Immunoregulatory Effects of Adjuvant therapy with Statins in Rheumatoid Arthritis Population

2021 ◽  
Vol 15 (8) ◽  
pp. 1999-2001
Author(s):  
Rao Salman Aziz ◽  
Usman Saeed ◽  
Muhammad Imran Ashraf ◽  
Shazana Rana ◽  
Asif Sohail ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Low Density Lipoprotein ◽  
Joint Destruction ◽  
Experimental Studies ◽  
Density Lipoprotein ◽  
Vital Role ◽  
Continuous Treatment ◽  
Beneficial Role ◽  
Conventional Dmards

Background: Rheumatoid arthritis (RA) is considered by symmetrical peripheral arthritis, synovitis & joint destruction. Statins, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme ductase, significantly reduce coronary artery disease by helping to lower plasma low-density lipoprotein cholesterol levels. Experimental studies, more recently, several clinical trials have convincingly shown that statins play a vital role in Rheumatoid arthritis, primarily due to their anti-inflammatory and immunomodulatory properties. Aim: To assess the effectiveness of statin adjunctive therapy versus standard treatment with disease-modifying antirheumatic drugs (DMARDs) in patients with RA. Methods: In this research, patients with a diagnosis of RA among the ages of 30 and 65 years were recruited according to the "Open Rheumatoid Pathologist" inclusion criteria. Among the selected patients, two distinct patient strata were identified. Strata 1 included 40 RA patients who are currently taking DMARDs with statins; Strata 2 included 40 patients with RA who are currently receiving DMARDs; observed for 6 months; To compare the outcomes of RA in both strata, standard parameters DAS28, ESR, and CRP were estimated. Results: There were eighty subjects included in the research; this study demonstrated a significant beneficial role of additional statin drugs when administered alongside conventional DMARDs in patients with active RA. The clinical significance index of disease activity in RA was significantly (P <0.05) lower in the statin adjuvant strata (strata 1) than in the conventional DMARD treatment strata (P <0.05). Strata 2) after 6 months of Continuous treatment. Two other important biochemical markers of RA disease activity, ESR and CRP, were also significantly lower in RA patients taking statins (strata 1) (P <0.05). Compared to strata 2, which includes only RA. the patient was treated with a conventional DMARD without statins. Conclusion: The results suggest a supportive and possibly beneficial role for statin therapy in cases of active RA, leading to clinically and biochemically significant improvements. Keywords: inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme is reductase, disease activity indicator 28,

scholarly journals Lipoprotein Subclasses Determined by Nuclear Magnetic Resonance Spectroscopy and Coronary Atherosclerosis in Patients with Rheumatoid Arthritis

2010 ◽  
Vol 37 (8) ◽  
pp. 1633-1638 ◽  
Author(s):  
CECILIA P. CHUNG ◽  
ANNETTE OESER ◽  
PAOLO RAGGI ◽  
TUULIKKI SOKKA ◽  
THEODORE PINCUS ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Nuclear Magnetic Resonance ◽  
Coronary Artery ◽  
Disease Activity ◽  
Coronary Atherosclerosis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Resonance Spectroscopy ◽  
Low Density ◽  
Lipoprotein Subclasses

Objective.Patients with rheumatoid arthritis (RA) are at increased risk of atherosclerosis, but routine lipid measurements differ little from those of people without RA. We examined the hypothesis that lipid subclasses determined by nuclear magnetic resonance spectroscopy (NMR) differed in patients with RA compared to controls and are associated with disease activity and the presence of coronary-artery atherosclerosis.Methods.We measured lipoprotein subclasses by NMR in 139 patients with RA and 75 control subjects. Lipoproteins were classified as large low-density lipoprotein (LDL; diameter range 21.2–27.0 nm), small LDL (18.0–21.2 nm), large high-density lipoprotein (HDL; 8.2–13.0 nm), small HDL (7.3–8.2 nm), and total very low-density lipoprotein (VLDL; ≥ 27 nm). All subjects underwent an interview and examination; disease activity was quantified by the 28-joint Disease Activity Score (DAS28) and coronary artery calcification (CAC) was measured with electron-beam computed tomography.Results.Concentrations of small HDL particles were lower in patients with RA (18.2 ± 5.4 nmol/l) than controls (20.0 ± 4.4 nmol/l; p = 0.003). In patients with RA, small HDL concentrations were inversely associated with DAS28 (rho = −0.18, p = 0.04) and C-reactive protein (rho = −0.25, p = 0.004). Concentrations of small HDL were lower in patients with coronary calcification (17.4 ± 4.8 nmol/l) than in those without (19.0 ± 5.8 nmol/l; p = 0.03). This relationship remained significant after adjustment for the Framingham risk score and DAS28 (p = 0.025). Concentrations of small LDL particles were lower in patients with RA (1390 ± 722 nmol/l) than in controls (1518 ± 654 nmol/l; p = 0.05), but did not correlate with DAS28 or CAC.Conclusion.Low concentrations of small HDL particles may contribute to increased coronary atherosclerosis in patients with RA.

