Annals of the Rheumatic Diseases最新文献

Objectives: Anticitrullinated protein antibodies (ACPAs) are associated with increased mortality in patients with rheumatoid arthritis (RA). Previous data suggest ACPAs might be associated with worse disease outcomes in patients without RA with coronary artery disease (CAD). Therefore, we investigated ACPA prevalence and its association with mortality in patients with CAD without RA. Furthermore, the role of systemic inflammation in the relation between ACPAs and mortality was investigated in RA.

Methods: The prevalence of ACPAs in patients with CAD without RA was investigated in 2 CAD cohorts (LUdwigshafen Risk and Cardiovascular Health n = 2189 patients and 656 controls; CLARIthromycin for patients with stable CORonary heart disease n = 959 patients) using a commercial enzyme-linked immunosorbent assay. Multivariable Cox proportional hazards models were performed to investigate the association between ACPAs and all-cause mortality. In 2 RA cohorts (Early Arthritis Clinic [EAC] n = 764; Better Anti-rheumatic Farmaco-therapy [BARFOT] n = 794), joint models were applied to investigate the role of C-reactive protein (CRP) on the association between ACPAs and (cardiovascular) mortality.

Results: Average follow-up time in the cohorts ranged between 8.2 and 11.8 years. In both CAD cohorts, ACPA prevalence was low (0.9% and 4.6%), and no association was found between seropositivity and all-cause mortality. In patients with RA, the association between ACPA positivity and all-cause mortality was no longer significant after adjustment for CRP. In contrast, CRP was significantly associated with all-cause and cardiovascular mortality in RA (indirect effect hazard ratio [95% CI]: EAC 1.24 [1.14-1.34], BARFOT 1.33 [1.24-1.42]).

Conclusions: ACPA prevalence is not increased in patients with CAD without RA. In RA, the association between ACPA positivity and increased (cardiovascular) mortality was primarily explained by CRP. This highlights the impact of chronic inflammation on cardiovascular outcomes in RA.

Objectives: Giant cell arteritis (GCA) is an immune-mediated vasculitis of large- and medium-sized arteries that can lead to systemic symptoms and irreversible vision loss. Glucocorticoids (GCs) remain the primary treatment but fail to induce sustained remission (SR) in approximately half of patients, resulting in disease relapses and significant treatment-related toxicity. We aimed to identify tissue-based markers at disease onset capable of distinguishing patients who later achieve SR from those who do not (non-remission [NR]) under GC monotherapy.

Methods: Using spatial biology techniques, we performed a comprehensive analysis of GCA-affected arterial tissues obtained at disease onset, correlating molecular profiles with clinical trajectory. We compared gene expression and immune cell populations between SR and NR groups, corroborated key findings by immunohistochemistry, and evaluated the diagnostic performance of identified biomarkers.

Results: Patients with NR exhibited an upregulation of extracellular matrix remodelling (ECM) and T cell activation pathways, reflecting persistent inflammation and fibrotic-like responses. By contrast, SR cases were distinguished by an enrichment of immunoglobulin G-producing plasma cells in the adventitia, which correlated with increased macrophage infiltration in the intima. Quantitative analyses suggested that combining plasma cell and macrophage markers could accurately predict GC responsiveness.

Conclusions: Our findings reveal an immunopathologic signature in GCA at diagnosis, characterised by plasma cell-rich infiltrates associated with favourable outcomes, and ECM- and T cell-associated inflammation enriched in GC-refractory cases. These insights could foster a precision medicine approach to GCA management, enabling patient stratification for GC-sparing therapies and optimising patient outcomes.

Objectives: This study aimed to test whether tirzepatide, a dual GLP-1RA/GIP agonist, approved for weight management, would be associated with lowered serum uric acid (SUA) levels via its weight reduction properties.

Methods: A post hoc analysis of the SURMOUNT-1 trial, a randomised placebo-controlled trial involving 2539 adults with obesity or overweight (body mass index [BMI] ≥ 30 kg/m² or ≥27 kg/m² and at least 1 weight-related complication), randomised to tirzepatide (5, 10, or 15 mg) or placebo for 72 weeks. Tirzepatide treatment over 72 weeks decreased weight by up to 20.9%. SUA was measured at baseline and multiple time points during the 72-week study across the 3 active trial arms, and changes were compared to the placebo arm. The association between weight changes and SUA changes was evaluated by mediation analysis.

Results: Treatment with all dose groups of tirzepatide was associated with significant reductions in SUA, compared to placebo. At week 72, the mean change in SUA was -0.69 mg/dL (SE: 0.04), -0.92 mg/dL (0.04), and -0.95 mg/dL (0.04) with 5, 10, and 15 mg of tirzepatide (all P < .001), respectively, and -0.18 mg/dL (0.04) with placebo. SUA levels reduced significantly over time compared to placebo, regardless of baseline uric acid quartiles (P = .610) and baseline BMI values (P = .362). Mediation analysis suggested that weight reduction explained 72.7% of SUA reduction.

Conclusions: In this post hoc analysis, in participants with obesity or overweight, tirzepatide was associated with meaningfully reduced SUA levels, regardless of participants' baseline BMI or SUA levels, and appeared to be so primarily via weight reduction. These findings warrant further investigation into the possible role that tirzepatide/intentional weight loss may play in the treatment of patients with gout living with obesity.

