Browse

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

ID PMID Title PublicationDate abstract
32931984 The clinical effectiveness of intensive management in moderate established rheumatoid arth 2020 Oct OBJECTIVES: Many trials have shown that intensive management is effective in patients with early active rheumatoid arthritis (RA). But its benefits are unproven for the large number of RA patients seen in routine care who have established, moderately active RA and are already taking conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). The TITRATE trial studied whether these patients also benefit from intensive management and, in particular, achieve more remissions. METHODS: A 12-month multicentre individually randomised trial compared standard care with monthly intensive management appointments which was delivered by specially trained healthcare professionals and incorporated monthly clinical assessments, medication titration and psychosocial support. The primary outcome was 12-month remission assessed using the Disease Activity Score for 28 joints using ESR (DAS28-ESR). Secondary outcomes included fatigue, disability, harms and healthcare costs. Intention-to-treat multivariable logistic- and linear regression analyses compared treatment arms with multiple imputation used for missing data. RESULTS: 459 patients were screened and 335 were randomised (168 intensive management; 167 standard care); 303 (90%) patients provided 12-month outcomes. Intensive management increased DAS28-ESR 12-month remissions compared to standard care (32% vs 18%, p = 0.004). Intensive management also significantly increased remissions using a range of alternative remission criteria and increased patients with DAS28-ESR low disease activity scores. (48% vs 32%, p = 0.005). In addition it substantially reduced fatigue (mean difference -18; 95% CI: -24, -11, p<0.001). There was no evidence that serious adverse events (intensive management =15 vs standard care =11) or other adverse events (114 vs 151) significantly increase with intensive management. INTERPRETATION: The trial shows that intensive management incorporating psychosocial support delivered by specially trained healthcare professions is effective in moderately active established RA. More patients achieve remissions, there were greater improvements in fatigue, and there were no more harms.
33254064 A novel use of combined thermal and ultrasound imaging in detecting joint inflammation in 2021 Jan PURPOSE: To evaluate the use of combined thermal and ultrasound imaging to assess joint inflammation in rheumatoid arthritis (RA). METHOD: 22-joint (bilateral hands) thermography and ultrasonography were performed. For each patient, the MAX, MIN and AVG represent the sum of the temperature differences with a control temperature, for the respective maximum (Tmax), minimum (Tmin) and average (Tavg) temperatures at the joints. MAX (PD), MIN (PD) and AVG (PD) represent the results of combined thermal imaging with a patient's total ultrasound power Doppler (PD) joint inflammation score (Total PD) (when Total PD > median score, MAX, MIN and AVG was multiplied by a factor of 2, otherwise MAX (PD), MIN (PD) and AVG (PD) remained the same as the MAX, MIN and AVG). Pearson correlation and linear regression were used to assess correlation and characterize relationships of imaging parameters with the 28-joint disease activity score (DAS28). RESULTS: In this cross-sectional study, 814 joints were examined in 37 adult RA patients (75.7 % female, 75.7 % Chinese; mean DAS28, 4.43). Among the imaging parameters, only MAX (PD) and AVG (PD) correlated significantly with DAS28 (correlation coefficient (95 % CI): MAX (PD), 0.393 (0.079, 0.636), P = 0.016; AVG (PD): 0.376 (0.060, 0.624), P = 0.022). Similarly, only MAX (PD) and AVG (PD) demonstrated a statistically significant relationship with DAS28 (regression coefficient (95 % CI): MAX (PD), 0.009 (0.002, 0.015), P = 0.016; AVG (PD), 0.011 (0.002, 0.020), P = 0.022). CONCLUSIONS: Novel use of combined thermal and ultrasound imaging in RA shows superiority to either imaging alone in terms of correlation with DAS28.
