The aim of the study was to investigate the dynamics of clinical and laboratory parameters of inflammatory disease activity and cytokines in patients with rheumatoid arthritis (RA) against the background of olokizumab (OKZ) treatment.Materials and methods. Ten patients with a reliable diagnosis of RA were examined: patients’ age was 46.00 (30.00; 60.00) years, duration of disease was 9.0 (3.0; 12,0) years. All patients had moderate to high disease activity: DAS28-ESR (Disease Activity Score 28 with Erythrocyte Sedimentation Rate) – 513 (4.34; 5,80); CDAI (Clinical Disease Activity Index) – 30.00 (24.00; 35.00); SDAI (Simplified Disease Activity Index) – 31.86 (24.36; 38.59). All patients were treated with OKZ at a dose of 64 mg subcutaneously every 4 weeks on the background of therapy with methotrexate, leflunomide, nonsteroidal anti-inflammatory drugs, and glucocorticoids. Observations were performed before treatment and after 3, 6 months of therapy. Serum levels of 15 cytokines: interleukin (IL) 1β, IL-4, IL-6, tumor necrosis factor α (TNF-α), interferon (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 xMAR technology.Results. After 3 and 6 months of OKZ therapy, there was a significant decrease in DAS28-ESR of 3.53 (2.83; 4.26) and 3.48 (2.8; 4.10); CDAI – 11.00 (6.0; 16.00) and 10.0 (5.0; 15.0); SDAI – 10.0 (5.0; 15.0) and 10.17 (7.02; 15.02); C-reactive protein (CRP) concentrations (initial – 14.30 (7.00; 24.70) mg/l, after 3 months – 0.70 (0.40; 0.90) mg/l and after 6 months – 0.65 (0.20; 3.00) mg/l). After 3 months of treatment we found an increase in IL-6 concentration (initial – 1.89 (1.61; 2.33) pg/ml and 89.98 (35.09; 165.84) pg/ml; p<0.01), after 6 months – its level decreased to 44.88 (5.25; 80.90) pg/ml without reaching, however, the initial values (p<0.05). Against the background of OCZ, after 3 months of treatment there was an increase in IL-25 concentration (p<0.01), and after 6 months of therapy – TNF-α (p<0.05).Conclusion. The use of OKZ leads to an increase in the concentration of total IL-6 in the blood serum of RA patients, while the clinical and laboratory activity of the disease decreases.

