scholarly journals Dynamics of clinical manifestations and cytokine concentrations in rheumatoid arthritis patients on tofacitinib therapy

2021 ◽  
Vol 59 (6) ◽  
pp. 693-699
Author(s):  
N. A. Lapkina ◽  
A. A. Baranov ◽  
N. E. Abaytova ◽  
N. Yu. Levshin ◽  
A. S. Avdeyeva ◽  
...  

Objective - to study the dynamics of clinical and laboratory parameters of inflammatory activity of the disease and cytokines in rheumatoid arthritis (RA) patients on a background of tofacitinib (TOFA) treatment.Material and methods. Ten patients with a reliable diagnosis of RA have been examined: patients' age was 51.0 (48.0; 62.0) years, duration of disease was 7.0 (3.0; 20.0) years. All patients had high disease activity: DAS28 -5.88 (5.53; 5.94), CDAI - 33.0 (29.0; 36.0), SDAI - 33.72 (30.75; 36.85). All patients were treated with TOFA at a dose of 5 mg 2 times a day on a background of methotrexate therapy, non-steroidal anti-inflammatory drugs, and glucocorticoids. Observations were performed before treatment and after 3 and 6 months of therapy. Serum levels of 15 cytokines (IL-1β, IL-4, IL-6, TNF-α, INF-γ, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, sCD40L) were examined using multiplex xMAP technology.After 3 and 6 months of TOFA therapy, there was a significant decrease in DAS28 of 4.55 (3.47; 5.16) and 3.92 (3.80; 4.60); CDAI - 16.5 (11.0; 23.0) and 18.0 (15.0; 19.0); SDAI - 16.6 (11.23; 23.06) and 18.07 (15.06; 19.10); ESR - 19.0 (11.0; 26.0) and 7.0 (4.0; 18.0); CRP - 0.56 (0.50; 1.99) and 0.71 (0.51; 1.1) respectively. IL-6 levels decreased after 3 and 6 months of therapy (p<0.05). The concentration of INF-γ significantly decreased after 3 months (p<0.05), but remained unchanged thereafter. Concentrations of IL-25 and IL-31 decreased after 3 months (p<0.05), and by the 6th month of treatment there was an increase, however, not reaching the initial values.Conclusion. The results of the study show the efficacy of TOFA in RA and create prerequisites for further study of the cytokine-dependent mechanisms of inflammation in this disease.

2015 ◽  
Vol 8 ◽  
pp. CMAMD.S22155 ◽  
Author(s):  
Katsuaki Kanbe ◽  
Junji Chiba ◽  
Yasuo Inoue ◽  
Masashi Taguchi ◽  
Akiko Yabuki

In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 including baseline characteristics in patients with rheumatoid arthritis (RA) treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S) score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metalloproteinase (MMP)-3, TNF-α, and IL–6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Khadiga Ahmed Ismail

Background: Tumor necrosis Factor-α (TNF-α) is encoded and controlled by TNF-α gene, which is involved in rheumatoid arthritis (RA) susceptibility. This research aimed to identify genetic variations of TNF-α (G308A) and to establish its association with inflammatory markers in Rheumatoid Arthritis predisposition. Methods: In the present study, fifty RA patients and fifty volunteers were involved and evaluated for the C-reactive protein, rheumatoid factor, and TNF-α were estimated by ELISA, Erythrocyte Sedimentation Rate (ESR) by Wintergreen method and for TNF-α-308 G>A polymorphism by polymerase chain reaction with amplification refractory mutation system (PCR-ARMS). Results: The CRP, RF, ESR and TNF-α were significantly elevated in RA patients relative to controls. The serum level TNF-α was also significantly elevated in female patients and in patients ≥50 years. Analysis of TNF-308 gene polymorphism revealed that GG genotypes were more prevalent in RA patients than in the healthy individuals and that GG genotype may be a potential factor to RA. The G allele was more common in RA than in the control. Elevated TNF-α serum levels were significantly associated the GG genotype and functional disability in RA patients. Conclusion: TNF-α promoter 308polymorphism GG genotype may be considered as a risk factor for RA and the TNF-α serum level was significantly related to the functional disability in the disease.


2020 ◽  
Vol 16 ◽  
Author(s):  
Dalia S. Saif ◽  
Nagwa N. Hegazy ◽  
Enas S. Zahran

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.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 625.2-626
Author(s):  
H. Gerasimova ◽  
T. Popkova ◽  
I. Kirillova ◽  
M. Cherkasova ◽  
A. Martynova ◽  
...  

