Interleukin-6 (IL-6) is one of the major proinflammatory cytokines, which, by interacting with hepatocytes, induces the synthesis of a broad spectrum of acute phase inflammatory proteins. IL-6 plays an important role in the development and progression of systemic lupus erythematosus (SLE), participates in the differentiation of CD4/CD8 regulatory T lymphocytes and in the production of autoantibodies by B lymphocytes, and increases the survival of plasmablasts. Tocilizumab (TCZ) is a humanized anti-IL-6 receptor antibody that neutralizes the pleiotropic effects of the cytokine. The use of this drug in SLE can have acceptable efficiency with the high inflammatory activity that is accompanied by fever, polyarthritis, polyserositis, skin lesions, and hemolytic anemia. The authors demonstrated the successful use of TCZ in a female patient with a documented diagnosis of SLE with a high activity (SLEDAI-2K-11). The use of the drug was justified by the prevalence of musculoarticular, constitutional (fever) disease, a high immunological activity (anti-DNA antibodies, 150 IU/ml; antinuclear factor, 1/1280 h; CRP, 88). This therapy could achieve complete relief of fever at day 2 after the first infusion of TCZ, a reduction, and subsequently complete relief of arthritis and normalization of laboratory blood parameters. TCZ has a satisfactory safety profile and may be considered as an alternative treatment for SLE when glucocorticoids, cytostatic agents, and rituximab are ineffective.

Objective: to evaluate the effect of different biological agents (BAs), including rituximab (RTM) and belimumab (BLM) combination therapy, on B-lymphocyte subpopulations during a follow-up of patients with systemic lupus erythematosus (SLE).Patients and methods. The investigation enrolled 64 patients with a verified diagnosis of SLE with high and moderate disease activities according to the Systemic Lupus Erythromatosus Disease Activity Index (SLEDAI)-2K scores; 47patients of them took RTM, 10 used BLM, and 7 received RTM + BLM combination therapy. Peripheral blood B-lymphocyte subpopulations were measured by multicolor flow cytofluorom-etry, using a panel of monoclonal antibodies to B-lymphocyte surface membrane markers. The results were assessed using the SLEDAI-2K scores and the British Isles Lupus Assessment Group (BILAG) index.Results and discussion. RTM therapy led to a marked decrease in major B-lymphocyte populations, the residual cells being naXve B-cells and different memory B cell populations, the percentage of which depended on the degree of depletion after a RTM cycle. Incomplete B-lymphocyte depletion was associated with the large baseline numbers of plasma cells (PCs) (>0.2%). One year after initiation of therapy, the percentage ratio of B-lymphocyte subpopulations returned almost completely to baseline values, except the whole memory B-cellpopulation. BLM therapy resulted in a decrease in PCs and plasmablasts (PBs) to the point of their complete depletion. There were reductions in total CD19+ B-lym-phocytes and naive B lymphocytes. The use of the combination of BAs permitted the monitoring of the total B-lymphocyte population; its slower recovery was seen in patients with its complete depletion after a rituximab cycle. The therapy promoted maintenance of low concentrations of PCs and PBs, total memory B-cell and naive B-cell populations.Conclusion. In patients with SLE, all the three therapy with BAs demonstrated a good efficiency manifested by a decrease in clinical and laboratory disease activity. The found time course of changes in B-lymphocyte subpopulations can be used for the selection of therapy and for the evaluation of its efficacy.

The literature virtually lacks the results of investigations aimed to study the clinical picture of ankylosing spondylitis (AS) in the real practice of rheumatologists in Russia. At the same time, these investigations may give information on not only the epidemiological aspects of the disease, but also a variety of its clinical presentation, its social importance, allow evaluation of the efficiency of therapy, and plan a system of further health care costs.Subjects and methods. In early 2015, the cross-sectional multicenter non-interventional trial EPICA2 was conducted to refine the clinical picture of AS in the real practice of a rheumatologist. The trial involved 402 patients with AS from 10 centers of Russia. The patients were examined using the international standards accepted for this disease. Results and discussion. 180 out of the 402 patients were treated in hospital; the others were examined during outpatient visits. The patients' mean age was 40.8±11.5 years; there were 292 (72.6%) men; 82.6% were HLA-B27 positive. The average age of onset was 27.6 years; the interval between symptom onset and diagnosis was 85.2 months. The rheumatologists established the diagnosis in 87.3% of the cases. BASDAI and BASFI averaged 4.3±2.1 and 4.1±1.8, respectively. At the trial, there was peripheral arthritis in 33.1% of the patients, enthesitis in 37.1%, and dactylitis in 1.2%. Joint endoprosthesis was carried out in 4.7% of the patients. The most common comorbidities were hypertension (25.1%), gastric ulcer (9.7%), coronary heart disease (4.0%), and diabetes mellitus (3.0%).Conclusion. AS is diagnosed in real practice more than 7 years after its onset mainly by rheumatologists.The delay of the diagnosis is mostly associated with the fact that specialists of other medical specialties are unaware of the clinical presentation of the disease. The examined group of patients with AS shows a relatively high activity and obvious functional impairments, which is primarily related to the specific features of patient selection in this trial.