Objective – to investigate clinical and diagnostic significance of IL-31 and IL-33 determination in patients with rheumatoid arthritis (RA).Material and methods. 154 patients with a reliable diagnosis of RA were examined. Serum levels of IL-31 and IL-33 were studied using multiplex xMAP technology on Bio-PlexTM 200 System analyzer (BIO-RAD, USA). The upper limit of the norm in the study of 20 healthy donor sera was (M+3σ): IL-31 – 15.08 pg/ml, IL-33 – 3.40 pg/ml.Results. IL-31 (Me (25th; 75th percentile) – 13.75 (5.63; 308.52) and 6.10 (2.87; 8.62) pg/ml (p<0.001), IL-33 – 18.86 (7.45; 65.95) and 0.52 (0.17; 0.78) pg/ml (p><0.001) levels were observed in RA patients in comparison with the control group. An increase in IL-33 concentration (more than 3.40 pg/ml) was observed in 87.0% of patients, and IL-31 (more than 15.08 pg/ml) in 48.1% of patients with RA. An increase in IL-33 alone was observed in 42.2% (65 of 154 patients) with RA, while an isolated increase in IL-31 concentration was observed in only 2 (1.3%) patients. Simultaneous hyperproduction of IL-33 and IL-31 occurred in 69 (44.9%) patients. We revealed positive correlation of clinical and laboratory parameters of RA with cytokine concentration: SDAI correlated with IL-33 (r=0.36; p><0.05); CRP – with IL-31 (r=0.49; p><0,05) and IL-33 (r=0.40; p><0.05). Conclusion. Concentrations of IL-31 and IL-33 are elevated in RA patients and correlate with the indices of inflammatory activity of the disease.>< 0.001), IL-33 – 18.86 (7.45; 65.95) and 0.52 (0.17; 0.78) pg/ml (p<0.001) levels were observed in RA patients in comparison with the control group. An increase in IL-33 concentration (more than 3.40 pg/ml) was observed in 87.0% of patients, and IL-31 (more than 15.08 pg/ml) in 48.1% of patients with RA. An increase in IL-33 alone was observed in 42.2% (65 of 154 patients) with RA, while an isolated increase in IL-31 concentration was observed in only 2 (1.3%) patients. Simultaneous hyperproduction of IL-33 and IL-31 occurred in 69 (44.9%) patients. We revealed positive correlation of clinical and laboratory parameters of RA with cytokine concentration: SDAI correlated with IL-33 (r=0.36; p><0.05); CRP – with IL-31 (r=0.49; p><0,05) and IL-33 (r=0.40; p><0.05). Conclusion. Concentrations of IL-31 and IL-33 are elevated in RA patients and correlate with the indices of inflammatory activity of the disease.>< 0.001) levels were observed in RA patients in comparison with the control group. An increase in IL-33 concentration (more than 3.40 pg/ml) was observed in 87.0% of patients, and IL-31 (more than 15.08 pg/ml) in 48.1% of patients with RA. An increase in IL-33 alone was observed in 42.2% (65 of 154 patients) with RA, while an isolated increase in IL-31 concentration was observed in only 2 (1.3%) patients. Simultaneous hyperproduction of IL-33 and IL-31 occurred in 69 (44.9%) patients. We revealed positive correlation of clinical and laboratory parameters of RA with cytokine concentration: SDAI correlated with IL-33 (r=0.36; p<0.05); CRP – with IL-31 (r=0.49; p><0,05) and IL-33 (r=0.40; p><0.05). Conclusion. Concentrations of IL-31 and IL-33 are elevated in RA patients and correlate with the indices of inflammatory activity of the disease.>< 0.05); CRP – with IL-31 (r=0.49; p< ,05) and IL-33 (r=0.40; p<0.05)Conclusion. Concentrations of IL-31 and IL-33 are elevated in RA patients and correlate with the indices of inflammatory activity of the disease.

логии хMАР.До начала терапии РТМ индексы DAS28 (6,12; 5,52-6,81), SDAI (34,3; 23,8-45,9) и CDAI (31,3; 21,8-38,5) соответствовали высокой активности РА. К 24-й неделе терапии хороший ответ по критериям EULAR регистрировался у 15 пациентов, умеренный – у 18 и отсутствовал у 1 больного. Ремиссия по DAS 28 достигалась реже среди пациентов с исходно негатив

The international recommendations «Treat to target» (T2T) underline the greatest importance of treatment strategy for the success of treating rheumatoid arthritis (RA). Evaluation of the efficiency of this approach obviously requires special strategic studies with an adaptive design, which substantially differ from classical randomized clinical trials and are much closer to clinical practice. To date, there are only single publications on the practical application of the T2T recommendations, there is a problem in the choice of effectiveness criteria and there are a number of other important problems associated with the introduction of these recommendations. The Russian study REMARCA is to answer these questions. Its design focuses on the practical adaptation of the T2T strategy to treat patients with earlyand extended-stage active RA who have poor prognostic factors, by using subcutaneous methotrexate and genetically engineered biological agents (GEBA). Preliminary analysis shows that therapy according to the REMARCA protocol is successful in the majority of patients. The high rate of low RA activity and remission has been achieved during subcutaneous methotrexate monotherapy. The patients who need GEBA to be incorporated may be initially more resistant to therapy. The patients with early RA have better chances of successful T2T therapy than those with extended-stage RA.