Objectives: As part of the ultrasound in psoriatic arthritis (PsA) treatment (Ultrasound in Psoriatic Arthritis Treatment-NCT03330769) study, 2 ultrasound scores for PsA (UPsA)-the UPsA activity score and the UPsA damage score-were developed and internally validated to assess musculoskeletal inflammation and structural damage in PsA. In addition, a simplified UPsA activity score (sUPsA) was also derived to enhance feasibility and applicability in routine clinical practice.

Methods: Baseline and 6-month data from patients with PsA across 19 Italian centres were analysed. Clinical evaluations included joint counts, enthesitis, dactylitis, and patient-reported outcomes. Ultrasound assessments, performed by trained sonographers, covered 42 joints, 36 tendons, 12 entheses, and 2 bursae. Factor analysis was used to derive composite scores (range 0-10). Construct validity was assessed by Spearman's correlations with clinical variables, and sensitivity to change was evaluated using the standardised response mean (SRM).

Results: A total of 312 patients with PsA were enrolled. The mean UPsA activity score was 3.7 (SD 1.86), correlating with Disease Activity for Psoriatic Arthritis (r_s = 0.42), 68-tender joint count (r_s = 0.31), and 66-swollen joint count (r_s = 0.45; all P < .001). The UPsA damage score averaged 4.1 (SD 2.26), correlating with the modified Sharp-van der Heijde score (r_s = 0.36, P < .001). The UPsA activity score showed moderate sensitivity to change overall (SRM = 0.63) and high responsiveness in patients achieving minimal disease activity (SRM = 1.03). The sUPsA retained 90% of the information from the full score while substantially improving feasibility.

Conclusions: The UPsA scores underwent internal validation and demonstrated responsiveness, representing valuable tools to assess PsA activity and damage.

Objectives: This study aims to identify circulating cellular immune cell endotypes in psoriatic arthritis (PsA), assess their association with treatment response, and explore key biological pathways linked to these immune profiles.

Methods: Using mass cytometry, we analysed CD3+ immune cell populations in patients with PsA initiating targeted therapies. Hierarchical clustering identified immune cell endotypes, and their associations with clinical features and treatment response were assessed using generalised estimating equation models. Proteomic profiling via an aptamer-based assay compared differentially expressed proteins across clusters, followed by pathway analysis. Imaging mass cytometry analysis was performed to characterise T cell subsets in synovial tissue samples.

Results: We analysed blood samples from 40 treatment periods involving 34 patients and identified 3 immune clusters (C); C1: 'memory CD4+ T cell endotype' - associated with higher sonographic musculoskeletal inflammation and peri-articular bone formation, and poorer response to therapy; C2: 'Nonclassical T cell endotype'-exhibited lowest levels of musculoskeletal inflammation; and C3: 'Terminal effector/Th1 cell endotype'-linked to higher sonographic peri-articular inflammation. The immune endotypes remained relatively stable 3 months posttreatment. The 'memory CD4+ T cell endotype' was characterised by deregulation of immune-related biological pathways, including several intracellular signalling pathways, the most notable being WNT signalling. CD4+ cells with memory and effector phenotypes were abundant in the synovial tissue sample from patients with PsA.

Conclusions: Heterogeneity in circulating immune cell profiles is associated with PsA clinical features and therapeutic response. The results underscore the potential of immune cell phenotyping to improve prognosis in PsA, which could inform personalised treatment strategies.

Objectives: The efficacy of low-dose belimumab for disease flare prevention in patients with lupus with low disease activity was evaluated (NCT04515719).

Methods: In this 52-week, randomised, placebo-controlled trial, patients who had a Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score of ≤6, with no A and ≤ 1 B on British Isles Lupus Assessment Group, and who had prednisone ≤20 mg/d at screening were enrolled and randomly assigned 1:1 to intravenous 120 mg belimumab or placebo (saline). The primary outcome was disease flares within 52 weeks. The trial was terminated prematurely on 10 April 2022 when Renji Hospital was designated as a COVID-19 referral centre during the Shanghai lockdown.

Results: Overall, 90.5% and 86.1% of patients in the belimumab (n = 116) and placebo (n = 115) arms completed the study within a follow-up of 31 ± 16.1 weeks. The primary endpoint was met. In total, 7.8% of patients receiving low-dose belimumab had disease flares, significantly lower than that in the placebo group (19.1%) (P = .012; difference 11.3%; 95% CI 1.8%-20.9%). Kaplan-Meier curves also demonstrated lower cumulative flare rates in the belimumab arm (P = .011, Hazard Ratio (HR), 0.38; 95% CI 0.17-0.83). Glucocorticoid-sparing effects were comparable (Δprednisone from baseline, -1.55 ± 10.11 mg/d vs -0.91 ± 7.43 mg/d, P = .075). SELENA-SLEDAI was reduced by 0.62 ± 2.14 in the belimumab group; however, it increased by 0.12 ± 2.80 in the placebo group (P = .009). Any adverse events were comparable (61.2% vs 64.3%). Only 4 (3.4%) and 6 (5.2%) severe adverse events occurred in 2 groups, respectively.

Conclusions: Treatment with low-dose belimumab helped reduce the risks of disease flares in Chinese patients with systemic lupus erythematosus at low disease activity. Belimumab was generally well-tolerated.