The treatment of early rheumatoid arthritis (RA) is usually started using one of the synthetic disease-modifying antirheumatic drugs. The choice of these drugs is very limited and leflunomide (LEF) is one of the most promising agents. The present study assessed the results of using the standard LEF regimen for patients with early RA in the everyday clinical practice of Russian health care facilities. Subjects and methods. The study enrolled the patients followed up in 20 medical centers of the Russian Federation in May 2008 to January 2010. The RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria, had a less than 2-year history of the disease, and had not received LEF before were included. All the patients were above 18 years of age and they signed an informed consent form. The physicians were recommended to give the drug in a dose of 100 mg/day for the first 3 days, then 20 mg/day continuously. If adverse reactions occurred, the dose might be reduced to 10 mg/day. The patients were examined before and 12, 24, 36, and 48 weeks after LEF therapy. The efficiency of the treatment was evaluated by the European League Against Rheumatism (EULAR) classification criteria using DAS 28 scores, by the ACR criteria, and functional changes using HAQ scores and quality of life using the EQ-5D questionnaire. Results. The study included 484 patients with RA. Its diagnosis corresponded to the 1987 ACR criteria. There were 80 men and 404 women in this group. The patients’ mean age was 48.1±13.4 years; the mean duration of the disease at its onset was 14.1±12.8 months. A significant decrease in the number of patients with high DAS 28 scores was recorded every 12 weeks during the treatment. It reduced from 355 (73.3%) to 41 (8.5%) by the end of the observation. At the same time, there was a significant increase in the number of patients with low activity and remission every 12 weeks (p < 0.01). During the last visit, a remission was recorded in 57 (11.8%) patients and low disease activity in 59 (12.2%) patients. Twelve weeks after initiation of treatment, 210 (43.4%) patients achieved a significant improvement according to the EULAR criteria. During a subsequent follow-up, the number of patients with a considerable improvement increased statistically significantly every 12 weeks and there were 373 (77%) patients by the end of the follow-up. Efficiency evaluation showed a 20% response according to the ACR criteria in 154 (31.8%) patients after the first 12 weeks. There was a significant rise in the number of patients with a 20% ACR improvement within the first 36 weeks of the follow-up and there were 323 (66.7%) patients following 48 weeks. The number of patients with 50% and 70% ACR responses considerably increased throughout the observation (p < 0.01). After 48-week treatment, 141 (29%) and 38 (8%) patients showed 50% and 70% ACR responses, respectively. The therapy significantly improved quality of life, as estimated by EQ-5D questionnaire, and resulted in a considerable functional improvement according to HAQ scores. ARs were seen in 51 (10.5%) patients during the study. At the follow-up, LEF was discontinued in 58 patients, including 23 (4.8%) because of its inefficiency, in 9 (1.9%) due to ARs, and in 26 (5.4%) for other reasons. The efficiency of the therapy and the rate and causes of its withdrawal were comparable in the patients receiving LEF in accordance with the standard regimen using its saturating dose in the first 3 days and in those who did not take the saturating dose. Conclusion. The standard treatment regimen of LEF using its high doses in the first 3 treatment days in patients with early RA enables the inflammatory activity to be effectively inhibited and does not cause any substantial increase in the frequency of ARs.

