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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.

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.

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: 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.

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.

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 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

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.

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 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.

Objective.Foot osteoarthritis (OA) is very common but underinvestigated musculoskeletal condition and there is little consensus as to common magnetic resonance imaging (MRI) features. The aim of this study was to develop a preliminary foot OA MRI score (FOAMRIS) and evaluate its reliability.Methods.This preliminary semiquantitative score included the hindfoot, midfoot, and metatarsophalangeal joints. Joints were scored for joint space narrowing (JSN; 0–3), osteophytes (0–3), joint effusion/synovitis, and bone cysts (present/absent). Erosions and bone marrow lesions (BML) were scored (0–3) and BML were evaluated adjacent to entheses and at sub-tendon sites (present/absent). Additionally, tenosynovitis (0–3) and midfoot ligament pathology (present/absent) were scored. Reliability was evaluated in 15 people with foot pain and MRI-detected OA using 3.0T MRI multi-sequence protocols, and assessed using ICC as an overall score and per anatomical site.Results.Intrareader agreement (ICC) was generally good to excellent across the foot in joint features (JSN 0.90, osteophytes 0.90, effusion/synovitis 0.46, cysts 0.87), bone features (BML 0.83, erosion 0.66, BML entheses 0.66, BML sub-tendon 0.60) and soft tissue features (tenosynovitis 0.83, ligaments 0.77). Interreader agreement was lower for joint features (JSN 0.43, osteophytes 0.27, effusion/synovitis 0.02, cysts 0.48), bone features (BML 0.68, erosion 0.00, BML entheses 0.34, BML sub-tendon 0.13), and soft tissue features (tenosynovitis 0.35, ligaments 0.33).Conclusion.This preliminary FOAMRIS demonstrated good intrareader reliability and fair interreader reliability when assessing the total feature scores. Further development is required in cohorts with a range of pathologies and to assess the psychometric measurement properties.

Background: Physical activity is both a therapeutic intervention and an important outcome in people with rheumatic and musculoskeletal disease (RMDs). Subjective methods are prone to response bias and underestimate low-intensity activities, which are common in older adults. Activity monitors may provide an objective solution by measuring step-count, but limited previous research has identified reduced accuracy in people with RMDs. This study aimed to evaluate the concurrent validity of the ActiGraph with both standard and Low Frequency Extension (LFE) algorithms; Fitbit-Zip in both recommended positions; and explore which factors influence device error in people with polymyalgia rheumatica (PMR). Methods: The ActiGraph (±LFE), Fitbit-Zip (waist) and Fitbit-Zip (shirt) were concurrently evaluated using a two-minute-walk-test (2MWT) and stairs test in people with PMR (>1 month glucocorticoid treatment). Participants walked at their normal pace and with any assistive devices required. A GAITRite instrumented walkway collected temporal and spatial gait parameters. Gold standard step-counts were derived from a mean of three manual counts taken from half speed video replays by two investigators. Bland-Altman plots describing the mean bias (95% confidence intervals (CI)) and 95% limits of agreement (LoA) were used to determine monitor accuracy. Spearman’s rho described association of step-count differences with demographic, clinical, and gait parameters. Results: Data was collected on 27 PMR patients (24 female; mean (SD) age 69.2 (8.8); BMI 28.3 (5.6) kg/m2; median (IQR) steroid dose 9.0 (5.0, 12.5) mg/day; Health Assessment Questionnaire (HAQ) 0.63 (0.13, 1.25); FACIT-F 38 (33, 45)). The median (IQR) gold standard step-counts were; 2MWT 206 (197, 220); stairs 15 (15, 16). All monitors systematically underestimated 2MWT step-counts. The Fitbit-Zip (waist) achieved closest agreement to the gold standard step-count in the 2MWT (mean (95%CI) bias 10 (-3, 23), 95%LoA -55, 74). Conversely, the ActiGraph (LFE) performed best during the stairs test (mean (95%CI) bias 0 (-1, 1), 95%LoA -5, 5 followed closely by the Fitbit-Zip (waist) (mean (95%CI) bias 1 (-1, 3), 95%LoA -8, 10). The LoA were particularly influenced by 2 outliers: one participant had a severe level of impairment (HAQ=2.13), which affected all accelerometers during both tests. The second was a Fitbit-Zip (waist) measurement on the stairs test, which was out by an order of magnitude, possibly due to operator error. On all devices, step count difference correlated negatively with gait velocity (rho=-.37 to -.58) and stride length (rho=-.31 to -.72) and positively with HAQ scores (rho=.32 to .57) and duration of double-limb support phase (rho=.33 to .61). Conclusion: Close agreement with the gold standard step-counts suggests the Fitbit-Zip (waist) is a reliable measure of physical activity in people with PMR receiving treatment. The ActiGraph however, cannot be recommended without activation of LFE filter. Device performance reduces in participants with higher levels of functional impairment.

