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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); however, this only included 88/183 confirmed GCA patients.Conclusion: This is the first study to validate the diagnostic code of GCA in the DNPR. The overall PPV of GCA in the DNPR was 62%. Requiring redeemed prescriptions of GCs and/or GCA-related hospital contacts increase the PPV, but also excludes a significant number of GCA patients.Keywords: rheumatology, giant cell arteritis, validation, positive predictive value, Danish National Patient Registry

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 years prior to the CTA had an adjusted OR of 1.37 (0.94– 2.00) for having CACS > 0 and 1.46 (0.92– 2.31) for CACS ≥ 400.Conclusion: This is the first large-scale, CTA-based study examining the occurrence and severity of CAD in RA patients with symptoms suggestive of cardiovascular disease. A higher prevalence of coronary artery calcification was found in RA patients. After adjusting for age, sex, cardiovascular risk factors and comorbidities, the tendency was less pronounced. We found a trend for increased coronary calcification in RA patients being seropositive or needing treatment with GCI for a relapse or flare.Keywords: rheumatoid arthritis, computed tomography angiography, coronary artery disease, coronary artery calcium score, cross-sectional

To compare the effect of treat-to-target-based escalations in conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologics on clinical disease activity and magnetic resonance imaging (MRI) inflammation in a rheumatoid arthritis (RA) cohort in clinical remission. One-hundred patients with established RA, Disease Activity Score based on 28-joint count–C-reactive protein (DAS28-CRP) < 3.2, and no swollen joints (hereafter referred to as 'in clinical remission') who received csDMARDs underwent clinical evaluation and MRI of the wrist and second to fifth metacarpophalangeal joints every 4 months. They followed a 2 year MRI treatment strategy targeting DAS28-CRP ≤ 3.2, no swollen joints, and absence of MRI osteitis, with predefined algorithmic treatment escalation: first: increase in csDMARDs; second: adding a biologic; third: switch biologic. MRI osteitis and Health Assessment Questionnaire (HAQ) (co-primary outcomes) and MRI combined inflammation and Simplified Disease Activity Index (SDAI) (key secondary outcomes) were assessed 4 months after treatment change and expressed as estimates of group differences. Statistical analyses were based on the intention-to-treat population analysed using repeated-measures mixed models. Escalation to first biologic compared to csDMARD escalation more effectively reduced MRI osteitis (difference between least squares means 1.8, 95% confidence interval 1.0–2.6), HAQ score (0.08, 0.03–0.1), MRI combined inflammation (2.5, 0.9–4.1), and SDAI scores (2.7, 1.9–3.5). Treat-to-target-based treatment escalations to biologics compared to escalation in csDMARDs more effectively improved MRI inflammation, physical function, and clinical disease activity in patients with established RA in clinical remission. Treatment escalation in RA patients in clinical remission reduces clinical and MRI-assessed disease activity. Clinicaltrials.gov identifier: NCT01656278 [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA).Method: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (ΔDAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group.Results: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (ΔDAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02).Conclusion: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA. [ABSTRACT FROM AUTHOR]

Objective: To investigate bone changes in the metacarpophalangeal (MCP) joints of anti-citrullinated peptide antibody (ACPA)-positive patients with arthralgia, but not arthritis, compared to healthy controls.Method: Using a cross-sectional study design, patients were recruited from hospitals and private care rheumatologists, and controls from a test subject website. All subjects underwent medical history interview, clinical examination, and biochemical screening including ACPA. Patients with positive ACPA, arthralgia, and no rheumatic disease were included. Controls without a history or signs of rheumatological disease or positive ACPA were included. A 2.7-cm-long region around the second and third MCP joints was evaluated using high-resolution peripheral quantitative computed tomography with a voxel size of 82 µm.Results: Twenty-nine ACPA-positive patients and 29 healthy controls were evaluated. Trabecular volumetric bone mineral density and bone volume fraction did not differ between the groups. In addition, the cortical bone was not affected in patients, as we found no difference in average cortical thickness and cortical bone area between the groups. In contrast, the trabeculae were significantly (p < 0.05) thinner in both second and third MCP heads compared with controls, whereas trabecular number and trabecular separation did not differ between the groups. No erosions were demonstrated and the number of non-specific breaks did not differ between the groups.Conclusion: Trabecular bone changes were observed in ACPA-positive patients with arthralgia compared with healthy controls. The results may reflect inflammatory up-regulated trabecular bone resorption leading to early bone loss before the onset of clinical arthritis. [ABSTRACT FROM AUTHOR]

The article presents the case study of the 62-year-old female patient who suffered from rheumatoid arthritis (RA), breath shortness, general malaise as well as productive cough in Denmark. The topics discussed include the number of years she suffered from RA, the medications she consumed, and the co-morbidities she suffered like diabetes mellitus as well as mild renal failure.

