Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
34811816 Measurement of synovium and serum dual specificity phosphatase 22 level: Their inter-corre 2022 Jan BACKGROUND: Dual specificity phosphatase 22 (DUSP22), also named as Jun N-terminal kinase pathway associated phosphatase recently, is reported to be closely engaged in immune and inflammation regulation. This study aimed to investigate the interaction between synovium DUSP22 and serum DUSP22 levels and to explore their correlation with rheumatoid arthritis (RA) risk, inflammation, and disease activity. METHODS: Synovium and serum samples from 42 RA patients with knee involvement underwent arthroscopy, and 20 knee trauma patients were collected. Besides, serum samples from 40 healthy controls were also obtained. Synovium DUSP22 expression was detected by reverse transcription quantitative polymerase chain reaction, while serum DUSP22 level was detected by enzyme-linked immunosorbent assay. RESULTS: Synovium DUSP22 level was greatly decreased in RA patients compared to trauma controls (p < 0.001), and it was negatively correlated with tender joint count (TJC) (r = -0.318, p = 0.040), C-reactive protein (CRP) (r = -0.330, p = 0.033), and Lysholm score (r = -0.423, p = 0.005) in RA patients. Serum DUSP22 level was lowest in RA patients, followed by trauma controls, then highest in healthy controls (p < 0.001). Serum DUSP22 level was negatively associated with TJC (r = -0.438, p = 0.004), swollen joint count (SJC) (r = -0.372, p = 0.015), CRP (r = -0.391, p = 0.011), and disease activity score in 28 joints (DAS28(ESR) ) score (r = -0.406, p = 0.008), and it increased after treatment (p = 0.001) in RA patients. In addition, serum DUSP22 level positively related to synovium DUSP22 level in RA patients (r = 0.394, p = 0.010). CONCLUSION: Synovium and serum DUSP22 are intercorrelated and insufficiently expressed in RA patients; meanwhile, their deficiency correlates with increased systemic inflammation, disease activity, and joint dysfunction.
32895043 Effect of Dietary Education on Cardiovascular Risk Factors in Rheumatoid Arthritis Patient 2021 AIM: The aim of this study was to investigate the effect of dietary education on cardiovascular risk factors in patients with rheumatoid arthritis. METHODS: In this randomized clinical trial, 112 patients with rheumatoid arthritis were randomly assigned into two groups, intervention and control. Dietary education was provided for the intervention group in 4 sessions; anthropometric measurements, serum levels of RF, triglycerides, cholesterol, HDL, LDL, and fasting blood sugar were measured before and three months after the intervention. Data were analyzed using SPSS software and appropriate statistical tests. RESULTS: The mean of total cholesterol (p <0.001), triglycerides (p = 0.004), LDL (p <0.001), systolic blood pressure (p = 0.001), diastolic blood pressure (p = 0.003), FBS and BMI (p <0.001) were decreased significantly in the intervention group after education compared the control group. CONCLUSION: Traditional care for rheumatoid arthritis patients is not enough. Patients need more education in order to improve their situation.
33515120 Non-surgical periodontal treatment improves rheumatoid arthritis disease activity: a meta- 2021 Aug OBJECTIVES: The aim of the meta-analysis was to clarify the efficacy of non-surgical periodontal treatment (NSPT) in improving rheumatoid arthritis (RA) disease activity. METHODS: A systematic literature search was conducted using the PubMed, Embase, and Cochrane databases up to October 2020. A total of nine studies were included for the comparison of RA-related indicator changes between the NSPT group and no treatment (NT) group. Mean differences (MD) and 95% confidence intervals (CI) were calculated for disease activity score (DAS28), erythrocyte sedimentation rate (ESR), tender joint counts (TJC), swollen joint counts (SJC), visual analogical scale (VAS), morning stiffness (MS), rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6). RESULTS: NSPT induced significant reductions of DAS28 (MD: 0.61, 95% CI: 0.37, 0.85, P < 0.001), TJC (MD: 0.65, 95% CI: 0.37, 0.93, P < 0.001), SJC (MD: 0.67, 95% CI: 0.18, 1.17, P = 0.008), VAS (MD: 0.48, 95% CI: 0.08, 0.88, P = 0.02), and CRP (MD: 0.34, 95% CI: 0.07, 0.64, P = 0.01) in RA patients with periodontitis. Other parameters showed a trend toward reduction, but results were not statistically significant. CONCLUSIONS: This meta-analysis indicates that NSPT could improve RA activity as assessed by DAS28, TJC, SJC, VAS, and CRP. CLINICAL RELEVANCE: The results emphasize the effectiveness and need for periodontal diagnosis and periodontal therapy in rheumatoid arthritis patients to reduce disease activity.