Objective: to assess an association between the levels of anti-cyclic citrullinated peptide antibodies (anti-CCP), anti-modified citrullinated vimentin antibodies (anti-MCV), rheumatoid factor (RF), and X-ray signs of destructive changes in RAjoints. Subjects and methods. One hundred and fourteen patients with RA were examined. All the patients received therapy with disease-modifying antirheumatic drugs and 61.4% took glucocorticoids. The investigators determined erythrocyte sedimentation rate (ESR) by the Westergren method, serum anti-MCV concentrations (U/ml) by enzyme immunoassay (EIA), anti-CCP levels by electrochemiluminescence and EIA. The modified Sharp method was used to quantify X-ray changes. Results. The total Sharp score (TSS; Me [the 25th and 75th percentile]) was 89 [57; 117]; the number of erosions and stenoses was 9 [3; 27] and 76 [51; 99], respectively; anti-MCV levels were 470.2 [106.9; 1000] U/ml. According to the level of RF IgM-, anti-CCP-, and anti-MCV-positivity, all the patients were divided into groups. High anti-MCV positive patients (n = 80) were observed to have higher TSS (96.5 [66.0; 120.0]), a larger number of stenosis (82.0 [60.5; 105.5]), and greater inflammatory disease activity (ESR, 40 [30; 61]) than negative/low positive patients (n = 25) who had 57 [31; 88], 50 [29; 82], 30 [21; 48.5] respectively; p < 0.05). No significant differences in joint destruction were found in the patient groups according to RF IgMand anti-CCP-positivity. Conclusion. Anti-MCV shows a greater degree of bone destruction and is associated with higher inflammatory disease activity than anti-CCP.

Objective: to estimate quality of life changes in patients with rheumatoid arthritis (RA) while adding tocilizumab (TCZ) to therapy with disease-modifying antirheumatic drugs (DMARDs) and to study the efficiency and safety of the therapy in RA patients with an inadequate response to previous DMARD treatment. Subjects and methods. 201 patients with RA were examined. All the patients received six intravenous infusions of TCZ 8 mg/kg at a 4-week interval during stable therapy with DMARDs and glucocorticoids. The EULAR/ACR classification criteria and SDAI and CDAI were used to evaluate the efficiency of TCZ therapy. Remission was assessed by the EULAR criteria. Results and discussion. Prior to TCZ therapy, median [25th to 75th percentiles] DAS28 6.8 [6.1 to 7.4], SDAI 41.8 [34.6 to 53.7], and CDAI 39.2 [31.4 to 49.5] corresponded to high RA activity. At week 4 of TCZ therapy, there was a reduction in DAS28 (4.6 [3.8 to 5.4]), SDAI (24.6 [17.8 to 33.4]), and CDAI (23.6 [17.5 to 32.0]), which was retained until 24 weeks (р < 0.01). At week 24 of TCZ therapy, good and fair effects according to the EULAR criteria were observed in 133 (70.4%) and 54 (28.6%) patients, respectively; no effect was seen in 2 (1.1%) patients. The ACR20/50/70 effect was recorded in 89.1, 70.6, and 44.3% of the patients, respectively. EULAR and SDAI remissions were achieved in 51.3 and 21.4%, respectively. There were improvements in functional status and quality of life according to the EQ-5D and SF-36 questionnaires. C-reactive protein levels and erythrocyte sedimentation rate normalized 4 weeks after the first infusion of the drug and remained until week 24 of treatment. Conclusion. Thus, an analysis of the data of the Russian trial convincingly suggests that TCZ is effective and well tolerated in severe RA resistant to standard therapy with DMARDs.

