Results of a 12-Week Open-Label, Non-Interventional Study of the Efficacy and Safety of Olokizumab Therapy in Patients with Rheumatoid Arthritis after Switching from Anti-B-Cell Therapy during the SARS-CoV-2 Pandemic.

ABSTTACT: -The COVID-19 pandemic has significantly changed the understanding of the safety profile of therapies for immunoinflammatory rheumatic diseases (IRDs). This is primarily due to the negative impact of a number of basic disease-modifying antirheumatic drugs (DMARDs) and genetically engineered biological drugs (biological DMARDs, or biologics) on the course and outcomes of a new coronavirus infection. A number of studies have shown that anti-B-cell therapy (rituximab) gave a statistically significant increase in the risk of severe COVID-19 and an increase in mortality. At the same time, the analysis of real clinical practice data dictated the need to establish a number of restrictions on the use of certain classes of biologics and to search for alternative therapy programs to maintain control over disease activity. PURPOSE OF THE STUDY: The purpose of the study was to evaluate the efficacy and safety of the drug Artlegia® (olokizumab), solution for subcutaneous injection, 160 mg/ml-0.4 ml, manufactured by R-Pharm JSC, Russia) for the treatment of patients with rheumatoid arthritis in real clinical practice after switching with rituximab during the COVID-19 pandemic. MATERIALS AND METHODS: The study included 14 patients with a confirmed diagnosis of rheumatoid arthritis (RA), who were previously on rituximab therapy at a dose of 1000-500 mg twice with an interval of 2 weeks, who received at least one course of therapy with this drug. As RA worsened, patients were switched to olokizumab against the background of standard DMARDs. On weeks 0, 4, 8, and 12 after the switch, the severity of pain was assessed on the VAS scale, the number of tender and swollen joints (TJC28 and SJC28), the level of acute-phase inflammation markers, the DAS28 (disease activity score), ESR, CRP, CDAI (clinical activity index), and the functional state index HAQ (Health Assessment Questionnaire) were determined, as well as the safety profile of therapy was assessed. RESULTS: Data analysis was performed using median values (Me) were used for data analysis. A significant decrease in TJC28 was detected after 8 and 12 weeks of treatment with olokizumab (Artlegia®) (Me baseline = 10, Me 8 weeks = 4, Me 12 weeks = 4, p < 0.05) and a decrease in TSC28 was detected after 4, 8, and 12 weeks of treatment (Me baseline = 9, Me 4 weeks = 3.5, Me 8 weeks = 2.5, Me 12 weeks = 2.0, p < 0.05). Laboratory markers of inflammation showed a decrease in CRP and ESR levels after 4 weeks of treatment (CRP: Me4 weeks = 21, Me4 weeks = 1, p < 0.05, ESR: Mesno = 31, Me4 weeks = 7, p < 0.05). Positive dynamics persisted on 8 and 12 weeks (CRP: Me 8 weeks = 1, Me 12 weeks = 0; ESR: Me 8 weeks = 4, Me 12 weeks = 5). The level of CRP by week 4 became within the normal range, regardless of the initial values. All activity indices improved from week 4 in each evaluation period compared to baseline: DAS28-ESR: Me baseline = 5.52, Me 4 weeks = 3.59, Me 8 weeks = 3.33, Me 12 weeks = 3.22, p < 0.05; DAS28CRP: Me baseline = 5.39, Me 4 weeks = 3.71, Me 8 weeks = 3.35, Me 12 weeks = 3.45, p < 0.05; CDAI: Me baseline = 28.5, Me 4 weeks = 18.0, Me 8 weeks = 16.5, Me 12 weeks = 16.0, p < 0.05. All patients showed a reduction in pain (VAS scale) by week 8. The functional status of patients, according to the HAQ index, showed a significant decrease only by week 12 of the study: Me baseline = 1.62, Me 12 weeks = 1.31, p < 0.05. CONCLUSIONS: The study found that switching from rituximab to olokizumab was effective and safe during the COVID-19 pandemic.