Effect of Atorvastatin on Inflammation and Modification of Vascular Risk Factors in Rheumatoid Arthritis

2010 ◽  
Vol 38 (2) ◽  
pp. 229-235 ◽  
Author(s):  
AMAL M. EL-BARBARY ◽  
MANAL S. HUSSEIN ◽  
ELSAYED M. RAGEH ◽  
HALA E. HAMOUDA ◽  
AYMAN A. WAGIH ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Disease Activity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Vascular Risk Factors ◽  
Lipoprotein Cholesterol ◽  
Vascular Risk ◽  
Tnf Α ◽  
Atorvastatin Therapy

Objective.To investigate the effect of atorvastatin therapy on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in patients with rheumatoid arthritis (RA).Methods.This study included 30 patients with early RA, randomly divided into 2 groups. Group 1 (n = 15) received methotrexate (MTX; 0.2 mg/kg/week; mean (15.5 ± SD 1.3) plus prednisone (10 mg/day). Group 2 (n = 15) received MTX and prednisone with the same previous doses plus atorvastatin therapy (40 mg/day). Ten healthy individuals of similar age and sex served as controls. Disease activity, lipid profile, serum malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), resistin, adiponectin, and brachial artery flow-mediated dilation (FMD) were measured before and after 6 months of treatment.Results.Atorvastatin combined with MTX therapy significantly reduced serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and increased high-density lipoprotein cholesterol (p < 0.001). Disease activity variables, serum MDA, TNF-α, resistin, adiponectin, and FMD were significantly improved by the drug combinations (p < 0.001).Conclusion.Atorvastatin therapy in patients with RA reduced disease activity and conventional and novel vascular risk factors that promote the atheromatous lesion. Therapy was also associated with concomitant improvement in endothelial function.

Tocilizumab for Rheumatoid Arthritis: A Cochrane Systematic Review

2010 ◽  
Vol 38 (1) ◽  
pp. 10-20 ◽  
Author(s):  
JASVINDER A. SINGH ◽  
SABA BEG ◽  
MARIA ANGELES LOPEZ-OLIVO
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Adverse Event ◽  
Adverse Events ◽  
Disease Activity ◽  
Low Density Lipoprotein ◽  
Health Assessment ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Serious Adverse Events

Objective.To compare the benefit and safety of tocilizumab to placebo in patients with rheumatoid arthritis (RA).Methods.We searched multiple databases for published randomized or controlled clinical trials comparing benefit and safety of tocilizumab to placebo, disease-modifying antirheumatic drugs (DMARD), or other biologics. For dichotomous outcomes, we calculated the relative risk, and for continuous outcomes, the mean difference.Results.Eight randomized controlled trials were included in this systematic review, with 3334 participants, 2233 treated with tocilizumab and 1101 controls. The US and Canadian approved dose of tocilizumab, 8 mg/kg every 4 weeks, was given to 1561 participants. In patients taking concomitant methotrexate, compared to placebo, patients treated with approved dose of tocilizumab were substantially and statistically significantly more likely than placebo to achieve the American College of Rheumatology 50 (absolute percentage, 38.8% vs 9.6%, respectively; RR 3.2, 95% CI 2.7, 3.7); Disease Activity Score remission (30.5% vs 2.7%; RR 8.7, 95% CI 6.3, 11.8); and a clinically meaningful decrease in Health Assessment Questionnaire (HAQ)/Modified HAQ scores (60.5% vs 34%; RR 1.8, 95% CI 1.6, 1.9). There were no substantive statistically significant differences in serious adverse effects (0.8% vs 0.7%; RR 1.2, 95% CI 0.8, 1.6) or withdrawals due to adverse events (4.9% vs 3.7%; RR 1.4, 95% CI 0.9, 2.1); however, tocilizumab-treated patients were significantly more likely to have any adverse event (74% vs 65%; RR 1.05, 95% CI 1.03, 1.07); elevation in the ratio of low-density lipoprotein to high-density lipoprotein cholesterol (HDL; 20% vs 12%; RR 1.7, 95% CI 1.2, 2.2); and increase in the ratio of total to HDL cholesterol (12% vs 7%; RR 1.7, 95% CI 1.2, 2.6); and they were less likely to withdraw from treatment for any reason (8.1% vs 14.9%; RR 0.6, 95% CI 0.5, 0.8).Conclusion.At the approved dose of 8 mg/kg every 4 weeks, tocilizumab in combination with methotrexate/DMARD is beneficial in decreasing RA disease activity and improving function. Tocilizumab treatment was associated with a significant increase in cholesterol levels and occurrence of any adverse event, but not serious adverse events. Larger safety studies are needed to address these safety concerns.

