RMD Open最新文献

Objective: Studies of dermatomyositis (DM) are frequently limited to single-centre cohorts. We used two large nationally representative US cohorts to conduct a descriptive epidemiological study of the characteristics, treatments and outcomes of patients with incident DM.

Methods: This retrospective study identified two DM inception cohorts using (1) commercial claims and (2) electronic health record (EHR) data from the Excellence Network in Rheumatology to Innovate Care and High-impact research (ENRICH), a community rheumatology practice-based research network. Patient characteristics, treatments and healthcare utilisation were assessed using the 18 months before and 12 months after diagnosis in claims and the 12 months before and after diagnosis in EHR data.

Results: We identified 2475 patients (claims) and 1196 patients (EHR) with incident DM. Among 998 patients in the EHR cohort with available laboratory data, 472 had available myositis panel results, with 165 (35.0%) having a positive myositis-specific antibody. Glucocorticoid use was common, 68.7% and 73.8% in the two cohorts, respectively, with initial doses most often >20 mg/day; among glucocorticoid users, mean cumulative dose was 1407 mg in the claims cohort. Hydroxychloroquine, methotrexate and mycophenolate were the most commonly used immunomodulatory therapies. During follow-up in the claims data cohort, incidence per 1000 person-years was 92.2, 15.3, 6.4, 2.9 and 2.1 for all-cause hospitalisation, malignancy, interstitial lung disease, gastrostomy tube placement and myocarditis, respectively.

Conclusion: Administrative claims and EHR data can be leveraged to assess treatment patterns and longitudinal outcomes/disease manifestations in incident dermatomyositis cohorts. This study highlights a high burden of glucocorticoid exposure, significant heterogeneity in treatment and high healthcare utilisation in this population.

Background: Existing proteomic studies have primarily focused on gout flares or symptomatic hyperuricaemia, and few have comprehensively investigated circulating proteomic profiles in serum urate (SU) concentration as a continuous quantitative trait. This cross-sectional study investigated the association between SU concentration and serum proteomic profiles.

Methods: We enrolled 176 Japanese individuals aged ≥50 years and measured serum proteins using the Olink Explore 3072. To analyse the association between SU concentration and serum proteins, we applied linear regression adjusting for age, sex, renal function and insulin resistance with a false discovery rate threshold of 5%. Tissue-specific and gene set enrichment analyses were conducted based on the regression results.

Results: A total of 2886 proteins were analysed, among whom 63 showed significant associations with SU concentration; uromodulin demonstrated the strongest association (adjusted p=2.21×10^-5). These 63 SU-associated proteins were significantly enriched in the liver, kidneys and duodenum by tissue-specific enrichment analysis. We further examined p.Q141K-a dysfunctional variant of adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2). Among p.Q141K minor allele carriers (n=91), 11 SU-associated proteins were identified, whereas no significant SU-associated proteins were detected in wild-type homozygotes (n=85). Gene set enrichment analysis highlighted xenobiotic metabolism in wild-types and additional inflammation- and disease-related gene sets in minor allele carriers.

Conclusions: To the best of our knowledge, this is the first study to report a proteomic signature of SU concentration. These findings suggest that SU-associated proteomic signatures vary according to ABCG2 genotypes, highlighting the genetic contribution to pathophysiological processes associated with SU concentration variation.

Trial registration number: NCT00262691.

Objectives: Understanding the molecular changes in the preclinical synovium is crucial for identifying factors that drive arthritis development. Persistent DNA damage in tissues is known to drive a senescent microenvironment, genomic instability and ultimately chronic inflammation. Here, we determined cellular DNA damage and repair capacity within synovial tissue from rheumatoid arthritis (RA) patients and individuals at risk of developing RA.

Methods: We investigated the presence of senescence-associated DNA damage in synovial biopsies and synovial fibroblasts obtained during different phases of RA. Histone 2A is phosphorylated (γH2AX) at the site of a double-stranded DNA break where DNA repair proteins are recruited and is therefore a proxy measurement for DNA damage. In this study, we employed immunofluorescence staining for γH2AX on synovial tissue sections and cultured synovial fibroblasts alongside quantitative PCR for a panel of DNA repair proteins.

