person-years). Predictors of SIEs included non-RTX-specific comorbidities (previous history of SIE, cancer, chronic lung disease, diabetes mellitus, and heart failure), higher corticosteroid dose, and RTX-specific factors, including low IgG (CONCLUSION: Immunoglobulin levels should be monitored at baseline and before each RTX cycle to identify patients at risk of SIEs. Individualized risk-benefit assessment should be undertaken in those with lower IgG as this is a consistent SIE predictor and may increase infection profiles when RTX is switched to different therapies.

Aims This study aimed to develop a virtual clinic for the purpose of reducing face-to-face orthopaedic consultations. Patients and Methods Anonymized experts (hip and knee arthroplasty patients, surgeons, physiotherapists, radiologists, and arthroplasty practitioners) gave feedback via a Delphi Consensus Technique. This consisted of an iterative sequence of online surveys, during which virtual documents, made up of a patient-reported questionnaire, standardized radiology report, and decision-guiding algorithm, were modified until consensus was achieved. We tested the patient-reported questionnaire on seven patients in orthopaedic clinics using a ‘think-aloud’ process to capture difficulties with its completion. Results A patient-reported 13-item questionnaire was developed covering pain, mobility, and activity. The radiology report included up to ten items (e.g. progressive periprosthetic bone loss) depending on the type of arthroplasty. The algorithm concludes in one of three outcomes: review at surgeon’s discretion (three to 12 months); see at next available clinic; or long-term follow-up/discharge. Conclusion The virtual clinic approach with attendant documents achieved consensus by orthopaedic experts, radiologists, and patients. The robust development and testing of this standardized virtual clinic provided a sound platform for organizations in the United Kingdom to adopt a virtual clinic approach for follow-up of hip and knee arthroplasty patients. Cite this article: Bone Joint J 2019;101-B:951–959.

Importance The prevalence of periodontitis is increased in patients with rheumatoid arthritis (RA) and periodontopathic bacteria can citrullinate proteins. Periodontitis may, therefore, be an initiator of RA and a target for prevention. Periodontal disease and periodontal bacteria have not been investigated in at-risk individuals with RA autoimmunity but no arthritis. Objective To examine periodontal disease and periodontopathic bacteria in anti–cyclic citrullinated protein (anti-CCP) antibody–positive at-risk individuals without arthritis. Design, Setting, and Participants This cross-sectional study took place at a teaching hospital from April 27, 2015, to May 8, 2017. Forty-eight anti-CCP–positive individuals without arthritis (CCP+ at-risk) were recruited nationally. Twenty-six patients with early RA (ERA) and 32 healthy control individuals were recruited locally. Data were analyzed between June 1, 2017, and December 1, 2017. Interventions Periodontal assessment and examination of joints using ultrasonography. Main Outcomes and Measures Prevalence of diseased periodontal sites, clinical periodontitis, and periodontal inflamed surface area in CCP+ at-risk individuals compared with patients with ERA and healthy individuals matched for age and smoking. Paired-end sequencing of DNA from subgingival plaque from diseased and healthy periodontal sites was performed and DNA was profiled and analyzed. Results A total of 48 CCP+ at-risk individuals (mean [SD] age, 51.9 [11.4] years; 31 [65%] female), 26 patients with ERA (mean [SD] age, 54.4 [16.7] years; 14 [54%] female), and 32 healthy individuals (mean [SD] age, 49.4 [15.3] years; 19 [59%] female) were recruited. Of 48 CCP+ at-risk individuals, 46 had no joint inflammation on ultrasonography. Thirty-five CCP+ at-risk individuals (73%), 12 healthy individuals (38%), and 14 patients with ERA (54%) had clinical periodontitis. The median (interquartile range) percentage of periodontal sites with disease was greater in CCP+ at-risk individuals compared with healthy individuals (3.3% [0%-11.3%] vs 0% [0%-0.7%]) and similar to patients with ERA (1.1% [0%-13.1%]). Median (interquartile range) periodontal inflamed surface area was higher in CCP+ at-risk individuals compared with healthy individuals (221 mm2[81-504 mm2] vs 40 mm2[12-205 mm2]). Patients with CCP+ at-risk had increased relative abundance ofPorphyromonas gingivalis(but notAggregatibacter actinomycetemcomitans) at healthy periodontal sites compared with healthy individuals (effect size, 3.00; 95% CI, 1.71-4.29) and patients with ERA (effect size, 2.14; 95% CI, 0.77-3.52). Conclusions and Relevance This study found increased prevalence of periodontitis andP gingivalisin CCP+ at-risk individuals. This suggests periodontitis andP gingivalisare associated with disease initiation and could be targets for preventive interventions in RA.