Analysis of T-cell and Humoral Immune Response to SARS-CoV-2 Antigens in Rituximab-Treated Patients with Rheumatoid Arthritis Vaccinated with Combined Vector Vaccine Gam-COVID-Vac.

The COVID-19 pandemic has brought significant changes in managing of patients with rheumatoid arthritis. Rituximab-treated patients were more susceptible to severe infection. This required a "switch" to another genetically engineered drug in the patients with high risk of adverse COVID-19. In this study, we assessed the severity of immune response to SARS-CoV-2 antigens in rituximab-treated patients with rheumatoid arthritis vaccinated with the combined vector vaccine Gam-COVID-Vac. Insufficient formation of the humoral response and a high level of T-cell response to SARS-CoV-2 antigens in this group of patients were revealed. An imbalance of cellular and humoral response may play a role in more severe COVID-19 in rituximab-treated patients with rheumatoid arthritis.

Lithium-Modified Sorbent: Effects on Hemostatic Responses In Vitro.

The effects of a lithium-modified sorbent based on aluminum oxide and polydimethylsiloxane (Al2O3@PDMS/Li) and a lithium-free sorbent (Al2O3@PDMS) on some indicators characterizing blood clotting under hemosorption conditions were compared in vitro. Sorbent Al2O3@PDMS/Li had significantly lower reactogenic effect on the blood passed through the column than the sorbent without lithium. This was seen from the degree of platelet reduction (66×109 vs 19×109/liter) as well as a less pronounced hypercoagulation shift in chronometric indicators. In contrast to lithium-free sorbent, Al2O3@PDMS/Li demonstrated the ability to reduce the concentration of fibrinogen. However, this had no impact on the density characteristics of the blood clot assessed by thromboelastometry such as maximum clot firmness, angle and fibrin clot formation time, amplitudes at 10 and 15 min after clotting time, which are known to depend on the quantity of platelets and the concentration of functionally active fibrinogen.

[Immuno-inflammatory rheumatic diseases and COVID-19: analysis of clinical outcomes according to the data of the register of patients of the Novosibirsk region receiving therapy with genetically engineered biological drugs].

BACKGROUND: Currently, observations are accumulating indicating the negative effect of therapy with a number of biologic disease-modifying anti-rheumatic drugs (bDMARDs) drugs on the course of COVID-19. These facts determine the relevance of studying the factors of severe course and unfavorable outcome in immuno-inflammatory rheumatic diseases (IIRD) patients treated with bDMARDs in order to develop tactics for managing this category of patients in a pandemic. AIM: To evaluate the influence of clinical and demographic factors on the risk of development, severity of the course and clinical outcomes of a new coronavirus infection in patients suffering from IIRD and receiving therapy with genetically engineered biological drugs. MATERIALS AND METHODS: A retrospective analysis of the database of the register of patients with IIRD receiving bDMARDs in the Novosibirsk region was performed, which included 318 patients, 94 of whom had indications of having suffered viral infection/pneumonia for the period from 01.04.2020 to 31.12.2020. RESULTS: According to the data obtained, at the time of the analysis, 94 people out of 318 patients with IIRD had a new coronavirus infection. Most (53%) of the patients had a mild infection. At the same time, the nosological form, the use of anti-rheumatic drugs and glucocorticoids did not increase the risks of severe coronavirus infection. When using bDMARDs, only anti-B-cell therapy (rituximab) associated with statistically significant increase in the risk of severe/extremely severe COVID-19. The mortality rate according to the analysis of the register was 6,38%. CONCLUSION: Patients with IIRD have a high risk of severe coronavirus infection, while the severity of the disease is associated with the type of therapy performed.

Clinical Diagnostic Value of Dkk-1 Level in Ankylosing Spondylitis: Comparison of Test Systems Based on Aptamers and Antibodies.