Summary Objective Sensitive biomarkers are needed to understand synovial response to therapy in osteoarthritis (OA). Dynamic, contrast-enhanced magnetic resonance imaging (DCE MRI) provides quantitative, novel measures of synovial inflammation. This exploratory study examined DCE-assessed synovial response to intra-articular corticosteroid (IACS). Methods People with ACR clinical criteria OA knee underwent 3 T MRI pre- and 2 weeks post-IACS. Five MRI variables were assessed blindly: total synovial volume (semi-automated computer program), early enhancement rate (EER) and late enhancement ratio of the entire knee, synovial volume × late enhancement and a semi-quantitative (SQ) score (six sites scored 0–3). Clinical symptoms were assessed using pain visual analogue score (VAS) and WOMAC. Results 13 participants (5 male, mean age 63, mean pain VAS 66 mm mean body mass index (BMI) 31.3 kg/m2) were included. The majority of MRIs demonstrated no change in SQ score although the DCE variables changed to some extent in all. There was generally a reduction in synovial volume ((Wilcoxon test) median (interquartile range (IQR)) reduction 14 cm3 (−1, 29)), EER (0.2% (−0.3, 0.6)) and late enhancement ratio (8% (−0.5, 41)). Synovial volume × late enhancement ratio demonstrated a substantive reduction (2250 (−930, 5630)) as well as the largest effect size, r = 0.45. There was a median 26% reduction in EER in participants with good symptomatic response to IACS, contrasting with a 23% increase in those who responded poorly. Conclusions DCE MRI may be more sensitive than a SQ score at detecting post-therapy synovial changes. The association between EER and symptomatic response to IACS may reflect a closer relation of this biomarker to synovial inflammation than with volumetric assessment.

Objectives To monitor progression to inflammatory arthritis (IA) in individuals with non-specific musculoskeletal (MSK) symptoms and positive anticyclic citrullinated peptide (anti-CCP) antibodies. To develop a pragmatic model to predict development of IA in this patient group. Methods In this prospective observational cohort, patients with new non-specific MSK symptoms and positive anti-CCP were recruited from regional primary care and secondary care referrals. Clinical, imaging and serological parameters were assessed at baseline. Cox regression analysis was performed to identify predictors of progression to IA and develop a risk score to stratify patients at presentation. Findings 100 consecutive patients (73 women, mean age 51 years) were followed up for median 19.8 months (range 0.1–69.0); 50 developed IA after a median 7.9 months (range 0.1–52.4), 34 within 12 months. The majority (43/50) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for rheumatoid arthritis. A model for progression to IA was devised using four variables: tenderness of hand or foot joints, early morning stiffness ≥30 min, high-positive autoantibodies, and positive ultrasonographic power Doppler signal. None of the five individuals at low risk (score 0) progressed to IA, compared with 31% of 29 at moderate risk (1–2) and 62% of 66 at high risk (≥3). Adding shared epitope increased the number at low risk (score 0–1; 0/11 progressed). Conclusions In patients presenting with non-specific MSK symptoms and anti-CCP, the risk of progression to IA could be quantified using data available in clinical practice. The proposed risk score may be used to stratify patients for early therapeutic intervention. Trial registration number NCT02012764 at ClinicalTrials.gov.