Background Rituximab (RTX) is effective in treating various rheumatic and musculoskeletal diseases (RMDs). Repeat cycles are often required for disease control but may lead to hypogammaglobulinaemia. Low IgG at baseline has been associated with increased risk of severe infection event (SIE) post-RTX. However, there are limited data on predictors of SIEs in repeat cycles including immunoglobulin levels and B-cell numbers as well as outcomes of hypogammaglobulinaemia. Objectives To assess predictors of SIEs in repeat RTX cycles and effects of hypogammaglobulinaemia in terms of SIEs rates, humoral response and its persistence post-cessation of RTX. Methods A retrospective study was conducted in the first 700 consecutive ARD patients treated with at least a cycle of RTX in Leeds. IgM, IgA and IgG levels were measured at baseline and 4-6 months after each cycle. For cycles 2-4 (C2-4), predictors for SIEs were analysed using mixed-effects logistic regression analysis. Results 550 patients were female, mean(SD) age 56(16) years and median (IQR) disease duration 7.9(3.4-15.0) years. 507(72%) had RA, 94(13%) SLE, 49(7%) AAV, 14(2%) inflammatory myopathies, 9(1%) pSS, 5(1%) APS, 6(1%) SSc and 16(3%) other CTDs. 364(52%) were biologic-naive and 514(73%) were on concomitant DMARDs. Total follow-up: 2880 patient-years (PY). 281 SIEs were recorded in 176 patients (9.8/100 PY). In C1, we had validated that low IgG was predictive of SIE within 12 months of C1. For cycles 2-4, in multivariable analysis, non-RTX-specific comorbidities [chronic lung OR (95% CI) 2.4 (1.3-4.4), diabetes 2.9 (1.2-6.9), heart failure 6.3 (1.4-28.1), previous cancer 3.0 (1.3-6.7) and severe infection 6.3 (3.0-13.4)] and RTX-specific variables [higher corticosteroid dose 1.08 (1.02-1.14), higher IgM 1.3 (1-1.7) and longer retreatment time 1.01 (1-1.02)] were associated with increased odds of SIEs, but not B-cell numbers or depletion status. Higher IgG reduced the risk 0.88 (0.8-0.96). Of 103 patients with low IgG for at least 4 months duration, SIEs rates were higher in those with low baseline IgG (16.4 PY) or acquired it during/post-RTX (21.3 PY) versus those with normal IgG (9.7 PY), 5/8(64%) had impaired humoral response to pneumococcal and haemophilus following vaccination challenge and only 4/11(36%) had IgG normalised after switching therapies. Overall, 7(1%) of the patients required Ig replacement based on recurrent sino-pulmonary SIEs and/or low IgG. Conclusion Immunoglobulin should be monitored at baseline and before each RTX cycle to identify patients at risk of SIEs. Vigilance is needed for those with lower IgG as this is a consistent predictor of SIE and may affect infection outcomes when patients are switched to a different bDMARD. For those at risk of SIEs, reduction of corticosteroid dose could reduce risk. Low B-cell numbers were not predictive of SIEs. Acknowledgement This research was supported by Octapharma and NIHR (DRF-2014-07-155). The views expressed are those of the author(s) & not necessarily the NHS, NIHR or DOH. Disclosure of Interests Md Yuzaiful Md Yusof: None declared, Edward Vital Grant/research support from: He has received honoraria and research grant support from Roche, GSK and AstraZeneca., Damien M McElvenny: None declared, Elizabeth Hensor: None declared, Sudipto Das: None declared, Shouvik Dass Grant/research support from: Roche and GSK, Andy C Rawstron: None declared, Maya Buch Grant/research support from: Pfizer LTD, UCB, Consultant for: AbbVie, Eli Lilly, EMD Serono, Pfizer Ltd., Sanofi, Paul Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Gilead,Samsung, Sandoz and Lilly, Sinisa Savic Grant/research support from: Novartis and Sobi