31282121 Development of Resilience Among Rheumatoid Arthritis Patients: A Qualitative Study. 2020 Sep OBJECTIVE: Resilience, the ability to recover from and adapt successfully to stressful situations, is a valuable resource for patients who live with chronic conditions. This qualitative study examines the development of resilience among rheumatoid arthritis (RA) patients. We aimed to describe the resilience development process and to describe strategies used by patients to cultivate resilience. METHODS: Our approach combined ethnographic data collection and narrative analysis methods. Semistructured interviews were conducted with adult RA patients in the US. Interviewees were asked to discuss their experiences with diagnosis, living with RA, coping with challenges, treatment, and health care providers. The interviews were audiorecorded, transcribed, and analyzed to describe the stages of resilience development and to identify patients' strategies for building/maintaining resilience. RESULTS: Eighteen patients were interviewed, ages 27-80 years and with RA duration of 5-41 years. Patient responses to challenging situations were grouped into 3 stages: 1) lacking capacity to handle the situation, 2) struggling but growing in capacity to handle the situation, and 3) attaining mastery. Patients used 10 strategies to cultivate resilience: perseverance, exchanging social support, pursuing valued activities, flexibility, positive reframing, acceptance, humor, avoiding threatening thoughts, equanimity, and maintaining a sense of control. CONCLUSION: RA patients acquire resilience in a dynamic process of learning in response to new challenges. Patients use a combination of behavioral and emotion management strategies to cultivate resilience. Awareness of these strategies may benefit patients, health care providers, and researchers developing behavioral interventions and social support programs in the context of RA and other chronic diseases.
32898607 Assessment of interleukin 6 gene polymorphisms with rheumatoid arthritis. 2021 Jan 10 BACKGROUND: Rheumatoid arthritis (RA) is complex autoimmune system disease and significant impact on the health of population in our world. Numerous studies confirmed that genetic factors play a crucial role in the pathogenesis of RA. In this current study, we aimed to investigate IL-6 polymorphisms and RA risk in Chinese Han population. METHODS: 508 RA patients and 494 age- and gender- matched healthy controls were recruited, all subjects were genotyped with an Agena MassARRAY platform. Subsequently, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression after adjusting for age and gender. RESULTS: Our results suggested that IL-6 rs2243289 allele and genotype frequencies were associated with reduced RA risk under all genetic models (all p < 0.05). Stratification analysis revealed that IL-6 rs2243289 polymorphism was significant associated with decreased the risk of RA in the old groups (age > 54) (all p < 0.05). However, IL-6 rs2069837 and rs1800796 polymorphisms were associated with increased risk of RA among the young groups (age ≤ 54) (all p < 0.05). In addition, subgroup analysis by gender suggested that IL-6 rs2069837 and rs1800796 polymorphism were interacted with increased the risk of RA in males (all p < 0.05). Besides, IL-6 rs2243289 was associated with reduced RA risk in females. CONCLUSIONS: In conclusion, our results demonstrated the correlation between IL and 6 polymorphisms and RA susceptibility and confirmed for the first time that the relationship was restricted to age and gender in Chinese Han population.
32906027 Risk of malignancy with non-TNFi biologic or tofacitinib therapy in rheumatoid arthritis: 2020 Oct OBJECTIVES: To assess the risk of developing cancer in patients with rheumatoid arthritis (RA) exposed to non-TNF inhibitors (TNFi) biologics or tofacitinib therapy. METHODS: Systematical search of PubMed, EMBASE and Cochrane Library plus a hand search of conference proceedings were performed. Observational studies that reported cancer incidence in patients with RA treated with biologics or tofacitinib with active comparator of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or TNFi were eligible for inclusion. The pooled relative risk (RR) and 95% confidence interval (CI) were calculated with fix-effects or random-effects model. RESULTS: Of 2,819 identified articles, a total of 10 studies involving over 40,587 patients with more than 87,622 patient-years of exposure to non-TNF inhibitors (TNFi) biologics and 2,221 patients with more than 4,506 patient-years of exposure to tofacitinib were included. Pooled analysis showed there was no increased risk of developing cancer in general or specific cancer types in RA patients receiving treatment with rituximab (pooled RR 0.87, 95% CI 0.74-1.03), tocilizumab (pooled RR 0.92, 95% CI 0.79-1.06), or tofacitinib, compared with those receiving csDMARDs or TNFi. But abatacept was associated with a slightly increased overall cancer risk (pooled RR 1.13, 95% CI 1.02-1.24) and non-melanoma skin cancer (pooled RR 1.26, 95% CI 1.09-1.45), relative to csDMARDs or TNFi in RA patients. CONCLUSION: Among RA patients, a small statistically significant increase in developing cancer was observed for abatacept exposure, while no increased cancer risk for rituximab, tocilizumab or tofacitinib, in comparison with csDMARDs or TNFi.