Immunoregulatory Role of Interleukin-37 in Rheumatoid Arthritis; Relation to Disease Activity and Joint Destruction

2018 ◽  
Vol 86 (September) ◽  
pp. 3341-3348
Author(s):  
DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽  
MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Destruction

scholarly journals FRI0127 Suppression of radiographic progression after gradual methotrexate tapering in patients with rheumatoid arthritis patients maintaining low disease activity - Prospective multicenter study-

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 645.1-645
Author(s):  
K. Katayama ◽  
K. Yujiro ◽  
T. Okubo ◽  
R. Fukai ◽  
T. Sato ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Destruction ◽  
Reduction Rate ◽  
Bone Destruction ◽  
High Response ◽  
Continuation Rate ◽  
Low Disease Activity ◽  
One Year ◽  
Response Group

Background:Many studies have been reported to reduce/discontinue Biologics in the treatment of rheumatoid arthritis (RA). In contrast, study for tapering methotrexate (MTX) has been limited (1,2).Objectives:We prospectively examined whether bone destruction will progress at 48 weeks after tapering or discontinuing MTX (UMIN000028875).Methods:The subjects were RA patients who have maintained low disease activity or lower for 24 weeks or more in DAS28-CRP after MTX administration. Patients having PDUS Grade 2 or 3 per site by bilateral hand ultrasonography (26 area) were excluded in this study owing to risk for joint destruction. The joint destruction was evaluated by the joint X-ray evaluation by modified total Sharp scoring (mTSS) at 1 year after the start of tapering MTX. Evaluation of clinical disease activities, severe adverse events, the continuation rate during MTX tapering were also evaluated. According to tapering response, prognostic factor for good response for tapering, joint destruction was determined. Predictors for successful tapering MTX and progression of bone destruction were determined. Statistical analysis was performed by t-test or Wilcoxon rank sum test using SAS .13.2 software.Results:The subjects were 79 (16 males, 63 females). Age average 60.9 years, disease duration 4 years 4 months, MTX dose 8.43 mg / w, DAS28-CRP 1.52, DMARDs (24.3%), ACPA 192.7 U / ml (70.5%), RF 55.6 IU / ml (65.4%).MTX was tapered from an average of 8.43 mg / w before study to 5.46 mg / w one year later. In the treatment evaluation, DAS28-CRP increased from 1.52 to 1.84. 89.7% of subjects did not progress joint damage. Other disease activities significantly increased (Table 1). The one-year continuation rate was 78.2%. Since tapering effects were varied widely, we divided patients into three groups; Flared group (N=14, initial MTX dose 8.71mg/w, final MTX dose 8.42mg/w), Low response group (N=31, final MTX reduction rate< 50%, initial MTX dose 8.93mg/w, final MTX dose 6.22mg/w), High response group (N=34, final MTX reduction rate≥ 50%, initial MTX dose 8.5mg/w, final MTX dose 3.15mg/w)(Table 2).Higher RF value at baseline and higher MTX dose at 3M, 6M were predictors of whether a subject was in Low response group or High Response group. Higher RF value and mTSS at baseline and higher MTX dose at 6M were predictors whether a subject was in Flared group or High response group. Lower age was predictor of whether a subject was in Flared group or Low responder group. Finally, mean ΔmTSS /y in Flared group (0.36) was not significantly higher than in low response group (0.07) and in high response group (0.01).Table 1Table 2.Predictors for successful tapering MTX and progression of bone destructionConclusion:Patients with MTX-administered low disease activity and finger joint echo PDUS grade 1 satisfy almost no joint destruction even after MTX reduction. For tapering, predictors may be helpful for maintaining patient’s satisfaction.References:[1]Baker KF, Skelton AJ, Lendrem DW et al. Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study. J. Autoimmunity. 2019;105: 102298.[2]Lillegraven S, Sundlisater N, Aga A et al. Tapering of Conventional Synthetic Disease Modifying Anti-Rheumatic Drugs in Rheumatoid Arthritis Patients in Sustained Remission: Results from a Randomized Controlled Trial. American College of Rheumatology. 2019; Abstract L08.Disclosure of Interests:None declared

LncRNA OIP5-AS1 accelerates ox-LDL-treated HUVECs injury by NF-κB pathway via miR-30c-5p