Chronic disease anemia (CDA) diagnosed in many patients with rheumatoid arthritis (RA) was described in the early 1970s. As earlier noted, iron metabolic disturbances in CDA are its diagnostic feature and the discovery of hepcidin, an iron-regulatory acute-phase protein, could largely clarify an association between the immune mechanism of impaired iron homeostasis and the development of CDA. Objective: to define the role of hepcidin in the differential diagnosis of CDA and true iron deficiency in patients with RA. Subjects and methods. The investigation enrolled 76 patients with RA (1987 ACR criteria) admitted to the Research Institute of Rheumatology, Russian Academy of Medical Sciences, to be treated. The patients were divided into two groups. A study group comprised anemic patients (n = 47). The WHO criteria for anemia were considered to be hemoglobin (Hb) levels of below 120 g/l for women and below 130 g/l for men. A control group consisted of non-anemic patients (n = 29). The anemic and non-anemic patients were matched for age (45.5±14.3 and 49.8±14.3 years, respectively) and disease duration (2 months to 20 years) (p > 0.05). Iron metabolic parameters, such as serum iron, total serum iron-binding capacity (TSIBC), iron transferrin saturation (ITS), transferrin receptors, and serum ferritin (SF), were studied and the level of hepcidin prohormone was estimated by direct enzyme immunoassay (Hepcidin Prohormone Enzyme Immunoassay Kit, IBL, Germany) in all the patients to be analyzed. Cytokines, such as interleukin 6, tumor necrosis factor-а) were determined by enzyme immunoassay (Bender MedSystems, Austria). The Institute’s differential diagnostic algorithm involving SF, TSIBC, and ITS was used to diagnose iron deficiency. The diagnosis was based on two stages of estimating iron values: isolated iron-deficiency anemia (IDA) was diagnosed if SF was below the normal value (< 40 μg/l). If the patient had SF of μ40 μg/l with a simultaneous rise of TSIBC above the normal level (> 70 μg/l) and a drop of ITS (> 20%), he/she might be suspected as having the mixed genesis of anemia, in which both iron deficiency and CDA are detectable. The other patients could be diagnosed as having isolated CDA. Results. The study has established that irrespective of the hemoglobin level, the content of serum hepcidin prohormone in the examined patients with RA averaged 89.2±65.1 pg/ml and was much higher than that in donors (64.9+21.6 pg/ml; р < 0.05). An analysis of the blood biochemical parameters characterizing iron metabolism showed that, whether they were anemic or non-anemic, the patients with RA, as compared with donors, were found to have an elevated level of SF that is an acute-phase indicator and reflects the high activity of an inflammatory process. To rule out IDA, the anemic patients with RA were subdivided into 3 subgroups according to the differential diagnostic algorithm. Subgroup 1 included patients with isolated CDA (n = 13 patients (28% of those in the study group)); Subgroup 2 consisted of 17 (32%) patients with anemia of mixed genesis (CDA ± IDA), and Subgroup 3 comprised 17 patients with IDA. An analysis of the clinical and laboratory parameters in RA independent of the nature of anemia demonstrated that only the patients with isolated CDA had significantly higher mean values of hepcidin prohormone (120.3±56.1 pg/ml) as compared to the control group (90.3±37.9 pg/ml) and RA patients with iron deficiency (both isolated IDA and that of mixed genesis). The same subgroup had a higher inflammatory RA activity characterized by the highest values of DAS 28, C-reactive protein, and SF. Conclusion. Hepcidin is a negative regulator of iron metabolism and may be used for the differential diagnosis of CDA and true iron deficiency in patients with RA.

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 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 compare different methods for estimating ankylosing spondylitis (AS) activity in the real practice of a rheumatologist in the Russian Federation. Subjects and methods. The investigation enrolled 464 patients with AS, who had consecutively visited rheumatologists for 4 months in 24 cities and towns of Russia. A specially designed clinical card was filled out for all patients. BASDAI and ASDAS scores were estimated by a physician and erythrocyte sedimentation rate (ESD) and C-reactive protein (CRP) were measured in all the patients. Mini-BASDAI scores were determined in patients with axial AS. The diagnosis of the disease was verified at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, according to the 1984 modified New York criteria, by including X-ray film estimation. All activity assessment methods were compared. Results. The valid diagnosis of AS was confirmed in 330 (71.1%) out of all 464 patients included into the study; axial AS was present in 178 of them; their mean age was 39.7+10.2 years; the mean duration of disease was 14.6+2.6 years; 86% were men and 14% were women. About 61 and 74% of the patients (n = 178) had high BASDAI and mini-BASDAI scores, respectively; 88% had high and very high ASDAI (ESR) scores; the mean ESR (Westergren method) was 33.8+29 mm/h and CRP (n = 249) was 30 mg/l. Conclusion. On assessing the activity of disease, rheumatologists are primarily oriented to total activity scores and blood acutephase indicators (ESR and CRP) in real clinical practice. Patients with high disease activity calculated from BASDAI and ASDAS scores proved to be more. In its turn, ASDAS more frequently reveals high AS activity than BASDAI.