31609524 Rheumatoid Arthritis Flares After Total Hip and Total Knee Arthroplasty: Outcomes at One Y 2020 Jul OBJECTIVE: Most patients with rheumatoid arthritis (RA) undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) have active RA and report postoperative flares; whether RA disease activity or flares increase the risk of worse pain and function scores 1 year later is unknown. METHODS: Patients with RA were enrolled before THA/TKA. Patient-reported outcomes, including the Hip disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury and Osteoarthritis Outcome Score (KOOS) and physician assessments of disease characteristics and activity (Disease Activity Score in 28 joints [DAS28] and Clinical Disease Activity Index), were collected before surgery. Patient-reported outcomes were repeated at 1 year. Postoperative flares were identified using the RA Flare Questionnaire weekly for 6 weeks and were defined by concordance between patient report plus physician assessment. We compared baseline characteristics and HOOS/KOOS scores using 2-sample t-test/Wilcoxon's rank sum test as well as chi-square/Fisher's exact tests. We used multivariate linear and logistic regression to determine the association of baseline characteristics, disease activity, and flares with 1-year outcomes. RESULTS: One-year HOOS/KOOS scores were available for 122 patients (56 with THA and 66 with TKA). Although HOOS/KOOS pain was worse for patients who experienced a flare within 6 weeks of surgery, absolute improvement was not different. In multivariable models, baseline DAS28 predicted 1-year HOOS/KOOS pain and function; each 1-unit increase in DAS28 worsened 1-year pain by 2.41 (SE 1.05; P = 0.02) and 1-year function by 4.96 (SE 1.17; P = 0.0001). Postoperative flares were not independent risk factors for pain or function scores. CONCLUSION: Higher disease activity increased the risk of worse pain and function 1 year after arthroplasty, but postoperative flares did not.
31507095 Sustained Long-Term Efficacy of Motivational Counseling and Text Message Reminders on Dail 2020 Nov OBJECTIVE: To evaluate the 18-month postintervention efficacy following a 4-month individually tailored behavioral intervention on daily sitting time in patients with rheumatoid arthritis (RA). METHODS: In an observer-blinded randomized trial, 150 RA patients were included. During 4 months, the intervention group (n = 75) received 3 motivational counseling sessions and tailored text messages aimed at increasing light-intensity physical activity through reduction of sedentary behavior. The control group (n = 75) maintained their usual lifestyle. The primary outcome was change from baseline to 18 months postintervention in objectively measured daily sitting time (using ActivPAL). Secondary outcomes included changes in clinical patient-reported outcomes and cardiometabolic biomarkers. A mixed-effect repeated measures analysis of covariance model in the intent-to-treat population was applied. RESULTS: At 22 months follow-up from baseline, 12 participants were lost to follow-up. Compared to baseline, sitting time in the intervention group decreased 1.10 hours/day, whereas it increased by 1.32 hours/day in the control group, a between-group difference of -2.43 hours/day (95% confidence interval [95% CI] -2.99, -1.86; P < 0.0001) favoring the intervention group. For most secondary outcomes, between-group differences favored the intervention: visual analog scale (VAS) pain -15.51 mm (95% CI -23.42, -7.60), VAS fatigue -12.30 mm (95% CI -20.71, -3.88), physical function -0.39 Health Assessment Questionnaire units (95% CI -0.53, -0.26), total cholesterol -0.86 mmoles/liter (95% CI -1.03, -0.68), triglycerides -0.26 mmoles/liter (95% CI -0.43, -0.09), and average glucose -1.15 mmoles/liter (95% CI -1.39, -0.91). CONCLUSION: The 4-month postintervention results showed that patients in the intervention reduced their daily sitting time and improved patient-reported outcomes and total cholesterol levels compared to the control group. Eighteen months after intervention, patients in the intervention group were still significantly less sedentary than controls. Findings suggest that a behavioral approach is beneficial for promoting long-term physical activity and health in patients with RA.