The literature virtually lacks the results of investigations aimed to study the clinical picture of ankylosing spondylitis (AS) in the real practice of rheumatologists  in Russia. At the same time, these investigations may give information  on not only the epidemiological aspects of the disease, but also a variety of its clinical presentation, its social importance, allow evaluation of the efficiency of therapy, and plan a system of further health care costs. Subjects and methods. In early 2015, the cross-sectional multicenter  non-interventional trial EPICA2 was conducted to refine the clinical picture of AS in the real practice of a rheumatologist. The trial involved 402 patients with AS from 10 centers of Russia. The patients were examined using the international standards accepted for this disease. Results and discussion. 180 out of the 402 patients were treated in hospital; the others were examined during outpatient visits. The patients' mean age was 40.8±11.5 years; there were 292 (72.6%) men; 82.6% were HLA-B27 positive. The average age of onset was 27.6 years; the interval between symptom onset and diagnosis was 85.2 months. The rheumatologists  established the diagnosis in 87.3% of the cases. BASDAI and BASFI averaged 4.3±2.1 and 4.1±1.8, respectively. At the trial, there was peripheral arthritis in 33.1% of the patients, enthesitis in 37.1%, and dactylitis in 1.2%. Joint endoprosthesis was carried out in 4.7% of the patients. The most common  comorbidities were hypertension (25.1%), gastric ulcer (9.7%), coronary heart disease (4.0%), and diabetes mellitus (3.0%). Conclusion. AS is diagnosed in real practice more than 7 years after its onset mainly by rheumatologists.The delay of the diagnosis is mostly associated with the fact that specialists of other medical specialties are unaware of the clinical presentation  of the disease. The examined group of patients with AS shows a relatively high activity and obvious functional impairments, which is primarily related to the specific features of patient selection in this trial.

Behçet's disease (BD) is a chronic, relapsing, inflammatory vascular disease with no pathognomonic test. Low sensitivity of the currently applied International Study Group (ISG) clinical diagnostic criteria led to their reassessment.

Objective: to study the comparative efficacy of the genetically engineered biological agents infliximab (INF) and adalimumab (ADA) in patients with ankylosing spondylitis (AS). Subjects and methods. The study included 86 patients with active AS who had failed to achieve remission with the maximal tolerated doses of nonsteroidal anti-inflammatory drugs, sulfasalazine, methotrexate, and glucocorticoids. The patients were divided into 2 groups: 1) 53 patients (mean age 35±9 years, disease duration 13.9±7.5 years) took INF; 2) 33 patients (mean age 35±12 years; disease duration 9.1±6.7 years) received ADA. Therapeutic effectiveness was evaluated by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI) scores, ASsessments in Ankylosing Spondylitis (ASAS) remission criteria, vertebral index changes, laboratory parameters, and HLA-B27 typing. INF was administered at a dose of 3—5 mg/kg body weight (300—400 mg) at 0, 2, and 6 weeks and then every 8 weeks, ADA was given in a dose of 40 mg once every 2 weeks. Therapeutic effectiveness was evaluated every 12 weeks. Results. At 48 weeks of therapy, there was a 50% decrease in BASDAI scores in 64 and 60% of the patients in the INF and ADA groups, respectively. ASDAS dropped in 69% and reached its minimal value in 51% in the INF group; those in the ADA group were 54 and 66%, respectively. The mean BASFI score was almost halved in both INF and ADA groups; its low score was recorded in 67 and 60%, respectively. Both groups showed a significant increase in the spine range of motion after 12 weeks of therapy. By the end of the study, there was a significant improvement of locomotion (BASMI) as compared to the baseline values: from 19.4±8.1 to 13.6±4.8 and from 17.3±6.2 to 15.9±7.3, respectively. According to the ASAS criteria, partial remission was achieved in 69% of the patients receiving INF and in 75% of those taking ADA. There were marked positive laboratory changes. The INF and ADA groups displayed decreases in erythrocyte sedimentation rate (ESR) from 37.7±18.9 to 19.0±16.8 and from 38.3±16.5 to 17.8±18.5, respectively (p<0.001 in both groups) and C-reactive protein (CRP) from 39.8+37.2 to 7.8±24.0 (p < 0.001) and from 23.2±21.2 to 1.0±2.5 (p > 0.13), respectively; and an increase in hemoglobin from 125.9±18.8 to 137.5±20.4 (p < 0.001) and from 129.7±16.2 to 146.3±11.5 (p > 0.10), respectively. Adverse reactions (AR) were found in 37 and 33% in the IFN and ADA groups, respectively. The most common AR (elevated hepatic enzymes) was seen in 11 and 9% in Groups 1 and 2, respectively. Serious ARs that caused to discontinue the use of a drug were observed in only 1 patient receiving INF. In Group 1, 3% of the patients were found to have a lower therapeutic effectiveness requiring that the biological drug be changed for ADA. Conclusion. BASDAI and BASMI scores indicated a more marked clinical response to INF therapy. Both groups showed a rapid decrease in acute-phase inflammatory markers, such as ESR and CRP, and elevated hemoglobin just in the early periods of therapy. Functional improvement in locomotion (in spondylitis, peripheral arthritis) was achieved in both groups. The genetically engineered biological agents were well tolerated.