34080783 Prevalence of metabolic syndrome in patients with rheumatoid arthritis in eastern China-A 2021 Sep OBJECTIVE: The purpose of this hospital clinic based study was to evaluate the potential risk factors associated with the prevalence of MetS in RA population. METHODS: From January 2015 to October 2018, 717 patients with RA and 717 healthy controls who were treated or performed physical examination in Tianjin First Central Hospital were enrolled in this study. The basic disease diagnoses were recorded. A questionnaire was performed on all participants to assess the demographic details of the RA cohort. Moreover, laboratory indicators related to glucose and lipid metabolism in patients with RA were also detected. The potential risk factors for MetS were also analyzed. RESULTS: The prevalence of MetS were 31.2% and 34.2% in case and control groups, respectively (P = .22). There were lower levels of HDL-C, obesity, TG, LDL-C and TC in case group than control group (all P < .05). The hypertension levels in healthy controls was decreased in compared with patients with RA (P < .05). Nevertheless, in patients with RA, complement 3 (OR: 1.02; 95% CI: 1.01-1.03, P = .007) and less glucocorticoids use (OR: 0.63, 95% CI: 0.39-0.99, P = .046) were associated with MetS. CONCLUSION: The prevalence of MetS was not associated with RA. Complement 3 may be associated with the higher prevalence of MetS in patients with RA. Glucocorticoids treatment may be associated with MetS.
34006854 Exploring the effect of alcohol on disease activity and outcomes in rheumatoid arthritis t 2021 May 18 To evaluate the effects of alcohol consumption on disease activity in rheumatoid arthritis. EMBASE, Pubmed, the Cochrane Library, and Web of Science were searched until July 29, 2020. English language studies that reported disease activity outcomes in rheumatoid arthritis were included. Studies were excluded if they were reviews, case reports, had fewer than 20 patients, or reported on prevalence but not disease activity in RA. Forest plots were used to determine pooled mean difference and were generated on RevMan5.3. Linear regression was used to determine correlations between alcohol and antibody status, gender, and smoking status. The search identified 4126 citations of which 14 were included. The pooled mean difference in DAS28 (95% CI) was 0.34 (0.24, 0.44) (p < 10(-5)) between drinkers and non-drinkers with lower DAS28 in non-drinkers, 0.33 (0.05, 0.62) (p = 0.02) between heavy drinkers and non-drinkers with lower DAS28 in heavy drinkers, and 0.00 (- 0.30, 0.30) (p = 0.98) between low- and high-risk drinkers. The mean difference of HAQ assessments was significantly different between those who drink alcohol compared to those who do not, with drinkers reporting lower HAQ scores (0.3 (0.18, 0.41), p < 10(-5)). There was no significant correlation between drinking and gender, smoking status, or antibody positivity. Alcohol consumption is associated with lower disease activity and self-reported health assessment in rheumatoid arthritis. However, drinking has no correlation with smoking, gender, or antibody status.