Results: We demonstrated the presence of DNA damage in both synovial fibroblasts and T cells during the preclinical, RA-risk phase of disease. Furthermore, cultured synovial fibroblasts from RA-risk individuals and RA patients exhibited increased DNA damage and a reduced capacity for DNA repair compared with synovial fibroblasts from control individuals. Finally, treatment with senolytic drugs partially restored the DNA damage repair capacity in RA and RA-risk synovial fibroblasts in vitro.

Conclusions: Our findings reveal persistent DNA damage in the preclinical phase of RA in both synovial tissue and fibroblasts, suggesting a role in disease progression. The partial restoration of DNA repair in synovial fibroblasts by senolytic treatment highlights its potential therapeutic target for preventative therapy in RA-risk individuals.

Objectives: To assess the incidence and risk factors for arrhythmias in patients with psoriatic arthritis (PsA).

Methods: We performed a cohort analysis of patients followed prospectively from 1994 to 2024. Participants were evaluated using standard protocols at 6-to-12-month intervals. The following events were assessed: (1) atrial tachyarrhythmia (including atrial fibrillation and supraventricular tachycardia); (2) ventricular tachyarrhythmia and (3) bradycardia/pacemaker. The cumulative incidence rate (CIR) of each arrhythmia was calculated. Cox proportional hazards models (reported as the current level HR (measured just prior to the event) and the adjusted mean HR) were fitted to assess the association between selected measures of PsA disease activity and the age of occurrence of arrhythmia events. Each model was adjusted for sex, PsA duration, cardiovascular risk factors and medications.

Results: A total of 1670 patients with PsA were analysed (80 atrial tachyarrhythmias, 17 bradyarrhythmias/pacemakers and 11 ventricular tachyarrhythmias). By age 70, the CIRs were 7.82%, 0.67% and 0.45% for atrial, ventricular and bradycardia, respectively. In multivariable analysis, remission/low versus high disease activity state was associated with lower risk of atrial tachyarrhythmia (current HR 0.49, 95% CI 0.26 to 0.92; adjusted mean HR 0.46, 95% CI 0.23 to 0.91). Similarly, a higher three-item Visual Analogue Scale (3-VAS) was associated with a higher risk of atrial tachyarrhythmia (current level HR 1.18, 95% CI 1.04 to 1.33; adjusted mean HR 1.22, 95% CI 1.04 to 1.44).

Conclusions: Higher PsA disease activity is associated with higher atrial tachyarrhythmia risk. These findings reinforce the importance of controlling inflammation in PsA to optimise cardiac health.

Objective: The aim of this study was to investigate the relationship between antineutrophil cytoplasmic antibodies (ANCA) specificity and the risk of major adverse cardiovascular events (MACE) in patients with ANCA-associated vasculitis (AAV).

Methods: We conducted a retrospective study using the ANCA-associated vasculitis Toulouse cohort. The incidence of MACE, defined as myocardial infarction (MI) and/or stroke and/or all-cause death, was compared among patients according to their ANCA specificity. We also applied Cox regression models adjusted for traditional cardiovascular risk factors, age and sex to assess the risk of MI, stroke and MACE.

Results: A total of 402 patients were included, of whom 166 (41%) had antiproteinase 3 (anti-PR3) ANCA and 236 (59%) had antimyeloperoxidase (anti-MPO) ANCA. We identified 78 MACE during the follow-up period, including 15 MIs, 12 strokes and 62 deaths. The incidence rate of MACE in the ANCA+anti-PR3+ group was 21.4 per 1000 patient-years compared with 33.1 per 1000 patient-years in the ANCA+anti-MPO+ group (p=0.036). The time elapsed between the diagnosis of AAV and MACE occurrence was significantly shorter in the ANCA+anti-MPO+ group. The Cox regression model found that patients with anti-MPO ANCA tend to present more MACE, but the association was not statistically significant (HR 1.62; 95% CI 0.98 to 2.66; p=0.06). An association was found between the presence of anti-PR3 ANCA and a lower risk of strokes (HR 0.61; 95% CI 0.37 to 0.99; p=0.049) and none with the risk of MI.