Objective: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR)., Methods: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated., Results: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care., Conclusions: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR., Competing Interests: Competing interests: KKK: Research grants from Independent Research Fund Denmark, Danish Rheumatic Association and Central Denmark Region unrelated to this project. SES: Research grants from Rheumatology Research Foundation, Bristol Myers Squibb Foundation. Clinical trial support from AstraZeneca, GlaxoSmithKline; Consulting fees from Sanofi (funds toward research support); Data Safety Monitoring Board on MINT trial, Advisory Board for Sanofi (funds toward research support). E-MH: Has received grants unrelated to this manuscript from Novo Nordic Foundation, Roche, Novartis; Personal fees from AbbVie, Sanofi, SOBI, Merck Sharp & Dohme and Union Chimique Belge. AD: Consulting fees from Sanofi; Participation on a Data Safety Monitoring Board or Advisory Board for Sanofi; Board member Vasculitis Foundation. LN: Has received Honorarium from Abbvie; Trustee of the charity PMR-GCA Scotland. SM: Consulting fees from Astrazeneca; Honoraria from Vifor. KJW: Grants from Eli Lilly, Kiniksa, BMS; Consulting fees from Amgen, Sanofi. Honoraria from Amgen. CP: Consulting fee from Pfizer. MP: Consulting fee from Novartis; Clinical trial participant for Abbvie, Amgen, AstraZeneca. HIK: Honoraria from Roche, eTherapeutic Guidelines Australia; Board member Australian Rheumatology Association; Clinical trials for Roche, Abbvie, Sun, Emerald, Novartis, Biogen, Sanofi, Syneos. CEO: Consultancy for Abbvie; Speaking honoraria from Abbvie, Janssen, Novartis and Roche; Advisory board for Abbvie. WAS: Has received honoraria from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi ; Support for attending meetings/travel from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi; Participated in advisory board from Abbvie, GlaxoSmithKline, Novartis, Sanofi; Principle investigator of phases 2 and 3 studies sponsored by Abbvie, GlaxoSmithKlinie, Novartis and Sanofi. EBrouwer: As an employee of the UMCG received a speaker fee for a talk on GCA at a post EULAR symposium in the Netherlands in 2023 which was paid to the UMCG; As an employee of the UMCG received grants from the Dutch Arthritis Society DAS and the EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking Immune-Image grant no 831514 which were paid to the UMCG. SM: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis and AbbVie; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SM is supported in part by the NIHR Leeds Biomedical Research Centre. VD-P has received honorarium from Abbvie, Chugai, Novartis, BMS, Support for attending meetings/travel from Novartis; Participated in advisory borad from Abbvie, Novartis. All other authors have no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Objectives: To evaluate sensitivity and scores of vascular ultrasound (US) before and after initiating glucocorticoid (GC) treatment in patients with new-onset giant cell arteritis (GCA)., Methods: Treatment-naïve patients with GCA were prospectively included. 18F-FDG PET/CT, US and temporal artery (TA) biopsy were performed in all patients. US was repeated 3 and 10 days after GC commencement. Intima-media thickness and presence of halo signs were assessed. Sonographers were unblinded to clinical data. The OMERACT GCA Ultrasonography score (OGUS) and halo count (HC) were calculated., Results: Forty-eight patients were included. Before GC exposure, US sensitivity was 94% (95% CI: 83-99), 73% (95% CI: 58-85) and 71% (95% CI: 56-83) when assessing all vessels, TAs, and large vessels (LVs), respectively. At day 3 and 10, overall US sensitivity was 92% (95% CI: 78-98, p= 0.16) and 83% (95% CI: 69-92, p= 0.10), respectively. At day 10, TA-US and LV-US sensitivity was 53% (95% CI: 38-68, p< 0.01), and 60% (95% CI: 44-74, p= 0.13), respectively. Median OGUS decreased from 1.06 (IQR 0.83-1.24)-0.95 (IQR 0.78-1.14, p< 0.01), and 0.90 (IQR 0.73-1.01, p< 0.001) after 3 and 10 days, respectively. Median HC decreased from 3 (IQR 2-5)-2 (IQR 1-4, p< 0.01) after 10 days., Conclusion: The vasculitic US findings expressed by OGUS diminish after 3 days of GC treatment. TA-US sensitivity decreased after 10 days, whereas LV-US was less likely to change, highlighting the importance of LV-assessment. Consistent with the EULAR recommendations, these findings encourage prompt US assessment, preferably within 3 days, to ensure an accurate diagnosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Osteoporosis is under-diagnosed while detectable by measuring bone mineral density (BMD) using quantitative computer tomography (QCT). Opportunistic screening for low BMD has previously been suggested using lumbar QCT. However, thoracic QCT also possesses this potential to develop upper and lower cut-off values for low thoracic BMD, corresponding to the current cut-offs for lumbar BMD. In participants referred with chest pain, lumbar and thoracic BMD were measured using non-contrast lumbar- and cardiac CT scans. Lumbar BMD cut-off values for very low (< 80 mg/cm 3 ), low (80-120 mg/cm 3 ), and normal BMD (> 120 mg/cm 3 ) were used to assess the corresponding thoracic values. A linear regression enabled identification of new diagnostic thoracic BMD cut-off values. The 177 participants (mean age 61 [range 31-74] years, 51% women) had a lumbar BMD of 121.6 mg/cm 3 (95% CI 115.9-127.3) and a thoracic BMD of 137.0 mg/cm 3 (95% CI: 131.5-142.5), p < 0.001. Categorization of lumbar BMD revealed 14%, 35%, and 45% in each BMD category. When applied for the thoracic BMD measurements, 25% of participants were reclassified into a lower group. Linear regression predicted a relationship of Thoracic BMD = 0.85 * Lumbar BMD + 33.5, yielding adjusted thoracic cut-off values of < 102 and > 136 mg/cm 3 . Significant differences in BMD between lumbar and thoracic regions were found, but a linear relationship enabled the development of thoracic upper and lower cut-off values for low BMD in the thoracic spine. As Thoracic CT scans are frequent, these findings will strengthen the utilization of CT images for opportunistic detection of osteoporosis., (© 2024. The Author(s).)

Introduction: Following the approval of tocilizumab (TCZ) for giant cell arteritis (GCA), recent studies have shown a high relapse frequency after abrupt discontinuation of TCZ. However, a thorough exploration of TCZ tapering compared to abrupt discontinuation has never been undertaken. Likewise, adverse events have only been scarcely investigated in routine care. This study aimed to compare the incidence of relapses in GCA patients undergoing TCZ tapering compared to abrupt discontinuation., Methods: We performed a single-center retrospective cohort study from 2012 to 2022. Data from GCA patients treated with TCZ was obtained from the Electronic Patients Record. Relapse-free survival is reported in Kaplan-Meier plots and tapering versus abrupt discontinuation were compared using a Wilcoxon-Brewlos-Gehan test., Results: We included 155 patients receiving TCZ treatment for GCA, of which 104 discontinued TCZ. Among the 104 patients discontinuing TCZ, 42 (40 %) experienced a relapse within the first year. A total of 57 patients underwent taper with 6/38 (16 %) and 2/19 (11 %) relapsing while receiving TCZ every second or third week, respectively. In comparison, 59 patients underwent abrupt discontinuation with 27 (46 %) relapsing during follow-up. The patients undergoing abrupt TCZ discontinuation demonstrated a significantly shorter time to relapse compared to all tapered patients (p = 0.02) as well as patients tapered from weekly TCZ treatment to every second week (p < 0.01). Furthermore, 15 % of patients discontinued TCZ due to adverse events., Conclusion: This is the first study indicating that TCZ taper induced longer relapse-free survival than abrupt discontinuation, implying that taper may be favored over discontinuation in patients with GCA., Competing Interests: Declaration of competing interest BDN has received speaking fees unrelated to this manuscript from Novartis an AbbVie. EMH has received fees unrelated to this manuscript for speaking and/or consulting from Novo, Novartis, AbbVie, Sanofi, Sobi; research funding to Aarhus University Hospital from Independent Research Fund Denmark, Novo Nordic Foundation, Danish Rheumatism Association, Aarhus University, Danish Regions Medicine Grants, Galapagos, AbbVie; travel expenses from Pfizer, Sobi, AbbVie. EMH has been the principal investigator in trials by SynACT Pharma and involved as site principal investigator in trials by AbbVie, Novartis, Novo Nordisk, Sanofi. All other authors have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

