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Background: Patient education is integral to the treatment and care of patients with rheumatoid arthritis. Change is taking place in the organisation of healthcare systems because of a demographic shift towards ageing populations, an increasing use of technology and advancements in digital technologies, allowing for new interventions. This study will aim to evaluate the effectiveness of a newly developed e-learning patient education programme based on self-management that targets patients with rheumatoid arthritis. Methods: A pragmatic multi-centre randomised controlled trial is planned. We intend to recruit approximately 200 patients with a new diagnosis (< 3 months) of rheumatoid arthritis. Participants will be randomised 1:1 to web-based patient education delivered through an e-learning programme at home or standard face-to-face patient education provided at the hospital. The primary outcome is self-efficacy. Secondary outcomes are improved knowledge of rheumatoid arthritis, adherence to medication, health literacy level and quality of life. Outcomes will be measured at baseline and follow-up occurring 1, 3, 6 and 12 months after enrolment. Furthermore, data on healthcare utilisation and utilisation of the e-learning programme will be assessed at the 12-month follow-up. Statistical analysis, including differences between groups, will be evaluated using the chi-square and Kruskal–Wallis tests. Statistical analysis will follow the intention-to-treat principle, and analysis of variance will be used to evaluate the within- and between-groups differences testing the hypothesis of the ‘superiority’ of web-based patient education over standard face-to-face education provided at the hospital. Per protocol analysis will be used to assess the impact of missing data. Enrolment started in February 2021 and will end in June 2022. Discussion: The study is expected to contribute to the evidence on the effectiveness of web-based patient education within rheumatic diseases.

Objective: To explore the perspectives of general practitioners (GPs) on facilitators and barriers in diagnosing rheumatoid arthritis (RA). Design: Qualitative study based on focus group interviews, and using latent thematic analysis. Setting: General practices from Central Region Denmark. Subjects: Eleven GPs participated in three different focus groups. Forty percent were female, the mean age was 53 years (range 37–64), and the mean since medical licensing was 16 years (range 5–23). Sixty percent of the GPs worked in an area served by a university hospital, and 40% were served by a regional hospital. Main outcome measure: Themes describing experiences and reflections about facilitators and barriers in diagnosing Rheumatoid Arthritis. Results: Four themes emerged: (A) If the patient is not a textbook example, (B) The importance of maintaining the gatekeeper function, (C) Difficulties in referral of patients to the rheumatologist, and (D) Laboratory tests—can they be trusted? Barriers were identified in all themes, but facilitators only in A, C, and D. The overarching theme was Like finding a needle in a haystack. Conclusion: The GPs found several barriers for diagnosing RA (symptom awareness, GP’s gatekeeper function, suboptimal collaboration with rheumatologists and limitations in laboratory tests). They identified education, more specific tests and better access to rheumatologists as possible facilitators for diagnosing RA. To facilitate earlier referral of suspected RA in general practice and strengthen mutual information and collaboration, future research should focus on these facilitators and barriers.Keypoints Early diagnosis is essential for the prognosis of RA, and the diagnostic process begins in general practice. Suggested facilitators: training courses in interpretation of laboratory tests and the clinical manifestation of RA, and videos on joint examinations. Suggested barriers: compliance with the gatekeeper function, suboptimal collaboration with r