Objective Arthritis activity assessments in psoriatic arthritis (PsA) have traditionally relied on tender and swollen joint counts, but in rheumatoid arthritis, multiple studies have demonstrated subclinical inflammation using modern imaging. The aim of this study was to compare clinical examination and ultrasound (US) findings in an early PsA cohort. Methods Forty-nine disease-modifying antirheumatic drug–naive patients with recent-onset PsA (median disease duration 10 months) underwent gray-scale (GS) and power Doppler (PD) US of 40 joints plus tender and swollen joint counts of 68/66 joints. GS and PD were scored on a 0–3 semiquantitative scale for each joint. Clinically active joints were defined as tender and/or swollen and US active joints were defined as a GS score ≥2 and/or a PD score ≥1. Results The most common sites for subclinical synovitis were the wrist (30.6%), knee (21.4%), metatarsophalangeal (MTP) joints (26.5–33.7%), and metacarpophalangeal joints (10.2–19.4%). Excluding MTP joints and ankles, 37 (75.5%) of 49 patients had subclinical synovitis with a median of 3 (interquartile range [IQR] 1–4) joints involved. In contrast, clinical overestimation of synovitis occurred most commonly at the shoulder (38%) and ankle (28.6%). Twelve of 49 patients were classified clinically as having oligoarthritis; of these, subclinical synovitis identified 8 (75%) as having polyarthritis with an increase in their median joint count from 3 (IQR 1–4) to 6 (IQR 5–7). Conclusion This study has demonstrated that subclinical synovitis, as identified by US, is very common in early PsA and led to the majority of oligoarthritis patients being reclassified as having polyarthritis. Further research is required into the relationship of such subclinical synovitis to structural progression.

Objectives Bisphosphonates have some reported beneficial effects in treating osteoarthritis (OA). This study examined the effects of bisphosphonate use on symptoms and structural progression of knee OA in participants from the NIH Osteoarthritis Initiative cohort. Methods People with typical OA trial entry criteria (KL2/3, minimum joint space width 2.5–5.0 mm and pain ≥4 on a numeric rating scale) were classified as bisphosphonate users (≥3 of the 5 years; n=55) or non-users (no use in the preceding 5 years or during follow-up; n=268). Annual data over 4 years were analysed using linear mixed modelling and generalised estimating equations. Results Bisphosphonate compliance was 85% at year 1, reducing to 76% by year 4. Numeric rating scale pain scores were significantly reduced among bisphosphonate users at years 2 and 3 (year 3, −0.9 vs −2.2, p=0.004), though not year 4, after adjustment for baseline pain and analgesic use. Differences in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and disability scores did not reach statistical significance at any time point. There was a trend to less joint space narrowing in bisphosphonate users over time (year 4, 0.51 vs 0.29 mm; p=0.06). Conclusions Significant reduction in numeric rating scale pain was observed in the first 3 years with bisphosphonate use; diminution of effects by year 4 may reflect reduced compliance. Differences in results obtained using numeric rating scale and WOMAC may reflect different constructs measured by these tools. The beneficial trend on structural progression should be considered in terms of the sample size.

Objective. This study used high-resolution PET to explore the pattern of DIP joint bone metabolism to test the hypothesis that the nail was functionally integrated with the bone, based on patterns of distal phalange (DP) bone metabolism in PsA compared with OA and normal joints. Methods. A total of 234 DIP joints were scanned in 30 subjects (10 PsA, 10 OA, 10 healthy control) with [ 18 F]fluoride using the quad-high-density avalanche chamber nano PET scanner. The images were assessed blinded to diagnosis and symptoms for site and intensity of increased [ 18 F]fluoride uptake. Results. [ 18 F]fluoride uptake in the DP was strong relative to the intermediate phalange in both PsA and OA. In PsA there was a trend for uptake to occur in a diffuse pattern involving the entire DP. There was also greater uptake at the enthesis, the periosteum and at the tufts of the DP of PsA compared with OA. In OA, uptake was greatest in the subchondral region adjacent to known sites of osteophytosis and erosions. Both PsA and OA joints with uptake at the subchondral or periosteal bone are likely to be more symptomatic. Conclusion. This exploratory study suggested diffuse increased bone metabolism involving the entire DP, periosteum and entheses, especially in PsA. The subchondral bone and periosteum at the DP have large concentrations of enthesis attachments, including attachments from the nail, supporting the concept of an integrated nail and joint apparatus leading to a wide area of abnormal bone metabolism in PsA.