In ankylosing spondylitis, the pathological metabolism of the bone tissue is regulated by various proteins; of these, Dkk-1 protein, an antagonist of the Wnt-signaling pathway, is of particular interest. We compared the methods of Dkk-1 detection in the blood serum of patients with ankylosing spondylitis (conventional ELISA and aptamer/antibody assay) and analyzed the relationship between Dkk-1 level and structural progression of ankylosing spondylitis and secondary osteoporosis. Dkk-1 levels in patients were significantly increased and depended on the stage of the disease, but not on the presence/absence of osteoporosis. Thus, Dkk-1 is a potential serum marker of progression of ankylosing spondylitis reflecting a tendency to structural progression of the disease before the appearance of radiographic changes. The results obtained by both methods practically coincided, which suggests good prospects for applying DNA aptamer-based test system.

[The opinions of social workers concerning means of development of medical social care of population].

The article reflects main problems and opinions of social workers about possibilities of improving medical social care of population and providing social medical services. This group of specialists is forced to implement significant amount of work that is not regulated by their official duties. The lack of necessary competencies does not allow social workers to provide medical social assistance to consumers of medical social services to sufficient extent. To ensure interaction between medical and social workers largely falls on shoulders of the latter ones. They have to undertake a number of medical functions (examination, temporary stop of bleeding, blood pressure measurement, etc.). It conceives appropriate to transfer some of functions of junior and paramedical staff to social workers. The study results can be applied as methodological basis of increasing accessibility of medical social care and provided social and medical services to various groups of population.

New Carbon-Mineral Sorbent Based on Aluminum Oxide, Polydimethylsiloxane, and Single-Wall Carbon Nanotubes: Assessment of the Effect on Erythrocytes In Vitro.

A comparative study of the effect of a sorbent with nanotubes (Al2O3@ WCNT-PDMS) and a carbon-mineral sorbent (Al2O3@C) on the parameters of human erythrocytes was carried out. Using scanning flow cytometry, the morphological and functional parameters of venous blood erythrocytes as well as drainage blood after its perfusion through columns with sorbents were determined. The compared samples Al2O3@SWCNT-PDMS and Al2O3@C are similar by their effect on the morphological and functional parameters of erythrocytes. The maximum membrane extensibility increased to a greatest extent after contact with Al2O3@C, the amount of hemoglobin in erythrocytes decreased to the greatest extent after perfusion through a column with Al2O3@SWCNT-PDMS sorbent. The scanning flow cytometry is promising for assessing the effect on erythrocytes of new sorption materials intended for blood detoxification. Changes in the parameters of erythrocytes of blood collected in a sterile drainage system for subsequent reinfusion were revealed.

The expression of apoptosis-regulating proteins Bcl-2 and Bad in liver cells of C57Bl/6 mice under light-induced functional pinealectomy and after correction with melatonin.

The presence of humans and animals under long-term continuous lighting leads to a suppression of melatonin synthesis, that is, to light-induced functional pinealectomy (LIFP), and the development of desynchronosis. To create LIFP, C57Bl/6 mice were kept under 24-hour lighting (24hL) for 14 days. The animals in the control group were kept under standard lighting conditions. In the next series of experiments, mice with LIFP received daily intragastrically either melatonin (1 mg/kg body weight in 200 µl of distilled water) or 200 µl of water as a placebo. The comparison group consisted of intact animals that received placebo under standard lighting conditions. Immunohistochemical analysis (using an indirect avidin-biotin peroxidase method) revealed the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bad in sinusoid liver cells (a heterogeneous population consisting of the endotheliocytes, Kupffer cells, Ito cells, and Pit cells) and in individual hepatocytes. The Bad expression area in the liver of LIFP mice increased 4 times against a background of the unchanged Bcl-2 expression area. Changes in the brightness (a parameter inversely proportional to the marker concentration) of Bad and Bcl-2 areas did not reach significance. Our results indicate a weakening of the antiapoptotic protection of liver cells of LIFP animals, which creates conditions for activation of the "mitochondrial branch" of apoptosis. Melatonin treatment of LIFP mice resulted in a 3.3-fold increase in Bcl-2 expression area and a 2.7 % decrease in Bcl-2 region brightness compared with the experimental untreated group. Bad protein parameters were unreliable. Thus, melatonin treatment of animals cancels the effect of LIFP, restoring the Bcl-2 expression area and increasing this protein concentration, which indicates an increase in antiapoptotic protection and creates conditions for blocking the development of the "mitochondrial branch" of apoptosis in liver cells.

