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.

Interstitial lung disease (ILD) is one of the major causes of death in systemic scleroderma (SSD). Treatment of these patients remains difficult and controversial. Mycophenolate mofetil (MPM) has been in vitro shown to inhibit overproduction of type I collagen and hence may be effective against SSD.
Objective: to study the efficiency and safety of MPM therapy in patients with SSD and clinically relevant ILD in an open-label prospective study. Subjects and methods. Ten patients with SSD (7 and 3 with its diffuse and limited forms, respectively) and ILD were given MPM in combination with glucocorticoids (mean daily dose was 10+4 mg). The mean MPM therapy duration was 11.4+1.3 months. The Rodnan total skin thickness score, flexion index, forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and European Scleroderma Study Group (EScSG) activity index were estimated and a 6-minute walk test (6MWT) was carried out before and after MPM therapy.
Results. After therapy, the whole group showed a significant reduction in skin scores from 12.9+9.8 to 5.6+3.2 (p=0.036) and EScSG from 3.9+1.4 to 2.25+1.03 (p=0.015) and an increase in exercise tolerance from 446+155 to 535+78 m (p=0.03) as evidenced by 6MWT. The degree of flexion contractures decreased from 15+21 to 3.7+11.3 mm (p>0.05). FVC (77.8+18.7% versus 73.8+11.3%) and DLCO (45+14.4% versus 42+16.4%) were significantly unchanged. A 10% or more clinically significant fall was noted in FVC and DLCO in 3 and 1 patients, respectively. In the remaining patients, the lung functional test results remained stable. MPM tolerability was satisfactory. All the patients completed their course of treatment.
Conclusion. Stabilization of lung function with higher exercise tolerance and significantly reduced skin density allow therapy with MPM in combination with low-dose glucocorticoids to be regarded as an effective and well-tolerated treatment in patients with ILD in the presence of SSD

Objective: to assess disease severity in relation to the expression of cell-division cycle genes: p21, a cyclin-dependent kinase inhibitor; caspase 3, an apoptotic activity indicator; mammalian target of rapamycin (mTOR), a major regulator of cell growth and proliferation; ATG1, a marker of autophagy; and the proinflammatory cytokine tumor necrosis factor-α (TNF-α) in the blood of rheumatoid arthritis (RA) patients. Subjects and methods. Thirty-nine early RA patients (mean age 47.1 years) and 47 healthy individuals (mean age 43.1 years) were examined. Gene expression in their peripheral blood cells was assessed using real-time polymerase chain reaction. RA activity was estimated according to DAS28 index and joint destruction.
Results. In accordance with mTOR gene expression, the group of RA patients were divided into three subgroups: 1) 18 patients had a significantly lower mTOR gene expression than did the healthy controls (p < 0.01) and upregulated ATG1; 2) 12 patients had the same mTOR gene expression levels as in the healthy controls; p21 ATG1, and caspase 3 were, however, much upregulated; 3) 9 patients showed significant upregulation of all the examined genes as compared to the healthy controls (p < 0.01). The patients from 3 subgroups differed in TNF-α gene expression that was statistically significantly exceeded that in the healthy individuals, the expression being highest in subgroup 3 patients. The subgroups of RA patients showed some differences in clinical and immunological parameters. Particularly, subgroup 2 patients exhibited the lowest morning stiffness values while subgroup 1 patients had much fewer swollen joints than did subgroup 3 patients. In addition, subgroup 2 patients had significantly statistically higher levels of anti-citrullinated antibodies whereas subgroup 3 patients had lower rheumatoid factor concentrations than the other subgroups.
Conclusion. Early RA patients represent a heterogeneous group. RA patient subgroups differ in the expression of cell-cycle and TNF-α genes and in some clinical and immunological parameters. Variability in the expression of the cell-division cycle genes in different subgroups of RA patients can indicate different mechanisms involved in the development and progression of the disease and hence the necessity of applying diverse approaches to their therapy.