Objective. Synovitis is very common in knee OA and associated with pain. This open-label study evaluated an anti-synovitis therapy, MTX, for pain relief in knee OA. Methods. Inclusion criteria included pain visual analogue scale (VAS) >40/100 mm, ACR clinical criteria for knee OA and intolerance/inefficacy of NSAID and opioids. US at baseline and 24 weeks assessed effusion and synovial thickness. Patients received MTX up to 20 mg/week for 24 weeks. Results. Thirty participants were recruited; mean age 64.5 years, median pain VAS 68 mm. At 24 weeks, 13/30 (43%) achieved 530% reduction in pain VAS, 7 (23%) achieved 550% reduction and 4 (13%) had worsened. Thirteen achieved Osteoarthritis Research Society International (OARSI) responder criteria. All had effusion/synovitis at baseline. There was no correlation between change in imaging and change in pain scores at 24 weeks. Conclusion. This open-label trial suggests analgesic efficacy for MTX in OA knee and suggests that a randomized controlled trial is warranted. Trial Registration. Current controlled trials, http://www.controlled-trials.com/, ISRCTN66676866.

The therapeutic goal for patients with rheumatoid arthritis (RA) is clinical remission. This is best achieved by early diagnosis and appropriate therapeutic intervention. RA is associated with dysregulation of T-cell subsets (naïve, regulatory (Treg) and inflammation-related cells (IRC)) early in the disease. Our aim was to test the hypothesis that T-cell subset quantification can predict the achievement of clinical remission with early treatment in RA.T-cell subsets were quantified in 108 drug-naïve, early RA patients commencing methotrexate (MTX) or MTX+antitumor necrosis factor (anti-TNF) and in 105 healthy controls (HC). The primary outcome assessed was remission (DAS282.6). A pilot study used frozen cells (38 patients and 35 HCs, see online supplementary material) and was validated with fresh blood (70 patients and 70 HCs).Immune dysregulation in early RA was confirmed with an association between age and reduced naïve cells compared with HCs (p=0.006), a lower age-adjusted Treg and higher IRC frequency (p=0.001). Anticitrullinated peptide antibody (ACPA) positivity was associated with lower naïve (p=0.031) and Treg frequencies (p=0.039). In 50 patients treated with MTX, ACPA/age-adjusted analysis demonstrated that higher naïve cell frequency (relative to HC) was associated with remission (OR 5.90 (1.66 to 20.98), p=0.006, sensitivity/specificity 62%/79%, Positive Predictive Value (PPV)/Negative Predictive Value (NPV) 66%/76%). Remission with MTX+anti-TNF (n=20) was not found to be associated with naïve cell frequency, and for patients with reduced naïve cells the remission rate increased from 24% (MTX) to 42% (MTX+anti-TNF).Baseline T-cell subset analysis has a value in predicting early RA remission with first therapy with MTX. Immunological analysis could be used in conjunction with clinical/serological features to predict response to MTX and help select the most appropriate therapy at disease presentation.

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.

