RMD Open最新文献

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.

Introduction: Patients with rheumatoid (RA) or psoriatic (PsA) arthritis can experience debilitating pain.

Methods: Post hoc analyses of phase 3, double-blind studies in patients with active disease despite treatment (SELECT-COMPARE, SELECT-PsA 1) assessed the effects of upadacitinib or adalimumab versus placebo on pain in patients with attenuation of inflammation (AoI) versus remaining inflammation at weeks 12 and 24/26 (PsA/RA). Further, a mediation analysis assessed the direct/indirect effect of treatment on pain using the Patient's Global Assessment of pain (PtGA) and 28 tender joint count (TJC28) at weeks 2/12/26 in RA, and weeks 16/24 in PsA.

Results: In patients with RA+AoI, PtGA scores improved more with upadacitinib (least squares mean change, -42.9) versus adalimumab (-34.7 (p<0.05)) or placebo (-33.1 (p<0.05)) at week 12 from baseline; improvements were similar across groups by week 26. For PsA+AoI, improvement was greater with upadacitinib (week 12, -2.7; week 24, -3.8) versus placebo (-1.8 (p<0.05); -2.8 (p<0.001), respectively) and similar to adalimumab (-2.8, -3.6). For RA, the direct effect on pain was nearly two times greater with upadacitinib versus placebo compared with adalimumab at weeks 12/26. For PsA, total effects on pain (TJC28 improvement) at weeks 16/24 were greater with upadacitinib (2.16 and 2.30) and adalimumab (1.35 and 1.71) versus placebo.

Conclusions: Upadacitinib effectively reduced pain in active RA and PsA, including in patients with AoI. The greater pain relief observed in RA with upadacitinib versus adalimumab might indicate both direct (relieving non-inflammatory pain) and indirect (suppressing inflammation) effects.

Objectives: To examine the association between social determinants of health (SDH) and outcomes in systemic lupus erythematosus (SLE), in a European setting.

Methods: We conducted a nationwide, register-based cohort study in Sweden including 2434 individuals aged 23-59 years with newly diagnosed SLE, 2005-2021. SDH were assessed at diagnosis and included education, income, marital status, work ability, unemployment and immigration status. Outcomes were organ damage (measured using the Lupus Register-Based Organ Damage Index) and all-cause mortality. Cox proportional hazards models estimated HRs, adjusting for age, sex and morbidity. Sensitivity analyses included SDH measured 2 years prior to diagnosis.

Results: During follow-up, a total of 1044 (42.4%) newly diagnosed patients with SLE developed organ damage and 140 (6%) died. There was an increased risk of organ damage associated with sick leave or disability (HR: 1.44; 95% CI 1.27 to 1.64), lower income (HR: 1.33; 95% CI 1.09 to 1.63), being divorced or widowed (HR: 1.30; 95% CI 1.10 to 1.54) at diagnosis. The same SDH were also associated with mortality, as was lower education level (HR: 1.67; 95% CI 1.05 to 2.66). Immigration status and unemployment did not associate with organ damage or mortality. Results were similar when examining SDH measured 2 years prior to diagnosis.

Conclusions: In this population-based SLE cohort, lower education, lower income, being divorced, widowed or single and reduced work ability were independently associated with increased risk of organ damage and mortality. These findings support integrating SDH into risk stratification models and equity-focused interventions to improve SLE care and outcomes.

Objective: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterised by progressive pulmonary fibrosis. This study aimed to investigate the role of programmed death-1 (PD-1)-expressing T cells in SSc-ILD pathogenesis and evaluate the therapeutic potential and mechanism of mesenchymal stromal cells (MSCs) in mitigating fibrosis.

