scholarly journals TNF-α Inhibitors Decrease Classical CD14hiCD16− Monocyte Subsets in Highly Active, Conventional Treatment Refractory Rheumatoid Arthritis and Ankylosing Spondylitis

2019 ◽  
Vol 20 (2) ◽  
pp. 291 ◽  
Author(s):  
Bogdan Batko ◽  
Agata Schramm-Luc ◽  
Dominik Skiba ◽  
Tomasz Mikolajczyk ◽  
Mateusz Siedlinski
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Peripheral Blood Monocyte ◽  
Placebo Treatment ◽  
Prior History ◽  
Monocyte Subset ◽  
Highly Active ◽  
Tnf Α

Monocytes are pivotal cells in inflammatory joint diseases. We aimed to determine the effect of TNF-α inhibitors (TNFi) on peripheral blood monocyte subpopulations and their activation in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients with high disease activity. To address this, we studied 50 (32 AS, 18 RA) patients with highly active disease with no prior history of TNFi use who were recruited and assigned to TNFi or placebo treatment for 12 weeks. Cytometric and clinical assessment was determined at baseline, four, and 12 weeks after initiation of TNFi treatment. We observed that treatment with TNFi led to a significant decrease in CD14hiCD16− monocytes in comparison to placebo, while circulating CD14dimCD16+ monocytes significantly increased. The TNFi-induced monocyte subset shifts were similar in RA and AS patients. While the percentage of CD14dimCD16+ monocytes increased, expression of CD11b and CD11c integrins on their surface was significantly reduced by TNFi. Additionally, CD45RA+ cells were more frequent. The shift towards nonclassical CD14dimCD16+ monocytes in peripheral blood due to TNFi treatment was seen in both AS and RA. This may reflect reduced recruitment of these cells to sites of inflammation due to lower inflammatory burden, which is associated with decreased disease activity.

Evaluating the efficacy of intra-articular injections of platelet rich plasma (PRP) in rheumatoid arthritis patients and its impact on inflammatory cytokines, disease activity and quality of life.

2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Platelet Rich Plasma ◽  
Joint Inflammation ◽  
Monthly Interval ◽  
Post Injection ◽  
Tnf Α

Background: Among rheumatoid arthritis patients (RA), general disease activity is well regulated by diseasemodifying anti-rheumatic medications (DMARDS), but sometimes local inflammation still persists among a few joints. Adjuvant modern molecular interventions as Platelet Rich Plasma (PRP) with a suggested down regulating effect on inflammatory mediators has a proven effect in management of RA. We aim to evaluate the therapeutic effect of intra-articular PRP versus steroid in RA patients and their impact on inflammatory cytokines IL1B , TNF α, local joint inflammation, disease activity and quality of life (QL). Methods: Open labeled parallel randomized control clinical trial was carried out on 60 RA patients randomly divided into 2 groups, Group 1: included 30 patients received 3 intra-articular injections of PRP at monthly interval, Group 2: included 30 patients received single intra-articular injection of steroid. They were subjected to clinical, laboratory, serum IL1B and TNF α assessment at baseline and at 3, 6 months post injection. Results: Patients of both groups showed improvements in their scores of evaluating tools at 3months post injection and this improvement was persistent in the PRP group up to 6 months post injection while it was continued only for 3 months in the steroid group. Conclusions: PRP is a safe, effective and useful therapy in treating RA patients who had insufficient response and persistent pain and inflammation in just one or two joints through its down regulating effect on inflammatory cytokines IL1B, TNF α with subsequent improvement of local joint inflammation, disease activity and QL.

scholarly journals Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1022
Author(s):  
Tatyana P. Makalish ◽  
Ilya O. Golovkin ◽  
Volodymyr V. Oberemok ◽  
Kateryna V. Laikova ◽  
Zenure Z. Temirova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Rat Model ◽  
Peripheral Blood ◽  
Antisense Oligonucleotide ◽  
Joint Inflammation ◽  
Blood Concentrations ◽  
Tnf Α ◽  
Effective Drugs ◽  
First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

scholarly journals OP0034 DOES THE RISK OF VENOUS THROMBOEMBOLISM VARY WITH DISEASE ACTIVITY IN RHEUMATOID ARTHRITIS?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 23.2-24
Author(s):  
V. Molander ◽  
H. Bower ◽  
J. Askling
Keyword(s):  
Rheumatoid Arthritis ◽  
Logistic Regression ◽  
Venous Thromboembolism ◽  
Disease Activity ◽  
Das28 Score ◽  
Logistic Regression Models ◽  
Highly Active ◽  
Increased Risk ◽  
Das28 Remission ◽  
One Year