Background:N-terminal pro-brain natriuretic peptide (NT-proBNP) is a recognized predictor of congestive heart failure (CHF) and cardiovascular death. Rheumatoid arthritis (RA) patients (pts) were shown to have higher NT-proBNP concentrations than in general population, but it remains unclear, whether NT-proBNP levels are related to RA duration, activity or treatment.Objectives:To investigate the effect of interleukin 6 receptor inhibitor - tocilizumab (TCZ) and JAK inhibitor - tofacitinib (TOFA) on NT-proBNP levels in RA pts during a 12-month (m) follow-up period.Methods:The study enrolled 60pts (50women/10men) with the lack of efficacy/resistance and/or intolerance of basic anti-inflammatory drugs (DMARDs); median age was 55[42;61] years, median disease duration 55[29;120]m, with moderate to high activity (DAS28-5,1[4,6;6,1], serum positivity for rheumatoid factor (RF)(85%)/ anti-cyclic citrullinated peptide antibodies (ACCP)(80%). The study did not include RA pts with CHF and clinically overt cardiovascular disease (CVD). Twenty nine RA pts received TCZ(8mg/kg) every 4 weeks: 61% received TCZ in combination with methotrexate (MTX), 35% - with low-dose glucocorticoids (GCs). Thirty one RA pts were prescribed oral TOFA at 5 mg BID with dose escalation to 10 mg BID in 8 (26%)pts. TOFA was used in combination with MTX in 90% pts, with GCs – in 29% pts. Pts treated with TCZ and TOFA were comparable in terms of age, sex, body mass index. RA activity rates (DAS28, SDAI, ESR, CRP) were higher in pts on TCZ -therapy compared with pts treated with TOFA. Echocardiography data and NT-proBNP levels using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland) were obtained at baseline and after 12m.Results:Significant positive changes in major disease activity, clinical and laboratory parameters were found in RA pts after 12 m of TCZ infusion and TOFA intake: remission (DAS28<2,6) was achieved in 54% and 39% pts, low activity levels (DAS28<3,2) – in 46% and 51% pts, respectively.The NT-proBNP levels were significantly higher in RA pts than in the control group (median 69,1 (37,9;105,8) pg/mL vs 55,3 (36,6;67,3) pg/mL,p<0.05).Six pts (10%) (three in each pts group) had NT-proBNP levels over 125pg/ml, but were asymptomatic and had unremarkable echocardiography.There was a good correlation between NT-proBNP level at baseline with age (r=0,55,p<0,001), SDAI (r=0,5, h=0,01), ACCP (r=0,23,p=0,01).Decrease of median NT-proBNP levels was documented after 12m of TCZ therapy (81,5[43,0;102,0]vs41,6[25,4;64,2]pg/ml (p<0,01) and after 12m TOFA therapy (66,1[30,5;105,0]vs16,8 [5,0;81,0]pg/ml,p=0,001).After 12m of TCZ correlations of ΔNT-proBNP were established with ΔESR (R=0,43;p<0,05], ΔСRP (R=0,46;p<0,05], ΔEe left ventricle (LV) (r=0,88,p=0,03).In the group of pts treated with TOFA ΔNT-proBNP level significantly correlated with the percentage change in DAS 28 (r=0,41,p=0,038), there was no direct correlation with changes in the parameters of the LV diastolic function.Conclusion:TCZ and TOFA treatment for 12 m reduced NT-proBNP levels in RA pts without clinically manifest CVD and CHF. Falling NT-proBNP concentrations are associated with positive dynamics of RA activity (DAS 28) and inflammatory markers (CRP, ESR), therefore allowing to suggest that increased NT-proBNP levels should be considered as a component of disease activity. Correlation between ΔNT-proBNP and ΔEeLF may be indicative as possible impact of these biomarkers on the LV diastolic function’s development in RA pts.Disclosure of Interests:None declared


Vascular ◽  
2021 ◽  
pp. 170853812098630
Author(s):  
Dobroslav Kyurkchiev ◽  
Tsvetelina Yoneva ◽  
Adelina Yordanova ◽  
Ekaterina Kurteva ◽  
Georgi Vasilev ◽  
...  

Background Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. “Classical” antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA. Objectives and methodology: We performed a cross-sectional study enrolling 34 patients diagnosed with GPA. Our study was aimed at looking for correlations between serum levels of LAMP-2 and plasminogen and the clinical manifestations of the GPA. Furthermore, we examined serum levels of tumor necrosis factor-alpha (TNF-α) and its associated indoleamine-pyrrole 2,3-dioxygenase (IDO), as well as we looked for a correlation between these cytokines and the clinical manifestations of GPA. Results The results showed that in GPA, serum plasminogen levels were negatively associated with renal involvement (receiver operating characteristic (ROC) area under the curve (AUC) of 0.78) (95% CI 0.53–0.91), p = 0.035, and the extent of proteinuria, Spearman’s Rho = –0.4, p = 0.015. Increased levels of TNF-α and IDO correlated with disease activity, Spearman’s Rho =0.62, p = 0.001 and Spearman’s Rho = 0.4, p = 0.022, respectively, whereas only TNF-α was increased in severe forms of GPA with lung involvement (ROC AUC of 0.8) (95% CI 0.66–0.94), p = 0.005. Conclusions In this study, we demonstrate the alteration of soluble factors, which play an important role in the pathogenesis of GPA and their relationship with the clinical manifestations of the disease. Our main results confirm the associations of increased secretory TNF-α and some clinical manifestations, and we describe for the first time decreased serum plasminogen levels and their association with renal involvement.


2012 ◽  
Vol 39 (7) ◽  
pp. 1320-1325 ◽  
Author(s):  
LAURINDO FERREIRA da ROCHA ◽  
ÂNGELA LUZIA BRANCO PINTO DUARTE ◽  
ANDRÉA TAVARES DANTAS ◽  
HENRIQUE ATAÍDE MARIZ ◽  
IVAN da ROCHA PITTA ◽  
...  

Objective.To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).Methods.IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulatedin vitrowith phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.Results.IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).Conclusion.IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.


2016 ◽  
Vol 75 (Suppl 1) ◽  
pp. A79.2-A79
Author(s):  
L Vernerová ◽  
L Andrés Cerezo ◽  
H Hulejová ◽  
K Pavelka ◽  
J Vencovský ◽  
...  

2021 ◽  
Vol 15 (3) ◽  
pp. 57-61
Author(s):  
R. M. Balabanova ◽  
E. V. Ilyinykh ◽  
M. V. Podryadnova ◽  
S. I. Glukhova ◽  
M. M. Urumova

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.


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