Objective: To compare disease activity and disability over 2 years in early rheumatoid arthritis (RA) before and after implementation of treat‐to‐target therapy and identify predictors of adverse outcome. Methods: The Yorkshire Early Arthritis Register (YEAR) recruited 725 patients with early RA between 2002 and 2009, treated with a step‐up approach. The Inflammatory Arthritis Continuum study (IACON) recruited cases between 2010 and 2014 and treated to target. A total of 384 IACON cases met 2010 American College of Rheumatology/European League Against Rheumatism criteria. Latent growth curves of change in Disease Activity Score in 28 joints (DAS28) and the Health Assessment Questionnaire (HAQ) were compared between YEAR and IACON. Latent class growth analysis identified trajectories of change. Baseline predictors of trajectories were identified using logistic regression. Results: The mean DAS28 over 2 years was lower in IACON than in YEAR. Latent trajectories of HAQ change in YEAR were high stable (21% of cohort), moderate reducing (35%), and low reducing (44%). Only moderate reducing (66%) and low reducing (34%) were seen in IACON. In both cohorts, female sex and fatigue predicted adverse HAQ trajectories (high stable and moderate reducing). Odds ratios (ORs) for moderate reducing compared to low reducing for women were 2.58 (95% confidence interval [95% CI] 1.69, 4.49) in YEAR and 5.81 (95% CI 2.44, 14.29) in IACON. ORs per centimeter fatigue visual analog score were 1.13 (95% CI 1.07, 1.20) in YEAR and 1.16 (95% CI 1.12, 1.20) in IACON. Conclusion: Treat‐to‐target therapy gave more favorable trajectories of change in DAS28 and HAQ, but adverse HAQ trajectory was more likely in women with greater fatigue, suggesting such patients would benefit from interventions to improve function as well as reduce inflammation.

Background Rheumatoid arthritis (RA) is a chronic inflammatory arthritis, with significant impact on quality of life and functional status. Whilst biologic disease modifying anti-rheumatic drugs (bDMARD) such as tumour necrosis factor-inhibitor (TNFi) agents have revolutionised outcomes in RA, early diagnosis with immediate conventional therapy, titrated in a treat to target approach is also associated with high remission rates. The main aim of the VEDERA study (Very Early versus Delayed Etanercept in Rheumatoid Arthritis) is to assess the depth of remission, sustainability of remission and immunological normalisation induced by very early TNFi with etanercept (ETN) or standard of care +/- delayed ETN. Methods/Design VEDERA is a pragmatic, phase IV single-centre open-label randomised superiority trial of 120 patients with early, treatment-naive RA. Patients will be randomised 1:1 to first-line ETN and methotrexate (MTX) or MTX with additional synthetic disease modifying anti-rheumatic drugs (sDMARDs) according to a treat to target (TT) protocol with further step up to ETN and MTX after 24 weeks if remission is not achieved. Participants will have regular disease activity assessments and imaging evaluation including musculoskeletal ultrasound and MRI. The main objective of this study is to assess the proportion of patients with early RA that achieve clinical remission at 48 weeks, following either treatment strategy. In addition, the participants are invited to take part in a cardio-vascular sub-study (Coronary Artery Disease in RA, CADERA), which aims to identify the incidence of cardiovascular abnormalities in early RA. Discussion The hypothesis underlining this study is that very early treatment with first-line ETN increases the proportion of patients with rheumatoid arthritis achieving clinical remission, in comparison to conventional therapy. Trial registration NCT02433184, 23/04/2015

Objectives To review the literature in order to estimate how many previously unknown thoracic aortic aneurysms (TAAs) and thoracic aortic dilatations (TADs) might be detected by systematic, cross-sectional aortic imaging of patients with giant cell arteritis (GCA). Methods A systematic literature review was performed using Ovid Medline, Embase and the Cochrane Library. Studies potentially relevant to TAA/TAD were evaluated by two authors independently for relevance, bias and heterogeneity. Meta-analysis was performed using a random-effects model to estimate pooled prevalence. Results Two analyses of routinely collected administrative data suggested a threefold risk of TAA/dissection in GCA compared with controls. In GCA cohorts without systematic imaging, 2–8% had TAA. In the two best-reported studies, aneurysm dissection/rupture occurred in 1% and 6% of GCA cases. Aortic imaging studies had a variety of TAA/TAD definitions, imaging methods and time points. There were limited data on age-matched controls. Three studies suggested that male sex may be a risk factor for TAA/TAD in GCA. On average, five to ten patients with GCA would need aortic imaging to detect one previously unknown TAA/TAD. Conclusions The data support an association between GCA and TAA/TAD compared with age-matched controls, but the true relative risk, and the time course of that risk, remains unclear. It is also unclear whether chest radiography is a sufficiently sensitive screening tool. Clinicians should retain a high index of suspicion for aortic pathology in patients with GCA. Before ordering imaging, clinicians should consider whether, and how, detecting aortic pathology would affect a patient9s management.