A search for new medicines for the treatment of rheumatoid arthritis (RA) has led to the design of the so-called genetic engineering biologicals (GEBs) whose mechanism of action lies in the depletion and impaired interaction of the cells involved in the development of i НАУЧНО-ПРАКТИЧЕСКАЯ РЕВМАТОЛОГИЯ, 2010, № 2, 21-29 21 ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ nflammation or in the inhibition of proinflammatory cytokine activities. In recent years, investigators' attention has been brought to interleukin (IL) 6 (pleiotropic cytokine) that is synthesized by many cells implicated in the development of inflammation and shows a broad range of proinflammatory biological effects. Tocilizumab (TCZ) is the first and only agent that is able to suppress IL-6-dependent inflammatory reactions and that is permitted for use in RA. The first Russian open-label, Phase IV, multicenter 24-week study of the efficacy and safety of TCZ in patients with rheumatoid arthritis (RA) is now under way. All the patients received an intravenous TCZ infusion in a dose of 8 mg/kg during continuous therapy with basic anti-inflammatory and nonsteroidal anti-inflammatory drugs (DMARDs and NSAIDs), and glucocorticoids. The patients receiving methotrexate (MT) took folic acid in a dose of at least 5 mg weekly. The study excluded patients with a history of DMARD use. To evaluate the efficiency of TCZ therapy, the authors used the EULAR criteria and analyzed individual clinical indicators of RA activity, including the intensity of pain, the duration of morning stiffness, the number of tender and swollen joints (TJC and SJC), indices of functional activity and quality of life (HAQ and EQ-5D), and laboratory parameters required to evaluate the efficiency and safety of TCZ therapy. Clinical and laboratory studies were conducted just before and 4 weeks after the first infusion of TCZ. Overall, the first administration of the drug caused a very rapid positive effect against all clinical indicators of disease activity (including pain magnitude, morning stiffness duration, TJC, SJC) and normalization of the indices characterizing the functional activity and quality of life of patients. The efficiency TCZ therapy was confirmed, by assessing the time course of changes in DAS 28 index values: before therapy, all the patients were observed to have a high activity of RA (DAS 28 >5,1). According to the changes in DAS 28 index values, a good/moderate effect was noted in 62% of the patients, 3 (7%) achieved remission (DAS 28

Tsel' issledovaniya - otsenit' effektivnost' i perenosimost' dlitel'nogo primeneniya tsiklosporina A (TssA) u bol'nykh s bolezn'yu Bekhcheta (BB). Materialy i metody. Sandimmun neoral (SiN) naznachali 50 bol'nym (40 muzhchin i 10 zhenshchin) v doze ot 1,5 do 5,0 mg/kg/sut. Rezul'taty issledovaniya. Dlitel'nost' priema SiN sostavila ot 1 do 168 mes: 28 bol'nykh prinimali preparat bolee 1 goda, 8 - bolee 5 let i 1 - bolee 10 let. U 40 (86,9%) iz 46 bol'nykh s uveitom kupirovalos' vnutriglaznoe vospalenie, u 31 povysilas' ostrota zreniya. Cherez 2-3 mes lecheniya SiN prakticheski ischezali vneglaznye proyavleniya. Tol'ko u 4 bol'nykh terapiya SiN ne prinesla effekta, chto bylo obuslovleno iskhodno tyazhelym i dlitel'nym techeniem BB. U 9 patsientov provodilas' kombinirovannaya terapiya, vklyuchavshaya TssA, glyukokortikoidy (GK), kolkhitsin, azatioprin, tsiklofosfan (TsF) v raznykh kombinatsiyakh. Dvum bol'nym dopolnitel'no vvodili infliksimab. Kombinirovannaya terapiya ne povliyala na perenosimost' TssA, naprotiv, narastal polozhitel'nyy effekt. Pobochnye yavleniya zaregistrirovany u 25 (50%) bol'nykh, oni byli netyazhelymi i ne trebovali otmeny preparata. Priveden primer dlitel'nogo (110 mes) primeneniya SiN. Effektivnost' TssA dostigaet 80%, drugie avtory privodyat skhodnye znacheniya. Zaklyuchenie. Preparat sleduet naznachat' uzhe na rannikh srokakh zabolevaniya, osobenno u molodykh muzhchin. SiN kontroliruet i drugie klinicheskie proyavleniya zabolevaniya (porazhenie kishechnika, nervnoy sistemy, tyazhelyy aftoznyy stomatit). SiN khorosho perenositsya v doze do 5-7mg/kg/sut, chashche ispol'zuetsya v sochetanii s nizkimi dozami GK.