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 evaluate the impact of tocilizumab (TCZ) therapy on the level of acute-phase indicators, autoantibodies, and immunoglobulins (Ig) G, M, and A after 2, 4, 8, 12, and 24 weeks as compared to the clinical efficacy of TCZ using DAS 28, SDAI, and CDAI scores and to reveal the immunological predictors of effective TCZ therapy. Subjects and methods. Forty-two patients with rheumatoid arthritis (RA) who had received 6 TCZ infusions in an intravenous dose of 8 mg/kg at a 4-week interval during stable therapy with disease-modifying antirheumatic drugs (DMARDs) and glucocorticosteroids were examined. Erythrocyte sedimentation rate (ESR) was determined by the Westergren method; the levels of C-reactive protein (CRP), IgM rheumatoid factor (RF), IgG, IgM, and IgA were measured by a nephelometric method; the content of anti-cyclic citrullinated peptide (anti-CCP) antibodies was estimated by an electrochemiluminescence technique. Results. In the respondents to TCZ therapy, the baseline Me values [25 th; 75 th percentiles] were 6.44 (5.87; 7.04) for DAS 28; 41.5 (32; 53) for SDAI; and 36.4 (19.2; 62.7) mg for CRP; 262.0 (95.3; 663.0) IU/l for IgM RF; 342.5 (106.9; 789.9) IU/ml for IgA RF; 366.8 (76.9; 500.0) for anti-CCP antibodies; 770.5 (190.7; 2393.1) IU/ml for anti-modified citrullinated vimentin (anti-MCV) antibodies; 16.1 (12.9; 21.1) g/l for IgG; 2.07 (1.68; 2.63) g/l for IgM; 4.19 (3.38; 5.71) g/l for IgA. At week 2 of TCZ therapy, there was a reduction in the levels of CRP to 0.5 (0.3; 1) mg/l, IgM RF to 191.5 (45.6; 507.5) IU/ml, IgA RF to 225.8 (74.2; 547.4) IU/ml; at week 4, there were decreases in anti-MCV titers to 312.15 (81.2; 925.5) IU/ml, which remained until week 24 (p < 0.01). By week 24 of therapy, there were falls of IgG to 9.41 (8.14; 11.8) g/l, IgM to 1.12 (0.89; 1.94) g/l, IgA to 2.15 (1.73; 2.73) g/l (р < 0.01); however, their mean level as a whole remained to be in the normal range. The anti-MCV-positive patients with RA more frequently achieved a CDAI remission at week 24 than did the anti-MCV-positive patients (odd ratio, 18.4; p = 0.03). DAS 28 remission rates increased in patients with lower baseline serum IgG and IgM (p = 0.01 and 0.04, respectively). Conclusion. Thus, the analysis of the results of therapy with TCZ following 24 weeks shows that the drug is able to promptly induce steady-state positive changes in immune and inflammatory markers and to cause a drop in autoantibody titers and immunoglobulins in patients with RA. Anti-MCV-seropositivity and lower baseline serum IgG and IgM levels can be considered as possible predictors of remission at 24 weeks of the therapy.

Objective: to evaluate the clinical efficiency of tocilizumab (TCZ) from the DAS 28, SDAI, and CDAI indices and to estimate remission rates from the European League Against Rheumatism (EULAR) criteria, and the new remission criteria proposed by the EULAR and the American College of Rheumatology (ACR) in 2011. Subjects and methods. Forty-two patients with rheumatoid arthritis (RA) who had received 6 infusions of TCZ in an intravenous dose of 8 mg/kg at a 4-week interval during stable therapy with disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids were examined. The EULAR criteria based on changes in the DAS 28 index and the SDAI and CDAI activity indices were used to evaluate the efficiency of TCZ therapy. Disease remission was assessed by the EULAR criteria and the new 2011 EULAR/ACR remission criteria. Results. The baseline values (median and interquartile range: 25-75th percentiles) were 6.44 (5.87-7.04) for DAS 28; 45 (36.2-57) for SDAI; and 41.5 (32-53) for CDAI. At week 2 of TCZ therapy, there was a reduction in the levels of DAS 28 to 4.86 (4.28-5.29) and at week 4, there were decreases in SDAI to 22.6 (19.4-29.3) and CDAI to 21.9 (19.3-30), which remained until week 24 (p < 0.01). By week 24 of TCZ therapy, according to the EULAR criteria, 35 and 7 patients were observed to have good and moderate effects, respectively. By week 24, 30 (71%), 13 (31%), and 14 (33%) patients achieved remission according to DAS 28, SDAI, and CDAI, respectively; low DAS 28 (2.6-3.2), SDAI (3.3-11), and CDAI (2.8-10) disease activity was observed in 5 (12%), 21 (50%), and 20 (47.6%) patients, respectively; high SDAI and CDAI activities remained in 2 (4.8%) patients. Remission was observed in 10 (24%) patients according to the 2011 criteria. Conclusion. The obtained results of the 24-week study suggest that TCZ therapy is highly effective according to the changes in DAS 28, SDAI, CDAI activity indices and to the new 2011 EULAR/ACR remission criteria in severe RA resistant to the standard treatment with DMARDs.