To evaluate tumour necrosis factor inhibitor (TNFi) drug-levels and presence of anti-drug antibodies (ADAb) in patients with inflammatory arthritis who taper TNFi compared to TNFi continuation. Patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis on stable TNFi dose and in low disease activity ≥ 12 months were randomised (2:1) to disease activity-guided tapering or control. Blood samples at baseline, 12- and 18-months were evaluated for TNFi drug-levels and ADAb. In total, 129 patients were randomised to tapering (n = 88) or control (n = 41). Between baseline and month 18, a significant shift in TNFi drug-levels were observed in the tapering group resulting in fewer patients with high drug-levels (change: - 14% [95% CI - 27 to - 1%]) and more with low drug-levels (change: 18% [95% CI 5-31%]). Disease activity was equivalent between groups at 18 months, mean difference: RA - 0.06 (95% CI - 0.44 to 0.33), PsA 0.03 (95% CI - 0.36 to 0.42), and axSpA 0.16 (- 0.17 to 0.49), equivalence margins ± 0.5 disease activity points. ADAb were detected in eight patients, all from the tapering group. TNFi drug-level category or ADAb were not predictive for achieving successful tapering at 18 months. TNFi drug-levels decreased during tapering which indicate adherence to the tapering algorithm. Despite the difference in TNFi drug-levels at 18 months, disease activity remained equivalent, and only few tapering patients had detectable ADAb. These data do not support using TNFi drug-level and/or ADAb to guide the tapering decision but future research with larger trials is needed.Trial registration: EudraCT: 2017-001970-41, December 21, 2017., (© 2024. The Author(s).)

Background: The integration of telehealth interventions into clinical practice is frequently delayed, hindering the full adoption. Previously, we developed a digital patient education (PE) programme for self-management in rheumatoid arthritis (RA). While the programme design considered crucial factors to ensure the likelihood of success in clinical practice, there is a need for a systematic evaluation of implementation perspectives. The purpose of this study was to explore perspectives crucial to implementation of a digital PE programme in clinical practice., Methods: The non-adoption, abandonment, scale-up, spread and sustainability (NASSS) framework was used to evaluate the successes and challenges of implementing the digital PE programme. We included a data set consisting of qualitative focus group discussions involving study nurses, rheumatologists, and leaders from rheumatology departments. Data analysis was guided by a deductive content analysis approach. Further we included data from earlier studies pertaining to the programme's implementation, comprising the programme development process, a randomized controlled trial evaluating the programme's effectiveness, and a qualitative study exploring patients' perspectives of the programme., Results: Facilitators and challenges of importance to implementation of digital PE were identified. While a wide range of patients could benefit from using digital PE, future implementation should aim for an even broader group than those studied. Both patients and healthcare providers embraced the technology, and the fact that it did not require specific technical skills enhances its potential for success. However, offering digital PE should be based on individual assessments, and expanding its use will require organizational adjustments. An adaptable structure is needed to accommodate unforeseen care needs that may arise following the use of digital PE at home. There was indication of some reluctance among healthcare providers toward the programme shown by concerns about changing roles, which could impact the adoption of the program., Conclusions: The design and ease of use of the technology, the program's effectiveness, its availability, and the potential to release healthcare resources may encourage the implementation of digital patient education. Challenges associated with implementing this mode of care pertains to the condition and the patient population, user adoption of the technology, and the organization of patient education., Trial Registration: The study is registered by the Central Denmark Region Scientific Committee (no. 1-16-02-52-19)., (© 2024. The Author(s).)