Methods: PD-1 expression in T cells from 30 patients with SSc (including SSc-ILD and SSc-non-ILD (nILD) subgroups) and 15 healthy controls (HCs) was analysed via flow cytometry. A bleomycin (BLM)-induced SSc-ILD mouse model was established to evaluate the effects of MSCs in the treatment of lung collagen deposition and inflammation in SSc-ILD. MSCs were administered intravenously to BLM-treated mice, with programmed death-ligand 1 (PD-L1) knockdown (using small interfering RNA targeting PD-L1, siPD-L1) used to explore the mechanism of MSCs on PD-1/PD-L1 pathway. The effects of MSCs on CD4⁺PD-1⁺ T cell proliferation and apoptosis were evaluated by in vitro co-culture experiment.

Results: PD-1 expression was significantly elevated in CD3⁺ and CD4⁺ T cells of patients with SSc-ILD compared with HCs and SSc-nILD subgroups. In BLM-induced mice, CD4⁺PD-1⁺ T cells in the lung tissues increased progressively, which was correlated with the severity of lung fibrosis. CD4⁺PD-1⁺ T cells directly stimulated fibroblasts to upregulate the expression of collagen and transforming growth factor β1. Treatment with MSCs reduced pulmonary inflammation, fibrosis and PD-1⁺ T cell frequencies in lung tissues of BLM-induced mice. This therapeutic effect was PD-L1-dependent, as it was mediated by the MSC-induced suppression.

Conclusion: CD4⁺PD-1⁺ T cells drive fibrosis in SSc-ILD, and MSCs ameliorate disease by suppressing PD-1⁺ T cells through PD-L1-mediated mechanisms. These findings highlight PD-1 as a therapeutic target and support the clinical investigation of MSC-based interventions for SSc-ILD.

Objective: Sjögren's disease (SjD) is a chronic systemic autoimmune disease with heterogeneous glandular and extraglandular manifestations. Although aetiology and pathogenesis of SjD remains elusive, emergence of autoreactive T and B lymphocytes is crucial in disease development. In this study, the metabolome of patients with SjD was characterised to improve disease understanding and to identify biomarkers as tools to aid drug development.

Method: The metabolome was investigated in saliva, tears and plasma samples from two independent cohorts from Poland (PL) and the UK using a mass spectrometry screening platform with 4500 reference metabolites. The PL cohort included 30 healthy subjects and 32 patients with SjD. The UK cohort encompassed longitudinal samples from 13 healthy subjects and 12 patients with SjD.

Results: Patient heterogeneity was reflected in the metabolome across all three matrices (plasma, saliva and tears) with consistent disturbances in the amino acid metabolism and transport pathway. A biomarker signature was developed using both cohorts, which allowed to characterise patients with milder and more severe disease activity. The relevance of the biomarker signature was supported by the presence of metabolites linked to pathways such as gamma-glutamyl cycle, pyrimidine metabolism and sex steroid hormones, which have previously been described to be deregulated in patients with SjD and other autoimmune diseases.

Conclusion: A plasma metabolome biomarker signature was developed that can be implemented in clinical studies by simple blood collection. The biomarker signature allows to characterise disease activity of patients with SjD at baseline and provides a basis for future studies to investigate its potential utility in monitoring therapeutic intervention.

Objective: To evaluate the prevalence and anatomical distribution of inflammatory and structural MRI lesions in axial spondyloarthritis (axSpA) and compare these between patients with isolated axial involvement and those with peripheral manifestations.

Methods: Data from the Assessment of SpondyloArthritis International Society (ASAS) Classification Cohort were analysed. Peripheral involvement was defined as past or current arthritis/dactylitis/enthesitis. Sacroiliac joint (SIJ) and spinal MRI lesions typical of axSpA were classified per ASAS lesion definitions and centrally read with multi-reader majority agreement (lesion present if called by the majority; SIJ ≥4/7, spine ≥5/9 readers). Comparisons between patients with and without peripheral manifestations were made.

