Clinical and experimental rheumatology最新文献

Objectives: We conducted a comprehensive analysis of the spatiotemporal dynamics of rheumatoid arthritis (RA), including age‑standardised prevalence (ASPR), incidence (ASIR), and disability‑adjusted life years (DALYs, ASDR), from 1990 to 2021, and projected trends through 2044 using data from the Global Burden of Disease (GBD) 2021 to inform and strengthen global prevention, control strategies, and public health policy for RA.

Methods: ASPR, ASIR, and ASDR estimates for 204 countries and territories (1990-2021) were retrieved from GBD 2021. We quantified temporal trends by the estimated annual percentage change (EAPC) and average annual percentage change (AAPC). We examined gender‑age‑specific differences in ASPR, ASIR, and ASDR and the relationships between RA‑related DALYs and risk factors across strata. What's more, we employed AutoRegressive Integrated Moving Average (ARIMA) and the Nordpred age‑period‑cohort model to forecast prevalence and incidence through 2044. All statistical analyses were performed in R 4.4.1 and Joinpoint Trend Analysis Software.

Results: Between 1990 and 2021, global ASPR and ASIR rose (AAPC: 0.44 and 0.40, respectively), while ASDR declined modestly (AAPC: -0.03). In 2021, Ireland exhibited the highest ASPR (529.08) and ASIR (35.08), whereas Mexico recorded the highest ASDR (87.45). Although higher sociodemographic index (SDI) regions bore a greater RA burden overall, lower SDI regions experienced more rapid increases. Across all metrics, women - particularly those aged ≥60 years - demonstrated higher rates than men. 'Smoking' emerged as a vital risk of DALYs across age groups, genders, and regions. Projections from Nordpred and ARIMA model indicate continued rapid growth in prevalence and incidence cases through 2044, with more gradual increases in ASPR and ASIR.

Conclusions: Global prevalence and incidence of RA are projected to rise further. Detailed knowledge of these trends and their drivers is essential to inform targeted interventions and mitigate the worldwide impact of RA.

Objectives: Rheumatoid arthritis (RA) is characterised by systemic inflammation, which elevates the risk of atherothrombotic cardiovascular (CV) events. Although Janus kinase inhibitors (JAKi) are effective in controlling RA inflammation, post-marketing data (ORAL Surveillance) have suggested an increased risk of major adverse CV events (MACE) in patients receiving tofacitinib (TOFA). The pathophysiological mechanisms for these findings remain unclear, especially regarding platelet aggregation and tissue factor (TF) expression, two key drivers of thrombosis. In this study, we aimed to investigate the effects of TOFA on platelet aggregation and TF-mediated coagulation pathways to elucidate potential pro- or anti-thrombotic properties at the cellular level.

Methods: Platelet-rich plasma (PRP) from 12 healthy volunteers was incubated with TOFA (20 or 40 ng/mL), and maximal platelet aggregation (AGGmax) in response to ADP was measured by light transmission aggregometry (LTA) at 30, 60, and 90 minutes. In parallel, platelets from 14 RA patients were evaluated at baseline and at 1, 3, and 6 months of TOFA treatment (5 mg bid). Human umbilical vein endothelial cells (HUVECs) were exposed to TOFA (20 or 40 ng/mL) and/or IL-6 (0.5 ng/mL) to assess TF mRNA (by real-time PCR) and TF procoagulant activity (by factor Xa generation assay).

Results: TOFA did not alter ADP-induced platelet aggregation ex vivo in either healthy volunteers or RA patients. However, it significantly reduced IL-6-induced TF mRNA expression and activity in HUVECs. These in vitro results suggest that TOFA may counteract IL-6-mediated prothrombotic mechanisms at the endothelial level.

Conclusions: Despite clinical concerns raised by ORAL Surveillance, our findings indicate no direct enhancement of platelet reactivity by TOFA. Instead, TOFA attenuated IL-6-driven TF expression in endothelial cells, pointing to a possible protective effect on vascular thrombogenic pathways. Further studies are warranted to reconcile these in vitro observations with real-world data on CV outcomes in RA.

Objectives: The incidence of Pneumocystis jirovecii pneumonia (PJP) in connective tissue diseases (CTD) patients is increasing and the mortality rate is high. We carried out this study to describe clinical characteristics in PJP patients with different underlying CTDs and identify prognostic risk factors in CTD-PJP patients.