34331380 Morin Acts as a USP7 Inhibitor to Hold Back the Migration of Rheumatoid Arthritis Fibrobla 2021 Oct INTRODUCTION: The aim of this study is to investigate the effect and detailed mechanisms of morin, an anti-arthritis compound widely distributed in foods of plant origin, on the pathological migration of fibroblast-like synoviocytes (FLS). METHODS AND RESULTS: The migration of FLS collected from arthritis rats and MH7A cells is induced by platelet-derived growth factor, and an arthritis model in rats is established by Freund's complete adjuvant. The results show that morin remarkably restrains FLS migration but slightly affects FLS apoptosis and proliferation. Moreover, in the progression of FLS migration, focal adhesion (FA) turnover is inhibited by morin via lowering the activation of Paxillin and focal adhesion kinase (FAK) and internalization of integrin β1. Morin disrupts the formation of mTOR complex 2 (mTORC2) and the activation of AKT (S473) and PKCα (S657), and MHY1485 reverses morin-limited FLS migration. Of note, the protein stability of Prickle1, a binding factor of Rictor, is reduced by morin, and MG132 but not Baf A1 shows a repressive effect. Finally, the target protein is identified as ubiquitin-specific protease 7 (USP7) but not USP9X. USP7 overexpressing plasmid weakens morin-affected protein and ubiquitination of Prickle1, and mechanisms are confirmed in vivo by using an overexpressing plasmid and inhibitor. CONCLUSION: Morin restricts FLS migration and arthritis by intervening in "USP7-Prickle1-mTORC2" signaling and FA turnover.
34166795 High patient global assessment scores in patients with rheumatoid arthritis otherwise in r 2021 Dec OBJECTIVES: To assess whether high patient global assessment (PGA) scores by patients with rheumatoid arthritis (RA) otherwise in remission reflect subclinical inflammation. METHODS: Cross-sectional, single-center study, including consecutive RA patients. Remission states were defined based on the ACR/EULAR Boolean definition: 4V-remission (tender and swollen 28-joint counts (TJC28/SJC28), C-reactive protein (CRP), and PGA all≤1), PGA-near-remission (the same, except PGA>1), and non-remission (any of TJC28, SJC28, CRP>1). A blinded expert musculoskeletal ultrasonographer scanned 44 joints, 38 tendon sheaths, 4 bursae on the same day of the clinical evaluation. Each structure was assessed for the presence of Grey Scale synovial hypertrophy (GS) and Power Doppler (PD), both scored using a semi-quantitative scale (0-3 points). The Global OMERACT-EULAR Synovitis Score (GLOESS, 0-132, primary outcome), and a global tenosynovitis/bursitis score (GTBS) were compared between remission states, using non-parametric tests. Different sensitivity analyses comparing GS and PD subscores were performed. RESULTS: In total, 130 patients (mean age 63 years, 86% female, average disease duration 14 years) were included 40 being in 4V-remission, 40 in PGA-near-remission, 50 in non-remission. 4v-remission and PGA-near-remission presented similar median (IQR) GLOESS, [6 (5-11) and 4 (1-7), P>0.05, respectively] and GTBS [0 (0-1) and 0 (0-2), P>0.05, respectively]. The same was observed in GS, PD scores, and in global synovitis score considering only the 16 joints not included in 28-joint counts. These observations were confirmed in patients with≤5 years disease duration. CONCLUSIONS: Subclinical inflammation is not present among persons with elevated PGA who are otherwise in remission. PGA-near-remission patients would be exposed to the risk of overtreatment if current treatment recommendations were strictly followed. This study supports the need to reconsider the role of PGA in definitions used to target immunosuppressive therapy and to provide a separate and enhanced focus to the patient's experience of the disease.