Background:Patients with rheumatoid arthritis (RA) are at increased risk for venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) (1). Several established risk factors of VTE, such as age, immobilization and comorbid conditions, occur more often patients with RA (2). In addition, inflammation may in itself also increase VTE risk by upregulating procoagolatory factors and causing endothelial damage (3). Recent reports indicate an increased risk of VTE in RA patients treated with JAK-inhibitors (4), pointing to the need to better understand how inflammation measured as clinical RA disease activity influences VTE risk.Objectives:To investigate the relationship between clinical RA disease activity and incidence of VTE.Methods:Patients with RA were identified from the Swedish Rheumatology Quality Register (SRQ) between July 1st2006 and December 31st2017. Clinical rheumatology data for these patients were obtained from the visits recorded in SRQ, and linked to national registers capturing data on VTE events and comorbid conditions. For each such rheumatologist visit, we defined a one-year period after the visit and determined whether a VTE event had occurred within this period or not. A visit followed by a VTE event was categorized as a case, all other visits were used as controls. Each patient could contribute to several visits. The DAS28 score registered at the visit was stratified into remission (0-2.5) vs. low (2.6-3.1), moderate (3.2-5.1) and high (>5.1) disease activity. Logistic regression with robust cluster standard errors was used to estimate the association between the DAS28 score and VTE.Results:We identified 46,311 patients with RA who contributed data from 320,094 visits. Among these, 2,257 visits (0.7% of all visits) in 1345 unique individuals were followed by a VTE within the one-year window. Of these, 1391 were DVT events and 866 were PE events. Figure 1 displays the absolute probabilities of a VTE in this one-year window, and odds ratios for VTE by each DAS28 category, using DAS28 remission as reference. The one-year risk of a VTE increased from 0.5% in patients in DAS28 remission, to 1.1% in patients with DAS28 high disease activity (DAS28 above 5.1). The age- and sex-adjusted odds ratio for a VTE event in highly active RA compared to RA in remission was 2.12 (95% CI 1.80-2.47). A different analysis, in which each patient could only contribute to one visit, yielded similar results.Figure 1.Odds ratios (OR) comparing the odds of VTE for DAS28 activity categories versus remission. Grey estimates are from unadjusted logistic regression models, black estimates are from logistic regression models adjusted for age and sex. Absolute one-year risk of VTE are estimated from unadjusted models.Conclusion:This study demonstrates a strong association between clinical RA inflammatory activity as measured through DAS28 and risk of VTE. Among patients with high disease activity one in a hundred will develop a VTE within the coming year. These findings highlight the need for proper VTE risk assessment in patients with active RA, and confirm that patients with highly active RA, such as those recruited to trials for treatment with new drugs, are already at particularly elevated risk of VTE.References:[1]Holmqvist et al. Risk of venous thromboembolism in patients with rheumatoid arthritis and association with disease duration and hospitalization. JAMA. 2012;308(13):1350-6.[2]Cushman M. Epidemiology and risk factors for venous thrombosis. Semin Hematol. 2007;44(2):62-9.[3]Xu J et al. Inflammation, innate immunity and blood coagulation. Hamostaseologie. 2010;30(1):5-6, 8-9.[4]FDA. Safety trial finds risk of blood clots in the lungs and death with higher dose of tofacitinib (Xeljanz, Xeljanz XR) in rheumatoid arthritis patients; FDA to investigate. 2019.Acknowledgments:Many thanks to all patients and rheumatologists persistently filling out the SRQ.Disclosure of Interests:Viktor Molander: None declared, Hannah Bower: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma

scholarly journals Significance of asymptomatic hyperuricemia in ankylosing spondylitis

2021 ◽  
Vol 15 (3) ◽  
pp. 57-61
Author(s):  
R. M. Balabanova ◽  
E. V. Ilyinykh ◽  
M. V. Podryadnova ◽  
S. I. Glukhova ◽  
M. M. Urumova
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Blood Serum ◽  
Disease Activity ◽  
Filtration Rate ◽  
Metabolic Disorders ◽  
Clinical Manifestations ◽  
The Past ◽  
The Metabolic Syndrome ◽  
Medical Histories