Effect of a New Lithium Preparation on the Behavior of CBA/CaLac Mice in an Experimental Conflict Model.

The use of lithium drugs in clinical practice requires constant monitoring of lithium plasma concentration, because toxicity is sometimes observed at therapeutic concentrations of lithium. This is often associated with fluctuations of plasma concentration of lithium ions after intake of individual doses. Therefore, the use of a porous carrier providing a stable blood level of the drug is extremely promising and important for clinical practice. We studied activity of a new lithium drug (lithium complex) consisting of aluminum-silicon base and lithium citrate immobilized on its surface. Lithium carbonate served as the reference drug. It was shown that lithium carbonate and lithium complex exhibited no anxiolytic activity in the conflict model, but produced an antidepressant effect and improved exploratory behavior of animals.

Cytotoxicity of Aluminum-Silica Matrices Modified with Carbon Nanotubes.

We studied the effect of aluminum-silicon matrices modified with carbon nanotubes on proliferation and production of nitric oxide by splenocytes, thymocytes, and bone marrow mononuclear cells of female db/db mice. Synthesized matrices decreased cell proliferation and suppressed NO production by the studied cells.

Effects of Melatonin on the Body Composition, Physical Performance, and Blood Erythrocyte Indexes of C57Bl/6J Mice Exposed to Continuous Illumination.

Male C57Bl/6J mice were exposed to daily 24-h illumination over 14 days and daily intragastrically received melatonin (1 mg/kg) or water (placebo). Controls were kept under standard day/night (14/10 h) conditions. Melatonin prevented the development of anemia in mice exposed to continuous illumination, which was proven by higher blood hemoglobin levels by the end of the experiment in melatonin-treated animals in comparison with the placebo group. Studies by the low-field NMR spectrometry detected lower lean body mass, total body water, and especially, fat content (by ~13%) in animals receiving placebo. Melatonin treatment led to an increase in the lean body mass and total body water on day 7 (in comparison with the placebo group) without affecting fat mass. On day 14 of continuous illumination, lean body mass increased in comparison with the corresponding parameter in the control and placebo groups. Melatonin had no effect on the physical endurance of mice exposed to continuous illumination (assessed by the grid hanging test).

Effect of Lithium Preparations on Cerebral Electrophysiological Activity in Rats.

The study examined the effects of a novel neurotropic medication based on a lithium complex composed of lithium citrate, polymethylsiloxane, and aluminum oxide on electrophysiological parameters of the rat brain. In contrast to lithium carbonate (the reference drug), the novel preparation resulted in a wave-like dynamics of electrical activity in the visual cortex. Rhythmic photic stimulation of the rats treated with lithium carbonate resulted in appearance of the signs attesting to up-regulation of excitability of cerebral cortex in all examined ranges. In contrast, the complex lithium preparation diminished the delta power spectrum, which was the only affected frequency band. It is hypothesized that the complex lithium medication induces milder activation of the cerebral cortex in comparison with lithium carbonate. The novel medication composed of lithium citrate, aluminum oxide, and polymethylsiloxane, is characterized by greater efficacy and safety than the preparation based on inorganic lithium salt (lithium carbonate).

Melatonin-Aluminum Oxide-Polymethylsiloxane Complex on Apoptosis of Liver Cells in a Model of Obesity and Type 2 Diabetes Mellitus.