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 impact of tocilizumab (TCZ) therapy on fatigue symptom in patients with rheumatoid arthritis (RA). Subjects and methods. The study covered 43 RA patients receiving therapy with TCZ in a dose of 8 mg/kg once four times for 24 weeks. Most patients were females, they were aged 25 to 69 years with a one-to-10-year history of the disease; 86% of the patients were rheumatoid factor-positive; 84% were anti-cyclic citrullinated peptide-positive; 42 and 49% had X-ray Stage II or III, respectively; 81% had Functional Class II; and 77% had high DAS 28 scores. Twelve (28%) of the 43 patients included into the study were found to have anemia with lower hemoglobin levels (< 110 g/l). Prior to TCZ therapy, all the patients had received for at least 6 months disease-modifying antirheumatic drugs, mainly methotrexate, in an average dose of 15.0+2.7 mg; 59.5% of the patients had taken glucocorticoids in the average dose of 7.5+2.22 mg/day, calculated with reference to prednisolone. Fatigue was rated in centimeters, by applying the visual analog scale of the RAPID-3 questionnaire. Results. The fatigue symptom was found to have the most pronounced correlations with depression (R = 0.49), pain (R = 0.48), DAS 28 scores (R = 0.47), erythrocyte sedimentation rate (ESR) (R = 0.49), and total disease activity scores (R = 0.55). The relationships to the number of tender and swollen joints, hemoglobin and interleukin-6 (IL-6) levels turned out to be less significant. The level of fatigue significantly decreased from 5.3 to 4.5 cm after the first TCZ infusion just at 4 weeks of a follow-up. Later on, it continued to fall and reached 2.5 cm at 24 weeks. During the therapy, fatigue generally diminished by 52%. There were significant reductions in the scores of DAS 28 (from 6.3 to 2.23), SDAI (from 41.75 to 4.55), CDAI (from 44.03 to 4.07), RAPID-3 (p < 0.01), pain (from 6.6 to 1.2 cm), ESR, C-reactive protein, IL-6, and a considerable functional improvement in HAQ (from 1.75 to 0.5 scores). It should be noted that all the indicators rapidly improved just after the first infusion of the drug. Following 8 weeks of TCZ therapy, low disease activity was observed in 24.4% of the patients; 26.8% achieved clinical and laboratory remissions. At 24 weeks, 11.9% had low DAS 28 scores and 71.4% had a remission.

Objective: to evaluate the clinical efficiency of tocilizumab (TCZ) versus rituximab (RTM) therapy using DAS 28, SDAI, and CDAI scores and to estimate remission rates using DAS 28 and the remission criteria proposed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) in 2011. Subjects and methods. Seventy-six patients with rheumatoid arthritis (RA) divided into 2 groups were examined. Group 1 included 42 patients receiving six TCZ infusions in an intravenous dose of 8 mg/kg at a 4-week interval during stable therapy with disease-modifying antirheumatic drugs (DMARDs) and glucocorticosteroids (GC); Group 2 comprised 34 persons who were given two RTM infusions in intravenous doses of 500 and 1000 mg at 2-week interval during therapy with DMARDS and GC in 12 (35%) and 22 (65%) patients, respectively. The EULAR criteria and SDAI and CDAI scores were used to evaluate therapeutic effectiveness. Remission was assessed using the EULAR criteria and the new 2011 EULAR/ACR remission ones. Results. In Group 1, the baseline DAS 28, SDAI, and CDAI scores were 6.44 [5.87; 7.04], 45.0 [36.2; 57.0], and 41.5 [32.0; 53.0]; in Group 2, these were 6.12 [5.52; 6.81], 34.3 [23.8; 45.9], and 31.3 [21.8; 38.5], respectively. At week 24 of therapy, Groups 1 and 2 patients achieved a DAS 28 remission in 71 and 23.5% of cases, a SDAI remission in 31 and 14.7%, and a CDAI remission in 33 and 17.6%, respectively. In the RTM-treated patients who had not previously received therapy with genetically engineered biological agents (GEBAs), DAS 28, SDAI, and CDAI remissions were observed more frequently (38, 23.8, and 28.6%, respectively) than in those receiving GEBAs (0%; p < 0.01) and their rate was comparable with that in Group 1 patients (according to SDAI and CDAI scores). In Groups 1 and 2, the remission rates according to the 2011 ACR/EULAR criteria were 24 and 11.8%, respectively. Conclusion. The results obtained during a 24-week trial are indicative of the high clinical efficiency of TCZ and RTM therapy. The number of TCZ-treated patients who had achieved a DAS 28 remission were much more while SDAI and CDAI remission rates among the patients who had not previously received GEBAs were virtually comparable with those when TCZ and RTM were administered.

