Changes in the plasma metabolic profile were characterised in newly diagnosed rheumatoid arthritis (RA) patients upon commencement of conventional disease-modifying anti-rheumatic drug (cDMARD) therapy. Plasma samples collected in an early RA randomised strategy study (NCT00920478) that compared clinical (DAS) disease activity assessment with musculoskeletal ultrasound assessment (MSUS) to drive treatment decisions were subjected to untargeted metabolomic analysis. Metabolic profiles were collected at pre- and three months post-commencement of nonbiologic cDMARD. Metabolites that changed in association with changes in the DAS44 score were identified at the three-month timepoint. A total of nine metabolites exhibited a clear correlation with a reduction in DAS44 score following cDMARD commencement, particularly itaconate, its derived anhydride and a derivative of itaconate CoA. Increasing itaconate correlated with improved DAS44 score and decreasing levels of C-reactive protein (CRP). cDMARD treatment effects invoke consistent changes in plasma detectable metabolites, that in turn implicate clinical disease activity with macrophages. Such changes inform RA pathogenesis and reveal for the first time a link between itaconate production and resolution of inflammatory disease in humans. Quantitative metabolic biomarker-based tests of clinical change in state are feasible and should be developed around the itaconate pathway.

Objective: To identify baseline prognostic indicators of disability at 1 year within a contemporary early inflammatory arthritis inception cohort and then develop a clinically useful tool to support early patient education and decision‐making.Methods: The Scottish Early Rheumatoid Arthritis (SERA) inception cohort is a multicenter, prospective study of patients with newly presenting RA or undifferentiated arthritis. SERA data were analyzed to determine baseline predictors of disability (defined as a Health Assessment Questionnaire [HAQ] score of ≥1) at 1 year. Clinical and psychosocial baseline exposures were entered into a forward stepwise logistic regression model. The model was externally validated using newly accrued SERA data and subsequently converted into a prediction tool.Results: Of the 578 participants (64.5% female), 36.7% (n = 212) reported functional disability at 1 year. Functional disability was independently predicted by baseline disability (odds ratio [OR] 2.67 [95% confidence interval (95% CI) 1.98, 3.59]), depression (OR 2.52 [95% CI 1.18, 5.37]), anxiety (OR 2.37 [95% CI 1.33, 4.21]), being in paid employment with absenteeism during the last week (OR 1.19 [95% CI 0.63, 2.23]), not being in paid employment (OR 2.36 [95% CI 1.38, 4.03]), and being overweight (OR 1.61 [95% CI 1.04, 2.50]). External validation (using 113 newly acquired patients) evidenced good discriminative performance with a C statistic of 0.74, and the calibration slope showed no evidence of model overfit (P = 0.31).Conclusion: In the context of modern early inflammatory arthritis treatment paradigms, predictors of disability at 1 year appear to be dominated by psychosocial rather than more traditional clinical measures. This indicates the potential benefit of early access to nonpharmacologic interventions targeting key psychosocial factors, such as mental health and work disability.

The Scottish Early Rheumatoid Arthritis (SERA) study is an inception cohort of rheumatoid (RA) and undifferentiated arthritis (UA) patients that aims to provide a contemporary description of phenotype and outcome and facilitate discovery of phenotypic and prognostic biomarkers Demographic and clinical outcome data are collected from newly diagnosed RA/UA patients every 6 months from around Scotland. Health service utilization data is acquired from Information Services Division, NHS National Services Scotland. Plain radiographs of hands and feet are collected at baseline and 12 months. Additional samples of whole blood, plasma, serum and filtered urine are collected at baseline, 6 and 12 months Results are available for 1073 patients; at baseline, 76 % were classified as RA and 24 % as UA. Median time from onset to first review was 163 days (IQR97-323). Methotrexate was first-line DMARD for 75 % patients. Disease activity, functional ability and health-related quality of life improved significantly between baseline and 24 months, however the proportion in any employment fell (51 to 38 %, p = 0.0005). 24 % patients reported symptoms of anxiety and/or depression at baseline. 35/391 (9 %) patients exhibited rapid radiographic progression after 12 months. The SERA Biobank has accrued 60,612 samples In routine care, newly diagnosed RA/UA patients experience significant improvements in disease activity, functional ability and health-related quality of life but have high rates of psychiatric symptoms and declining employment rates. The co-existence of a multi-domain description of phenotype and a comprehensive biobank will facilitate multi-platform translational research to identify predictive markers of phenotype and prognosis

Modern early rheumatoid arthritis strategies are usually based upon a number of important overarching principles: 1. early diagnosis facilitates early commencement of disease modifying anti-rheumatic therapy; 2. early commencement of treatment reduces the long-term risk of erosive damage and functional decline; 3. composite disease activity measures should be used to quantify global rheumatoid arthritis disease activity; and 4. therapy should be intensified until a predefined disease activity target has been achieved. A substantial minority of rheumatoid arthritis patients (approximately 40%) will experience an adequate response to methotrexate monotherapy; however, the remainder may require disease modifying anti-rheumatic combination therapy, and/or biologic therapy, to achieve disease activity targets. Importantly, short term trials of methotrexate monotherapy do not appear to disadvantage outcomes provided treatment continues to be intensified if disease activity targets are not achieved.

Background and aims: Ultrasound training for rheumatology practice in the UK is variable. Currently, there is no agreed minimum standard for training in ultrasound applied to rheumatology patient management. We present our experiences of implementing a competency driven ultrasound training, focused on hands and feet. Methods and results: The Rheumatology Sonography Course (RSC) was developed by the Scottish Rheumatology Ultrasound Group in collaboration with Glasgow Caledonian University. The RSC is delivered via a blended learning approach and includes training workshops, mentorship and clinical competency assessments. Mentors are supported and developed within their role. 31 trainees have enrolled on the course between 2014 and 2019. To date, 22 (71%) have completed. Change of job role was the main factor leading to non-completion. Thirteen mentors have supported the training and assessment of RSC trainees. All trainees reported positively that ultrasound training via the RSC model fulfilled their learning needs. Conclusion: The RSC is a feasible ultrasound training model for rheumatology practitioners. Whilst it provides a robust training framework, mentorship fees and university overheads increase the cost. The RSC provides motivation to mentors to train external trainees and supports the development of new ultrasound-based rheumatology services.