32813188 Does healthcare regime affiliation influence the clinical outcomes of patients with rheuma 2021 Mar BACKGROUND/PURPOSE: Adequate control of disease activity in rheumatoid arthritis (RA) depends, to a great extent, on the access to a rheumatologist. This study aimed to compare the disease outcomes of patients with RA, based on their healthcare regime affiliation. METHODS: A retrospective observational study of Colombian patients with RA in three outpatient services of different regimes: Contributory (CR, workers and their families with a monthly income above a yearly defined threshold, approximately US$ 220, who allocate a percentage of their income to financing the national health fund and to get access to healthcare services), subsidized (SR, a vulnerable population with a monthly income below the threshold, who have access to healthcare through the national health fund; comparable to the USA Medicaid population), and an excellence clinical care center (C3, access to specialized care, regardless of their healthcare affiliation regime). Data were collected from clinical records for 2 years of follow-up and included demographics, lag times between appointments, and time in high disease activity. We used the Mantel-Cox test for the analysis of time to remission/low disease activity. RESULTS: A total of 240 patients were included (80 patients per regime). At the start of follow-up, mean age was 53.7 years; 21.6% of patients were men; 79.6% of patients had established RA; 72.9% of patients had high disease activity. Patients in the CR had longer lag times between scheduled appointments (p < 0.0001). During follow-up, SR had the highest proportion of patients with high disease activity. Survival curve analysis showed no significant difference between SR and CR groups (p = 0.2903), but was significantly different compared with the C3 group (p < 0.0001). Median survival in high disease activity was greater in the SR group (293 days), followed by CR (254 days), and finally by C3 (64 days). CONCLUSION: Patients that were treated in the excellence clinical care center had better outcomes when compared with other regimes. These data support that healthcare regime may influence disease outcome in patients with RA. Key Points • Prompt access to healthcare in patients with rheumatoid arthritis is pivotal for an adequate control of the disease, for timely adjustment of treatment, and to reduce both the societal burden of the disease and its impact on individual well-being. • As an example of "structural iatrogenesis," healthcare regime affiliation appears to influence disease outcomes in patients with rheumatoid arthritis, in whom differences between regimes are observed. The most vulnerable patients appear to experience the worst outcomes. • Excellence clinical care centers for patients with rheumatoid arthritis should be implemented as an alternative to counteract structural healthcare barriers and as an approach to improve clinical outcomes through a tighter disease control.
34763513 Systematic review and meta-analysis on the efficacy of methotrexate in rheumatoid arthriti 2021 Oct BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease dominated by chronic inflammation of the synovium of the joints. Methotrexate (MTX) is the most widely used in the treatment of RA. This study systematically evaluated the clinical efficacy of MTX on RA and provided a theoretical basis for the clinical treatment of RA. METHODS: Four English databases (PubMed, Embase, Medline, and Web of Sciences) were searched for randomized controlled trials (RCTs) on MTX treatment of RA published from the date of establishment of the database to 2021. The Cochrane Handbook 5.0.2 was used to perform risk bias evaluation and Review Manager 5.3 was used to conduct a meta-analysis. RESULTS: A total of eight articles were included. The meta-analysis showed that, compared to the control group, the number of patients with DAS28-ESR ≤2.6 [erythrocyte sedimentation rate (ESR)] in the MTX alone or MTX combined treatment groups was higher, and the incidence of adverse events was also higher. However, there was no significant difference in the level of alanine aminotransferase (ALT) after treatment versus the control group. DISCUSSION: MTX alone or MTX combined treatment can better control the condition of RA patients without causing damage to the patient's blood system or liver and kidney function, but may increase the probability of adverse events.
33511203 Shentong Zhuyu Decoction Inhibits Inflammatory Response, Migration, and Invasion and Promo 2021 INTRODUCTION: The current study is aimed at exploring the effect of Shentong Zhuyu Decoction on the proliferation, migration, invasion, and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and its underlying molecular mechanism. MATERIALS AND METHODS: The type II collagen-induced arthritis (CIA) model was established. Subsequently, the RA-FLS were isolated from the CIA rat model and identified by immunohistochemistry. The viability, apoptosis, cell cycle, migration, and invasion of RA-FLS were detected by the cell counting kit 8 (CCK-8) assay, flow cytometry, wound-healing assay, and transwell invasion assay, respectively. The levels of MAPK p38, PPARγ, CTGF, Bcl-2, Bax, caspase-3, IL-1β, MMP-3, CDK4, and cyclin D1 were determined by qRT-PCR and western blotting, respectively. RESULTS: After treatment with Shentong Zhuyu Decoction medicated serum, the OD(570) value, migrative and invasive abilities, and the secretion of IL-1β, MMP-3 were remarkably decreased in RA-FLS, while the apoptosis rate was increased. Further, results showed that Shentong Zhuyu Decoction inhibited the transition from the G1 phase to S phase. Additionally, Shentong Zhuyu Decoction significantly inhibited the expression of Bcl-2, CDK4, cyclin D1, MAPK p-p38, and CTGF, whereas elevated the levels of Bax, caspase-3, and PPARγ. Importantly, the effects of Shentong Zhuyu Decoction were consistent with the trends of MAPK P38 inhibitor (SB203580) and PPARγ agonist (GW1929). CONCLUSIONS: Shentong Zhuyu Decoction inhibited viability, inflammatory response, migration, invasion, and transition from the G1 phase to S phase and promoted apoptosis of RA-FLS via the MAPK p38/PPARγ/CTGF pathway.
