Objective: to study the time course of changes in acute-phase parameters and in the levels of autoantibodies, B lymphocytes, immunoglobulin (Ig) classes G, M, and A in patients with rheumatoid arthritis (RA) 2, 8, 16, and 24 weeks after initiation of therapy with rituximab (RTM).
Objective: to study the time course of changes in acute-phase parameters and in the levels of autoantibodies, B lymphocytes, immunoglobulin (Ig) classes G, M, and A in patients with rheumatoid arthritis (RA) 2, 8, 16, and 24 weeks after initiation of therapy with rituximab (RTM).
Along with its basic activity in removing B-lymphocytes, rituximab (RTM) causes depletion of a population of CD20+ T cells that can pro- duce a variety of immunoregulatory and proinflammatory cytokines and chemokines. Objective: to define a role of multiplex cytokine analysis in the evaluation of the efficiency of using RMT in rheumatoid arthritis (RA). Subjects and methods. Thirty-four patients with the valid diagnosis of RA according to the ACR criteria of 1987 were examined. The con- centrations of cytokines were measured using the xMAP technology (27-plex). Results and discussion. In the group of patients with a clinical response to therapy with the gene engineering biological agent, there was a decrease in the concentrations of interleukins (IL) 1β, 1ra, 2, 4, 6, 9, and 13, granulocyte macrophage colony-stimulating factor (GM- CSF), γ-interferon (IFN-γ), monocyte chemoattractant 1 at week 8 of therapy; that in IL 1β, 1ra, 2, 5, 6, 9, 10, 12, 13, and 15, fibroblast growth factor 2 (FGF-2), GM-CSF, IFN-γ, and tumor necrosis factor-α at week 24, and that in IL-9 at week 40. The no-clinical response group showed a reduction in GM-CSF at week 8 and in IL-2 and macrophage inflammatory protein 1β (MIP-1β) at week 40, and an increase in IL-8 at week 8. At week 8 after drug infusion, the elevated levels of IL-17 and MIP-1β can be identified as possible early pre- dictors of a response (at week 40). Comparison of the baseline cytokine levels in the groups with different clinical response demonstrated a more than three-fold increase in the concentrations of IL 4, 5, 7, 8, 10, 12, 13, 15, 17, IFN-γ, and vascular endothelial growth factor, and IL-8 at weeks 8 and 40, respectively.
Objective: To study the time course of changes in the indices of the blood lipid spectrum in patients with rheumatoid arthritis (RA) treated with rituximab during a 24-week follow-up. Subjects and methods. The study enrolled 39 patients (36 females and 3 males) with a valid diagnosis of RA; their mean age was 50 years; disease duration 93.5 months; duration activity scale (DAS) 6.1 scores. A previous ineffective treatment with methotrexate was found in 6 patients; that with two basic anti-inflammatory drugs or more in 30, and previous TNF- inhibitor therapy failed in 14 of the 39 patients. The blood lipid spectrum and intima-media thickness (IMT) were determined before and 24 weeks after the first injection of rituximab. The drug was intravenously administered dropwise in a dose of 1000 mg twice at a 14-week interval. Therapeutic efficiency was estimated according to the RA activity index DAS28. All the patients showed a satisfactory/good response to rituximab therapy. Results. There was a double reduction in the frequency of hypoalfalipoproteinemia and in the increased atherogenicity index (AI). Elevated cholesterol (CH), triglycerides (TG), and low-density lipoprotein (LDL CH) levels were found in equal frequencies before and 24 week after rituximab administration. There was a 5% rise in CH concentrations, a considerable (22%) increase in high-density lipoprotein CH, and an 18.6% decrease in AI (p
Objective: To study the time course of changes in the indices of the blood lipid spectrum in patients with rheumatoid arthritis (RA) treated with rituximab during a 24-week follow-up. Subjects and methods. The study enrolled 39 patients (36 females and 3 males) with a valid diagnosis of RA; their mean age was 50 years; disease duration 93.5 months; duration activity scale (DAS) 6.1 scores. A previous ineffective treatment with methotrexate was found in 6 patients; that with two basic anti-inflammatory drugs or more in 30, and previous TNF- inhibitor therapy failed in 14 of the 39 patients. The blood lipid spectrum and intima-media thickness (IMT) were determined before and 24 weeks after the first injection of rituximab. The drug was intravenously administered dropwise in a dose of 1000 mg twice at a 14-week interval. Therapeutic efficiency was estimated according to the RA activity index - DAS28. All the patients showed a satisfactory/good response to rituximab therapy. Results. There was a double reduction in the frequency of hypoalfalipoproteinemia and in the increased atherogenicity index (AI). Elevated cholesterol (CH), triglycerides (TG), and low-density lipoprotein (LDL CH) levels were found in equal frequencies before and 24 week after rituximab administration. There was a 5% rise in CH concentrations, a considerable (22%) increase in high-density lipoprotein CH, and an 18.6% decrease in AI (p