Objectives: To evaluate the effectiveness of a novel digital patient education (PE) programme in improving self-management in patients newly diagnosed with rheumatoid arthritis (RA)., Methods: This was a parallel, open-label, two-armed, randomized controlled trial with superiority design. Patients from five rheumatology clinics were randomized into digital PE (intervention) or face-to-face PE (control). The primary outcome was self-efficacy, measured by average difference in the Rheumatoid Arthritis Self-Efficacy (RASE) score from baseline to month 12. Secondary outcomes were RA knowledge, health literacy, adherence and quality of life. Healthcare utilization data and digital PE programme usage were recorded. Self-efficacy, knowledge and health literacy data were analysed using mixed-effects repeated measures modelling; adherence using logistic regression, and quality of life and healthcare utilization using descriptive statistics with the Wilcoxon rank-sum test., Results: Of the 180 patients randomized (digital PE, n = 89; face-to-face PE, n = 91), 175 had data available for analysis. Median age was 59.0 years and 61% were women. The average difference in self-efficacy between groups from baseline to month 12 was significant by a -4.34 difference in RASE score, favouring the intervention group (95% CI: -8.17 to -0.51; P = 0.026). RA knowledge, health literacy and quality of life showed minor improvements over time but no difference between groups, except out-patient clinic contacts, which were fewer in the intervention group., Conclusion: The findings suggest that digital PE is effective in improving self-efficacy and therefore self-management in patients with early RA. This intervention has potential to lower healthcare costs by decreasing out-patient clinic contacts., Trial Registration Number: clinicaltrials.gov, NCT04669340., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The objective was to investigate the incidence of late-onset giant cell arteritis (GCA) within the first year in patients diagnosed with polymyalgia rheumatica (PMR)., Methods: In this prospective study, treatment-naïve individuals with a new clinical diagnosis of PMR and without GCA symptoms underwent baseline assessments, including vascular ultrasonography and 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (FDG-PET/CT). To prevent biased inclusion, rapid referral clinics were established for all patients suspected of PMR. Additionally, the patients underwent GCA monitoring during clinical visits at weeks 8 and 10, which involved vascular ultrasonography and FDG-PET/CT scans. After one year, a follow-up visit was performed to confirm the PMR diagnosis and perform vascular ultrasonography., Results: A final PMR diagnosis was assigned to 62 patients, excluding 2 patients with concurrent subclinical GCA and PMR at baseline, corresponding to a baseline prevalence of subclinical GCA of 3%. During the one-year follow-up, two PMR patients developed late-onset GCA corresponding to an incidence rate of 32 per 1000 person-years. One patient developed GCA 14 weeks after the PMR diagnosis, exhibiting cranial symptoms and positive vascular ultrasonography. The other patient presented with subclinical large vessel GCA at the one-year visit detected with vascular ultrasonography and confirmed by FDG-PET/CT., Conclusion: This study is the first to demonstrate a low incidence rate of late-onset GCA in PMR patients within the first year, employing repeated imaging to exclude GCA at baseline and diagnose GCA during follow-up. Additionally, it provides evidence of a low prevalence of subclinical GCA across the entire PMR population., Trial Registration: ClinicalTrials.Gov, NCT04519580., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Rituximab (RTX)-treated patients exhibit suboptimal responses to COVID-19 vaccines. However, existing research primarily involves patients already receiving RTX when vaccines were introduced, failing to account for the current landscape where patients are vaccinated before initiating RTX. Our objective was to compare the serological response to COVID-19 vaccines in patients vaccinated before or after RTX initiation., Methods: We included 254 RTX-treated patients with autoimmune inflammatory rheumatic diseases (AIIRDs) and 113 blood donors (BDs) in a retrospective, observational cohort study. Patients were categorized based on the timing of RTX treatment relative to primary COVID-19 vaccination. Serological vaccine responses were assessed using three immunoassays, and logistic regression analysis was used to identify predictors of serological response., Results: Patients vaccinated before initiating RTX treatment had significantly higher seroconversion rates of SARS-CoV-2 immunoglobulin G (87%) and neutralizing antibodies (91%) compared with those receiving RTX before and after vaccination (n = 132) (61% and 65%, respectively). In the logistic regression analysis, a positive serological response was associated with the number of vaccines administered >9 months after the last RTX treatment. Patients receiving the highest number of vaccines with >9 months after RTX showed a response comparable to that of the BDs., Conclusion: Vaccinating before RTX initiation yields a robust serological response in patients with AIIRDs. Furthermore, we highlight the reversibility of antibody impairment after RTX treatment cessation, provided that adequate vaccinations occur within a minimum of 9 months after RTX. Our findings offer essential insights for clinical decision-making regarding COVID-19 vaccination and RTX treatment, alleviating concerns about future RTX use., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Purpose: In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) computed tomography (CT) to validate their initial clinical diagnosis of polymyalgia rheumatica (PMR). Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR., Methods: An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven-score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after twelve or six months in the investigation and validation cohorts, respectively., Results: In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven-score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven-score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven-score., Conclusion: Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA., Methods: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease., Results: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk., Conclusions: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The DANIsh VASculitis cohort study, DANIVAS, is an observational national multicenter study with the overall aim to prospectively collect protocolized clinical data and biobank material from patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) diagnosed and/or followed at Danish rheumatology departments. A long-term key objective is to investigate whether the use of new clinically implemented diagnostic imaging modalities facilitates disease stratification in the GCA-PMR disease spectrum. In particular, we aim to evaluate treatment requirements in GCA patients with and without large-vessel involvement, treatment needs in PMR patients with and without subclinical giant cell arteritis, and the prognostic role of imaging with respect to aneurysm development. Hence, in GCA and PMR, imaging stratification is hypothesized to be able to guide management strategies. With an established infrastructure within rheumatology for clinical studies in Denmark, the infrastructure of the Danish Rheumatologic Biobank, and the possibility to cross-link data with valid nationwide registries, the DANIVAS project holds an exceptional possibility to collect comprehensive real-world data on diagnosis, disease severity, disease duration, treatment effect, complications, and adverse events. In this paper, we present the research protocol for the DANIVAS study. Clinical trial registration : https://clinicaltrials.gov/, identifier NCT05935709., Competing Interests: BN has received speaker’s fees from Novartis and AbbVie. AC has received research grants from Novartis, Janssen, GSK, Syneos, and personal fees from UCB. LT has received speaker’s fees from Janssen, Pfizer, and Novartis. LD has received a research grant (paid to the institution) from BMS and AbbVie outside the present work; travel expenses from Janssen, UCB, and Boehringer Ingelheim. MH has received a research grant (paid to Institution) from AbbVie, BMS, Eli Lilly, MSD, Pfizer, Sandoz, and Novartis; speaker’s fee (paid to Institution) from Medac, Pfizer, Sandoz, and speaker’s fee (personal) from Novartis. E-MH has received fees for speaking and/or consulting from Novo, Novartis, and SynAct Pharma; research funding to Aarhus University Hospital from Novo Nordic Foundation, Galapagos, AbbVie; travel expenses from Pfizer, Sobi, and AbbVie. SC received speaker’s fee from Pfizer, Novartis, and Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Nielsen, Kristensen, Donskov, Terslev, Dreyer, Colic, Hetland, Højgaard, Ellingsen, Hauge, Chrysidis and Keller.)

Purpose: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation., Methods: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year., Results: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%., Conclusion: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy., Trial Registration: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020., (© 2024. The Author(s).)

Objective: To assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc., Methods: HR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales., Results: Forty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66-99%) and 80% (95% CI: 59-93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47-90%) and 95% (95% CI: 76-99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1-3) versus 0 (IQR: 0-1) (P<0.01). Grade 3 changes were observed exclusively in patients with AO (n=6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability., Conclusion: HR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear., Objectives: This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk., Methods: The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated., Results: During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81)., Conclusions: Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases., Competing Interests: Funding Support and Author Disclosures This study was funded by Aarhus University Hospital. The funding source had no influence on study design, conduct or reporting. Dr Blaha has received grants from the National Institutes of Health, U.S. Food and Drug Administration, American Heart Association, and Aetna Foundation; has received grants and personal fees from Amgen; and has received personal fees from Sanofi, Regeneron, Novartis, Bayer, and Novo Nordisk outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Gout attacks are treated with uric-lowering and anti-inflammatory drugs. In patients with gout, non-steroidal anti-inflammatory drugs (NSAIDs) could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic side effects. We, therefore, examined the risk of cardiovascular events associated with NSAID use in patients with gout. We conducted a nationwide, population-based case-crossover study of all Danes ≥ 18 years of age with first-time gout during 1997-2020, who experienced a cardiovascular event (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation/flutter, or cardiovascular death) (n = 59,150). The exposure was use of NSAIDs, overall and according to type (ibuprofen, naproxen, or diclofenac). We used the dates 300, 240, 180, and 120 before the outcome date as reference dates. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and cardiovascular events. NSAID use was overall associated with 12% decreased odds of a cardiovascular event (OR = 0.88, 95% CI: 0.85-0.91). This decreased odds ratio was observed for the use of ibuprofen (OR = 0.92, 95% CI: 0.88-0.97) and naproxen (OR = 0.85, 95% CI: 0.74-0.97), but not for the use of diclofenac (OR = 0.97, 95% CI: 0.90-1.05). Overall, use of NSAIDs was associated with decreased odds of all the individual components of the composite outcome. NSAIDs were not associated with an increased cardiovascular event rate when used in gout patients. Ibuprofen and naproxen appeared to have better cardiovascular risk profiles than diclofenac., (© 2024. The Author(s).)