Background: Rituximab (RTX) is used for resistant SLE but clinical response varies. We previously validated two interferon-stimulated gene expression scores (IFN-Score-A and IFN-Score-B) that improved prediction of clinical outcomes in SLE. IFN-Score-A included most commonly reported ISGs and predicted flares and glucocorticoid requirements. IFN-Score-B included ISGs that respond to multiple IFN subtypes and predicted development of SLE in At-Risk individuals. Diagnosis of SLE was associated with both scores, while only IFN-Score-B was elevated in RA. The British Society for Rheumatology Biologics Registry (BILAG-BR) collects samples for RTX-treated patients in the UK. MASTERPLANS is a consortium to identify predictors of drug response. Objectives: To investigate whether IFN-Score-A and IFN-Score-B predict BILAG response to RTX at 6 months. Methods: This is a preliminary analysis of the first RTX-treated patients in the BILAG-BR with complete data. Patients were recruited if they were starting a first cycle of RTX for active SLE (BILAG A or 2xBILAG B) despite previous cyclophosphamide or mycophenolate mofetil. Disease activity was measured using BILAG-2004. Clinical response was defined as improvement by >=1 grade in active BILAG-2004 systems with no worsening in other systems. Whole blood was collected into TEMPUS tubes and RNA extracted. IFN-Scores were measured using a custom Taqman array as previously described [El Sherbiny et al., 2018]. Multivariate logistic regression was used to test IFN-Scores and baseline clinical covariates as predictors of BILAG response at 6 months. Results: Samples were available from 147 patients, of whom 84 had complete baseline and 6 month clinical data available and were included in this analysis. 40/84 (47.6%) patients had BILAG response at 6 months. In univariate and multivariate analysis, high IFN-Score-B expression was significantly associated with clinical response (see table 1). Conclusion: This preliminary analysis suggests that assessment of IFN activity has a role in predicting response to RTX. A novel IFN score (Score B) was more predictive than classic ISGs (Score A). These results add to a body of work showing that IFN-Score-B predicts clinically significant outcomes independently of overall IFN activity. Future work will analyse this biomarker in a larger cohort of patients and integrate with other putative clinical and biological predictors of response. Reference: [1] El-Sherbiny, Y. M.… E. M. Vital (2018). Sci. Rep. 8: 5793. Acknowledgement: We would like to thank the Medical Research Council, National Institute of Health Research, UK for funding the MASTERPLANS project. Disclosure of Interests: Adewonuola Alase: None declared, Zoe Wigston: None declared, Agata Burska: None declared, Elizabeth Hensor: None declared, Md Yuzaiful Md Yusof: None declared, John Reynolds: None declared, The Masterplans Consortium: None declared, Miriam Wittmann Consultant for: consultancy honoraria from Abbvie, Celgene, Janssen, L’Oreal, Novartis and Pfizer, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GlaxoSmithKline, Consultant for: AstraZeneca, Eli Lilly, GlaxoSmithKline, ILTOO Pharma, MedImmune, Merck Serono, Speakers bureau: GlaxoSmithKline, UCB Pharma, Edward Vital Grant/research support from: He has received honoraria and research grant support from Roche, GSK and AstraZeneca.

Background Musuloskeletal (MSK) manifestations are common in SLE. Many recent clinical trials were negative or had small benefits vs. placebo. SRI is a common primary endpoint but has not been independently validated. Ultrasound is an objective measure of synovitis validated in inflammatory arthritis. We previously reported that in patients with inflammatory symptoms, 38% had swollen joints, 27% had subclinical inflammation (abnormal US but no clinically swollen joints) and 35% had no clinical or US inflammation. We also showed that subclinical tenosynovitis and PD were associated with significantly higher IgG, physician visual analogue score, tender joint count (Zayat et al. Rheumatology 2018). The purpose of the present study was to use ultrasound as a gold standard to evaluate clinical outcome measures of MSK lupus. Methods A prospective pilot study was conducted in consecutive SLE patients with inflammatory musculoskeletal symptoms. Clinical assessments including SLEDAI-2K, BILAG-2004, 28-tender and swollen joint counts, physician and patient VAS and ultrasound were performed at 0, 2 and 4 weeks following 120 mg intramuscular methylprednisolone acetate. Responsiveness was analysed using changes and effect sizes using Cohens criteria. Results 20 patients were recruited. 15/20 had clinical swelling at baseline. The others had abnormal ultrasound and/or early morning stiffness and tenderness. All clinical and US parameters were significantly improved at week 4 (all p0.01). Musculoskeletal-BILAG score improved in 16/20. Musculoskeletal-SLEDAI improved in 7/20. SRI-4 criteria were assessed in 19 patients with SLEDAI ≥4 at baseline met in 9/19 at 4 weeks. Effect sizes at 4 weeks were large (>0.5) for US (power Doppler and Greyscale), physician VAS and BILAG and medium (>0.3) for joint counts and SLEDAI. Large effect sizes for improvement in US greyscale and power Doppler were observed in both SRI responders (r=−0.51 and −0.56 respectively) and non-responders (r=−0.62 and −0.59) at 4 weeks. In SRI non-responders swollen joint counts improved by 20%, 50% and 70% in 7/10, 7/10 and 6/10 patients respectively. Conclusions This is the first study to measure the responsiveness of clinical outcome measures in musculoskeletal SLE against an objective inflammation measure. BILAG-2004 and physician VAS were the most responsive clinical instruments. US was highly responsive in musculoskeletal SLE, while SLEDAI-2K and joint counts appeared suboptimal for detection of improvement. These results suggest that clinical trials based on the SLEDAI-2K and SRI-4 may underestimate the efficacy of therapy in SLE. Funding Source(s): LupusUK, NIHR

