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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.

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 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