Conclusion: Patients with anti-MPO ANCA appear to be at a higher risk of a composite MACE-all-cause mortality outcome than patients with anti-PR3 ANCA.

Objective: Transcortical pores and the bare area have been suggested as structural determinants of bone erosions in rheumatoid arthritis (RA). We aimed to map the spatial distribution of transcortical pores and bare areas in whole finger joints of postmortem subjects and to determine the anatomical relationship between erosions in patients with RA and the bare areas.

Methods: This was a descriptive, cross-sectional study including the second and/or third fingers from deceased individuals (n=8), obtained postmortem, for mapping the number, size and spatial distribution of transcortical pores in four quadrants using micro-CT (n=33 joints). The extent of the bare area at the erosion-prone radial and ulnar quadrants (n=12 joints) was mapped histologically and pores assessed intra-articularly and extra-articularly. In patients with RA (n=22), bone erosions were identified using high-resolution peripheral quantitative CT of the second metacarpophalangeal (MCP) joint.

Results: In postmortem subjects, transcortical pores were located both intra-articularly and extra-articularly. The spatial pore distribution along the finger at the MCP, proximal interphalangeal (PIP) joint and distal interphalangeal (DIP) joint was comparable. The radial quadrant did not show more or larger pores compared with the other quadrants. The number of pores was not consistently higher in joints and areas prone to erosion. The bare area was more frequently and more extensively present in joints commonly affected by erosions. In RA, all erosions (n=26) were confined to or overlapping with the bare areas.

Conclusions: These findings support the bare areas, but not transcortical pores, as structural determinants for erosion location in finger joints in RA.

Trial registration number: NCT04645381 and NCT03429426.

Objective: This study (the SpACT study) aimed to investigate the frequency and localisations of different types of spinal new bone formation (NBF) in patients with axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), rheumatoid arthritis (RA) and healthy controls (HCs) using low-dose CT (ldCT).

Methods: Patients with axSpA, PsA or RA, and HC without a history of chronic back pain were included and underwent ldCT of the entire spine. Three readers blinded to all clinical information, including diagnosis, assessed sagittal and coronal images for NBF: (1) marginal syndesmophytes, (2) non-marginal syndesmophytes and (3) osteophytes.

Results: 69 participants (33 females, mean age 51.4 years) were included: AxSpA: 30; PsA: 19; RA: 10; HC: 10. Across all groups, the thoracic spine consistently showed the highest number of NBFs, especially for marginal syndesmophytes and osteophytes. Furthermore, on sagittal images, NBF, regardless of type, occurred predominantly at the anterior vertebral corners. Coronal images showed right-sided dominance of NBFs, particularly osteophytes and non-marginal syndesmophytes, whereas marginal syndesmophytes had an almost equal overall distribution. Both sagittal and coronal reconstructions demonstrated high inter-reader reliability (intraclass correlation coefficient >0.9) for almost all groups for detecting any type of NBF.

Conclusion: AxSpA exhibited a distinct NBF pattern characterised by frequent marginal syndesmophytes, particularly in the thoracic spine. In contrast, the most prevalent findings in the other groups were osteophytes, and no consistent NBF pattern was observed to distinguish the groups from each other. Further studies, especially longitudinal assessments using ldCT or equally bone-sensitive imaging methods, are needed to further increase our understanding of NBF patterns.

Objectives: The TREAT EARLIER trial showed in clinically suspect arthralgia (CSA) that methotrexate induced reductions in subclinical inflammation and related disease burden during the year of treatment, which was sustained thereafter. We studied whether the treatment response defined at the level of subclinical joint inflammation was present in all treated CSA patients and, if not, what characterises the subgroup of responders.

Methods: CSA patients with subclinical inflammation were randomised to receive an intramuscular glucocorticoid injection and a 1-year course of methotrexate. Treatment response was defined as a reduction of MRI-detected synovitis, tenosynovitis or osteitis levels beyond the smallest detectable change at 12 months. Baseline clinical and imaging characteristics were studied in relation to treatment response. Predictive values were determined.