Background Rituximab is used for resistant SLE but clinical response varies. Although biomarkers of time to relapse have been validated, there are few biomarkers to predict initial response. Interferon status may predict response to rituximab and anti-TNF in RA. We previously validated two interferon-stimulated gene expression scores (IFN-Score-A and IFN-Score-B) that improved prediction of clinical outcomes in SLE. IFN-Score-A included most commonly reported ISGs and predicted flares and glucocorticoid requirements. IFN-Score-B included ISGs that respond to multiple IFN subtypes and predicted development of SLE in At-Risk individuals. Diagnosis of SLE was associated with both scores, while only IFN-Score-B was elevated in RA. The British Society for Rheumatology Biologics Registry (BILAG-BR) collects data and samples for rituximab-treated patients in the UK. MASTERPLANS is an MRC-funded consortium to identify predictors of response. Methods This is a preliminary analysis of the first rituximab-treated patients in the BILAG-BR with complete data. Patients were recruited if they were starting a first cycle of rituximab for active SLE (BILAG A or 2xBILAG B) despite previous cyclophosphamide or mycophenolate mofetil. Disease activity was measured using BILAG-2004. Clinical response was defined as improvement by ≥1 grade in active BILAG-2004 systems with no worsening in other systems. Whole blood was collected into TEMPUS tubes and RNA extracted. IFN-Scores were measured using a custom Taqman array as previously described, normalised to PP1A [El Sherbiny et al. Sci Rep 2018]. Multivariate logistic regression was used to test IFN-Scores and baseline clinical covariates as predictors of BILAG response at 6 months. Results Samples were available from 147 patients, of whom 84 had complete baseline and 6 month clinical data available and were included in this analysis. 40/84 (47.6%) patients had BILAG response at 6 months. In univariate and multivariate analysis, high IFN-Score-B expression was significantly associated with clinical response (see table 1). Conclusions This preliminary analysis suggests that assessment of IFN activity has a role in prediction of response to rituximab. A novel IFN score (Score B) was more predictive than classic ISGs (Score A). These results add to a body of work showing that IFN-Score-B predicts clinically significant outcomes independently of overall IFN activity. Future work will analyse this biomarker in a larger cohort of patients and integrate with other putative clinical and biological predictors of response. Funding Source(s): Medical Research Council, National Institute of Health Research

ObjectiveType I interferon (IFN-I) responses are broadly associated with autoimmune disease including SLE. Given the cardinal role of autoantibodies in SLE, we investigated whether a B lineage cell-specific IFN assay might correlate with SLE activity.MethodsB cells and PBMCs were stimulated with IFN-I and IFN-II. Gene expression was scrutinised for pathway-related membrane protein expression. A flow-cytometric assay for tetherin (CD317), an IFN-induced protein ubiquitously expressed on leucocytes, was validated in vitro then clinically against SLE diagnosis, plasmablast expansion, and BILAG-2004 score in a discovery cohort (156 SLE; 30 RA; 22 healthy controls). A second longitudinal validation cohort of 80 patients was also evaluated for SLE flare prediction.ResultsIn vitro, a close cell-specific and dose-responsive relationship between IFN-I responsive genes and cell surface tetherin in all immune subsets existed. Tetherin expression was selectively responsive to the IFN-I compared to IFN-II and -III. In the discovery cohort memory B-cell tetherin was best associated with diagnosis (SLE/HC: effect size=0.11, p=0.003;SLE/RA: effect size=0.17, pConclusionMemory B cell surface tetherin, a reflection of cell-specific IFN response in a convenient flow cytometric assay, was associated with SLE diagnosis, disease activity and predicted flares better than other cell subsets or whole blood assays in independent validation cohorts.