Methods: We retrospectively enrolled consecutive patients with CTD-PJP in our centre between January 2014 and December 2022. We included 248 participants who were classified according to underlying CTD or clinical outcomes.

Results: In our study, there were 57 CTD-PJP patients (41, 66) years, 64.5% of whom were female, 108 (43.5%) of whom died. There were more interstitial lung disease (ILD) (p<0.001), pneumomediastinum (p=0.004), and a higher corticosteroid dosage (p=0.003) in the idiopathic inflammatory myopathy (IIM) group of patients. Patients in the IIM group had a significant highest mortality (65.5%), whereas those in the rheumatoid arthritis (RA) group had a lower mortality rate (30.4%) (p=0.006). Multivariate analysis indicated that IIM (HR=6.657, p<0.001, 95% CI: 2.883-15.368), hospital-acquired pneumonia (HAP) (HR=2.175, p<0.05, 95% CI: 1.028-4.601), lower minimal albumin (Alb) (HR=0.869, p<0.001, 95% CI: 0.802-0.942) and higher lactate dehydrogenase (LDH) (HR=1.002, p<0.001, 95% CI: 1.001-1.003) were independent risk factors for the survival of CTD-PJP patients. The optimal cut-off point of serum minimal Alb was 26.5 g/L and serum LDH was 612 U/L, respectively.

Conclusions: CTD-PJP patients were mainly middle-aged female, with a high mortality rate. IIM patients had a relatively worse outcome, while RA patients had a relatively better survival rate. IIM, HAP, lower serum minimal Alb and higher LDH were independent survival risk factors for them.

Objectives: We aimed to evaluate the modification of cardiovascular risk factor parameters after intra-articular injection with hyaluronic acid in patients with symptomatic hip and knee osteoarthrtitis. This was a retrospective cohort study of 101 patients meeting the clinical and radiological criteria of the American College of Rheumatology for hip and knee osteoarthritis, Kellgren-Lawrence grades I-IV.

Methods: Patients received four intra-articular injections of hyaluronic acid in the knee and/or hip in the period of study. After the injections, changes in weight and BMI, pain using the visual analogue scale, consumption of pain medications, and physical activity were recorded at each follow-up visit. Analytical variations in blood glucose, HbA1c, total cholesterol, LDL, HDL, and triglycerides were also evaluated.

Results: Over the 24-month study period, weight and BMI were stabilised. A reduction in pain of 1.2 points (p<0.001), a 20,76% reduction in analgesic consumption (p<0.001), and a 19.81% increase in physical activity (p<0.001) and a 21.8% increase in frequency (p=0.001) were observed. Total cholesterol (p=0.002), LDL (p=0.009), HDL (p=0.023), and triglycerides (p=0.021) showed a significant decrease in all cases when analysed in patients whose baseline levels were pathological.

Conclusions: Intra-articular viscosupplementation with hyaluronic acid in symptomatic hip and knee osteoarthritis achieves a decrease in pain, potentially allowing patients to increase their physical activity levels, which helps control weight and BMI. Secondarily it could influence the improvement of CVRF analytical outcomes in the medium term in those patients who had altered levels.

Objectives: This study aimed to explore the potential of plasma micro-ribonucleic acids (miRNAs) in predicting joint damage in patients with rheumatoid arthritis (RA).

Methods: This subanalysis of the MIRACLE study, a randomised, open-label, non-inferiority trial, explored and compared the efficacy and safety of treatment with adalimumab (ADA), an anti-tumour necrosis factor (TNF) α, plus a maximum tolerated dose of methotrexate (MTX) with a reduced dose of MTX in early RA. Plasma levels of miRNAs (miR-143-3p, miR-146a-5p, miR-155-5p, miR-182-5p, miR-21-5p, and miR-221-3p) and serum levels of inflammatory cytokines (interleukin-6 [IL-6], vascular endothelial growth factor [VEGF]) and matrix metalloprotease-3 (MMP-3) were measured at 24 weeks. Their association with joint destruction assessed by the modified total Sharp score [mTSS] over the 24-week period were analysed.