Results: Among 199 axSpA patients with SIJ MRI, 67 also had spinal MRI. Subchondral SIJ bone marrow oedema (BMO) was observed in 49%, without quadrant preference or subgroup differences. Other SIJ inflammatory lesions ranged from 4%-18%. Erosions (35%) and fat lesions (22%) were the most frequent structural lesions. In the spine, BMO, fat lesions and syndesmophytes/ankylosis were detected in 38%, 25% and 5%, respectively, with similar subgroup frequencies. Among 40 patients with both SIJ and whole spine MRI, inflammatory lesions were observed in both sites in 18%, SIJ only in 38%, and spine only in 20%. Structural lesions occurred in both sites in 19%, SIJ only in 30%, and spine only in 5%, with no subgroup differences.

Conclusion: The prevalence and anatomical distribution of ASAS-defined MRI lesions was similar across axSpA subgroups. Notably, 20% exhibited spine-only inflammation, suggesting potential added diagnostic and monitoring value of spinal MRI, warranting further study.

Objectives: The European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of systemic lupus erythematosus (SLE) and lupus nephritis provide important guidance for practitioners on diagnosis, monitoring and treatment. However, practical barriers, such as time constraints, may pose challenges to practitioners when implementing these recommendations in real-world settings. We provide practical, expert-driven advice on how practitioners may effectively and efficiently implement the EULAR recommendations in routine clinical practice.

Methods: Eight international SLE experts convened and contributed opinions and advice for practitioners via an online survey containing 17 open-ended questions on implementation of the EULAR recommendations for early diagnosis, treatment targets and the use of glucocorticoids (GCs), immunosuppressants and biologics. Survey results were compiled and analysed to reach consensus on key advice points for each topic.

Results: Expert advice covered four key topics-setting standardised targets to help modify disease course and prevent organ damage; taking action to achieve these targets; monitoring of target achievement through validated clinical tools and frameworks; and optimising the therapeutic strategy to prevent flares and GC-associated toxicities. A total of 13 core expert-driven advice points were developed across these topics, including scenarios for consideration of earlier biological and/or conventional immunosuppressive use, specific risk factors for poorer prognosis to inform treatment decisions and suggestions on GC tapering.

Conclusions: These expert insights could facilitate implementation of the EULAR recommendations for the management of SLE in clinical practice, thereby helping patients achieve treatment targets and prevent and/or delay organ damage progression.

Background: Axial spondyloarthritis (axSpA) impairs trunk strength, mobility and cardiorespiratory fitness. Despite exercise being a key treatment, few studies have examined a combined trunk mobility, strength and cardiorespiratory training programme. This prospective interventional study assessed the benefits of a personalised training programme based on baseline physical tests.

Methods: People with axSpA underwent cardiopulmonary exercise testing (CPET) and trunk strength/mobility assessments using the David Back Concept (DBC) devices. Strength and mobility deficits were calculated, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI) and chest expansion (CE) were recorded pre-intervention and post-intervention. The 8-week programme included two sessions per week of cardiorespiratory training (based on ventilatory threshold, heart rate monitored via a Polar device), followed by resistance/mobility exercises on DBC devices. Training intensity was tailored to each individual's one-repetition-maximum and range of motion at baseline. Post-intervention, CPET and DBC tests were repeated. Changes were analysed using linear mixed models.

Results: 30 individuals with axSpA (14 males/16 females, age 42±11.2 years, BASDAI 3.5±2.1, BASFI 2.8±2.2, BASMI 2.0±1.1, CE 4.5±2.0 cm) participated; two were lost to follow-up. Strength increased by 14.1% (p<0.001) and mobility by 14.9% (p<0.001). Significant improvements occurred in oxygen pulse (p=0.004), ventilatory efficiency (p<0.001), anaerobic threshold (p=0.002) and mechanical efficiency (p=0.021). BASDAI (2.9±2.2, p=0.021) and CE (5.0±2.1, p=0.020) improved significantly; BASMI (1.8±1.0, p=0.053) showed borderline improvement, while BASFI remained unchanged (2.4±2.1, p=0.092).