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.

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.ObjectivesTo 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.MethodsHand 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.ResultsThe proportion of subjects with ITI and the number of inflamed interosseous tendons (ITs) increased along the disease continuum (pConclusionsITI 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.

AIM To assess whether magnetic resonance imaging (MRI)-based measurements of T2, fat fraction, diffusion tensor imaging, and muscle volume can detect differences between the muscles of myositis patients and healthy controls, and to identify how they compare with semi-quantitative MRI diagnosis. MATERIALS AND METHODS Sixteen myositis patients and 16 age- and gender-matched healthy controls underwent MRI of their thigh. Quantitative MRI measurements and radiologists' semi-quantitative scores were assessed. Strength was assessed using an isokinetic dynamometer. RESULTS: Fat fraction and T2 values were higher in myositis patients whereas muscle volume was lower compared to healthy controls. There was no difference in diffusion. Muscle strength was lower in myositis patients compared to healthy controls. In a subgroup of eight patients, scored as unaffected by radiologists, T2 values were still significantly higher in myositis patients. CONCLUSIONS Quantitative MRI measurements can detect differences between myositis patients and healthy controls. Changes in the muscles of myositis patients, undetected by visual, semi-quantitative scoring, can be detected using quantitative T2 measurements. This suggests that MRI T2 values may be useful for the management of myositis patients.

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.

Objective.To assess whether the “spread” of joint pain is related to pain-associated muscle loss in 1 joint leading to increased loading and subsequent pain in other joints.Methods.Associations between persistent knee pain (pain in 1 or 2 knees over 0–3 years vs no persistent pain) and incident shoulder pain at Year 4 were examined in participants from the longitudinal National Institutes of Health Osteoarthritis Initiative. Associations were assessed using log multinomial modeling, adjusted for age, sex, body mass index, depression score, other lower limb pain, and baseline leg weakness (difficulty standing from a sitting position).Results.In older adults with clinically significant knee osteoarthritis (OA) or at risk of knee OA (n = 3486), the number of painful joints increased yearly, from 2.1 joints (95% CI 2.0–2.2) at baseline increasing by 5.2% (95% CI 2.2–8.3) at Year 4. Shoulders were the next most commonly affected joints after knees (28.5%). Persistent pain in 1 or 2 knees increased risk of bilateral shoulder pain at Year 4 [1 knee: relative risk (RR) 1.59, 95% CI 0.97–2.61; 2 knees: RR 2.02, 95% CI 1.17–3.49] after adjustment for confounders. Further adjustment for leg weakness attenuated effect sizes (1 knee: RR 1.13, 95% CI 0.60–2.11; 2 knees: RR 1.44, 95% CI 0.75–2.77), indicating mediation by functional leg weakness.Conclusion.Spread of joint pain is not random. Persistently painful knees predict new bilateral shoulder pain, which is likely mediated by leg weakness, suggesting that biomechanical factors influence the spread of pain.

To determine if quantitative and qualitative shear wave elastography have roles in evaluating musculoskeletal masses. 105 consecutive patients, prospectively referred for biopsy within a specialist sarcoma centre, underwent B-mode, quantitative (m/s) and qualitative (colour map) shear wave elastography. Reference was histology from subsequent biopsy or excision where possible. Statistical modelling was performed to test elastography data and/or B-mode imaging in predicting malignancy. Of 105 masses, 39 were malignant and 6 had no histology but benign characteristics at 12 months. Radiologist agreement for B-mode and elastography was moderate to excellent Kw 0.52-0.64; PABAKw 0.85-0.90). B-Mode imaging had 78.8% specificity, 76.9% sensitivity for malignancy. Quantitatively, adjusting for age, B-mode and lesion volume there was no statistically significant association between longitudinal velocity and malignancy (OR [95% CI] 0.40[0.10, 1.60], p=0.193), but some evidence that higher transverse velocity was associated with decreased odds of malignancy (0.28[0.06, 1.28], p=0.101). Qualitatively malignant masses tended to be towards the blue spectrum (lower velocities); 39.5% (17/43) of predominantly blue masses were malignant, compared to 14.3% (1/7) of red lesions. Quantitatively and qualitatively there is no statistically significant association between shear wave velocity and malignancy. There is no clear additional role to B-mode imaging currently. • Correlation between shear wave velocity and soft tissue malignancy was statistically insignificant • B-mode ultrasound is 76.9 % sensitive and 78.8 % specific • Statistical models show elastography does not significantly add to lesion assessment