Objectives: To investigate the diagnostic accuracy of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess erosive progression during one year compared to conventional radiography (CR) in rheumatoid arthritis (RA)., Methods: This prospective study included 359 patients with RA (disease duration ≥ 5 years) between March 2018 and October 2020. HR-pQCT and CR were obtained at inclusion and after one year. Erosive assessment was performed at two metacarpophalangeal joints of the dominant hand using HR-pQCT and progression was defined as an increase in erosion number ≥ 1 or an increase in erosive volume > least significant change. CR of hands, wrists, and feet were evaluated using Sharp/van der Heijde scores and erosive progression was defined as a 1.1-point increase in erosion score according to the smallest detectable change., Results: In paired analyses (n = 310), erosive progression was identified in 30 patients using CR and in 40 patients using HR-pQCT. In the 40 patients with erosive progression on HR-pQCT, progression was not identified by CR in 33 patients. Adding HR-pQCT to CR doubled the proportion of patients identified with progression from 30 (10%) to 63 (20%) patients. Using CR as the reference, the sensitivity (% (95% CI)) of HR-pQCT for identifying erosive progression was 23.3 (9.9-42.3) and the specificity was 88.2 (83.8-91.7)., Conclusion: A substantial proportion of patients with erosive progression are overlooked using CR only to monitor erosive progression. Adding high-resolution peripheral CT to CR doubles the proportion of patients, who may benefit from individualised therapy targeting erosive progression in RA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To investigate whether a 2-year MRI treat-to-target strategy targeting the absence of osteitis combined with clinical remission, compared with a conventional treat-to-target strategy targeting clinical remission only (IMAGINE-rheumatoid arthritis (RA) trial) improves clinical and radiographic outcomes over 5 years in patients with RA in clinical remission., Methods: IMAGINE-more was an observational extension study of the original 2-year IMAGINE-RA randomised trial (NCT01656278). Clinical examinations and radiographs (hands and feet) were obtained yearly. Prespecified coprimary outcomes at year 5 were Disease Activity Score in 28 joints C reactive protein (DAS28-CRP) remission rate (DAS28-CRP<2.6) and no radiographic progression (van der Heijde-modified Sharp score (vdHSS) ≤0) from baseline. Secondary outcomes included 5-year changes in radiographic, MRI and clinical measures of disease activity and physical function., Results: In total 131 patients, 86 women (67%), mean age 61.2, disease duration 9.5 years, median baseline DAS28-CRP 1.9 (IQR 1.6-2.2) and vdHSS 16.0 (IQR 7.0-36.0) were included in the study; 59 (59%) patients from the original MRI treat-to-target group and 72 (72%) from the conventional group. At year 5, 47 patients (80%) in the MRI treat-to-target group vs 54 patients (75%) in the conventional treat-to-target group were in DAS28-CRP remission (OR 2.00 (95% CI 0.76 to 5.28); p=0.16) while 14 patients (24%) vs 19 patients (26%) had no radiographic progression (OR 0.70, (95% CI 0.28 to 1.71); p=0.43)., Conclusion: A 2-year combined MRI and clinical treat-to-target strategy, compared with a conventional clinical treat-to-target strategy alone, had no effect on the long-term probability of achieving DAS28-CRP remission and of avoiding radiographic progression., Competing Interests: Competing interests: SMB has received research support from AbbVie and support for attending meetings and/or travl from Medac and Novartis. KHP has received research support from AbbVie. LMØ has received research grant from Novartis. MLH has received research grant from AbbVie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Nordforsk and speaking fees and/or honoraria from Pfizer, Medac, Sandoz paid to institution and has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from the hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylorthritis based on secondary data and is partly funded by Novartis. DG has received consulting fees from Janssen and speaking fees from Eli Lilly and Advisory board activity for AbbVie and Eli Lilly. MB has received research support from AbbVie and speaking fees from AbbVie, UCB, Eli Lilly, Image Analysis Group, Esaote. EMH has received research grants from Independent Research Fund Denmark, Novo Nordic Foundation, Danish Rheumatism Association, Aarhus University, Danish Regions Medicine Grants, Galapagos, AbbVie, Roche, Novartis, consulting fees from Novo Nordic, Novartis, AbbVie, Sanofi, Sobi, MSD, UCB, spekin fees from Novo Nordic, Novartis, AbbVie, Sanofi, Sobi, MSD, UCB, support for attending meetings and/or travl from Pfizer Sobi, AbbVie, Celgene, MSD, Roche, advisory board SynACT Pharma and principal trial investigator/site investigator for trials supported by AbbVie, Novartis, Novo Nordic, Sanofi, SynACT Pharma. OH has received speaking fees from Abbvie, Pfizer, Novartis, Eli-Lilly and support for attending meetings and/or travl from Pfizer, Abbvie. NSK has received grants from ScandRA and EuroStar. MØ has received research support 15 from AbbVie and grants from Amgen, BMS, Merck, Celgene and Novartis, Galapagos, Gilead, Hospira, Janssen, Merck, Novartis, Pfizer, UCB and consulting fees from Abbvie, BMS, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, UCB, speaking fees from Abbvie, BMS, EliLilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, UCB. BE, JM, SMN, KSP, ORM, BJ, JAV, HL, AGJ, HST, RC, have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: Cementless arthroplasty fixation relies on early bone ingrowth and may be poor in patients with low proximal tibial bone density or abnormal bone turnover. We aimed first to describe the baseline bone properties in patients undergoing medial unicompartmental knee replacement (UKR), and second to investigate its association with cemented and cementless tibial component migration until 2 years., Methods: A subset investigation of 2 patient groups from a 3-armed randomized controlled trial was conducted. There were 26 cemented and 25 cementless medial UKRs with twin-pegged femoral components. Volumetric bone mineral density (vBMD) and microstructure of the excised medial tibial plateau were ascertained with µCT. Bone turnover was estimated using dynamic histomorphometry (eroded surface/bone surface = ES/BS, osteoid surface/bone surface = OS/BS, mineralizing surface/bone surface = MS/BS). Tibial component migration in 4 feature points was followed for 2 years with radiostereometry., Results: At the 2-year follow-up, the cementless tibial components migrated 0.38 mm (95% confidence interval [CI] 0.14-0.62) total translation more than the cemented components at the posterior feature point. The greatest migration in the cementless group was subsidence at the posterior feature point of 0.66 mm (CI 0.48-0.84) until 6 weeks, and from 3 months the components were stable. Cemented tibial components subsided very little. Between 1- and 2-year follow-ups, no cementless but 4 cemented tibial components revealed continuous migration. OS/BS was half of the ES/BS. No µCT or histomorphometric parameters showed any clinically relevant correlation with tibial component migration at the posterior feature point for either cemented or cementless UKR at 6 weeks' or 2 years' follow-up after adjustment for age, BMI, and sex., Conclusion: Preoperative vBMD, bone turnover, and microstructure were not associated with postoperative tibial component migration of cemented and cementless medial UKR.