We studied the effects of a melatonin-aluminum oxide-polymethylsiloxane complex (complex M) on the expression of apoptosis regulators Bcl-2 and Bad in the liver of homozygous db/db BKS.Cg-Dock7m+/+Leprdb/J mice with obesity and type 2 diabetes. Complex M or placebo was administered daily through the gastric tube during weeks 8-16 of life. In mice with type 2 diabetes mellitus receiving placebo, enhanced immunohistochemical reactions for proapoptotic Bad protein and weak response for anti-apoptotic Bcl-2 protein were observed. Administration of complex M shifted the ratio of apoptosis regulators: the area of Bcl-2 expression significantly increased and against the background of reduced Bad expression area. These findings attest to antiapoptotic effect of complex M in the liver on the model of type 2 diabetes mellitus.

[Polymorphism in the regulatory regions -С2578A and +C936T of the vascular endothelial growth factor (VEGF-A) gene in Russian women with rheumatoid arthritis]. / Polimorfizm reguliatornykh regionov ­S2578A i +C936T gena faktora rosta sosudistogo éndoteliia (VEGF-A) u russkikh zhenshchin s revmatoidnym artritom.

AIM: To analyze polymorphism in the regulatory regions of the vascular endothelial growth factor (VEGF) gene in female patients with rheumatoid arthritis (RA). SUBJECTS AND METHODS: The investigation enrolled 257 female patients with RA. A control group consisted of 297 women without chronic diseases. The investigators examined the single-nucleotide polymorphism of VEGF-А2578С in the promoter region (rs699947) and that of VEGF+С936Т 3 in the retranslated region (rs3025039) of the gene. Genotyping was performed by restriction fragment length polymorphism analysis. RESULTS: There was an increase in the frequency of VEGF+936 CT and a reduction in that of the VEGF+936СС genotypes in the seronegative patients as compared to the healthy women. The VEGF+936СС genotype frequency was higher in the patients with seropositive RA than in the subgroup of seronegative patients. The frequency of the VEGF-2578СС genotype was increased in the patients with RA and rheumatoid nodules, as compared to the healthy women. CONCLUSION: The data presented suggest that the presence of certain VEGF gene variants located in the regulatory regions may reflect the nature of immunopathological mechanisms in RA.

[Analysis of the state-of-the-art of consulting medical care to patients with glucocorticoid-induced osteoporosis or its risk according to the data of a questionnaire survey (GLUCOST study)].

AIM: To analyze the state-of-the-art of consulting medical care to Russian patients with glucocorticoid-induced osteoporosis (GCOP) or its risk. SUBJECTS AND METHODS: This GLUCOST study was organized and conducted by the Russian Association of Osteoporosis. A total of 1129 patients with chronic inflammatory diseases, who had been taking oral glucocorticosteroids (OGCSs) a long time (3 months or more), were examined. The patients filled out an anonymous questionnaire on their own. Whether the measures taken to diagnose, prevent, and treat GCOP complied with the main points of Russian clinical guidelines was assessed. RESULTS: 61.8% of the patients knew that the long-term treatment of GCOP might cause osteoporosis. 48.1% of the respondents confirmed the results of bone densitometry; 78.1% of the patients reported that they had been prescribed calcium and vitamin D supplements by their physician, but their regular intake was confirmed by only 43.4%; 25.4% of the patients had sustained one low-energy fracture or more. Treatment for GCOP was prescribed for 50.8% of the patients at high risk for fractures, but was actually received by 40.2%. Therapeutic and diagnostic measures were implemented in men less frequently than in women. When the patient was aware of GCOP, the probability that he/she would take calcium and vitamin D supplements rose 2.7-fold (95% Cl; 2.1 to 3.5; p = 0.001) and that he/she would follow treatment recommendations did 3.5-fold (95% Cl; 2.3 to 5.3; p = 0.001). Bone densitometry increased the prescription rate for antiosteoporotic medication and patient compliance. CONCLUSION: According to the data of Russia's large-scale GLUCOST survey, every four patients with chronic inflammatory disease who are on long-term OGCS therapy have one low-energy fracture or more. Due to inadequate counseling, the patients are little aware of their health and do not get the care required to prevent the disease. Less than 50% of patients who have GCOP and a high risk for fractures undergo examination and necessary treatment aimed at preventing fractures.