Aim. To study joint pathology in patients with Behcet's disease (BD). Material and methods. The trial enrolled 183 BD patients (128 males, 54 females, mean age 32,0 ± 9.8 years, age at BD onset 22.3 ± 9.9 years, mean duration of the disease 9.5 ± 8.9 years. Results. Joint pathology occurred in 74.8% patients, in 10.9% patients the disease onset was associated with arthritis and arthralgia. 3 patients had aceptic necrosis of the head of the femur and knee joint, 3 patients - bone marrow infarction. Knee joints were affected more frequently than others (up to 40%) followed by ankle, elbow and radiocarpal and other joints. In BD duration about 10 years, none of the examinees had stage III of sacroiliitis, stage II was diagnosed only in 4 patients, stage I (suspicion) - in 9. Significant sacroillitis was not registered, bilateral sacroillitis occurred only in 9 patients. HLA B5 was detected in 61% patients while HLA B27 - only in 9.7%. Conclusion. The articular syndrome was seen in 3/4 of BD patients. Arthritis runs a recurrent course. Erosive arthritis, sacroillitis and combination of the latter with HLA B27 are rare.

AIM To characterize vascular symptoms of Behcet's disease (BD) in patients treated for the last 10 years in the Institute of Rheumatology. MATERIAL AND METHODS Vascular symptoms of BD were studied in 151 patients with BD (mean age 33.5 +/- 9.5 years, duration of the disease 14.0 +/- 10.1 years, 104 males and 47 females, 67.4% carried HLA B51(5) antigen). Duplex vascular scanning was made to detect venous thrombosis. RESULTS Thrombotic complications were found in 37 of 151 (24.5%) patients with BD (30 males and 7 females, mean age 37.1 +/- 9.1 years, mean duration of the disease 7.3 +/- 9.7 years). Venous thromboses prevailed (36 patients). Four males (2.6%) had arterial lesions: aneurysms of the iliac arteries (n = 1), thrombosis of the iliac artery (n = 1), pulmonary infarction and thrombosis of the pulmonary arteries (n = 2). Combination of venous and arterial manifestations occurred in 3 patients. One patient had thrombosis of the venous sinus, occlusion of the retinal vessels was diagnosed in 7 patients. CONCLUSION Incidence of vascular disorders was observed in 1/4 of the patients. This corresponds to those observed worldwide and concerns venous thrombosis and other thromboses. Among the examinees, vascular disorders were associated with a young age, earlier development of thrombotic complications in males than in females.

Summary Aim: to assess the efficacy and tolerability of Consupren (Galena, Chekia ) in some rheumatic diseases. Material and methods. Three months’ therapy by Consupren was studied in 12 patients: 4 with SLE, 4 with Behcet’s disease, 2 with rheumatoid arthritis with systemic manifestations, 2 with juvenile rheumatoid arthritis. Sandimmune therapy was changed for Consupren in 9 patients. All patients were controlled for the level of serum creatinine and AD and had consultations with ophtalmologist. Results. 3 SLE patients treated by Consupren demonstrated decreasing of proteinuria, disease activity by SLAM and SLEDA1, the fourth patient demonstrated fading of diskoid rash and normalizing of temperature. Patients with Behcet’s disease had no episodes of ulcerous stomatitis and uveitis exacerbation, in one patient stable nodular erythema disappeared. Patients with JRA improved articular syndrome, normalized temperature, reduced acute phase indices. Both patients continue taking Consupren, RA patients had long term of onset of the disease and 111-IV radiological stage , thus the effect on the articular syndrome was not so demonstrative but the activity of the disease reduced. Conclusion: consupren is effective and well tolerable drug for patients with systemic manifestations of rheumatic diseases. No side effects were noticed.