Rheumatology最新文献

Background: The definition of Takayasu arteritis (TAK) remission and disease activity is still unclear. Vascular imaging is an essential tool for following-up patients. Herein, we aimed to compare the evolution of vascular lesions (i.e. vessel wall thickening and stenosis) under conventional cDMARDs relatively to biological DMARDs (bDMARDs) in TAK patients followed with the same CT angiography modalities.

Method: We compared 75 lines of therapy in TAK patients who received cDMARDs (n = 40 lines) and bDMARDs (n = 35 lines) using CT angiography. We established 1-3 main target vessels with vessel wall thickening and/or stenosis. Every targeted vessel had its thickness and its lumen diameter measured at the initiation of immunosuppressive treatment and at 12 months.

Results: We observed an overall reduction in arterial wall thickness in 73% of cases and 31% had >25% relative decrease in the wall thickness. Using a linear mixed effects model, first-line immunosuppressive therapy (P = 0.012) and bDMARDs relatively to cDMARDs (P = 0.026) were independently associated with vessel wall thickness reduction in TAK. Thirty-eight percent of the stenotic vessels had a > 25% relative increase in lumen diameter under immunosuppressive therapy. The relative increase >25% in lumen diameter was noted in 56% vs 17% with bDMARDs compared with cDMARDs.

Conclusion: Immunosuppressive treatments can reduce arterial wall thickness and widen lumen diameter in TAK. bDMARDs seem to be more effective than cDMARDs to improve arterial lesions in TAK.

Objective: CD4+CXCR5+PD-1hi follicular helper T (Tfh) cells dwell in the germinal centres (GCs) of lymphoid organs and participate in RA pathogenesis. The frequency of their circulating counterparts (cTfh frequency) is expanded in RA and correlates with the pool of GC Tfh cells. Our objective was to study the effect of abatacept (ABT) or TNF blockers (TNFbs) on the cTfh frequency in RA.

Methods: Peripheral blood was drawn from seropositive, long-standing RA patients chronically receiving conventional synthetic DMARDs (csDMARDs; n = 45), TNFb (n = 59) or ABT (n = 34) and healthy controls (HCs; n = 137). Also, patients with an incomplete response to csDMARDs (n = 41) who initiated TNFb (n = 19) or ABT (n = 22) were studied at 0 and 12 months. The cTfh frequency was examined by cytometry.

Results: As compared with HCs, an increased cTfh frequency was seen in seropositive, long-standing RA patients chronically receiving csDMARDs or TNFb but not ABT. After changing from csDMARDs, the cTfh frequency did not vary in patients who were given TNFb but decreased to HC levels in those given ABT. In the ABT group, the baseline cTfh frequency was higher for patients who attained 12-month remission (12mr) vs those who remained active (12ma): 0 month cut-off for remission >0.38% [sensitivity 92%, specificity 90%, odds ratio (OR) 25.3]. Conversely, in the TNFb group, the baseline cTfh frequency was lower for 12mr vs 12ma: 0 month cut-off for non-remission >0.44% (sensitivity 67%, specificity 90%, OR 8.5).

Conclusion: ABT but not TNFb was able to curtail the cTfh frequency in RA. A higher baseline cTfh frequency predicts a good response to ABT but a poor response to TNFb.

Objectives: To determine the clinical associations and predictive value of two thresholds of negative dual-energy CT (DECT) for MSU crystal deposition in gout patients initiating urate-lowering therapy (ULT) and identify which threshold is more clinically relevant.

Methods: Patients from the CRYSTALILLE cohort with a diagnosis of gout naïve to ULT with baseline DECT scans of the knees and feet were selected. Two thresholds of positivity for DECT detection of MSU crystal deposition were considered (<0.01 cm3 and <0.1 cm3). Baseline characteristics and the prediction of key outcomes after ULT initiation, including reaching serum urate (SU) levels <6.0 and 5.0 mg/dl and occurrence of flares at 6, 12 and 24 months, associated with both thresholds of negative DECTs were compared with those of patients having positive DECT scans.