OBJECTIVES: To study if clinical, radiographic and MRI markers can predict MRI and radiographic damage progression and achievement of stringent remission in patients with established RA in clinical remission followed by a targeted treatment strategy. METHODS: RA patients (DAS28-CRP <3.2, no swollen joints) receiving conventional synthetic DMARDs were randomized to conventional or MRI-targeted treat-to-target strategies with predefined algorithmic treatment escalations. Potentially predictive baseline variables were tested in multivariate logistic regression analyses. RESULTS: In the 171 patients included, baseline MRI osteitis independently predicted progression in MRI erosion [odds ratio (OR) 1.13 (95% CI 1.06, 1.22)], joint space narrowing [OR 1.15 (95% CI 1.07, 1.24)] and combined damage [OR 1.23 (95% CI 1.13, 1.37)], while tenosynovitis independently predicted MRI erosion progression [OR 1.13 (95% CI 1.03, 1.25)]. A predictor of radiographic erosion progression was age, while gender predicted progression in joint space narrowing. Following an MRI treat-to-target strategy predicted stringent remission across all remission definitions: Clinical Disease Activity Index remission OR 2.94 (95% CI 1.25, 7.52), Simplified Disease Activity Index remission OR 2.50 (95% CI 1.01, 6.66), ACR/EULAR Boolean remission OR 5.47 (95% CI 2.33, 14.13). Similarly, low tender joint count and low patient visual analogue scale pain and global independently predicted achievement of more stringent remission. CONCLUSION: Baseline MRI osteitis and tenosynovitis were independent predictors of 2 year MRI damage progression in RA patients in clinical remission, while independent predictors of radiographic damage progression were age and gender. Following an MRI treat-to-target strategy, low scores of patient-reported outcomes and low tender joint count predicted achievement of stringent remission. TRIAL REGISTRATION: ClinicalTrials.gov (https://clinicaltrials.gov), NCT01656278.

Objectives: This study aimed to determine the prevalence of ultrasound-detected tendon abnormalities in healthy subjects (HS) across the age range. Methods: Adult HS (age 18-80 years) were recruited in 23 international Outcome Measures in Rheumatology ultrasound centres and were clinically assessed to exclude inflammatory diseases or overt osteoarthritis before undergoing a bilateral ultrasound examination of digit flexors (DFs) 1-5 and extensor carpi ulnaris (ECU) tendons to detect the presence of tenosynovial hypertrophy (TSH), tenosynovial power Doppler (TPD) and tenosynovial effusion (TEF), usually considered ultrasound signs of inflammatory diseases. A comparison cohort of patients with rheumatoid arthritis (RA) was taken from the Birmingham Early Arthritis early arthritis inception cohort. Results: 939 HS and 144 patients with RA were included. The majority of HS (85%) had grade 0 for TSH, TPD and TEF in all DF and ECU tendons examined. There was a statistically significant difference in the proportion of TSH and TPD involvement between HS and subjects with RA (HS vs RA p<0.001). In HS, there was no difference in the presence of ultrasound abnormalities between age groups. Conclusions: Ultrasound-detected TSH and TPD abnormalities are rare in HS and can be regarded as markers of active inflammatory disease, especially in newly presenting RA. Keywords: rheumatoid arthritis; tendinopathy; ultrasonography.

Andreas Bugge Tinggaard,1 Annette de Thurah,2 Ina Trolle Andersen,3 Anders Hammerich Riis,3 Josephine Therkildsen,1 Simon Winther,4 Ellen-Margrethe Hauge,2 Morten Bøttcher1 1Department of Cardiology, Hospital Unit West, Herning, Denmark; 2Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 4Department of Cardiology, Aarhus University Hospital, Aarhus, DenmarkCorrespondence: Andreas Bugge Tinggaard Tel +0045 30272717Email andreas.bugge@midt.rm.dkPurpose: To examine the occurrence and severity of coronary artery disease (CAD) in patients with rheumatoid arthritis (RA) compared to non-RA patients in a population referred for coronary computed tomography angiography (CTA) due to chest pain.Patients and Methods: In this cross-sectional study, 46,210 patients from a national CTA database were included. Patients with RA were stratified on serology, treatment with conventional synthetic or biological disease-modifying antirheumatic drugs (DMARDs), and the need for relapse or flare treatment with intraarticular or -muscular glucocorticoid injections (GCIs). Primary outcomes were coronary artery calcium score (CACS) > 0 and CACS ≥ 400, and secondary outcome was obstructive CAD. Associations between RA and outcomes were examined using logistic regression and results were adjusted for age, sex, cardiovascular risk factors and comorbidities.Results: A total of 395 (0.9%) RA patients were identified. In overall RA, crude odds ratio (OR) for having CACS > 0 was 1.48 (1.21– 1.82) and 1.52 (1.15– 2.01) for CACS ≥ 400, whereas adjusted ORs were 1.08 (0.86– 1.36) and 1.21 (0.89– 1.65), respectively. Seropositive RA patients had adjusted OR of 1.16 (0.89– 1.50) for CACS > 0 and 1.37 (0.98– 1.90) for CACS ≥ 400. Patients who had received ≥ 1 GCI in the period of 3 ye