2021 ◽  
pp. 1-12
Author(s):  
Lei Zhang ◽  
Qiulai Li ◽  
Yanxia Chen ◽  
Qiao Zhu
Keyword(s):  
Oxidative Stress ◽  
Vascular Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Vital Role ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Sod Activity ◽  
Interacting Protein ◽  
Rna Immunoprecipitation

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) could induce endothelial injury and played a vital role in the progression and development of atherosclerosis. This study aimed to investigate the role of Opa-interacting protein 5 antisense RNA 1 (OIP5-AS1) in ox-LDL-induced human umbilical vascular endothelial cells (HUVECs) injury and the potential mechanisms. METHODS: Cell proliferation and apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry assay, respectively. The levels of lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and nitric oxide (NO) were detected by corresponding detection kits, respectively. Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of OIP5-AS1 or microRNA-30c-5p (miR-30c-5p) in HUVECs. Binding between OIP5-AS1 and miR-30c-5p was predicted through bioinformatics analysis and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP). Western blot was used to analyze p-IκB, IκB, p-p65 and p65 levels. RESULTS: In HUVECs, exposure to ox-LDL led to a decrease in cell viability and an increase in LDH release and apoptosis with concomitant enhancement of oxidative stress, as evidenced by increased ROS and MDA generation, as well as decreased SOD activity and NO levels, while OIP5-AS1 knockdown or miR-30c-5p upregulation could rescue these effects above. Mechanically, OIP5-AS1 functioned as a sponge of miR-30c-5p. OIP5-AS1-induced injury and apoptosis, oxidative stress and activation of NF-κB pathway were reversed by miR-30c-5p in ox-LDL-treated HUVECs. CONCLUSION: OIP5-AS1 contributed to ox-LDL-treated HUVECs injury by activation of NF-κB pathway via miR-30c-5p.

Synovial Infiltration with CD79a-positive B Cells, But Not Other B Cell Lineage Markers, Correlates with Joint Destruction in Rheumatoid Arthritis

2011 ◽  
Vol 38 (11) ◽  
pp. 2301-2308 ◽  
Author(s):  
YING-QIAN MO ◽  
LIE DAI ◽  
DONG-HUI ZHENG ◽  
LANG-JING ZHU ◽  
XIU-NING WEI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Cell Density ◽  
Joint Destruction ◽  
Chinese Patients ◽  
Positive Staining ◽  
Synovitis Score ◽  
Sharp Score

Objective.The efficacy of B cell depletion in the treatment of patients with rheumatoid arthritis (RA) has revitalized interest in the pathogenic role(s) of B cells in RA. We evaluated the distribution of synovial B lineage cells and their correlation with histologic disease activity and joint destruction in RA.Methods.Synovial tissue samples were obtained by closed-needle biopsy from 69 Chinese patients with active RA, from 14 patients with osteoarthritis (OA), and from 15 with orthopedic arthropathies (OrthA) as disease controls. Serial tissue sections were stained immunohistochemically for CD79a (pro-B cell to plasma cell), CD20 (B cells), CD38 (plasma cells), CD21 (follicular dendritic cells), CD68 (macrophages), CD3 (T cells), and CD34 (endothelial cells). Densities of positive-staining cells were determined and correlated with histologic disease activity (Krenn 3-component synovitis score) and radiographic joint destruction (Sharp score).Results.Mean sublining CD79a-positive cell density was significantly higher in RA than in OA (p <0.001) or OrthA (p = 0.003). Receiver operating characteristic curve analysis showed that CD79a-positive cell density differentiated RA well from OA [area under the curve (AUC) = 0.79] or OrthA (AUC = 0.75). Spearman’s rank order correlation showed significant correlations between sublining CD79a-positive cell density and the synovitis score (r = 0.714, p < 0.001), total Sharp score (r = 0.490, p < 0.001), and the erosion subscore (r = 0.545, p < 0.001), as well as the joint space narrowing subscore (r = 0.468, p = 0.001) in RA.Conclusion.Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.

scholarly journals Histamine index and clinical expression of rheumatoid arthritis activity

2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Joint Destruction ◽  
Clinical Expression ◽  
Histamine Concentration ◽  
Significant Difference ◽  
Rheumatoid Arthritis Activity

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.

scholarly journals Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score

2007 ◽  
Vol 66 (10) ◽  
pp. 1356-1362 ◽  
Author(s):  
S. M van der Kooij ◽  
J. K de Vries-Bouwstra ◽  
Y. P M Goekoop-Ruiterman ◽  
D. van Zeben ◽  
P. J S M Kerstens ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Score ◽  
Recent Onset ◽  
Limited Efficacy ◽  
Conventional Dmards
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