31162824 Association of Pain Centralization and Patient-Reported Pain in Active Rheumatoid Arthriti 2020 Aug OBJECTIVE: Pain is a significant burden for patients with rheumatoid arthritis (RA) despite advancements in treatment. We undertook this study to examine the independent contribution of pain centralization to the pain experience of patients with active RA. METHODS: A total of 263 RA patients with active disease underwent quantitative sensory testing (QST), including assessment of extraarticular pressure pain thresholds (PPTs), temporal summation (TS), and conditioned pain modulation (CPM). The pain experience was assessed by a pain intensity numeric rating scale and the Patient-Reported Outcomes Measurement Information System pain interference computerized adaptive test. We examined associations between QST measures and pain intensity and pain interference. Multiple linear regression models were adjusted for demographic and clinical variables, including swollen joint count and C-reactive protein level. RESULTS: Patients with the lowest PPTs (most central dysregulation) reported higher pain intensity than patients with the highest PPTs (adjusted mean difference 1.02 [95% confidence interval (95% CI) 0.37, 1.67]). Patients with the highest TS (most central dysregulation) had higher pain intensity than those with the lowest TS (adjusted mean difference 1.19 [95% CI 0.54, 1.84]). CPM was not associated with differences in pain intensity. PPT and TS were not associated with pain interference. Patients with the lowest CPM (most centrally dysregulated) had lower pain interference than patients with the highest CPM (adjusted mean difference -2.35 [95% CI -4.25, -0.44]). CONCLUSION: Pain centralization, manifested by low PPTs and high TS, was associated with more intense pain. Clinicians should consider pain centralization as a contributor to pain intensity, independent of inflammation.
32090129 In Vitro ELISA and Cell-Based Assays Confirm the Low Immunogenicity of VNAR Therapeutic Co 2020 Anti-drug antibodies (ADAs), specific for biotherapeutic drugs, are associated with reduced serum drug levels and compromised therapeutic response. The impact of ADA on the bioavailability and clinical efficacy of blockbuster anti-hTNF-α monoclonal antibodies is well recognised, especially for adalimumab and infliximab treatments, with the large and complex molecular architecture of classical immunoglobulin antibody drugs, in part, responsible for the immunogenicity seen in patients. The initial aim of this study was to develop solid-phase enzyme-linked immunosorbent assays (ELISA) and an in vitro cell-based method to accurately detect ADA and estimate its impact on the preclinical in vivo efficacy outcomes of two novel, nonimmunoglobulin VNAR fusion anti-hTNF-α biologics (Quad-X™ and D1-NDure™-C4) and Humira®, a brand of adalimumab. Serum drug levels and the presence of ADA were determined in a transgenic mouse model of polyarthritis (Tg197) when Quad-X™ and Humira® were dosed at 1 mg/kg and D1-NDure™-C4 was dosed at 30 mg/kg. The serum levels of the Quad-X™ and D1-NDure™-C4 modalities were consistently high and comparable across all mice within the same treatment groups. In 1 mg/kg and 3 mg/kg Quad-X™- and 30 mg/kg D1-NDure™-C4-treated mice, an average trough drug serum concentration of 8 μg/mL, 50 μg/mL, and 350 μg/mL, respectively, were estimated. In stark contrast, Humira® trough serum concentrations in the 1 mg/kg treatment group ranged from <0.008 μg/mL to 4 μg/mL with trace levels detected in 7 of the 8 animals treated. Trough serum Humira® and Quad-X™ concentrations in 3 mg/kg treatment samples were comparable; however, the functionality of the detected Humira® serum was significantly compromised due to neutralising ADA. The impact of ADA went beyond the simple and rapid clearance of Humira®, as 7/8 serum samples also showed no detectable capacity to neutralise hTNF-α-mediated cytotoxicity in a murine fibrosarcoma (L929) cell assay. The neutralisation capacity of all the VNAR constructs remained unchanged at the end of the experimental period (10 weeks). The data presented in this manuscript goes some way to explain the exciting outcomes of the previously published preclinical in vivo efficacy data, which showed complete control of disease at Quad-X™ concentrations of 0.5 mg/kg, equivalent to 10x the in vivo potency of Humira®. This independent corroboration also validates the robustness and reliability of the assay techniques reported in this current manuscript, and while it comes with the caveat of a mouse study, it does appear to suggest that these particular VNAR constructs, at least, are of low inherent immunogenicity.