Biomechanical factors including occupational joint physical stressing and joint injury have been linked to spondyloarthritis. We explored such factors in ankylosing spondylitis (AS). A retrospective, online survey was developed alongside the UK National Ankylosing Spondylitis Society (NASS). Questions on early entheseal symptoms, potential precipitating trauma, sporting activity, and physiotherapy were asked. A total of 1026 patients responded with 44% recalling an instance of injury or trauma as a potential trigger for their AS. After symptom onset, 55% modified sporting activities and 28% reported that the initial AS recommended exercises exacerbated symptoms. Patients report physical trauma, exercise and physiotherapy as potential triggers for AS symptoms. These findings further support the experimental evidence for the role of biomechanical factors in disease.

Measurement of type I interferon (IFN-I) has potential to diagnose and stratify autoimmune diseases, but existing results have been inconsistent. Interferon-stimulated-gene (ISG) based methods may be affected by the modularity of the ISG transcriptome, cell-specific expression, response to IFN-subtypes and bimodality of expression. We developed and clinically validated a 2-score system (IFN-Score-A and -B) using Factor Analysis of 31 ISGs measured by TaqMan selected from 3-IFN-annotated modules. We evaluated these scores using in-vitro IFN stimulation as well as in sorted cells then clinically validated in a cohort of 328 autoimmune disease patients and healthy controls. ISGs varied in response to IFN-subtypes and both scores varied between cell subsets. IFN-Score-A differentiated Systemic Lupus Erythematosus (SLE) from both Rheumatoid Arthritis (RA) and Healthy Controls (HC) (both p

Objectives. To analyse long-term survival and efficacy of TNFi, reasons for switching or discontinuing, baseline predictors of response and remission in axial spondyloarthritis (axSpA) patients in a UK cohort. Methods. All patients with a physician-verified diagnosis of axSpA attending two specialist centres who fulfilled the eligibility criteria for TNFi were included. Routinely recorded patient data were reviewed retrospectively. Initial TNFi was recorded as the index drug. Results. Six hundred and fifty-one patients (94% AS) were included; adalimumab (n = 332), etanercept (n = 205), infliximab (n = 51), golimumab (n = 40) and certolizumab pegol (n = 23) were index TNFi. The mean (S.D.) duration from symptom onset to time of diagnosis was 8.6 (8.7) years and mean (S.D.) duration from diagnosis to TNFi initiation was 12.6 (11.5) years. A total of 224 (34.4%) stopped index TNFi, and 105/224 switched to a second TNFi. Median drug survival for index and second TNFi were 10.2 years (95% CI: 8.8, 11.6 years) and 5.5 years (95% CI: 2.7, 8.3 years), respectively (P < 0.05). Survival rates were not influenced by choice of TNFi. HLA-B27 predicted BASDAI50 and/or two or more point reduction within 6 months and long-term drug survival (P < 0.05). Low disease activity was predicted by non-smoking and low baseline BASDAI (P < 0.05). Conclusion. We have observed good TNFi survival rates in axSpA patients treated in a real-life setting. This is best for first TNFi and not influenced by drug choice.