Results: A total of 134 patients who showed an inadequate response to MTX and started treatment with ADA were included in the analyses. Logistic regression analyses revealed that higher plasma levels of miR-143-3p, miR-146a-5p, miR-21-5p, and miR-221-3p were significantly associated with increases in mTSS >0.5 points during the observation period. In particular, positive correlation was derived from the progression of joint space narrowing. In contrast, MMP-3, VEGF, and IL-6 levels were not associated with joint destruction. Cartilage damage occurred mainly in patients treated with reduced dose of MTX.

Conclusions: Higher circulating miRNA levels predicted subsequent cartilage damage in early RA treated with a TNF inhibitor in addition to MTX. Thus, the MTX dose at ADA initiation should not be reduced in patients with high microRNA levels.

Objectives: Janus kinase inhibitors (JAKi) are increasingly used to treat autoimmune rheumatic diseases (ARDs), despite concerns regarding their potential cardiovascular risks. Cardiac strain, a sensitive marker for subclinical myocardial dysfunction, can predict the risk of heart failure. This study aims to evaluate the effect of JAKi on cardiac strain and function in patients with ARDs in routine clinical practice.

Methods: This prospective Greek cohort study enrolled patients diagnosed with RA, PsA, or axSpA initiating treatment with a JAKi (baricitinib, tofacitinib, or upadacitinib). Comprehensive assessments were performed at baseline, 6 months, and 12 months including disease-specific scores and laboratory tests. Transthoracic speckle-tracking echocardiography was used to assess global longitudinal strain (GLS), left ventricular ejection fraction (EF), and right ventricular function (including RV GLS, TAPSE, and S'RV). Diastolic function was evaluated through the E/A and E/E' ratios.

Results: Thirty patients completed the study: 12 with axSpA, 10 with RA, and 8 with PsA. Disease activity significantly improved across all cohorts. No significant changes in GLS, EF, E/A, E/E', TAPSE, S'RV or heart rate were observed from baseline to 12 months. Additionally, the GLS of the left ventricle did not show a decline.

Conclusions: In this cohort, JAKi did not result in significant changes in cardiac strain or function over one year in patients with ARDs, suggesting that JAKi may not have a detrimental impact on cardiac function in the short term. However, longer-term studies with larger cohorts are necessary to evaluate potential delayed effects and confirm the cardiovascular safety of JAKi.

Objectives: The concept of Comprehensive Disease Control (CDC) underlines as the control of disease activity should be associated with damage inhibition. Recently, this concept has been proposed in Systemic Lupus Erythematosus (SLE) patients (LupusCDC) with long-standing disease. In the present analysis we evaluated the incidence of LupusCDC in a cohort of newly diagnosed patients.

Methods: We analysed data from the multicentre cohort of the Early Lupus Project. Disease activity was evaluated by ECLAM and chronic damage by SDI. At each available time point, the presence of remission condition was assessed, defined as: Complete remission in GCs (GCon): ECLAM=0, antimalarials and/or immunosuppressants, PDN ≤5 mg/day; and Complete remission without GCs (GCoff): ECLAM=0, antimalarials and/or immunosuppressants. The presence of LupusCDC was analysed, defined as remission in the absence of progression of chronic damage (LupusCDC-GCon and LupusCDC-GCoff).

Results: We included 239 patients [205F; mean±DS age 45.8±14.6 years] with a follow-up of 36 months. During this period, 33.08% of patients achieved LupusCDC-GCon, while 12.03% LupusCDC-GCoff in at least one evaluation. Univariate analysis showed the association between failure to achieve LupusCDC-GCon and musculoskeletal manifestations (p<0.001), activity in renal and neuropsychiatric domains (p=0.01, p<0.001, respectively), association confirmed by the multivariate analysis.

Conclusions: CDC in early onset SLE is not uncommon. Indeed, one-third of patients achieved LupusCDC-GCon in at least one evaluation. More severe disease, characterised by active renal and neuropsychiatric manifestations represented a risk factor for failure to achieve LupusCDC. The lower incidence of LupusCDC-GCoff suggested the difficulty in discontinuing GC treatment in early disease phase.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by a complex pathogenesis, heterogeneous clinical manifestations and a variable disease course. This review summarises the most relevant contributions on SLE published during 2025, following the framework of the One Year in Review series. In particular, we focus on emerging pathogenetic insights, novel and refined biomarkers, clinical manifestations and outcomes, comorbidities, and evidence from clinical trials and real-world studies, highlighting both recent progress and persistent unmet needs in the management of SLE.