Objectives: Patients with giant cell arteritis (GCA) primarily have their infections managed by primary care providers and hospitalisation is rarely necessary. Existing studies in GCA focus on infection-related hospitalisations only, whereas the use of antibiotic prescriptions is largely unknown. This study aims to examine the one-year overall infection risk among patients with GCA., Methods: This nationwide observational cohort study included patients aged ≥50 years with a first-time GCA diagnosis in the Danish National Patient Registry (1996-2022). Patients with GCA were matched 1:10 by sex and date of birth with general population individuals and followed from date of diagnosis. Overall infections were defined as redeemed antibiotic prescriptions or infection-related hospitalisations. Utilising a pseudo-observation approach, we assessed 1-year cumulative incidence proportions (CIP), risk differences (RD), and relative risks (RR) of infections., Results: The study included 17 773 incident patients with GCA and 177 730 reference individuals. Patients with GCA had a 1-year CIP of 52.4% (95% CI: 51.7-53.2) for overall infections and 17.6% (95% CI: 17.1-18.2) for infection-related hospitalisations. Compared with the reference cohort, patients with GCA had a RR of 1.40 (95% CI: 1.38-1.42) for overall infections and 2.71 (95% CI: 2.61-2.82) for infection-related hospitalisations. Additionally, higher cumulative glucocorticoid doses, advanced age (≥70 years), and higher comorbidity were associated with an increased risk of infections among patients with GCA., Conclusions: The use of antibiotic prescriptions and infection-related hospitalisations in the first year after a GCA diagnosis is high compared with the background population. The cumulative glucocorticoid dose is associated with the infection risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) can all lead to the formation of bony proliferations (BP). This systematic review aimed to examine the characteristics of BPs in patients with RA, PsA, OA, and healthy controls (HC) using high-resolution peripheral quantitative computed tomography (HR-pQCT). Secondarily, we examined any treatment-related effect on BP number and size., Methods: A systematic literature search was conducted in PubMed and Embase, and a total of 15 studies were included., Results: Seven studies demonstrated a disease-specific variation in BP location. One study showed no difference in the number of BPs between patients with PsA and OA. The number of BPs was greater in patients with PsA compared to RA in one study, and to HC in another study, while one study documented no difference in the number of BPs between patients with RA and HC. Five studies showed larger BPs in patients with PsA compared to HC, and one study larger BPs in patients with PsA compared to RA. One study showed no difference in BP size between patients with PsA and OA. Secukinumab may have a potential effect on arresting BP progression. Otherwise, no other treatment was reported to influence BP size and progression. No standard definitions or measurement techniques for BPs using HR-pQCT have been identified., Conclusion: BPs showed disease-specific variations in location, size, and number. Results regarding treatment-related effects are sparse. An agreement on the definition and measurement technique for BPs using HR-pQCT is warranted for diagnostic accuracy, disease comparability, and monitoring potential., (© 2024 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: To investigate the effect of COVID-19 mRNA revaccination (two doses) on the antibody response in patients with rheumatic diseases (RD) who were initial vaccine non-responders. Further, to examine if B-cell levels or T-cell responses before revaccination predicted seroconversion., Methods: From a RD cohort vaccinated with the standard two-dose COVID-19 vaccinations, we enrolled cases without detectable antibody responses (n=17) and controls with detectable antibody response (n=29). Blood donors (n=32) were included as additional controls. Samples were collected before and six weeks after completed revaccination. Total antibodies and specific IgG, IgA, and IgM against SARS-CoV-2 spike protein, SARS-CoV-2 neutralising antibodies, and SARS-CoV-2 reacting CD4+ and CD8+ T-cells were measured before and after revaccination. B-cells (CD19+CD45+) were quantified before revaccination., Results: Forty-seven percent of cases had detectable neutralising antibodies after revaccination. However, antibody levels were significantly lower than in controls and blood donors. Revaccination induced an antibody class switch in cases with a decrease in IgM and increase in IgG. No significant difference was observed in T-cell responses before and after revaccination between the three groups. Only 29% of cases had measurable B-cells compared to 100% of controls and blood donors. Fifty percent of revaccinated cases who seroconverted had measurable B-cells before revaccination., Conclusions: Forty-seven percent of initial non-responders seroconverted after two-dose revaccination but still had lower levels of SARS-CoV-2 antibodies compared with controls and blood donors. RD patients without a detectable serological response after the initial COVID-19 mRNA vaccine had a T-cell response similar to immunocompetent controls and blood donors.

Purpose: Osteoporosis is under-diagnosed and often co-exists with other diseases. Very low bone mineral density (BMD) indicates risk of osteoporosis and opportunistic screening for low BMD in CT-scans has been suggested. In a non-contrast enhanced thoracic CT scan, the scan-field-of-view includes vertebrae enabling BMD estimation. However, many CT scans are obtained by administration of contrast material. If the impact of contrast enhancement on BMD measurements could be quantified, considerably more patients are eligible for screening., Methods: This study investigated the impact of intravenous contrast on thoracic BMD measurements in cardiac CT scans pre- and post-contrast, including different contrast trigger levels of 130 and 180 Hounsfield units (HU). BMD was measured using quantitative CT with asynchronous calibration., Results: In 195 participants undergoing cardiac CT (mean age 57±9 years, 37 % females) contrast increased mean thoracic BMD from 116±33 mg/cm 3 (non-enhanced CT) to 130±38 mg/cm 3 (contrast-enhanced CT) (p<0.001). Using clinical cut-off values for very low (<80 mg/cm 3 ) and low BMD (<120 mg/cm 3 ) showed that 24 % (47/195 participants) were misclassified when BMD was measured on contrast-enhanced CT-scans. Of the misclassified patients, 6 % (12/195 participants) were categorized as having low BMD despite having very low BMD on the non-enhanced images. Contrast-CT using a higher contrast trigger level showed a significant increase in BMD compared to the lower trigger level (119±32 vs. 135±40 mg/cm 3 , p<0.01)., Conclusion: For patients undergoing cardiac CT, using contrast-enhanced images to assess BMD entails substantial overestimation. Contrast protocol trigger levels also affect BMD measurements. Adjusting for these factors is needed before contrast-enhanced images can be used clinically., Mini Abstract: Osteoporosis is under-diagnosed. Contrast-enhanced CT made to examine other diseases might be utilized simultaneously for bone mineral density (BMD) screening. These scans, however, likely entails overestimation of BMD due to the effect of contrast. Adjusting for this effect is needed before contrast-enhanced images can be implemented clinically for BMD screening., (Copyright © 2023 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Objective: To explore patients' perceptions of digital patient education (PE), and how this contributes to self-management of rheumatoid arthritis (RA)., Methods: Individual interviews based on 'interpretive description' methodology. The patients were purposively selected from a randomized controlled trial that investigated the effects of digital PE. The analysis included a descriptive section, followed by the interpretation and extraction of the main messages., Results: Overall, participants had positive perceptions of the e-learning program. Advantages were flexibility, the possibility for repetition, entertainment, availability, and learning in familiar surroundings. Disadvantages were unmet relational support needs due to missing dialogue with health care providers (HCPs). For the majority, a need for insight into the condition led to an active approach to using e-learning. The e-learning program facilitated knowledge acquisition about RA, but relational support from HCPs and a positive attitude toward living with RA were also important for achieving self-management., Conclusion: Digital PE is useful for self-management support in RA, however different forms and combinations of PE must be offered in the future to accommodate various needs throughout the disease course., Practice Implications: These results may inform future development and implementation of digital PE that adequately takes individual preferences for self-management support into account., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The role of integrating genomic scores (GSs) needs to be assessed. Adding a GS to recommended stratification tools does not improve the prediction of very low bone mineral density. However, we noticed that the GS performed equally or above individual risk factors in discrimination., Purpose: We aimed to investigate whether adding a genomic score (GS) to recommended stratification tools improves the discrimination of participants with very low bone mineral density (BMD)., Methods: BMD was measured in three thoracic vertebrae using CT. All participants provided information on standard osteoporosis risk factors. GSs and FRAX scores were calculated. Participants were grouped according to mean BMD into very low (<80 mg/cm 3 ), low (80-120 mg/cm 3 ), and normal (>120 mg/cm 3 ) and according to the Bone Health and Osteoporosis Foundation recommendations for BMD testing into an "indication for BMD testing" and "no indication for BMD testing" group. Different models were assessed using the area under the receiver operating characteristics curves (AUC) and reclassification analyses., Results: In the total cohort (n=1421), the AUC for the GS was 0.57 (95% CI 0.52-0.61) corresponding to AUCs for osteoporosis risk factors. In participants without indication for BMD testing, the AUC was 0.60 (95% CI 0.52-0.69) above or equal to AUCs for osteoporosis risk factors. Adding the GS to a clinical risk factor (CRF) model resulted in AUCs not statistically significant from the CRF model. Using probability cutoff values of 6, 12, and 24%, we found no improved reclassification or risk discrimination using the CRF-GS model compared to the CRF model., Conclusion: Our results suggest adding a GS to a CRF model does not improve prediction. However, we noticed that the GS performed equally or above individual risk factors in discrimination. Clinical risk factors combined showed superior discrimination to individual risk factors and the GS, underlining the value of combined CRFs in routine clinics as a stratification tool., (© 2023. The Author(s).)