34740730 Epigenetically-regulated RPN2 gene influences lymphocyte activation and is involved in pat 2022 Feb 5 BACKGROUND: To identify RA-associated genes and to ascertain epigenetic factors and functional mechanisms underlying RA pathogenesis. METHODS: Peripheral blood mononuclear cells (PBMC) transcriptome- and proteome- wide gene expressions were profiled in a case-control study sample. Differentially expressed genes (DEGs) were discovered and validated independently. In-house PBMC genome-wide SNP genotyping data, miRNA expression data and DNA methylation data in the same sample were utilized to identify SNPs [expression quantitative trait locus (eQTLs) and protein quantitative trait locus (pQTLs)], miRNAs, and DNA methylation positions (DMPs) regulating key DEG of interest. Lentivirus transfection was conducted to study the effects of RPN2 on T lymphocyte activation, proliferation, apoptosis, and inflammatory cytokine expression. Rpn2 protein level in plasma was quantitated by ELISA to assess its performance in discriminating RA cases and controls. RESULTS: Twenty-two DEGs were discovered in PBMCs. The most significant DEG, i.e., RPN2, was validated to be up-regulated with RA in PBMCs. A complex regulatory network for RPN2 gene expression in PBMCs was constructed, which consists of 38 eQTL and 53 pQTL SNPs, 3 miRNAs and 2 DMPs. Besides, RPN2 expression was significantly up-regulated with RA in primary T lymphocytes, as well as in PHA-activated T lymphocytes. RPN2 over-expression in T lymphocytes significantly inhibited apoptosis and IL-4 expression and promoted proliferation and activation. PBMCs-expressed RPN2 mRNA and plasma Rpn2 protein demonstrated superior and modest performances in discriminating RA cases and controls, respectively. CONCLUSIONS: RPN2 gene influences T lymphocyte growth and activation and is involved in the pathogenesis of RA. Rpn2 may serve as a novel protein biomarker for RA diagnosis.
34924117 Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mic 2022 Jan Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib or etanercept on joint inflammation, and consequently decreased bone mineral density (BMD) was evaluated in mice with collagen-induced arthritis (CIA). Additionally, the effect on RANKL production from osteoblasts differentiated from the mesenchymal stem cells of RA patients was evaluated. Administration of peficitinib for established CIA ameliorated arthritis and improved BMD in the femoral metaphysis, but not in the femoral diaphysis. Conversely, etanercept suppressed an increase in synovial inflammatory markers but did not improve arthritic conditions or the reduction of BMD in either region. All elevated bone formation and bone resorption markers were decreased with peficitinib but only partially decreased with etanercept. Furthermore, production of RANKL by human osteoblasts was suppressed by peficitinib but enhanced by etanercept. Unlike etanercept, peficitinib is thought to increase BMD by ameliorating the high bone turnover associated with RA states, resulting in improvement of bone fragility. Our data provide evidence that peficitinib would be expected to show efficacy for osteoporosis associated with RA.