Peter Engholm Hjort,1,2,* Philip Therkildsen,1,2,* Berit Dalsgaard Nielsen,1– 3 Ib Tønder Hansen,1,2 Mette Nørgaard,2,4 Annette de Thurah,1,2 Ellen-Margrethe Hauge1,2 1Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 3Diagnostic Centre, Silkeborg Regional Hospital, Silkeborg, Denmark; 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark*These authors contributed equally to this workCorrespondence: Philip TherkildsenDepartment of Rheumatology, Aarhus University Hospital, Aarhus, DenmarkEmail philther@rm.dkPurpose: To investigate the positive predictive value (PPV) of the giant cell arteritis (GCA) diagnosis in the Danish National Patient Registry (DNPR).Patients and Methods: A total of 293 patients aged ≥ 50 years with a first-time diagnosis of GCA in the DNPR between January 2012 and December 2017 were included. Patients were sampled from two secondary and one tertiary care hospitals in the Central Region Denmark. Two independent investigators (PH & PT) reviewed all medical files, including medical records, treatment, biochemistry, histopathology and imaging, and either confirmed or dismissed the diagnosis of GCA. In case of disagreement, a consensus agreement was reached. Sub-analyses including number of redeemed prescriptions performed temporal artery biopsies (TABs), and number of GCA-related hospital contacts were performed.Results: We confirmed the diagnosis of GCA in 183/293 patients resulting in a PPV of 62% (95% CI: 57– 68). In patients with ≥ 3 redeemed prescriptions of glucocorticoids (GCs), we confirmed the diagnosis in 166/214 resulting in a PPV of 78% (95% CI: 71– 83). In patients with ≥ 3 redeemed prescriptions of GCs and ≥ 3 GCA-related hospital contacts, we confirmed the diagnosis in 88/95 resulting in a PPV of 93% (95% CI: 85– 96)

Objective: Active rheumatoid arthritis (RA) is accompanied by increased appendicular and axial bone loss, closely associated to the degree of inflammation. The programmed death-1 (PD-1) pathway is important for maintaining peripheral tolerance, and its ligand PD-L2 has recently been associated with bone morphogenetic protein activity. Here, we report that PD-L2 plays a central role in RA osteoimmunology. Methods: Femoral bone mineral density (BMD) and trabecular bone microstructure were evaluated by micro-CT in wild type (WT) and PD-L2−/− mice. Osteoclasts were generated from RA synovial fluid mononuclear cells and peripheral blood monocytes. The effects of recombinant PD-L2, was evaluated by tartrate-resistant acid phosphatase (TRAP) activity and the development of bone erosions in the presence of anti-citrullinated protein antibodies (ACPA). Plasma soluble (s)PD-L2 levels were measured in patients with early (e)RA (n ​= ​103) treated with methotrexate alone or in combination with the TNF inhibitor Adalimumab. Results: PD-L2−/− mice had a decreased BMD and deteriorated trabecular bone microstructure that was not related to the RANKL/OPG pathway. PD-L2 decreased TRAP activity in osteoclasts and decreased ACPA-induced erosions. In the RA synovial membrane PD-L2 was highly expressed especially in the lining layer and plasma sPD-L2 levels were increased in eRA patients and decreased with treatment. One-year sPD-L2 correlated inversely with erosive progression two years after treatment initiation with methotrexate and placebo. Conclusion: PD-L2 regulates bone homeostasis in RA. Our findings provide new insight into the relationship between the immune system and bone homeostasis, and suggest a potential therapeutic target for limiting inflammatory bone loss in RA.

