Научно-практическая ревматология (Jun 2011)
TIME COURSE OF CHANGES IN LABORATORY BIOMARKERS IN PATIENTS WITH RHEUMATOID ARTHRITIS DURING TOCILIZUMAB THERAPY
Abstract
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
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