34229044 Role of interleukin-6 in bone destruction and bone repair in rheumatoid arthritis. 2021 Sep Rheumatoid arthritis (RA) is a common inflammatory form of arthritis leading to the progressive bone and joint destruction. Many factors are closely involved in the pathology of RA, in particular bone-related cells and inflammatory cytokines such as TNF-α and interleukin-6 (IL-6). Because RA patients with progressive bone destruction experience accelerated deterioration of their quality of life, inhibition of disease progression and joint destruction has become an important clinical goal. Recent studies have also found that drug intervention targeting proinflammatory cytokines such as IL-6 results in bone repair in addition to suppression of bone and joint destruction, and these results suggest the potential for new therapeutic goals. Regarding the relationship between IL-6 and bone destruction, essential roles of osteoclasts have been reported over many years; however, more recent studies have explored the relationship of IL-6 with osteoblasts and osteocytes. In this review, we highlight the perspectives of basic and clinical research, adding new findings on the relationships between IL-6 and bone-related cells associated with inflammation, and the possibility of bone repair by blocking IL-6.
32739894 Use of Disease-modifying Antirheumatic Drugs, Biologics, and Corticosteroids in Older Pati 2021 Jul OBJECTIVE: To examine changes in prescribing patterns, especially the use of corticosteroids (CS), in patients with rheumatoid arthritis (RA) over 2 decades. METHODS: This was a secondary analysis of health administrative data using a previously validated dataset and case definition for RA. Cases were matched 1:4 by age and sex to controls within a population of approximately 1 million inhabitants with access to universal health care. Longitudinal data for incident and prevalent RA cases were studied between 1997 and 2017. RESULTS: There were 8240 RA cases (all ≥ 65 yrs) with a mean (SD) age 72.2 (7.5) years and 70.6% were female. Over 20 years, annual utilization of coxibs in prevalent RA cases fell with a concomitant increase in disease-modifying antirheumatic drugs (DMARDs) and biologics. Over the same period, CS use was largely unchanged. Approximately one-third of patients had at least 1 annual prescription for CS, most frequently prednisone. The mean annual dose showed a modest reduction and the duration of utilization in each year shortened. Rheumatologists prescribed CS less frequently and in lower doses than other physician groups. For incident RA cases, there was a significant fall in annual prescribed dose of prednisone by rheumatologists over time. CONCLUSION: In older adults with RA, the utilization of DMARDs and biologics has increased over the past 20 years. However, the use of CS has persisted. Renewed efforts are required to minimize their use in the long-term pharmacological management of RA.
34689102 Regulation of Sirt1 on energy metabolism and immune response in rheumatoid arthritis. 2021 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease. Synovial hyperplasia and persistent inflammation serve as its typical pathological manifestations, which ultimately lead to joint destruction and function loss. Both clinical observations and metabolomics studies have revealed the prevalence of metabolic disorders in RA. In inflammatory immune microenvironments, energy metabolism is profoundly changed. Increasingly evidences suggest that this abnormality is involved in the occurrence and development of RA-related inflammation. Unsurprisingly, many energy metabolism sensors have been confirmed with immunoregulatory properties. As a representative, silent information regulator type 1 (Sirt1) controls many aspects of immune cells, such as cell lifespan, polarization, and secretion by functioning as a transcriptional regulator. Because of the profound clinical implication, researches on Sirt1 in the regulation of energy metabolism and immune functions under RA conditions have gradually gained momentum. This signaling balances glycolysis, lipid metabolism and insulin secretion orchestrating with other metabolism sensors, and consequently affects immune milieu through a so-called metabolism-immune feedback mechanism. This article reviews the involvement of Sirt1 in RA by discussing its impacts on energy metabolism and immune functions, and specially highlights the potential of Sirt1-targeting anti-rheumatic regimens. It also provides a theoretical basis for clarifying the mystery about the high incidence of metabolic complications in RA patients and identifying new anti-rheumatic reagents.