Objectives Anticitrullinated protein antibody (ACPA)+ individuals with non-specific musculoskeletal symptoms are at risk of inflammatory arthritis (IA). This study aims to demonstrate the predictive value of T cell subset quantification for progression towards IA and compare it with previously identified clinical predictors of progression. Methods 103 ACPA+ individuals without clinical synovitis were observed 3-monthly for 12 months and then as clinically indicated. The end point was the development of IA. Naive, regulatory T cells (Treg) and inflammation related cells (IRCs) were quantified by flow cytometry. Areas under the ROC curve (AUC) were calculated. Adjusted logistic regressions and Cox proportional hazards models for time to progression to IA were constructed. Results Compared with healthy controls (age adjusted where appropriate), ACPA+ individuals demonstrated reduced naive (22.1% of subjects) and Treg (35.8%) frequencies and elevated IRC (29.5%). Of the 103 subjects, 48(46.6%) progressed. Individually, T cell subsets were weakly predictive (AUC between 0.63 and 0.66), although the presence of 2 T cell abnormalities had high specificity. Three models were compared: model-1 used T cell subsets only, model-2 used previously published clinical parameters, model-3 combined clinical data and T cell data. Model-3 performed the best (AUC 0.79 (95% CI 0.70 to 0.89)) compared with model-1 (0.75 (0.65 to 0.86)) and particularly with model-2 (0.62 (0.54 to 0.76)) demonstrating the added value of T cell subsets. Time to progression differed significantly between high-risk, moderate-risk and low-risk groups from model-3 (p=0.001, median 15.4 months, 25.8 months and 63.4 months, respectively). Conclusions T cell subset dysregulation in ACPA+ individuals predates the onset of IA, predicts the risk and faster progression to IA, with added value over previously published clinical predictors of progression.

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 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.

Background Individuals at risk of rheumatoid arthritis (RA) demonstrate systemic autoimmunity in the form of anti-citrullinated peptide antibodies (ACPA). MicroRNAs (miRNAs) are implicated in established RA. This study aimed to (1) compare miRNA expression between healthy individuals and those at risk of and those that develop RA, (2) evaluate the change in expression of miRNA from “at-risk” to early RA and (3) explore whether these miRNAs could inform a signature predictive of progression from “at-risk” to RA. Methods We performed global profiling of 754 miRNAs per patient on a matched serum sample cohort of 12 anti-cyclic citrullinated peptide (CCP) + “at-risk” individuals that progressed to RA. Each individual had a serum sample from baseline and at time of detection of synovitis, forming the matched element. Healthy controls were also studied. miRNAs with a fold difference/fold change of four in expression level met our primary criterion for selection as candidate miRNAs. Validation of the miRNAs of interest was conducted using custom miRNA array cards on matched samples (baseline and follow up) in 24 CCP+ individuals; 12 RA progressors and 12 RA non-progressors. Results We report on the first study to use matched serum samples and a comprehensive miRNA array approach to identify in particular, three miRNAs (miR-22, miR-486-3p, and miR-382) associated with progression from systemic autoimmunity to RA inflammation. MiR-22 demonstrated significant fold difference between progressors and non-progressors indicating a potential biomarker role for at-risk individuals. Conclusions This first study using a cohort with matched serum samples provides important mechanistic insights in the transition from systemic autoimmunity to inflammatory disease for future investigation, and with further evaluation, might also serve as a predictive biomarker. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1492-9) contains supplementary material, which is available to authorized users.

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.

Summary Objectives Meniscal pathology is integral to knee osteoarthritis (OA) and its progression; it provides a progression biomarker and a potential treatment target. Magnetic resonance imaging (MRI) demonstrates large heterogeneity in meniscal damage; this structural complexity means measurement is difficult. The aim of this study was to apply novel 3D image analysis to determine which meniscal pathologies demonstrated most change during OA progression. Methods Knee images were selected from the progression cohort of the Osteoarthritis Initiative choosing participants with risk factors for medial OA progression. Medial and lateral menisci were manually segmented then analysed using a statistical shape model of the tibia as a reference surface. Responsiveness was assessed at 1 year using standardised response means (SRMs) for four constructs: meniscal volume, extrusion volume, thickness and tibial coverage; anatomical sub-regions of these constructs were also explored. Results Paired images from 86 participants (median age 61.5, 49% female, 56% obese) were included. Reliability of the novel meniscal measurements was very good intraclass correlation coefficients (ICCs all > 0.98). Meniscal volume and extrusion demonstrated no significant change. Moderate responsiveness was observed for medial meniscus thickness (SRM −0.35) and medial tibial coverage (SRM −0.36). No substantial change was seen for the lateral meniscus measures. Sub-region analysis did not improve responsiveness; while greater change was seen in the posterior medial compartment, it was associated with increased variance of the change. Conclusions The location of meniscal damage was consistently in the posterior medial region, and two measurements (thickness and tibial coverage) were most responsive. Meniscal measures should add to discriminatory power in OA progression assessment.