Over the past decades, there has been an increase in the incidence of asymptomatic hyperuricemia (AHU), which includes an increased level (>360 μmol/L) of uric acid (UA) in the blood serum of patients with no clinical manifestations of gout. AHU is reported in various rheumatic diseases, mainly in osteoarthritis, in which AHU is one of the manifestations of the metabolic syndrome. There is relationship between AHU and pulmonary hypertension in systemic sclerosis, arterial hypertension (AH) in men with seronegative rheumatoid arthritis, extensive cutaneous psoriasis and metabolic disorders in psoriatic arthritis. There are almost no data on AHU in ankylosing spondylitis (AS), which served objective for this work.Objective: to assess the association of AHU with AS duration and activity and the presence of comorbid diseases.Patients and methods. A retrospective analysis of 48 medical histories of patients with diagnosed AS, who were treated in V.A. Nasonova Research Institute of Rheumatology from 2015 to 2019 years, whose serum UA level was >360 μmol/L.Results and discussion. More than half of patients with AS and AHU were overweight, 21% were obese. AH was diagnosed in 43.7% of patients. Stage II–III chronic kidney disease was detected in 16.7% of patients, urolithiasis – in 18.8%. 4 (8.3%) patients had diabetes mellitus. The serum UA level in patients with AS was 422.0 ± 61.6 μmol/L. In patients with AS, an association between AHU and age, duration and disease activity was noted. There was no statistically significant rela- tionship between HG and blood glucose, cholesterol, creatinine levels, body mass index. Correlation analysis revealed a statistically significant relationship between the glomerular filtration rate (GFR) and the age of patients (r=-0.54, p<0.001), the duration of the disease (r=-0.40, p<0.05), cholesterol level (r=-0.48, p=0.01), UA level (r=-0.45, p=0.03) and blood pressure (r=-0.54, p<0.001). There was no association between disease activity and GFR (p>0.05).Conclusion. In AS, an association between an increased level of UA in the blood serum and the duration and activity of the disease, and patient's age, was established.

Association of RETN and TNFRSF1B polymorphisms with TNF-α inhibitor response in rheumatoid arthritis patients

2020 ◽  
Author(s):  
Nga Thi Trinh ◽  
Hyun Jeong Kim ◽  
Woorim Kim ◽  
Sang Oh Kang ◽  
Kyung Hyun Min ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Multivariable Logistic Regression Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Final Model ◽  
Asian Populations ◽  
Tnf Α

Abstract Background: Despite the improvement from the introduction of tumor necrosis factor inhibitors (TNFi) in the rheumatoid arthritis (RA), TNFi therapy fails for more than 30% or results in a partial response. Thus, we aimed to explore treatment marker by examining the association of single nucleotide polymorphisms (SNPs) with response to TNFi therapy.Method: Genes associated with RA or RA treatment were reviewed and fourteen SNPs with minor allele frequency ≥ 20% in the East Asian populations were selected and analyzed. Data were collected from 105 RA patients. Our primary endpoint was the disease activity score using 28-joint count after six months of treatment (DAS28-6month). The secondary outcomes were the subcomponents of DAS28.Results: A total of 88 patients were included in the final analyses. Among the 14 SNPs analyzed, one SNP showed statistical significance in DAS28-6month: patients with the GG allele of RETN rs1862513 had a 4.7 times higher chance of low disease activity at 6-months than GC or CC-carriers (p = 0.033), as indicated by multivariable logistic regression analysis. Rs3397 was marginally significant in univariate analysis (p=0.059), but was significant in the multivariable model (p=0.041). The final model explained 24.5% (Nagelkerke R2) of the variance in DAS28-6month.Conclusion: Our results demonstrated that, among the genes related to RA, SNPs in RETN and TNFRSF1B were associated with the response of TNFi treatment.

Levels of Plasma-soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) Are Correlated with Disease Activity in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 933-938 ◽  
Author(s):  
SANG TAE CHOI ◽  
EUN-JIN KANG ◽  
YOU JUNG HA ◽  
JUNG-SOO SONG
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Myeloid Cells ◽  
Disease Status ◽  
Joint Disease ◽  
Healthy Controls ◽  
Cell Counts ◽  
Tnf Α ◽  
White Blood Cell Counts ◽  
Factor Α