31435754 Efficacy and retention rate of adalimumab in rheumatoid arthritis and psoriatic arthritis 2020 Feb Few studies have compared the efficacy of switching from etanercept to adalimumab in the real-life setting in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). This study evaluated the 2-year retention rate and 12-month efficacy of adalimumab in RA and PsA patients, previously treated with etanercept. RA and PsA patients from 11 Italian Rheumatology Units received adalimumab after first-line etanercept failure. Two-year adalimumab retention rate was calculated by the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of drug persistence. Univariate and multivariate logistic regression analyses were developed to examine potential predictors of 12-month DAS-28 remission. The study population included 117 RA (disease duration of 10.1 ± 7.7 years and baseline DAS28-ESR of 4.97 ± 1.3) and 102 PsA (disease duration of 7.1 ± 5.1 years and baseline DAPSA of 24.6 ± 11.8). The 2-year retention rate was 48.2% in RA and 56.5% in PsA patients. Concomitant methotrexate treatment was not associated with increased drug survival in both groups. Similarly, cause of etanercept discontinuation or treatment duration was not associated with retention rate. 12-month remission and low disease activity were achieved, respectively, in 27.3% and 23.9% of RA patients and 27.4% and 23.5% PsA of patients. In multivariate models, etanercept discontinuation due to inefficacy (OR 0.27, 95% CI 1.03-0.73; p = 0.009) and baseline DAS-28 (OR 0.45, 95% CI 0.29-0.69; p < 0.001) remained significant negative predictors of remission in RA patients. No variable was associated with remission in PsA patients. Adalimumab after etanercept failure was highly effective and safe in both RA and PsA patients.
32373926 Comment on: Variables associated with subclinical atherosclerosis among rheumatoid arthrit 2020 May [No Abstract Available].
32514887 Lactate Production Precedes Inflammatory Cell Recruitment in Arthritic Ankles: an Imaging 2020 Oct PURPOSE: Inflammation is involved in many disease processes. However, accurate imaging tools permitting diagnosis and characterization of inflammation are still missing. As inflamed tissues exhibit a high rate of glycolysis, pyruvate metabolism may offer a unique approach to follow the inflammatory response and disease progression. Therefore, the aim of the study was to follow metabolic changes and recruitment of inflammatory cells after onset of inflammation in arthritic ankles using hyperpolarized 1-(13)C-pyruvate magnetic resonance spectroscopy (MRS) and (19)F magnetic resonance imaging (MRI), respectively. PROCEDURE: Experimental rheumatoid arthritis (RA) was induced by intraperitoneal injection of glucose-6-phosphate-isomerase-specific antibodies (GPI) containing serum. To monitor pyruvate metabolism, the transformation of hyperpolarized 1-(13)C-pyruvate into hyperpolarized 1-(13)C-lactate was followed using MRS. To track phagocytic immune cell homing, we intravenously injected a perfluorocarbon emulsion 48 h before imaging. The animals were scanned at days 1, 3, or 6 after GPI-serum injection to examine the different stages of arthritic inflammation. Finally, to confirm the pyruvate metabolic activity and the link to inflammatory cell recruitment, we conducted hematoxylin-eosin histopathology and monocarboxylase transporter (MCT-1) immune histochemistry (IHC) of inflamed ankles. RESULTS: Hyperpolarized 1-(13)C-pyruvate MRS revealed a high rate of lactate production immediately at day 1 after GPI-serum transfer, which remained elevated during the progression of the disease, while (19)F-MRI exhibited a gradual recruitment of phagocytic immune cells in arthritic ankles, which correlated well with the course of ankle swelling. Histopathology and IHC revealed that MCT-1 was expressed in regions with inflammatory cell recruitment, confirming the metabolic shift identified in arthritic ankles. CONCLUSIONS: Our study demonstrated the presence of a very early metabolic shift in arthritic joints independent of phagocytic immune cell recruitment. Thus, hyperpolarized 1-(13)C-pyruvate represents a promising tracer to monitor acute arthritic joint inflammation, even with minor ankle swelling. Furthermore, translated to the clinics, these methods add a detailed characterization of disease status and could substantially support patient stratification and therapy monitoring.