Background: Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including hormonal signalling. Glucocorticoids (GC) are corticosteroid hormones that promote adipogenic differentiation and are endogenously increased in patients with Cushing´s syndrome (CS). Here, we investigate bone marrow adiposity changes in response to endogenous or exogenous GC increases. For that, we characterize bone biopsies from patients with CS and post-menopausal women with glucocorticoid-induced osteoporosis (GC-O), compared to age-matched controls, including postmenopausal osteoporotic patients (PM-O)., Methods: Transiliac crest bone biopsies from CS patients and healthy controls, and from postmenopausal women with GC-O and matched controls were analysed; an additional cohort included biopsies from women with PM-O. Plastic-embedded biopsies were sectioned for histomorphometric characterization and quantification of adipocytes. The fraction of adipocyte area per tissue (Ad.Ar/T.Ar) and marrow area (Ad.Ar/Ma.Ar), mean adipocyte profile area (Ad.Pf.Ar) and adipocyte profile density (N.Ad.Pf/Ma.Ar) were determined and correlated to steroid levels. Furthermore, the spatial distribution of adipocytes in relation to trabecular bone was characterized and correlations between bone marrow adiposity and bone remodeling parameters investigated., Results: Biopsies from patients with CS and GC-O presented increased Ad.Ar/Ma.Ar, along with adipocyte hypertrophy and hyperplasia. In patients with CS, both Ad.Ar/Ma.Ar and Ad.Pf.Ar significantly correlated with serum cortisol levels. Spatial distribution analyses revealed that, in CS, the increase in Ad.Ar/Ma.Ar near to trabecular bone (<100 µm) was mediated by both adipocyte hypertrophy and hyperplasia, while N.Ad.Pf/Ma.Ar further into the marrow (>100 µm) remained unchanged. In contrast, patients with GC-O only presented increased Ad.Ar/Ma.Ar and mean Ad.Pf.Ar>100 µm from trabecular bone surface, highlighting the differential effect of increased endogenous steroid accumulation. Finally, the Ad.Ar/Ma.Ar and Ad.Ar/T.Ar correlated with the canopy coverage above remodeling events., Conclusion: Increased cortisol production in patients with CS induces increased bone marrow adiposity, primarily mediated by adipocyte hypertrophy. This adiposity is particularly evident near trabecular bone surfaces, where hyperplasia also occurs. The differential pattern of adiposity in patients with CS and GC-O highlights that bone marrow adipocytes and their progenitors may respond differently in these two GC-mediated bone diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sørensen, Andreasen, Jensen, Hauge, Bollerslev, Delaissé, Kassem, Jafari, Diaz-delCastillo and Andersen.)