33719195 Left ventricular hypertrophy predicts poorer cardiovascular outcome in normotensive normog 2021 Apr INTRODUCTION: Patients with rheumatoid arthritis (RA) develop early changes in left ventricular (LV) geometry and experience cardiovascular events in excess than in the general population. This study was designed to assess prevalence, predictors and prognostic role of LV hypertrophy (LVH) in a selected group of RA patients with normal blood pressure and glycemia who should be at low risk for LVH. METHODS: We prospectively analyzed 241 normotensive normoglycemic RA patients (mean age 53 ± 12 years, 61% women) involved in a primary prevention program for cardiovascular diseases who were followed-up for 40 (24-56) months. LVH was detected by echocardiography and defined as LV mass ≥49.2 g/m(2.7) for men and ≥46.7 g/m(2.7) for women. Primary outcome was a composite of cardiovascular death/hospitalization. RESULTS: LVH was detected in 39 patients (16%). Older age (>53 years), greater body mass index (BMI > 25 kg/m(2) ), longer duration of RA disease, anti-cyclic citrullinated peptide antibody (ACPA) positivity and concentric LV geometry were the variables associated with LVH. During the follow-up, a cardiovascular event occurred in 12 of 39 (31%) patients with LVH and in 22 of 202 (11%; P < .001) patients without LVH. LVH independently predicted cardiovascular events (hazards ratio 3.28 [95% CI 1.03-9.20], P = .03) at Cox regression analysis together with C-reactive protein and ACPA positivity. CONCLUSIONS: Nearly one-sixth of normotensive normoglycemic RA patients analyzed in a primary prevention program for cardiovascular diseases has LVH which is associated with obesity and older age, and strongly predicts cardiovascular event in these subjects.
34313866 Abatacept in rheumatoid arthritis-associated interstitial lung disease: short-term outcome 2021 Dec INTRODUCTION: Interstitial lung disease in rheumatoid arthritis (RA-ILD) is an extra-articular involvement that impairs the prognosis and for which there is still no well-coded treatment. The aim of this study was to evaluate abatacept (ABA) effectiveness and safety in patients with RA-ILD. METHODS: RA-ILD patients who started ABA treatment were consecutively enrolled. Chest high-resolution computed tomography (HRCT), clinical, laboratory and respiratory function variables were collected at baseline and after 18 months of ABA treatment. HRCT abnormalities were evaluated using a computer-aided method (CaM). ABA response was established based on the change in the percentage of fibrosis evaluated at HRCT-CaM, dividing patients into "worsened" (progression ≥ 15%), "improved" (reduction ≥ 15%), and "stable" (changes within the 15% range). The multivariate regression model was used to assess the associations between RA characteristics and ABA response. RESULTS: Forty-four patients (81% women, mean age 59.1 ± 8.0, mean disease duration of 7.5 ± 3.1 years) were studied. Five patients (11.4%) showed RA-ILD progression, 32 patients (72.6%) were considered stable, and 7 patients (16.0%) showed an RA-ILD improvement. The proportion of current smokers was significantly different between "worsened" patients, respect to those defined as "improved/stable" (p = 0.01). Current smoking habit (p = 0.005) and concomitant methotrexate treatment (p = 0.0078) were the two variables related to RA-ILD progression in multivariate regression analysis. CONCLUSION: Treatment with ABA is associated with a RA-ILD stability or improvement in the 88.6% of patients. Current smoking habit and concomitant treatment with methotrexate are the modifiable factors associated with RA-ILD worsening. Key Points • Abatacept plays a favourable role in the control of RA-ILD, with a significant worsening in only 11.4% of patients during a 18-month follow-up period. • The predictive variables related to RA-ILD progression during abatacept therapy are the concomitant treatment with methotrexate and current smoking habit.