Conclusion: A combined, tailored and baseline-guided training programme significantly enhanced cardiorespiratory fitness, trunk strength and trunk mobility in individuals with axSpA, supporting individualised exercise interventions to improve outcomes and reduce functional limitations.

Background: The diagnosis of antiphospholipid syndrome (APS) uses standard antibodies (lupus anticoagulant (LAC), anticardiolipin antibodies (aCL) IgG/IgM, β2-glycoprotein I antibodies (β2GPI) IgG/IgM), which results in some patients with 'seronegative APS' being overlooked. The diagnostic value of an extended antibody profile, including antiphosphatidylserine/prothrombin complex (aPS/PT) and aCL/β2GPI IgA, requires clarification.

Objective: This study aimed to define antibody heterogeneity in APS and determine the diagnostic and risk-stratification value of novel antibodies.

Methods: We retrospectively enrolled 2994 patients with clinical features suggestive of APS who underwent testing for criteria antibodies (LAC, aCL IgG/IgM and β₂GPI IgG/IgM) and extended markers (aPS/PT IgG/IgM and aCL/β₂GPI IgA). Principal component analysis (PCA) explored antibody reactivity patterns. Multivariate logistic regression identified independent diagnostic predictors, and receiver operating characteristic curve analysis evaluated diagnostic performance. Associations between antibodies and clinical parameters defined clinical phenotypes.

Results: PCA revealed three dimensions explaining 73.56% of variance: principal component (PC)1 (IgG/LAC axis; 41.42%), PC2 (specific IgM axis; 18.12%) and PC3 (specific IgA axis; 14.02%). aPS/PT-IgM was a strong independent predictor of clinical diagnosis (adjusted OR 1.147, 95% CI 1.129 to 1.165, p<0.001). The area under the curve for diagnosing triple-negative APS was 0.868 for aPS/PT-IgM. Standard criteria antibodies lost independent significance in the full model. Phenotypic analysis identified three subtypes: a 'classical type' (PC1-High) with prolonged coagulation times and complement consumption; an 'inflammatory type' (PC3-High) with elevated systemic inflammation markers without complement consumption; and a 'restricted type' (PC2-High) associated with anaemia.

Conclusion: Distinct antiphospholipid antibody heterogeneity exists, categorisable into 'classical', 'inflammatory' and 'restricted' subtypes. This study identifies aPS/PT-IgM as a strong independent serological marker associated with clinical status. Incorporating aPS/PT-IgM into routine testing could significantly reduce seronegative APS misdiagnosis.

Objective: To investigate the concordance between organ involvement at diagnosis and relapse in granulomatosis with polyangiitis and factors associated with new disease features at relapse.

Methods: Data from a national database of newly diagnosed patients was analysed. Clinical features were recorded at diagnosis and relapse, grouped by organ system. ORs and HRs were used to assess associations between baseline features and first relapse. Factors independently associated with new organ involvement at relapse were identified using multivariable logistic regression.

Results: Among 795 patients (median follow-up 3.5 years), 394 (50%) relapsed; organ involvement at relapse was available for 376 patients. Relapses most often affected ear, nose and throat (ENT), lungs and kidneys. Organ involvement at diagnosis was associated with a higher likelihood of relapse in the same organ: eyes (OR 6.69), lungs (OR 3.35), kidneys (OR 3.58), nervous system (OR 2.90), and mucocutaneous (OR 4.53). Major manifestations associated with a higher likelihood of recurrence were scleritis, pachymeningitis, subglottic stenosis and worsening renal function. For 56% of patients, the first relapse affected only the initially involved organs. Of the 165 patients with new organ manifestations, these were rarely isolated (n=34) and usually occurred alongside involvement of at least one previously affected organ (n=131). In multivariable analysis, systemic, ENT and lung manifestations at diagnosis were associated with a lower risk of new organ disease at relapse.

Conclusion: Although new features can still emerge, organ involvement at diagnosis is associated with a higher likelihood of relapse in the same organ.