Aims: To evaluate predictors for successful biologic tapering among patients with inflammatory arthritis using baseline characteristics from the BIODOPT trial., Methods: Adult patients with rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis on stable biologic dose and in low disease activity ≥12 months were enrolled. Participants were randomized (2:1) to disease activity-guided biologic tapering or continuation of baseline biologic. Patients achieving successful tapering reduced their biologic dose by ≥50%, had no protocol deviations and were in low disease activity at 18 months. Modified Poisson regression with robust variance estimator was applied., Results: In total, 142 patients were randomized to tapering (n = 95) or control (n = 47). Successful tapering was achieved by 32 and 2%, respectively. Tapering group was the only statistically significant independent predictor for successful tapering, risk ratio (RR): 14.0 (95% confidence interval [CI]: 1.9 to 101.3, P = .009). However, higher Short Form Health Survey 36 mental component summary (SF-36 MCS) was observed to be a predictor of potential importance, RR: 1.06 (95% CI: 0.99 to 1.13, P = .097). When limiting the analyses to the tapering group only, none of the baseline variables were statistically significant independent predictors but SF-36 MCS was still considered to be of potential importance, RR: 1.05 (95% CI: 0.99 to 1.12, P = .098)., Conclusion: Successful tapering is a reachable target for 1 in 3 patients with inflammatory arthritis who are interested in reducing their biological therapy. No statistically significant predictors (besides allocation to tapering) were identified. Future research on mental health and tapering is encouraged., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: To identify socioeconomic, disease-related, and personal factors associated with participation in remote follow-up in patients with rheumatoid arthritis (RA)., Methods: Following the implementation of a patient-reported outcome-based remote follow-up intervention in RA patients in Denmark, a cross-sectional study was conducted among 775 prevalent patients. In 2019, an electronic questionnaire was sent to eligible RA patients, covering health literacy and patient experience regarding involvement and confidence with remote care. Questionnaire data were linked to nationwide registries regarding socioeconomic status, labor market affiliation, and comorbidity level. Associations between registry- and questionnaire-based factors and remote follow-up were analyzed using multiple logistic regression analysis., Results: All 775 patients were included in the registry-based analyses, but only 394 of 646 (61%) completed the questionnaire. No attachment to the labor market or low household income was associated with lower odds of remote follow-up participation (odds ratio [OR] 0.53 [95% confidence interval (95% CI) 0.34-0.83]) and (OR 0.69 [95% CI 0.48-1.00]). Further, a high level of comorbidity was associated with lower odds of remote follow-up participation compared to a low/medium level of comorbidity (OR 0.53 [95% CI 0.34-0.81]). No association was found between health literacy and remote follow-up, but remote follow-up attendees reported more confidence in remote care (OR 1.33 [95% CI 1.21-1.47])., Conclusion: Participation in remote follow-up was associated with attachement to the labor market, household income, degree of comorbidity, and confidence with remote care. Additional research is necessary to investigate whether a larger and more divergent group of RA patients should be considered for inclusion in remote follow-up programs., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Precision medicine in rheumatoid arthritis (RA) requires a good understanding of treatment outcomes and often collaborative efforts that call for data harmonisation. We aimed to describe how harmonisation across study cohorts can be achieved and investigate how the observed proportions reaching remission vary across remission criteria, study types, disease-modifying antirheumatic drugs (DMARDs) and countries, and how they relate to other treatment outcomes., Methods: We used data from eight existing large-scale, clinical RA registers and a pragmatic trial from Sweden, Denmark and Norway. In these, we defined three types of treatment cohorts; methotrexate monotherapy (as first DMARD), tumour necrosis factor inhibitors (TNFi) (as first biological DMARD) and rituximab. We developed a harmonised study protocol defining time points during 36 months of follow-up, collected clinical visit data on treatment response, retention, persistence and six alternative definitions of remission, and investigated how these outcomes differed within and between cohorts, by treatment., Results: Cohort sizes ranged from ~50 to 22 000 patients with RA. The proportions reaching each outcome varied across outcome metric, but with small to modest variations within and between cohorts, countries and treatment. Retention and persistence rates were high (>50% at 1 year), yet <33% of patients starting methotrexate or TNFi, and only 10% starting rituximab, remained on drug without other DMARDs added and achieved American Congress of Rheumatology/European Alliance of Associations for Rheumatology or Simplified Disease Activity Index remission at 1 year., Conclusion: Harmonisation of data from different RA data sources can be achieved without compromising internal validity or generalisability. The low proportions reaching remission, point to an unmet need for treatment optimisation in RA., Competing Interests: Competing interests: SS is a part-time employee at deCODE genetics. E-MH has received institutional grants or contracts from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Rocke, Novartis or Abbvie, payment or honoraria for lecture, presentations, speakers bureaus, manuscript writing or educational events from Sobi, support from attending meetings and/or travel from Pfizer, Sobi and Abbvie. participated on data safety monitoring board or advisory board for Novartis, Abbvie and Sanofi and is principal investigator in trials by SynACT Pharma, site principal investigator in trials by AbbVie, Novartis, Novo and Sanofi. HBH has received honoraria for lectures from AbbVie, Novartis, Lilly and UCB, and participated on advisory board for AbbVie, UCB and Novarties. Karolinska Institutet has entered into agreements with the following companies, with JA as PI: Abbvie, BMS, Eli Lilly, Galapagos, Janssen, Pfizer, Roche, Samsung Bioepis and Sanofi. BG has received research grant from Pfizer, AbbVie, BMS and Sandoz. The remaining authors have nothing to declare., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate whether disease activity-guided tapering of biologics compared to continuation as usual care enables a substantial dose reduction while disease activity remains equivalent., Method: In this pragmatic, randomized, open-label, equivalence trial, adults with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis in low disease activity on stable-dose biologics for ≥ 12 months were randomized 2:1 into either the tapering group, i.e. disease activity-guided prolongation of the biologic dosing interval until flare or withdrawal, or the control group, i.e. maintaince of baseline biologics with a possible small interval increase at the patients request. The co-primary outcome in the intention-to-treat population was met if superiority in ≥ 50% biologic reduction at 18 months was demonstrated and disease activity was equivalent (equivalence margins ± 0.5)., Results: Ninety-five patients were randomized to tapering and 47 to control, of whom 37% (35/95) versus 2% (1/47) achieved ≥ 50% biologic reduction at 18 months. The risk difference was statistically significant [35%, 95% confidence interval (CI) 24%-45%], while disease activity remained equivalent [mean difference 0.05, 95% CI -0.12-0.29]. A statistically significant flare risk was observed [tapering 41% (39/95) vs control 21% (10/47), risk difference 20%, 95% CI 4%-35%]; but, only 1% (1/95) and 6% (3/47) had persistent flare and needed to switch to another biological drug., Conclusions: Disease activity-guided tapering of biologics in patients with inflammatory arthritis enabled one-third to achieve ≥ 50% biologic reduction, while disease activity between groups remained equivalent. Flares were more frequent in the tapering group but were managed with rescue therapy.

Objectives: We evaluated sensitivity to change and discriminative abilities of vascular US scores in disease monitoring in the follow-up of a prospective cohort of new-onset cranial and large-vessel (LV) GCA patients., Methods: Baseline and follow-up (8 weeks, 24 weeks and 15 months) US of temporal arteries (TA), carotid and axillary arteries (LV) included assessment of halo and measurement of the intima media complex (IMC). Max IMC, max halo IMC, sum IMC, sum halo IMC, mean IMC, halo count and the Southend halo score were calculated. The provisional OMERACT US score, OGUS, was obtained, taking the average of temporal arteries and axillary arteries IMCs divided by their normal cut-off values., Results: Baseline US was positive in 44/47 patients (72% TA, 72% LV). Sensitivity to change of all composite US scores containing TAs was evident by week 8 onward. LVs responded poorly and new axillary US lesions emerged in six patients despite clinical remission. The OGUS showed a large magnitude of change and is considered the score least prone to potential bias. All TA-based US scores showed moderate-strong correlation with disease activity markers. OGUS, TA halo count, Southend TA halo score, TA sum IMC and TA mean IMC showed potential to discriminate remission and relapse with area under the curve ≥0.8., Conclusions: The OGUS is suggested as an outcome measurement for the assessment of treatment response in clinical trials. The abilities of US scores to discriminate remission and relapse are encouraging and should be further explored., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)