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Endothelial dysfunction plays a key role in the pathogenesis of atherosclerosis. An increased cardiovascular risk in patients with rheumatoid arthritis (RA) suggests that inflammation is of importance for the occurrence and progression of atherosclerosis. Rituximab (RTM, monoclonal antibodies to CD20-positive B lymphocytes) is used to treat patients with active RA. Objective. To evaluate the effect of RTM on endothelial function in patients with active RA. Subjects and methods. The study enrolled 20patients with active RA (DAS 28 >5.0); their mean age was 50 (range 41.5 to 63) years; mean disease duration was 95.7 (range 24 to 144) months. Intravenous RTM was used (as a course of 2 infusions in a dose of 1000 mg at a 2-week interval) in all the patients. Brachial artery flow-dependent vasodilation (FDVD) that was carried out in all the patients at screening (before the first infusion) and also at 2, 8, 16, and 24 weeks after the second infusion was employed to evaluate endothelial function. Results. Before RTM therapy, the study group of patients showed no statistically significant deviations of FDVD values from those in the gender- and age-matched control group. FDVD correlated with age (r=-0.44; p=0.049), disease duration (r = 0.6; p=0.017), cholesterol level (r=0.48; p=0.045), common carotid artery intima-media thickness (r=0.52; p=0.023), and cardiovascular risk factors (r=0.51; p=0.027). No statistically significant differences were found in the baseline value of FDVD and those observed after a course of RTM therapy and at weeks 8, 16, 24 (12.8±5.7, 11.3±5.2, 14.3±7.1, and 12.5±5.2%, respectively). All the patients were divided into 2 groups according to their response (an increase or a reduction in FDVD over time). Group 1 patients (n=10) demonstrated a significant increase in this index from 10.74±5.75 (at screening) to 14.17±5.13% (at week 24) (p<0.05). In Group 2 patients (n = 10), the reduction in FDVD was also statistically significant (from 14.87±5.15 to 10.88±4.89%). Four patients from Group 2 had endothelial dysfunction by week 24. Patients with improved endothelial function were found to have a longer RA duration (144±111 versus 47±38 months), a lower baseline C-reactive protein level (26.5 versus 35.6 mg/l), and a lower screening FDVD index ((10.1±5.8 versus 14.9±5.2%). No group differences found in age, disease activity (DAS 28), and cardiovascular risk factors and/or carotid artery atherosclerosis. Conclusion. Our study has shown that the use of RTM generally fails to affect endothelial function in patients with active RA. The found heterodirectional postocclusive reactive hyperemia makes it necessary to widely introduce methods for evaluating the cardiovascular system in patients with RA.
Endothelial dysfunction plays a key role in the pathogenesis of atherosclerosis. An increased cardiovascular risk in patients with rheumatoid arthritis (RA) suggests that inflammation is of importance for the occurrence and progression of atherosclerosis. Rituximab (RTM, monoclonal antibodies to CD20-positive B lymphocytes) is used to treat patients with active RA. Objective. To evaluate the effect of RTM on endothelial function in patients with active RA. Subjects and methods. The study enrolled 20patients with active RA (DAS 28 >5.0); their mean age was 50 (range 41.5 to 63) years; mean disease duration was 95.7 (range 24 to 144) months. Intravenous RTM was used (as a course of 2 infusions in a dose of 1000 mg at a 2-week interval) in all the patients. Brachial artery flow-dependent vasodilation (FDVD) that was carried out in all the patients at screening (before the first infusion) and also at 2, 8, 16, and 24 weeks after the second infusion was employed to evaluate endothelial function. Results. Before RTM therapy, the study group of patients showed no statistically significant deviations of FDVD values from those in the gender- and age-matched control group. FDVD correlated with age (r=-0.44; p=0.049), disease duration (r = 0.6; p=0.017), cholesterol level (r=0.48; p=0.045), common carotid artery intima-media thickness (r=0.52; p=0.023), and cardiovascular risk factors (r=0.51; p=0.027). No statistically significant differences were found in the baseline value of FDVD and those observed after a course of RTM therapy and at weeks 8, 16, 24 (12.8±5.7, 11.3±5.2, 14.3±7.1, and 12.5±5.2%, respectively). All the patients were divided into 2 groups according to their response (an increase or a reduction in FDVD over time). Group 1 patients (n=10) demonstrated a significant increase in this index from 10.74±5.75 (at screening) to 14.17±5.13% (at week 24) (p