[Matrix metalloproteinase 2, 3, and 9 gene polymorphisms in women with rheumatoid arthritis].

AIM: To study the promoter regions of the matrix metalloproteinase (MMP)2, MMP3, and MMP9 genes to assess their associations with the risk of rheumatoid arthritis (RA) and with the types of its clinical course in women. SUBJECTS AND METHODS: 162 female patients with RA and 329 women without this condition were examined. Polymorphisms in the gene promoter region for MMP2 (-1306 С→Т), MMP3 (-1171 5A→6А), and MMP9 (-1562 С→Т) were studied. Genotyping was carried out using the restriction fragment length polymorphism method. RESULTS: In the RA group, the -1306TT genotype of MMP2 was significantly more frequently encountered and the 6A6A genotype was less frequently seen. In the seropositive RA group, the frequency of the -1306ТТ genotype of MMP2 was significantly higher than that in the healthy individuals. The significant differences shown for the entire group of patients with RA were preserved when they were divided into groups according to the presence or absence of rheumatoid nodules. Furthermore, the frequency of the homozygous -1306 genotypes of MMP2 was higher in both groups than in the healthy individuals. CONCLUSION: The presence of the allelic variants of the MMP genes may be one of the genetic factors that predispose to RA in women.

[Genetic factors of angiogenic dysregulation in women with rheumatoid arthritis].

AIM: To study genotype distribution in the MMP and VEGF genes, angiogenesis regulators, and their combinations with genotypes in other cytokines genes with proangiogenic activity in female patients with rheumatoid arthritis (RA) and healthy individuals. SUBJECTS AND METHODS: 509 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 135 female patients aged 27-66 years with RA, were examined. TNF-alpha gene promoter single nucleotide polymorphisms (SNP) -863 C --> A, TNFA -308 G --> A, TNFA -238 G --> A; IL 1beta-31 C --> T, IL4 -590 C --> T, IL6 -174 G --> C, IL10 -1082 G --> A and IL10 -592 A --> C; VEGF -2578 C --> A, VEGF +936 C --> T; MMP 2 -1306 C --> T, MMP 9 -1562 C --> T were investigated by the restriction analysis of amplification products. RESULTS: The patients with RA show a preponderance of the combinations of genotypes in vascular endothelial growth factor (VEGF) synthesis inducers, which are related to the high-level production of this factor, and those of genotypes in the degradation of the extracellular matrix of MMP2 and MMP9, which characterize the low baseline elaboration of matrix metalloproteinases (MMP) with a high capability for their induced synthesis, which is specific to the dysregulated states of the angiogenesis control system. Along with MMP and VEGF genotypes, the combinations most commonly contain IL1beta, IL4, IL10, IL6, and TNF-alpha genotypes. CONCLUSION: The study of the pathogenesis of RA must comprehensively investigate the role of the genes of the factors involved in the regulation of angiogenesis and inflammation, with particular emphasis on molecular genetic mechanisms for monitoring the baseline level of production of these regulatory factors.

[Cytokine gene polymorphism in type 2 diabetes mellitus in Russian women from eastern Europe].