Results: A total of 211 patients, median age 66.2 years [interquartile range (IQR) 57-75.8], with a median symptom duration of 3 years (IQR 0-7.8) were included. A total of 38/211 (18%) and 90/211 (43%) had negative DECT scans for the 0.01 and 0.1 cm3 thresholds, respectively. Factors associated with negative DECT scans were younger age, shorter symptom duration and an absence of cardiovascular disease for both volume thresholds. A total of 9/39 (23.1%), 3/26 (11.5%) and 1/18 (5.6%) patients with <0.1 cm3 MSU crystals had flares at 6, 12 and 24 months, respectively, compared with 18/45 (40.0%), 9/36 (25.0%) and 2/18 (11.1%) patients with ≥0.1 cm3 (P > 0.05). Overall, 95 patients (68.3%) reached SU levels <6.0 mg/dl and 68 (48.9%) reached levels <5.0 mg/dl, without any difference between positive and negative DECTs, with ULT dosages that tended to be lower in patients with negative DECTs.

Conclusion: The 0.1 cm3 threshold was better correlated with clinical presentation and evolution than the 0.01 cm3 threshold. Gout patients with negative DECTs exhibit milder disease and a lower comorbidity burden. They do not exhibit particularly easy-to-treat hyperuricaemia but they may have a lower risk of flares.

Objective: This post-hoc analysis was carried out on data acquired in the longitudinal Sonographic Tenosynovitis Assessment in RheumaToid arthritis patiEnts in Remission (STARTER) study. Our primary aim was to determine the predictive clinical and musculoskeletal ultrasonographic (MSUS) features associated with disease flare in RA patients in clinical remission, while our secondary aim was to evaluate the probability of disease flare based on clinical and MSUS features.

Methods: We analysed data for a total of 389 RA patients in DAS28-defined remission. All patients underwent a MSUS examination according to the OMERACT guidelines. Logistic regression and results, presented as odds ratio and 95% CI, were used for the evaluation of the association between selected variables and disease flare. Significant clinical and MSUS features were incorporated into a risk table for predicting disease flare within at least 12 months of follow-up in patients with RA remission.

Results: Within 12 months, 137 (35%) RA patients experienced a disease flare. RA patients who experienced a flare disease differed from those with persistent remission in terms of ACPA positivity (75.9% vs 62.3%, respectively; P = 0.007), percentage of sustained clinical remission at baseline (44.1% vs 68.5%, respectively; P = 0.001) and synovium power Doppler signal presence (58.4% vs 33.3%, respectively; P < 0.001). Based on these results, these three features were considered in a predictive model of disease flare with an adjusted odds ratio of 3.064 (95% CI 1.728-5.432). Finally, a risk table was constructed including the three significant predictive factors of disease flare occurring within 12 months from the enrolment.

Conclusion: An adaptive flare-prediction model tool, based on data available in outpatient settings, was developed as a multiparametric risk table. If confirmed by external validation, this tool might support the defining of therapeutic strategies in RA patients in DAS28-defined remission status.

Objective: Immune-mediated necrotizing myopathy (IMNM) is pathologically characterized by diffuse myofibre necrosis and regeneration, myophagocytosis and a sparse inflammatory infiltrate. Monocyte chemoattractant protein-1 (MCP-1) is a key chemokine that regulates monocyte/macrophage infiltration into injured tissues. IL-6 signalling in the induction of MCP-1 expression has not been investigated in IMNM.

Methods: MCP-1 expression in muscle specimens was assessed using immunohistochemistry and Reverse transcription quantitative polymerase chain reaction (RT-qPCR). Levels of multiple serological cytokines were evaluated using the electrochemiluminescence-based immunoassays. Flow cytometry, RT-qPCR, enzyme-linked immunosorbent assay, western blot, dual-luciferase reporter assays and chromatin immunoprecipitation qPCR were performed to explore the effects of IL-6 signalling on MCP-1 production in human myoblasts.