Results: 44 of 115 (38%) treated patients had an MRI-defined treatment response. These patients also significantly improved in pain and physical functioning (-22 Visual Analogue Scale pain, -0.29 Health Assessment Questionnaire). Baseline clinical variables were not independently associated with this response, in contrast to the severity of subclinical joint inflammation. Tenosynovitis and osteitis levels in particular were predictive. Patients with ≥2 sites with tenosynovitis or a combination of osteitis and tenosynovitis (with ≥1 of these features at ≥2 sites) had high positive predictive values (PPV 77%, 79%). PPVs were similar in ACPA-positive and ACPA-negative patients at increased risk for rheumatoid arthritis (RA).

Conclusions: CSA patients with subclinical inflammation who responded best to methotrexate during the first year were identified by increased levels of subclinical inflammation at diagnosis, primarily due to multiple sites of tenosynovitis with/without osteitis. These data may contribute to personalised medicine for arthralgia at risk for RA.

Objectives: To compare the 2-year clinical effectiveness of the four globally approved Janus kinase inhibitors (JAKis; tofacitinib (TOF), baricitinib (BAR), upadacitinib (UPA) and filgotinib (FIL)) in patients with rheumatoid arthritis (RA) in real-world settings.

Methods: This retrospective cohort study used data from FIRST registry, a multicentre registry of patients with RA. The primary endpoint was the change in Clinical Disease Activity Index (CDAI) score at year 2. Secondary endpoints included changes in individual CDAI components, patient-reported outcomes (PROs) and reasons for JAKi discontinuation. Multivariable mixed-effects models adjusted for baseline characteristics were used to compare the four JAKis.

Results: A total of 607 treatment courses with JAKis (TOF: 159, BAR: 262, UPA: 122, FIL: 64) were included. Baseline characteristics differed notably among treatment groups: UPA and FIL were frequently used as the second-line JAKis for older patients with comorbidities. The 2-year overall retention rate was 78%. The most common reason for discontinuation was insufficient effectiveness, with 6.5/100 person-years (py), followed by adverse events of 4.2/100 py. As-observed analysis demonstrated the slower improvement in the UPA and FIL groups. However, multivariable analysis revealed no significant differences in CDAI or PROs. The UPA group demonstrated greater improvement in two CDAI components: tender joint count and evaluator's global assessment.

Conclusion: This real-world study found no clinically meaningful differences in 2-year effectiveness among four JAKis, although the study was not powerful enough to detect differences in safety. Further long-term, real-world data are needed to evaluate the safety of these agents and refine their risk-benefit profiles.

Objective: To develop a deep learning algorithm for semiquantification of spinal inflammation in patients with axial spondyloarthritis (SpA).

Methods: The study included 330 participants with axial SpA. All patients underwent whole spine MRI with short τ inversion recovery (STIR) sequence by 3T MR unit. Three independent readers identified regions of interest to locate bone marrow oedema (BMO) and performed Spondyloarthritis Research Consortium of Canada (SPARCC) scoring. Two deep learning models based on attention Unet were developed. The BMO model differentiated image with or without spinal inflammation. The vertebral body (VB)-intervertebral disc (IVD) model identified discovertebral units for localisation. The intraclass correlation coefficient (ICC) and Pearson coefficient were used to evaluate agreement and correlation between scorings by human readers and deep learning-based pipeline. Performance of the models was evaluated using sensitivity, specificity, accuracy and Dice coefficient.

Results: The ICC and the Pearson coefficient of SPARCC scores between human readers and the deep learning-based scoring pipeline were 0.80 and 0.82, respectively. The sensitivity and specificity of spinal inflammation identification were 0.90 and 0.84, respectively. The Dice coefficients were 0.81 (VB) and 0.80 (IVD) in images with spinal inflammation.

Conclusion: The high consistency of the scoring pipeline with human readers suggested that the deep learning-based algorithm has the potential to provide semiquantitative assessment of spinal inflammation based on SPARCC in axial SpA.