Objective: to study the clinical features and to define the frequency of postoperative complications in patients with rheumatic diseases (RD) who had undergone endoprosthetic knee and hip joint replacement (EKJR and EHJR) during therapy with genetically engineered biological agents (GEBAs). Subjects and methods. The study included 37 patients with RD: 30 with rheumatoid arthritis (RA), 6 with ankylosing spondylitis (AS), and 1 with psoriatic arthritis (PsA). All the patients had indications for endoprosthetic joint replacement (EJR): evident deformity and dysfunction of the joint; pain unrelieved by analgesics and nonsteroidal antiinflammatory drugs; and low quality of life (QL). EHJR and EKJR were performed in 21 and 16 patients, respectively. Their mean age was 40.6+15.8 years (range 18 to 64 years); 78.4% were women; the mean duration of disease was 15 years. 73% patients received synthetic disease-modifying antirheumatic drugs (DMARDs); 68% took small-dose glucocorticosteroids (GCs). All the patients were on GEBA therapy: 16 patients on rituximab, 15 on infliximab, 1 on adalimumab, 3 on abatacept, and 2 on tocilizumab. The activity of RA was determined using DAS 28 scores, that of AS and PsA was estimated using BASDAI and DAS 4 scores, respectively; functional activity was calculated from HAQ scores; QL was defined using the EQ-5D questionnaire. Results. The diagnosis was established in 73% of the patients within the first 2 years after disease onset; at that time, half of them started receiving DMARD therapy. GEBAs were given to patients with high disease activity, inefficacy or intolerance of synthetic DMARDs at an average of 13 years of disease. Addition of GEBAs could lessen preoperative disease activity in the majority of patients (to moderate and low activities in 60 and 27% of the patients, respectively) and the activity remained high only in 13%. During their disease, 84% of the patients took small-dose GCs long (for 1 to 19 years); however, only 68% continued to receive this therapy within 6 months before surgery. In the period of 1 to 12 months following surgery, there was venous thrombosis in 1 (2.7%) patients and instability of the ligamentous apparatus in the replaced joint in 2 patients. No cases of replaced joint infection were found throughout the follow-up. Conclusion. The use of GEBAs made it possible to diminish disease activity in most patients, to reduce needs for GCs, and to perform EJR with a more favorable background. This therapy was not accompanied by the development of infectious complications at the site of prosthetic replacement.

Objective: to evaluate the time course of inflammatory changes (ICs) in the spinal column and sacroiliac articulations (SIA) from magnetic resonance imaging (MRI) data in patients with ankylosing spondylitis (AS) during treatment with tumor necrosis factor-α (TNF-а) inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs), which were first used. Subjects and methods. MRI of the most painful part of the spine and SIA was performed in 58 patients with AS at baseline and 12 weeks later. MRI T2 STIR and T1 (SIGNA EXCITE, General Electrics; 0.35 T, matrix 288x192) regimens were used. Bone marrow edema was regarded as active inflammation. Active ICs in the most painful part of the spine were assessed by the AS spinal MRI activity (ASspiMRI-a) score and those in SIA by the Leeds scoring system. MRI was interpreted independently by two specialists; one of them did not know about the number of a visit and performed therapy. The patients were divided into two groups: 1) those who first used TNF-а inhibitors and 2) those who were first given NSAIDs. Both groups were matched for demographic indicators. Results. In both groups, the mean pain level in the spinal part under study decreased significantly in both groups: from 5.7±1.7 to 2.3±1.8 in the TNF-а inhibitor group (p = 0.000006) and from 4.8±2.3 to 2.6±2.3 in the NSAID group (р = 0.00001). After 12 weeks of treatment, the patients receiving TNF-а inhibitors (n = 28) showed a considerable reduction in the MRI signs of spinal ICs from 4.8±2.3 to 1.6±1.6 (p = 0.00001); moreover, this trend was more pronounced in patients (n = 17) with more baseline IC foci (≥ 5) than in those (n = 11) with fewer baseline IC foci (< 5) (the mean а was 4.3±1.5 and 1.6±1.4, respectively; р = 0.0003). In the patients taking NSAIDs (n = 30), the decrease in the number of spinal MRI ICs (from 2.8±2.5 to 2.3±2.1) was insignificant (p = 0.17). After 12 weeks, regression of active sacroiliitis was noted in 28 patients from the TNF-а inhibitor group with lower Leeds scores from 2.1±2.0 to 0 (p = 0.01). At baseline, 28.5% of the patients had MRI signs of active sacroiliitis, which were not found in any case at 12 weeks. At this time, the reduction in active sacroiliitis was also observed in the NSAID group patients (n = 30), but it was insignificant; the Leeds scores decreased from 2.6±2.5 to 2.1±2.0 (р = 0.083). At baseline and 12 weeks, the MRI signs of active sacroiliitis were present in 73.3 and 60% of the patients, respectively. During treatment with TNF-а inhibitors, the mean reduction in MRI IC scores during the follow-up was more marked than that in the use of NSAIDs (p = 0.003 for the spinal column and p = 0.013 for SIA). Conclusion. Pain intensity in the examined spinal part was significantly reduced in both the use of both TNF-а inhibitors and NSAIDs. MRI ICs significantly decreased when treated with TNF-а inhibitors rather than NSAIDs. With the greater magnitude of baseline MRI ICs, their drop was more significant during treatment with TNF-α inhibitors.