Results: MCP-1 was scattered and was positively expressed within myofibres and a few inflammatory cells in the muscles of patients with IMNM. Sarcoplasmic MCP-1 expression significantly correlated with myonecrosis, myoregeneration and inflammatory infiltration. Serum MCP-1, IL-6 and the soluble form of the IL-6 receptor (sIL-6R) were elevated in patients with IMNM compared with controls. Serological MCP-1 levels were significantly associated with serum IL-6 expression and clinical disease severity in IMNM patients. The IL-6/sIL-6R complex induced MCP-1 expression via the signal transducer and activator of transcription 3 (STAT3) pathway in human myoblasts. Mechanistically, phospho-STAT3 was enriched in the MCP-1 promoter region and promoted the transcription.

Conclusion: IL-6 trans-signalling may contribute to the immunopathogenesis of IMNM by augmenting inflammation through regulation of MCP-1 expression in IMNM.

Objectives: We investigated the effectiveness and safety of very-low-dose (<5 mg/day) glucocorticoids (GCs) in patients with RA treated with biologic and targeted synthetic DMARDs (b/tsDMARDs).

Methods: In this prospective cohort study, we included all RA patients who started their first b/tsDMARDs at our institution between 2015 and 2020 and were monitored every 6 months for 3 years. Relationships between exposure to very-low-dose GCs and disease activity were examined through multivariable logistic regression and repeated-measures analysis of variance. The impact of very-low-dose GCs on safety was also evaluated.

Results: We enrolled 229 RA patients, of whom 68% were prescribed very-low-dose GCs and 32% received no GCs. After 3 years on b/tsDMARDs, 32% had never abandoned, 20% had gone on and off and 23% had permanently discontinued very-low-dose GCs, while 25% had never taken GCs. Shorter disease duration at b/tsDMARD initiation was the single modifiable predictor of very-low-dose GC cessation [odds ratio 1.1 (95% CI 1.03, 1.14) for any 1-year decrease; P = 0.001]. A significant association existed between ongoing utilization of very-low-dose GCs and persistent moderate disease activity. Use of very-low-dose GCs was associated with hypertension (20% vs 11%) and myocardial infarction (2.3% vs 0%).

Conclusion: A substantial proportion of RA patients treated with b/tsDMARDs continue to receive very-low-dose GCs without significantly improving disease control. However, this appears to increase cardiovascular morbidity.

Objectives: The objective of this study was to explore the prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIMs) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.

Methods: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after two vaccine doses. We compared BI characteristics and severity among patients with IIMs, patients with other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HCs). Multivariable Cox regression models were used to assess the risk factors for BI, severe BI ,and hospitalizations among patients with IIMs.

Results: Among the 9449 included responses, BIs occurred in 1447 respondents (15.3%). The median age was 44 years [interquartile range (IQR) 21], 77.4% were female, and 182 BIs (12.9%) occurred among the 1406 patients with IIMs. Multivariable Cox regression among the data for patients with IIMs showed increasing age to be a protective factor for BIs [hazard ratio (HR) = 0.98, 95% CI = 0.97-0.99], and HCQ and SSZ use were risk factors (HR = 1.81, 95% CI = 1.24-2.64, and HR = 3.79, 95% CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for a severe BI (HR = 3.61, 95% CI = 1.09-11.8). Non-white ethnicity (HR = 2.61, 95% CI = 1.03-6.59) was a risk factor for hospitalization. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIMs = 6.0% vs AIRDs = 1.8%, nrAIDs = 2.2% and HCs = 0.9%), intensive care unit admission (IIMs = 2.2% vs AIRDs = 0.6%, nrAIDs and HCs = 0%), advanced treatment with antiviral or monoclonal antibodies (IIMs = 34.1% vs AIRDs = 25.8%, nrAIDs = 14.6% and HCs = 12.8%) and had more hospitalization (IIMs = 7.7% vs AIRDs = 4.6%, nrAIDs = 1.1% and HCs = 1.5%).

Conclusion: Patients with IIMs are susceptible to severe COVID-19 BIs. Age and immunosuppressive treatments were related to the risk of BIs.