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 laboratory biomarkers in patients with rheumatoid arthritis (RA) 2, 4, and 8 weeks after the initiation of tocilizumab (TCZ) therapy. Subjects and methods. Forty-two RA patients receiving two intravenous infusions of TCZ (8 mg/kg each) at a 4-week interval during steady-state therapy with disease-modifying anti-inflammatory agents and glucocorticoids were examined. At week 8 of therapy, there were good and moderate effects in 21 and 20 patients, respectively, according to the EULAR criteria; no effect was found in 1 patient. Erythrocyte sedimentation rate (ESR) was determined by the Westergren method; the serum levels of C-reactive protein (CRP) and IgM rheumatoid factor (RF) were measured by the nephelometric method; anti-cyclic citrullinated peptide antibodies (ACCPA) were estimated by an ummunoluminescence assay. Serum interleukin (IL) 6 concentrations were measured by multiplex analysis; IgA RF, anti-modified citrullinated vimentin (anti-MCV) antibodies, and soluble IL-6 receptors (sIL-6R) were determined by enzyme immunoassay. Results. The patients who showed a response to TCZ therapy had the basal values: Me (RI 25-75 percentile) was 42 (30-70) mm/hr for ESR, 35.2 (19.2-62.7) mg/l for CRP, 263.0 (95.3-663.0) IU/ml for IgM RF, 347.0 (131.2-789.0) IU/ml for IgA RF, 378.8 (85.8-500.0) IU/ml for ACCPA, 778.6 (190.7-2393.1) IU/ml for anti-MCV, 182.2 (106.1-462.3) pg/ml for IL-6, and 267.2 (212.5-310.0) ng/ml for sIL-6R. At TCZ therapy week 2, there were reductions in ESR [12 (6-18) mm/hr], CRP [0.5(0.3-0.9) mg/l], IgM RF [174.0 (40.8-513.0) IU/ml], and IgA RF [227.2 (62.1-570.8) IU/ml]; at week 4, anti-MCV titers were 313.5 (79.9-960.3) IU/ml, which remained until week 8 (p < 0.01). IL-6 concentrations were increased at week 2 and reduced at week 8; these were 418.4 (287.0-678.3) and 103.4 (39.1-208.5) pg/ml, respectively (p < 0.01). The elevated sIL-6R level of 1250.0 (1250.0-1475.0) ng/ml was recorded at weeks 2 to 8 of TCZ use (p < 0.01). Conclusion. The interim analysis of the efficacy of two TCZ infusions 2, 4, and 8 weeks after the initiation of the therapy suggests that TCZ is able to induce steady-state positive changes in immune-inflammatory markers very rapidly in patients with RA

Objective: to evaluate the efficiency of two tocilizumab (TCZ) infusions in patients with rheumatoid arthritis (RA). Subjects and methods. The study enrolled 43 middle-aged patients with RA, mainly female ones (male/female ratio 10:33) with a RA history of 5.6±4.74 years, who were seropositive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies and had high disease activity scores (DAS 28 - 6.3) prior to TCZ treatment and received disease-modifying anti-inflammatory agents, including methotrexate and glucocorticoids without providing any therapeutic effect. Therapy with TCZ was performed by the standard regimen; the dose of the drug was 8 mg/kg per infusion. The therapeutic effectiveness was evaluated 4 weeks after each infusion and by the time course of changes in DAS 28, its individual components, and health assessment questionnaire scores. Results. After the first TCZ infusion, the patients with RA were found to have significant positive changes in the major clinical and laboratory parameters of disease activity (p < 0.0001 in all cases) that progressed after the second TCZ infusion. There were reductions in DAS 28 to 4.1 and 3.1 after each infusion and in the number of patients with high disease activity and an increase in that of patients with low/moderate one. At the same time, more than 20% of the patients developed remission after the second infusion. A good therapeutic effect was noted in 14 and 51% of the patients after the first and second infusions, respectively. Conclusion. TCZ exerts a rapid statistically significant positive effect on the major clinical and laboratory parameters of RA activity.