Pyrophosphate arthropathy (PPA) is a disease that arises due to the formation and deposition of calcium pyrophosphate crystals within the articular cartilage and thereby develops into immune inflammation. Its diagnosis requires the detection of characteristic calcium pyrophosphate crystals in the synovial fluid from the affected joint, as well as the signs of cartilage calcification or chondrocalcinosis visible on conventional X-ray films. The paper considers reasons why it is difficult to visualize chondrocalcinosis by knee joint radiography and compares the importance of three techniques for the radiodiagnosis of chondrocalcinosis as one of the important criteria for diagnosing PPA.

Objective: to study the impact of the clinical characteristics of rheumatoid arthritis (RA) on work efficiency. Subjects and methods. One hundred and thirty-seven patients (116 women and 21 men) with RA were examined. Their mean age was 52.03+13.17 years; mean age at disease onset was 42.12+14.43 years. Median RA duration was 84 (range 24-174) months. DAS 28 for RA was moderate. The HAQ score was 1.42+0.82. Results. Fifty-nine (43%) of the 137 patients were in work. Absenteeism was 28.2%. It was equal to 0 in 28 of the 59 working subjects. The mean presenteeism was 42.3±27.9%. The reduction of overall work efficiency was 54.8±34.4%. The day-to-day activity determined in all the patients was reduced by 53.6±25.7%. Absenteeism turned out to be negatively related to RA duration (R = 0.26). DAS 28 scores were directly related to all WPAI indicators: absenteeism (R = 0.28), presenteeism (R = 0.63), lower overall work efficiency (R = 0.47), day-to-day activity (R = 0.64). The WPAI indicators (R >0.5), exclusive of absenteeism, were noted to have the strongest correlation with VAS pain intensity. The HAQ score was unassociated with absenteeism, but its association with presenteeism, lower overall work efficiency, and day-to-day activity proved to be high (R = 0.65; R = 0.43; R = 0.75, respectively). The correlation of the WPAI components with the transformed index of a patient's physical state (SF-36 PCS) was much higher than that with mental one (MCS). Conclusion. RA activity had a major influence on work efficiency. Presenteeism was much stronger related to the clinical characteristics of RA than with absenteeism. All WPAI scores were associated with activity, degree of functional defect, quality-of-life values, and fatigability. At the same time, absenteeism was least related to the clinical characteristics of RA.

Objective: to assess awareness of drug and non-drug treatments for rheumatoid arthritis (RA) and compliance in patients before and after their participation in an education program, as well as the survival of the knowledge and the need for retraining. Subjects and methods. The study included 43 patients with RA: 23 study group patients were trained according to an education program (Rheumatoid Arthritis Health School), 20 patients formed a control group. The education program consisted of 4 daily 90-min studies. Adherence to drug and non-drug treatments was assessed at baseline and at 3 and 6 months. Results. In the study group, the basic therapy remained stably high (about 100%) within 6 months. At 3 months after studies, nonsteroidal anti-inflammatory drugs could be discontinued in 23.8% (p < 0.05). After 6 months, the proportion of patients using laser therapy increased by 57.1% (p < 0.01) and accounted for 47.8%; the use of electric and ultrasound treatments showed a 55.6% increase (p < 0.01) and was 60.9%. The number of patients who were compliant to the procedures for shaping a correct functional stereotype increased by 14 and 10 times following 3 and 6 months (60.9% and 43.5%, respectively; p < 0.01). After 3 months, there was a rise in the number of patients using hand ortheses by 75.0% (30.4%; p < 0.01); knee ortheses by 50.0% (39.1%; p < 0.01); individual inner soles by 71.4% (52.2%; p < 0.01); and walking sticks and crutches by 60.0% (34.8%; p < 0.01). Following 6 months, the positive changes remained only after the relative use of inner soles (60.9%) and support means (34.8%; p < 0.05). The number of patients who regularly did physical activity increased by 5.3 (69.6%; р < 0.01) and 3.7 (47.8%; p < 0.01) times at 3 and 6 months, respectively. The trend in the control group was less pronounced, determining statistically significant differences between the groups in most indicators (р < 0.05). Conclusion. The education program retains high compliance to the basic therapy, reduces needs for symptomatic drugs, and enhances adherence to physiotherapy, methods for shaping a correct motor stereotype, orthesis wearing, and regular physical activity. The maximum positive result of the Rheumatoid Arthritis Health School was achieved after 3 months; this effect slightly diminished at 6 months. This necessitates retraining in the following 3-6 months.