AIM: To study the distribution of genotypes in the cytokine genes and their combinations with immunoregulatory activity in patients with type 2 diabetes mellitus (T2DM) and in healthy women. SUBJECTS AND METHODS: 586 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 212 women aged 28-69 years with T2DM complicated and uncomplicated by osteoporosis, were examined. Seven polymorphisms located in the promoter regions of the interleukin (IL) gene: TNF-alpha at positions C-863A, G-308A, G-238A, IL1B T-31C, IL6 G-174C, IL10 C-592A, VEGFA C-2578A were investigated. Restriction analysis of amplification products was applied. RESULTS: There were high associations of the predisposition and resistance to the development of T2DM with a number of polylocus cytokine genotype combinations having pro- and anti-inflammatory, angiogenic, and immunoregulatory activities. The association of the cytokine genes with T2DM was found to be mediated in nature through a relationship of the genotypes to the high or low production of regulatory cytokines and to different factors of regulation of lipid and carbohydrate metabolisms, inflammation, and bone remodeling. CONCLUSION: The high odds ratio and high specificity of the detected genetic combinations allow one to hope that they will be clinically used as predictors.

[Distribution of allelic variants of promotor sites of cytokine genes and endothelial growth factor gene among healthy subjects and patients with rheumatoid arthritis in a Russian Europeoid population].

The article reports results of the first study of cytokine gene polymorphic sites and analysis of distribution of their complexes among healthy subjects and patients with rheumatoid arthritis (RA) representative of the Russian Europeoid population; their possible prognostic significance is evaluated. Comprehensive analysis of the frequency of allelic variants of cytokine genes IL1B C-31T, IL6 G-174C, TNFA A-238G, TNFA A-308G, TNFA A-863C, IL4 C-590T, IL10 A-592C and VEGF C-2578A was performed for 513 residents of the Novosibirsk region showing no obvious signs of any diseases and 125 RA patients. The results suggest association of RA with certain alleles of pro- and anti-inflammatory cytokine genes. Complex indices reflecting combinations of genotypes of two, three, four, five, six and seven loci of the explored cytokine genes found in individual patient demonstrate their high specificity for RA. It is supposed that these findings can be used in further clinical studies for the development of algorithm designed to detect risk groups among clinically healthy subjects.

[Pharmacogenetic criteria for the efficacy of basic anti-inflammatory therapy for rheumatoid arthritis].

AIM: To analyze the prognostic value of detection of allelic variants of the promoter regions of cytokine genes in patients with rheumatoid arthritis (RA) with varying efficiency of basic anti-inflammatory therapy (BAIT). SUBJECTS AND METHODS: Eighty-nine patients with a valid diagnosis of RA, of them there were 79 females and 10 males (mean age 52.5 +/- 13.1 years), were examined. The patients received BAIT with methotrexate in a dose of 10.0-17.5 mg/week (77.5%) or with sulfasalazine in a dose of 2.0 g/day (22.5%) for 24 weeks. The efficiency of BAIT was evaluated using the European League Against Rheumatism (EULAR) criteria (DAS28) following 24 weeks. A high therapeutic effect was stated when DAS28 decreased by more than 1.2 scores. Changes in DAS28 by less than 0.6 scores were regarded as ineffective BAIT. Cytokine gene polymorphisms were studied by restriction analysis of amplification products. The following polymorphic sites in the interleukin genes: FNOA at positions C-863A, G-308A, G-238A, IL-1BT-31C, IL-4 C-590T, IL-6 G-174C, and IL-10 C-592A, were explored. RESULTS: The IL-6 G-174G genotype associated with the high production of this proinflammatory cytokine and the IL-IB C-31C genotype associated with the low production of interleukin-1beta (IL-1beta) were most frequently encountered in a group of patients with the high efficiency of BAIT (22 and 24.7%). At the same time the C allele associated with the low production of IL-6 and the IL1B T-31C genotype associated with the high production of this cytokine were most frequently detected at position of G-174C of the promoter regions in the IL-6 gene in patients unresponsive to BAIT (32 and 36%). CONCLUSION: The allelic variants of the promoter regions of the IL-6 G-174G, IL-1B C-31C, IL-4 C-590T, and IL-10 C-592A can be genetically prognostic factors of formation of the high efficiency of BAIT.