RMD Open最新文献

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.

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.

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: 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.

Objective: Insomnia often co-exists with hip or knee pain and is associated with greater pain severity. However, there is limited evidence on whether insomnia contributes to progression to joint replacement. Using data from the UK Biobank, we tested whether symptoms of insomnia among people with hip or knee pain are associated with undergoing total hip or knee joint replacement surgery.

Methods: UK Biobank data from participants with hip (n=41 737) or knee pain (n=81 958) in the past 3 months were included. Using self-reported baseline data, participants were classified as 'never', 'sometimes' or 'usually' having insomnia symptoms (ie, trouble falling asleep or waking in the night). We examined associations between baseline symptoms of insomnia and undergoing total hip or knee replacement surgery using adjusted Cox proportional hazards models.

Results: In knee pain, 'usually' experiencing insomnia symptoms was associated with undergoing total knee replacement (adjusted HR 1.14 (95% CI 1.04 to 1.25)), within, but not beyond, 4.7 years of enrolment, compared with 'never' experiencing insomnia symptoms. No association was observed for 'sometimes' experiencing insomnia symptoms and total knee replacement among individuals with knee pain, nor for insomnia symptoms ('usual' or 'sometimes') and total hip replacement among individuals with hip pain.

Conclusion: Insomnia may be a modifiable factor contributing to earlier progression to knee replacement. Targeting insomnia through interventions could form part of a holistic approach to managing chronic knee pain. Further research is needed to determine whether managing insomnia can reduce the risk of knee replacement surgery.

Objectives: This study aimed to develop and validate a prediction model for the future progression of difficult-to-treat rheumatoid arthritis (D2T RA) and support the precise use of biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).

Methods: Data were analysed from 1221 patients with rheumatoid arthritis in the FIRST registry, a multicentre collaborative database, who initiated their first b/tsDMARD. 25 prediction models for D2T RA were generated using 43 baseline characteristics prior to initiating the first b/tsDMARD. Model performances were tested. A scoring system based on the selected model was designed and internally validated for use in routine clinical practice.

Results: Among the 1221 patients, 193 (15.8%) progressed to D2T RA after a median of 54.0 months. These patients had higher tender joint count, global assessment, pain scale, Health Assessment Questionnaire score and Clinical Disease Activity Index score and more frequent coexisting lung disease. Among the machine learning models tested, Lasso logistic regression performed best (area under the curve 0.71), identifying pain scale, erythrocyte sedimentation rate and coexisting lung disease as key predictors. The scoring system based on these predictors demonstrated comparable performance. Among patients identified as high risk for D2T RA by the scoring system, interleukin-6 receptor inhibitors (IL-6Ri) significantly reduced D2T RA progression (relative risk (RR): 0.48).

Conclusion: This study developed and validated a scoring system to predict D2T RA progression and identify patients at high risk and suggested the advantages of IL-6Ri. This system may advance precision medicine in RA and may contribute to controlling unmet needs.

Background: Chronic pain due to osteoarthritis (OA) causes considerable burden, and current treatment options are limited. This phase III study aimed to compare the efficacy and safety of fasinumab, an investigational, anti-nerve growth factor monoclonal antibody, with placebo and naproxen in patients with moderate-to-severe pain due to OA of the knee or hip.

Methods: Patients with difficult-to-treat OA were randomised 3:3:3:1 to fasinumab 1 mg subcutaneous (SC) every 4 weeks (Q4W), fasinumab 1 mg SC every 8 weeks (Q8W), naproxen 500 mg orally two times a day or placebo. The co-primary endpoints were changes in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain and physical function subscale scores (0-10) from baseline to week 16 for fasinumab versus placebo; comparison with naproxen was a secondary endpoint. Safety was also assessed.

Results: Of 3307 patients randomised, 1801 were included in the analysis for efficacy, and 3014 were included in the safety analysis. Statistically significantly greater reductions in the WOMAC pain and physical function scores, respectively, at week 16 were seen for fasinumab 1 mg Q4W (-2.90 and -2.78) compared with placebo (-2.32 and -2.10) and naproxen (-2.61 and -2.41); all p<0.005. Adjudicated arthropathies (AAs) and joint replacements occurred in all treatment groups, but were higher in the fasinumab 1 mg Q8W and 1 mg Q4W groups than in the placebo and naproxen groups. Patients with AAs: 7.2%, 9.7%, 1.1% and 2.6%, respectively; patients with joint replacements: 5.6%, 6.4%, 3.4% and 3.1%, respectively. Of the AAs in the fasinumab arms, 95.0% and 75.5% were rapid-progressive OA type 1 in the 1 mg Q8W and 1 mg Q4W arms, respectively. No new safety concerns were identified.

Conclusion: In a difficult-to-treat population with OA, fasinumab 1 mg Q4W achieved clinically meaningful improvements by week 16 versus placebo and naproxen. The safety profile was similar to that previously observed for fasinumab.

Trial registration number: NCT03161093.

Objective: Sjögren's is a chronic systemic autoimmune disease characterised by dryness symptoms (eyes, mouth, skin), alongside other systemic manifestations such as fatigue, muscle and joint pain, neuropathies and organ involvement. Despite its prevalence, research into the patient perspective of Sjögren's is limited. This study aimed to better understand the burden, unmet needs and treatment satisfaction among adults with Sjögren's.

Methods: Data were collected using a cross-sectional survey of adult patients with Sjögren's across China, France, Germany, Italy, Japan, Spain, the UK and the USA (December 2023 to September 2024). Patients were recruited via physicians or patient advocacy organisations. The Work Productivity and Activity Impairment (WPAI) tool assessed work-related productivity and daily activity impact. Analyses were descriptive.

Results: 1155 patients completed the survey. Mean (SD) age was 54.5 (13.0) years; 88.2% were female and 95.3% white. Most frequently reported symptoms were dry mouth, dry eyes, dry skin, physical fatigue/tiredness and joint stiffness/soreness. High emotional burden from Sjögren's (rating 5-7 out of 7) was reported by 57.7%. WPAI scores showed 46.6% work and 48.4% activity impairment. Of those receiving prescription therapy, 77.2% were dissatisfied and/or believed disease control could improve. Among those not fully satisfied, 52.9% felt current treatments only addressed symptoms, not the underlying systemic nature of Sjögren's.

Conclusion: The Spotlight on Sjögren's study reveals the substantial, multifaceted burden of Sjögren's, extending beyond dryness to significantly impair physical, emotional and functional well-being. Findings underscore the need for comprehensive, patient-centred care and therapies addressing both symptoms and the underlying systemic disease.