OBJECTIVE: Anti-inflammatory therapies are effective analgesics for OA. This study determined whether low-dose oral prednisolone (PNL) was an effective analgesic for hand OA. METHODS: This was a randomized, double-blind, placebo-controlled trial of people with ACR criteria hand OA and baseline hand pain visual analogue scale (VAS) of >40/100 mm. Participants received 5 mg PNL or placebo daily for 4 weeks. Pain VAS, disease activity VAS, Australian/Canadian Hand Osteoarthritis Index and joint counts were performed at baseline, 4 and 12 weeks. Primary outcome was the change in hand pain VAS at 4 weeks. Analysis of covariance was used for analysis, controlling for baseline values. To explore potential mechanism of action of PNL, non-contrast 0.2 Tesla MRI was performed on the most painful hand at baseline and 4 weeks. RESULTS: A total of 70 participants were recruited (57 women, mean age 61 years, mean baseline pain VAS 61.5 mm); 75% had more than one joint with definite MRI synovitis/effusion. At 4 weeks the adjusted mean reduction in pain VAS was 19.9 mm (PNL group) and 16.8 mm (placebo group) (P = 0.54). There were no statistically significant differences in VAS, Australian/Canadian Hand Osteoarthritis Index or joint counts between placebo and PNL groups at 4 or 12 weeks. A total of 20 participants in each group achieved an Outcome Measures in Rheumatology-Osteoarthritis Research Society International response. Baseline synovitis/effusion did not predict response to treatment. CONCLUSION: This is the first randomized controlled trial of low-dose corticosteroid alone for painful hand OA, which demonstrated that short-term low-dose oral PNL is not an effective analgesic treatment for hand OA. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Register, www.isrctn.org, Trial number 99697616.

Objective.Our exploratory study of painful lesser metatarsophalangeal (MTP) joints in patients with rheumatoid arthritis (RA) primarily aimed to compare the clinical, biomechanical, and plain radiography findings with magnetic resonance (MR) arthrography findings. Our secondary aim was to compare standard unenhanced MR with MR arthrography in imaging the lesser MTP joints in RA.Methods.In 15 patients with RA, the more symptomatic forefoot was imaged using 3T MR imaging. Proton density fat-suppressed images were acquired through the lesser MTP joints prior to arthrography. Under ultrasound guidance, contrast agent was injected into 2 lesser MTP joints. T1-weighted fat-suppressed sequences were subsequently acquired. The MR images were read by 2 musculoskeletal radiologists and consensus was reached. Spearman’s correlation coefficient was used to assess the association between abnormalities seen on MR arthrography and the clinical, biomechanical, and plain radiography findings.Results.MR arthrography demonstrated pathology at 18 of 28 lesser MTP joints (64%) examined in patients with RA. MR arthrography abnormalities were associated with RA disease duration, forefoot deformity, Larsen score, subluxation, and peak plantar pressure. Unenhanced MR had a sensitivity of 78% and specificity of 90% for detecting pathology compared to MR arthrography.Conclusion.Capsule and plantar plate pathology occurs in the painful forefoot of patients with RA and is associated with features of disease and deformity at the lesser MTP joints. Compared with MR arthrography, standard MR imaging was highly specific and moderately sensitive for diagnosing lesser MTP joint pathology in patients with RA.