32199257 Experience of a Performance-Based Risk-Sharing Arrangement for the Treatment of Rheumatoid 2020 May OBJECTIVES: To describe the process and results of the implementation of a performance-based risk-sharing arrangement for the use of certolizumab pegol (Cimzia) in patients with rheumatoid arthritis (RA), based on rational pharmacotherapy. METHODS: In 2014, the area of Management of Drugs and Supplies of the health maintenance organization of the Hospital Italiano de Buenos Aires signed a performance-based risk-sharing arrangement with Montpellier Laboratory for the use of certolizumab pegol in patients with RA. The laboratory would reimburse the hospital the cost of the first 10 doses of the drug if an optimal clinical response was not achieved (difference greater than or equal to 1.2 in the Disease Activity Score 28 with erythrocyte sedimentation [Δ DAS28 ESR] measured at the beginning and at the end), or if the patient presented with an adverse drug reaction, during the first 12 weeks of treatment. RESULTS: Forty patients with RA were included between September 2014 and January 2018. Thirty-six patients completed 12 weeks of treatment, of which 25 (69.4 %) had an optimal clinical response (Δ DAS28 ESR ≥ 1.2). The laboratory reimbursed the hospital 116 doses of certolizumab pegol, corresponding to 12 patients (12 of 40, 30%). Eleven of them did not reach the optimal clinical response, and 1 presented with an adverse drug reaction. CONCLUSIONS: The performance-based risk-sharing arrangement proved to be a useful tool to optimize the resources of the healthcare payer and contributed to the collection of scientific evidence in real-life patients.
31342120 CCL21/CCR7 signaling in macrophages promotes joint inflammation and Th17-mediated osteocla 2020 Apr In rheumatoid arthritis (RA), synovial tissue abundantly expresses CCL21, a chemokine strongly associated with RA susceptibility. In this study, we aimed to characterize the functional significance of CCL21/CCR7 signaling in different phases of RA pathogenesis. We determined that CCR7 is a hallmark of RA M1 synovial fluid (SF) macrophages, and its expression in RA monocytes and in vitro differentiated macrophages is closely associated with disease activity score (DAS28). In early stages of RA, monocytes infiltrate the synovial tissue. However, blockade of SF CCL21 or CCR7 prevents RA SF-mediated monocyte migration. CCR7 expression in the newly migrated macrophages can be accentuated by LPS and IFNγ and suppressed by IL-4 treatment. We also uncovered that CCL21 stimulation increases the number of M1-polarized macrophages (CD14+CD86+), resulting in elevated transcription of IL-6 and IL-23. These CCL21-induced M1 cytokines differentiate naïve T cells to Th17 cells, without affecting Th1 cell polarization. In the erosive stages of disease, CCL21 potentiates RA osteoclastogenesis through M1-driven Th17 polarization. Disruption of this intricate crosstalk, by blocking IL-6, IL-23, or IL-17 function, impairs the osteoclastogenic capacity of CCL21. Consistent with our in vitro findings, we establish that arthritis mediated by CCL21 expands the joint inflammation to bone erosion by connecting the differentiation of M1 macrophages with Th17 cells. Disease progression is further exacerbated by CCL21-induced neovascularization. We conclude that CCL21 is an attractive novel target for RA therapy, as blockade of its function may abrogate erosive arthritis modulated by M1 macrophages and Th17 cell crosstalk.
32641647 Drug-induced Bullous Pemphigoid and Lupus Erythematosus Occurring under Anti-TNF-α and IL 2020 Oct 15 A 65-year-old Japanese woman, who was diagnosed with rheumatoid arthritis and Sjögren's syndrome with various autoantibodies including anti-DNA antibody, developed bullous pemphigoid (BP) and hematological abnormalities like lupus erythematosus after adalimumab therapy. The discontinuation of adalimumab resolved those disorders but polyarthritis thereafter relapsed. The introduction of abatacept was not effective, but tocilizumab was found to be effective for polyarthritis, however, thereafter both bullous disease and severe pancytopenia developed. Discontinuation of tocilizumab was effective, but polyarthritis again developed, and baricitinib resolved it. There is an increasing number of reports of drug-induced BP and lupus erythematosus, and biologics might trigger an alteration in the pathophysiological/clinical course of rheumatic disorder.
