Objective: to analyze the relationship of the clinical and antidestructive effect of infliximab (INF) to its total dose in patients with rheumatoid arthritis (RA). Subjects and methods. A one-year investigation included 135 patients with RA. All patients received INF 3 mg/kg at weeks 0, 2, 4 and then every 8 weeks. During each visit, the number of tender and swollen joints, C-reactive protein level, and erythrocyte sedimentation rate were determined and the Health Assessment Questionnaire (HAQ) was filled out. DAS-28 changes were used to assess therapeutic effect of INF. Joint destruction was evaluated by the Sharp method modified by van der Heijde. All patients were examined according to the protocol before each INF infusion. The result of INF therapy was assessed at week 54 in all patients (including in those who had not completed a one-year INF therapy cycle). According to the total dose of INF, the patients were divided into three groups: 1) ≤4 infusions (low-dose, n = 63); 2) 5–7 infusions (medium-dose, n = 31); 3) ≥8 infusions (full-dose, n = 41). Group 1 received an average of 2.5 IFN infusions; Group 2 and 3 – 5.8 and 8.8 infusions, respectively. Results. Baseline high disease activity (DAS28 > 5.1) was noted in the majority of the patients: 69% in Group 1, 86.6% in Group 2, and 62.1% in Group 3. All the patients showed a prompt (just at 14 weeks of treatment) and significant (p < 0.05) decrease of RA activity. This reduction remained significant at week 54. By the end of follow-up there were more patients with low disease activity (including those with DAS28 remission) in Group 3 than the other groups (53.9% versus 27.3 and 50% in Groups 1 and 2, respectively). After the completion of therapy, the highest percentage of patients with high disease activity was seen in Group 1 (36.4%). The number of remissions was comparable in Groups 2 and 3 (28.6 and 23.1%, respectively) and smaller in Group 1 (18.2%). Significantly more obvious radiographic disease progression was noted in Group 1 than in the two other groups. Conclusion. The lower total dose of INF can cause a long-lasting clinical effect in some patients with RA, but it does not substantially suppress joint destruction. There were no significant differences between patients receiving medium and full doses of this drug in and the degree of radiographic disease progression.

Objective: to determine the predictors of the efficiency of rituximab (RTM) therapy through analysis of blood gene expressions in patients with rheumatoid arthritis (RA). Subjects and methods. Sixteen patients (mean age 53.4±10.8 years) with RA (mean duration 8.2±7.1 years) who had previ- ously received disease-modifying antirheumatic drugs and tumor necrosis factor- α (TNF- α ) inhibitors without effects were examined. Each patient underwent a treatment cycle with RTM in a dose of 0.5-1 g. A control group included 26 healthy individuals. Clinical response was assessed with DAS28. Erythrocyte sedimentation rate (ESR), serum levels of anti-cyclic citrullinated peptide antibodies, C-reactive protein (CRP), and rheumatoid factor (RF) were estimated. Bone erosions and joint space narrowing were evaluated radiologically. RNA was isolated from blood and used to estimate the expression of the mTOR, ULK1, caspase 3, p21, TNF- α , cathepsin K, matrix metalloproteinase-9 (MMP-9), interleukin-1 β (IL-1 β ), inter- feron- γ (IFN- γ ), and cyclooxygenase-2 (COX-2) genes by real-time reverse transcriptase polymerase chain reaction. Results. At the beginning of the investigation, the expression of all the genes under study was increased (p < 0.05) in the patients with RA versus the healthy individuals. RTM therapy resulted in reductions in DAS28, ESR, CRP levels, and CD10+ B lymphocyte depletion (p < 0.05). There were no changes in the number of erosions and the width of the joint space during RTM therapy. The blood expression of the mTOR, p21, caspase 3, ULK1, TNF- α , IL-1 β , and cathepsin K genes was suppressed to that of healthy individuals. As compared to the beginning of the investigation, the expression of MMP-9 was also reduced (p < 0.05); however, it remained far higher than that in the controls and no drastic changes occurred in the expression of the IFN-р and COX-2 genes. Conclusion. Blood gene expression analysis may serve as a source of information on the status of patients with RA dur- ing RTM therapy. The higher residual expression of MMP-9, IFN- γ , and COX-2 may be a reason for the preserved activity of RA and its exacerbation.

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.