33782288 Prospective Comparison of Angiogenesis-Specific 68Ga-RGD2 PET/CT Imaging Parameters and DA 2021 Jul 1 OBJECTIVE: The aim of this study was to compare the performance of angiogenesis-specific 68Ga-RGD2 PET/CT with Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) in assessing disease activity and treatment response in rheumatoid arthritis (RA). METHODS: This was a prospective study comparing the performance of 68Ga-RGD2 PET/CT and DAS28-ESR in 30 RA patients. All of them underwent 68Ga-RGD2 PET/CT scan from head to toe and clinical examination at the baseline. A repeat scan and clinical examination were done in 27 patients after 3 months of treatment with disease-modifying antirheumatic drugs ± steroids. Three PET parameters, that is, PJC (PET-positive joint count), aSUVmax (average SUVmax), and hSUVmax (highest SUVmax), of positive joints were compared with the DAS28-ESR for disease activity assessment and response evaluation. RESULTS: Among the 3 PET parameters, PJC showed a significant correlation with the DAS28-ESR (0.64, P < 0.01). A significant change was observed with treatment in the DAS28-ESR and PET parameters of 27 patients at follow-up. There was significant correlation between percentage changes in DAS28-ESR and scan parameters such as PJC (0.689, P < 0.001), aSUVmax (0.712, P < 0.001), and hSUVmax (0.555, P = 0.003) values. The absolute change in aSUVmax value could accurately discriminate (area under the curve, 0.98; P = 0.001) European League Against Rheumatism responders from nonresponders. CONCLUSIONS: 68Ga-RGD2 PET/CT is a promising tool for objective assessment of disease activity and treatment response in patients with RA.
33790392 Prediction of response of methotrexate in patients with rheumatoid arthritis using serum l 2021 Mar 31 Methotrexate (MTX) is a common first-line treatment for new-onset rheumatoid arthritis (RA). However, MTX is ineffective for 30-40% of patients and there is no way to know which patients might benefit. Here, we built statistical models based on serum lipid levels measured at two time-points (pre-treatment and following 4 weeks on-drug) to investigate if MTX response (by 6 months) could be predicted. Patients about to commence MTX treatment for the first time were selected from the Rheumatoid Arthritis Medication Study (RAMS). Patients were categorised as good or non-responders following 6 months on-drug using EULAR response criteria. Serum lipids were measured using ultra-performance liquid chromatography-mass spectrometry and supervised machine learning methods (including regularized regression, support vector machine and random forest) were used to predict EULAR response. Models including lipid levels were compared to models including clinical covariates alone. The best performing classifier including lipid levels (assessed at 4 weeks) was constructed using regularized regression (ROC AUC 0.61 ± 0.02). However, the clinical covariate based model outperformed the classifier including lipid levels when either pre- or on-treatment time-points were investigated (ROC AUC 0.68 ± 0.02). Pre- or early-treatment serum lipid profiles are unlikely to inform classification of MTX response by 6 months with performance adequate for use in RA clinical management.
33119082 The dysregulation of monocyte subpopulations in individuals at risk of developing rheumato 2021 Apr 6 OBJECTIVES: Individuals carrying antibodies against citrullinated proteins (ACPA) are at high risk of developing RA. EULAR provided a clinical definition of individuals with arthralgia suspicious for progression to RA (clinically suspect arthralgia, CSA). The alteration of monocyte subpopulations in patients with established RA has been previously described. We analysed peripheral blood monocyte subpopulations in individuals with arthralgia at risk of RA. METHODS: We included 70 at-risk individuals, defined as having arthralgia without arthritis and being either ACPA+ or meeting the clinical CSA definition, 23 patients with early RA (ERA) and 19 healthy controls (HCs). Monocytes classified as classical (CD14++CD16-), intermediate (CD14++CD16+/++) and nonclassical (CD14-/+CD16++) were analysed by flow cytometry. RESULTS: Of the 70 at-risk individuals, 46 were ACPA+ and 45 met the CSA definition. The at-risk individuals and, especially, ERA patients had a lower percentage of classical monocytes and a higher percentage of nonclassical monocytes than the HCs. ACPA positivity had no effect on the difference in the distribution of the monocyte subsets between at-risk individuals and ERA patients, but a difference was determined in those reaching the ERA phase. However, when compared with HCs, the shift of monocyte subsets was more significant in ACPA+ than in ACPA- individuals with arthralgia. This trend was observed in individuals who did not meet the CSA definition. This finding was, however, determined by a selection bias, as these individuals were solely ACPA+. CONCLUSION: The shift from classical to nonclassical monocyte subpopulations was observed already in individuals at risk of developing RA.