32828147 Receptor activator of nuclear factor kappa-Î’ ligand (RANKL) serum levels are associated w 2021 May OBJECTIVES: The aim of this study was to establish whether serum RANKL levels in early inflammatory arthritis (IA) were associated with rheumatoid arthritis (RA) diagnosis at follow-up, and to evaluate the added value of RANKL for RA diagnosis. METHODS: Serum from 298 patients was collected. Demographic and clinical (swollen/tender joint counts, CRP, DAS28-CRP, RF, ACPA and shared-epitope data were recorded. Baseline ultrasound of 26 joints was performed, including total power Doppler (PD). An ELISA was used to measure RANKL. Predictors of progression were identified using multivariable logistic regression analysis. Area under the receiver operating characteristics (AUROC) was used to assess the performance of the prediction models and quantify the added value of RANKL in RA diagnosis. RESULTS: 151 patients developed RA and 147 were non-RA (undifferentiated IA, other inflammatory diagnoses or non-persistent inflammation). RANKL levels were significantly higher in RA (median [IQR]: 474.1 [270.8-1430.6]) than in non-RA (median [IQR]: 301.0 [174.1-477.5]. Three clinical factors (age, SJC and PD) were identified by multivariable logistic regression with model performance AUROC of 77.9% (95% CI 72.1-83.8%). Adding RANKL resulted in a relative increase of 6.5% in the model classification performance of an AUROC of 83.0% (95% CI 77.9-88.1%). In ACPA-negative patients, the model performance increased from 77.6% (95% CI 69.5-85.7%) with clinical data only to 81.9% (95% CI 73.7-89.8%) with added value of RANKL and imaging. CONCLUSIONS: RANKL levels can predict RA diagnosis over clinical biomarkers alone, both seropositive and particularly in seronegative IA patients.
33076960 Long-term follow-up of patients with anti-cyclic citrullinated peptide antibody-positive c 2020 Oct 19 BACKGROUND: The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD. METHODS: In total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. Anti-CCP antibody titers were obtained from a retrospective chart review or measured using stored sera. RA was diagnosed according to the 1987 revised American College of Rheumatology classification criteria. Thirty-three anti-CCP-positive non-RA CTD patients were retrospectively followed up for the development of RA. Bone erosions on the hands and feet were assessed by X-ray. Citrullination dependency was evaluated by an in-house ELISA, the HLA-DRB1 allele was typed, and the results obtained were then compared between RA-overlapping and non-RA anti-CCP-positive CTD patients. RESULTS: Two out of 33 anti-CCP-positive CTD patients (6.1%) developed RA during a mean follow-up period of 8.9 years. X-rays were examined in 27 out of the 33 patients, and only one (3.7%) showed bone erosions. The frequency of the HLA-DRB1 shared epitope (SE) and anti-CCP antibody titers were both significantly higher in anti-CCP-positive RA-overlapping CTD patients than in anti-CCP-positive non-RA CTD patients, while no significant differences were observed in citrullination dependency. CONCLUSIONS: Anti-CCP-positive non-RA CTD patients rarely developed RA. HLA-DRB1 SE and anti-CCP antibody titers may facilitate the differentiation of RA-overlapping CTD from anti-CCP-positive non-RA CTD.