Introduction Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic, systemic, inflammatory diseases, primarily in the musculoskeletal system. Pain and fatigue are key symptoms of RA and AS. Treatment presents a clinical challenge for several reasons, including the progressive nature of the diseases and the involvement of multiple pain mechanisms. Moreover, side effects of pain treatment pose an implicit risk. Currently, no well-controlled studies have investigated how medical cannabis affects pain and cognitive functions in RA and AS. The present study aims to evaluate the efficacy and safety of medical cannabis in the treatment of persistent pain in patients with RA and AS with low disease activity. Methods and analysis A double-blinded, randomised, placebo-controlled study of cannabidiol (CBD), followed by an open label add-on of tetrahydrocannabinol (THC) with collection of clinical data and biological materials in RA and AS patients treated in routine care. The oral treatment with CBD in the experimental group is compared with placebo in a control group for 12 weeks, followed by an observational 12-week period with an open label add-on of THC in the primary CBD non-responders. Disease characteristics, psychological parameters, demographics, comorbidities, lifestyle factors, blood samples and serious adverse events are collected at baseline, after 12 and 24 weeks of treatment, and at a follow-up visit at 36 weeks. Data will be analysed in accordance with a predefined statistical analysis plan. Ethics and dissemination The Danish Ethics Committee (S-20170217), the Danish Medicines Agency (S-2018010018) and the Danish Data Protection Agency approved the protocol. The project is registered in the European Clinical Trials Database (EudraCT 2017-004226-15). All participants will give written informed consent to participate prior to any study-related procedures. The results will be presented at international conferences and published in peer-reviewed

IMPORTANCE Whether using magnetic resonance imaging (MRI) to guide treatment in patients with rheumatoid arthritis (RA) improves disease activity and slows joint damage progression is unknown. OBJECTIVE To determine whether an MRI-guided treat-to-target strategy vs a conventional clinical treat-to-target strategy improves outcomes in patients with RA in clinical remission. DESIGN, SETTING, AND PARTICIPANTS Two-year, randomized, multicenter trial conducted at 9 hospitals in Denmark. Two hundred patients with RA in clinical remission (disease activity score in 28 joints-C-reactive protein [DAS28-CRP] <3.2 and no swollen joints) were enrolled between April 2012 and June 2015. The final follow-up visit was April 2017. INTERVENTIONS Patients were randomly allocated (1:1) to an MRI-guided vs a conventional treat-to-target strategy. In the MRI-guided group, the treatment goal was absence of MRI bone marrow edema combined with clinical remission, defined as DAS28-CRP of 3.2 or less and no swollen joints. In the conventional group, the treatment goal was clinical remission. MAIN OUTCOMES AND MEASURES Co-primary outcomeswere proportions of patients achieving DAS28-CRP remission (DAS28-CRP <2.6) and with no radiographic progression (no increase in total van der Heijde-modified Sharp score) at 24 months. Significance testing for the primary outcome was based on 1-sided testing. Secondary outcomes were clinical and MRI measures of disease activity, physical function, and quality of life. RESULTS Of 200 patients randomized (133 women [67%]; mean [SD] age, 61.6 [10.5] years; median baseline DAS28-CRP, 1.9 [interquartile range, 1.7-2.2]; van der Heijde-modified Sharp score, 18.0 [interquartile range, 7.0-42.5]), 76 patients (76%) in the MRI-guided group and 95 (95%) in the conventional group completed the study. Of these, 64 (85%) vs 83 (88%), respectively, reached the primary clinical end point (risk difference, -4.8%[1-sided 95%CI, -13.6%to + ∞; 1-sided P = .19]) and 49