Objective.To determine whether levels of plasma-soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) are elevated in patients with rheumatoid arthritis (RA) and whether levels are correlated with disease activity and other variables.Methods.Our study included 71 patients with RA and 50 age- and sex-matched healthy controls. Clinical characteristics and laboratory measures, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and 28-joint Disease Activity Score (DAS28) were assessed. Plasma levels of sTREM-1 and tumor necrosis factor-α (TNF-α) were measured by ELISA.Results.Patients with RA had significantly higher plasma sTREM-1 levels than healthy controls (170.10 ± 84.71 pg/ml vs 97.41 ± 40.64 pg/ml; p < 0.001). In patients with RA, plasma sTREM-1 levels were found to be correlated with DAS28, ESR, CRP, white blood cell counts, neutrophil counts, and plasma TNF-α levels (r = 0.329, p = 0.005; r = 0.241, p = 0.043; r = 0.314, p < 0.001; r = 0.261, p = 0.028; r = 0.278, p = 0.019; and r = 0.313, p = 0.009, respectively). Plasma sTREM-1 levels in patients with active disease status (DAS28 > 3.2) were significantly higher than in those with low disease status (DAS28 ≤ 3.2; 208.89 ± 100.14 pg/ml vs 150.29 ± 68.70 pg/ml; p = 0.005).Conclusion.Patients with RA had higher plasma sTREM-1 levels than healthy controls, and plasma sTREM-1 levels were correlated with disease activity measures, suggesting that plasma sTREM-1 could play a role in the inflammatory process associated with TNF-α, and that it may be a useful disease activity marker in RA.

scholarly journals Real-world evidence of the impact of adalimumab on work productivity and sleep measures in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis

2020 ◽  
Vol 12 ◽  
pp. 1759720X2094908
Author(s):  
Maria G. Tektonidou ◽  
Gkikas Katsifis ◽  
Athanasios Georgountzos ◽  
Athina Theodoridou ◽  
Eftychia-Maria Koukli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Real World ◽  
Sleep Problems ◽  
Work Productivity ◽  
Routine Care ◽  
Activity Impairment ◽  
Work Impairment

Objective: Our aim was to evaluate the effect of adalimumab on work productivity measures, overall activity impairment, and sleep quality in patients with active moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) treated in routine care settings in Greece and determine factors associated with work impairment and sleep disturbance. Methods: Patients with active moderate to severe RA ( n = 184), PsA ( n = 166), and AS ( n = 150) were enrolled in this 24-month, prospective, observational study at 80 hospital outpatient clinics and private practices throughout Greece. Patients received adalimumab alone or in combination with standard antirheumatic therapies according to routine care. Work productivity and sleep were assessed through two patient-reported outcome measures: the Work Productivity and Activity Impairment–General Health questionnaire and the Medical Outcomes Study Sleep Scale (MOS-SS). Pearson correlation coefficients were estimated to assess the association of work impairment and sleep disturbances with disease activity scores. Results: In the overall population, adalimumab significantly lowered absenteeism [mean (95% confidence interval) reduction, 18.9% (13.3–24.5%); n = 100]; presenteeism [40.0% (33.8–46.3%); n = 98], overall work productivity impairment [46.8% (40.4–53.2%); n = 94], activity impairment [47.0% (44.3–49.6); n = 421], and the MOS-SS sleep problems index [31.6 (29.5–34.1); n = 421] after 24-month treatment ( p < 0.001). Significant improvements were also noted across the RA, PsA, and AS subpopulations ( p < 0.05). Improvements in overall work impairment and sleep disturbance positively correlated with improvements in disease activity measures. Conclusion: Adalimumab improves work productivity and sleep problems while lowering disease activity in patients with moderate to severe RA, PsA, and AS managed in real-world settings.

Increase in MEG3, MALAT1, NEAT1 significantly predicts the clinical parameters in patients with rheumatoid arthritis

2020 ◽  
Vol 17 (6) ◽  
pp. 445-457
Author(s):  
Sudipta Chatterjee ◽  
Dipanjan Bhattcharjee ◽  
Sanchaita Misra ◽  
Ayindrila Saha ◽  
Nitai Pada Bhattacharyya ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Multivariate Analysis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Peripheral Blood ◽  
Multivariate Analyses ◽  
Clinical Parameters

Aim: This study investigated deregulation of lncRNAs MEG3, MALAT1, NEAT1 and their associations with clinical parameters in rheumatoid arthritis (RA). Materials & methods: LncRNAs MALAT1, MEG3, NEAT1 were quantified from peripheral blood mono-nuclear cells (PBMCs) and plasma of 82 RA patients with 15 matched controls and from knee fluid of 24 RA patients with ten osteoarthritis controls. Multivariate analyses were performed among lncRNAs and clinical parameters of RA. Results: MALAT1, MEG3, NEAT1 were increased in PBMCs, plasma, synovial fluid (p < 0.05) of RA patients. Significant correlations were observed for MEG3 with TJC (r = 0.29), NEAT1 with TJC (r = 0.49), swollen joint count (r = 0.20), DAS28-CRP (r = 0.29). Multivariate analysis revealed that 48.5% of TJC and 31.5% of swollen joint count could be predicted by lncRNAs. Conclusion: The findings suggested that the lncRNAs might be explored as probable markers in monitoring disease activity.

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