32945205 β-Sitosterol-loaded solid lipid nanoparticles ameliorate complete Freund's adjuvant-induc 2020 Dec Rheumatoid arthritis (RA), autoimmune disease that is categorized via chronic inflammation manifestation, obesity, cardiovascular risk and even enhanced the mortality and affect the 0.3 and 1% of population worldwide. The current experimental study was scrutinize the anti-arthritic effect of β-sitosterol loaded solid lipid nanoparticles (SLN) against complete Fruend adjuvant (CFA)-induced arthritis via dual pathway. Double emulsion solvent displacement method was used for the preparation of β-sitosterol solid lipid nanoparticles (SLN). CFA was used to induce arthritis and rats were divided into different groups for 28 days. Biochemical, anti-inflammatory, pro-inflammatory cytokines and inflammatory mediator were estimated, respectively. Receptor activator of nuclear factor kappa-B ligand (RANKL), signal transducer and activator of transcription-3 (STAT3) nuclear factor erythroid 2-related factor 2 (Nrf(2)), Heme Oxygenase-1(HO-1) and Nuclear factor-κB (NF-κB) expression were estimated. β-sitosterol-SLN significantly (p < .001) reduced the paw edema, arthritic index and increased the body weight. β-sitosterol-SLN increased the redox status of synovium {reduce the malonaldehyde (MDA) and increase superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT)} level and reduced the cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-2, interleukin-6, interleukin-16, interleukin-17 and increased level of interleukin-10, Transforming growth factor beta (TGF-β). β-sitosterol-SLN significantly (p < .001) reduced the level of cyclooxygenase-2 (COX-2), prostaglandin E(2) (PGE(2)), vascular Endothelial Growth Factor (VEGF) and NF-κB. β-sitosterol-SLN significantly increased the expression of HO-1,Nrf(2) and decreased the expression of NF-κB, RANKL, STAT3. In conclusion, β-sitosterol SLN showed the antiarthritic effect via suppression of NF-kB and activation of HO-1/Nrf-2 pathway.
32314641 Immunoglobulin A antibodies to oxidized collagen type II as a potential biomarker for the 2020 Jul OBJECTIVES: The discovery of diseased tissue-specific neoantigens offers the opportunity to develop important disease tissue-specific biomarkers that can help in the prediction, diagnosis, and stratification of diseases. This opportunity is specifically significant for autoimmune diseases where diagnostic biomarkers are not available. Inflammatory autoimmune diseases are commonly associated with local generation of large amounts of reactive oxidants. We have previously identified oxidative post-translationally modified (oxPTM) tissue-specific neoantigens in rheumatoid arthritis (RA) and type 1 diabetes that elicit an immune response. In the current study, we studied the presence and clinical significance of antibodies to oxPTM collagen type II (CII) in patients with spondyloarthritis (SpA). METHOD: Levels of antibodies specific to native CII and oxPTM-CII were assessed by enzyme-linked immunosorbent assay. RESULTS: Immunoglobulin G (IgG) binding to oxPTM-CII was observed in 52%, 83%, and 28% of serum samples from patients with axial spondyloarthritis (axSpA), RA, and psoriatic arthritis (PsA), respectively. Importantly, while strong IgA anti-oxPTM-CII responses were detected in axSpA and PsA patients, with 47% and 84% respective binders, no IgA anti-oxPTM-CII was detected in RA patients. IgA anti-oxPTM-CII reactivity in axSpA patients treated with biologics was higher and more frequent, with 85% binders compared to 9% binders in patients treated with synthetic disease-modifying anti-rheumatic drugs. CONCLUSION: Our data imply that SpA and PsA are associated with the presence of antibodies to oxPTM-CII, suggesting that there may be a humoral component that may distinguish patients with SpA from RA. Our approach could be adapted to other diseases, particularly to inflammatory autoimmune diseases.
32510258 Protocatechuic acid inhibits proliferation, migration and inflammatory response in rheumat 2020 Dec Rheumatoid arthritis (RA) is a chronic joint inflammatory disease that is closely associated with dysregulation of fibroblast-like synoviocytes (FLSs). Protocatechuic acid (PCA), a phenolic compound of anthocyanins, has been proven to possess anti-inflammatory activity. However, the role of PCA in RA has not been investigated. In the present study, we aimed to explore the effects of PCA on the RA-FLSs. The results showed that PCA suppressed the proliferation, invasion, and migration of RA-FLSs in a dose-dependent manner. PCA treatment also inhibited the expressions of matrix metalloproteinase (MMP)-3 and MMP-13, as well as the secretion of inflammatory cytokines including TNF-α, IL-1β, IL-6 in RA-FLSs. Moreover, cell apoptosis of RA-FLSs was significantly induced by PCA treatment. PCA was found to repress the activation of NF-κB signalling, which was evidenced by the decreased expression of p-p65 and increased expression of IκBα. Furthermore, PCA significantly decreased the phosphorylation levels of Akt and mTOR in RA-FLSs. In conclusion, the results indicated that PCA exhibited an inhibitory effect on RA-FLSs via inhibiting the NF-κB and Akt/mTOR signalling pathways. These findings supported the concept that PCA might be a therapeutic agent for RA treatment.