Small bowel (SB) injury is a common complication from the use of nonsteroidal anti-inflammatory drugs (NSAIDs). According to clinical trials, selective cyclooxygenase-2 inhibitors are safer in this respect. Meloxicam belongs to selective NSAIDs; however, its effect on the SB has been inadequately investigated.
Objective: to compare the effects of meloxicam 15 mg/day and diclofenac 150 mg/day on the SB mucosa.
Subjects and methods. A study group comprised 15 patients, including 6 men and 9 women (mean age 42.3+17.1 years), with ankylosing spondylarthritis (AS); 7 of them took meloxicam 15 mg/day for at least one month and 8 had diclofenac 100-150 mg/day. The SB was evaluated from capsule endocopy (CE) readings.
Results. SB erosions (n = 3 to 20 or more) were found in 11 patients: 5 (71.3%) and 6 (75.0%) subjects taking meloxicam and diclofenac, respectively (p = 0.82). The average amount of erosions in those receiving meloxicam (6.2+4.7) was less than in those having diclofenac (9.4+7.3; p = 0.13). One patient taking diclofenac was suspected of having Crohn's disease shown by CE and then confirmed by colonoscopy. Conclusion. Meloxicam has demonstrated a less negative effect than diclofenac on SB, although this difference was statistically insignificant. Small and bowel pathology frequently occurs in patients with AS and may be associated not only with the negative effect of the drugs, but also with comorbid inflammatory bowel diseases. There is a need for further studies of the distal gastrointestinal tract and for those of the effect of NSAIDs on the SB.

Objective: to evaluate the psychometric properties of the Russian-language version of the routine assessment of patient index data (RAPID-3) questionnaire in patients with rheumatoid arthritis (RA).
Subjects and methods. The reliability, sensitivity, and validity of the RAPID-3 index were estimated in 100 patients with verified RA. Reliability assessment comprised the study of the reproducibility and internal consistency of the index. The reproducibility was assessed by the test-retest method; the internal consistency was estimated calculating the Cronbach-alpha coefficient; the sensitivity was determined comparing the RAPID-3 values with a response to treatment according to the ACR-50 criteria. Design validity was ascertained using correlation analysis with external criteria.
Results. Test-retest analysis in patients with unchanged health status failed to reveal statistically significant differences between the initial (15.17±5.57) and repeat (13.1±5.89) values of the RAPID-3 index; the Cronbach-alpha coefficient was 0.8. Improved health according to the ACR-50 criteria was correlated with better RAPID-3 values. Lower disease activity in accordance with the RAPID-3 index was more marked in patients who had achieved 50% improvement as shown by the ACR criteria. The posttreatment decline in the RAPID-3 index averaged 3.9±0.1 scores. In patients who had not achieved 50% improvement by the hospital discharge, the disease activity change was less pronounced (Δ RAPID-3 = 1.9±0.2 scores).
There were high correlations of RAPID-3 values with clinical parameters: the number of swollen joints (R=0.61) and tender joints (R = 0.46), combined DAS 28 indices (R=0.72), simple (R=0.60) and clinical (R=063) disease activity indices (SDAI and CDAI), inflammation activity index (IAI) (R=0.62), health assessment questionnaire (HAQ) (R=0.64), and quality of life questionnaire (EQ-5D) scores (R=0.52). Conclusion. The RAPID-3 index is a reliable, sensitive, and valid tool to evaluate inflammation activity and functional status in patients with RA

Objective: to identify the capacities of a Cardiovisor-06C device in the diagnosis of the cardiological aspects of the joint hypermobility syndrome (JHMS).
Subjects and methods. The study covered 12 students with JHMS. All the respondents were examined using a Cardiovisor-06C device. Results. All the students were found to have deviations from the normal integral indicators: Myocardium, Rhythm, Pulse, Specification code, as well as some electrocardiogram indicators: the durations of P-Q and Q-T intervals and P wave. Conclusion. The early and preclinical manifestations of possible heart abnormalities in the JHMS can be detected by a Cardiovisor-06C device.

Objective: to study the time course of rituximab therapy-induced changes in the synovial fluid levels of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), interleukins (IL) 1β and 6, and tumor necrosis factor-α (TNF-α) in patients with rheumatoid arthritis (RA).
Results and discussion. The synovial fluid levels of IL-1ß, IL-6, TNF-α, OPG, and RANKL were studied in 54 RA patients who were seropositive for rheumatoid factor and cyclic citrullinated peptide. Differences were found in the levels of the study cytokines in patients with a varying duration of the disease.
Conclusion. Rituximab was observed to be highly effective in correcting cytokine parameters in early RA.