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
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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 <2,6). The difference in HAQ scores was 0,5 (a reduction from 1,89 to 1,39 scores) and EQ-5D quality of life scores improved by virtually twice (from 0,28 to 0,49). There were two adverse reactions (decreased hemoglobin and respiratory infection) during the therapy. There was a moderate increase in ALT concentrations and a trend towards a decrease in the percentage of neutrophils (with their normal absolute count), which is occasionally seen during TCZ therapy.
Thus, preliminary analysis of the data of the Russian study strongly suggests that TCZ is effective in severe RA resistant to therapy with DMARDs, primarily MT. TCZ therapy makes it possible to achieve a very rapid reduction in the clinical and laboratory activity of the disease and to substantially enhance the functional activity and quality of life of patients.

Objective. To study the functional outcomes of rheumatoid arthritis (RA) 1, 3, 5, and 8 years after use of various procedures of anti-inflammatory therapy.
Subjects and methods. One hundred patients with valid RA were examined. The patients were divided into 3 groups: 1) 38 patients received basic anti-inflammatory drugs (BAIDs) only; 2) 37 patients took BAIDs in combination with glucocorticoids (GCs); 3) 25 patients had synchronous programmed intensive therapy.
Results. The early use of therapy with BAIDs without GCs in controlled therapy allows functional outcome improvement in patients in RA to greater extent. No therapy control leads to functional outcome worsening in RA. During a long follow-up, there is a reduction in the correlation of the Health Assessment Questionnaire (HAQ) scores with the parameters reflecting disease activity and an increase in the correlation of the HAQ with those reflecting the progression of RA. The development of the structural and anatomic changes in hand periarticular tissues with the formation of irreversible deformities does not correlate with the HAQ score in patients with RA.

Objective: To test the significance of new criteria for axial spondyloarthritis (axSPA) in the early stages of ankylosing spondylitis (AS) and spondyloarthropathies (SPA) and that of changed ASAS criteria for inflammatory back pain.
Subjects and methods. The study enrolled patients aged 16 to 49 years who were consecutive visitors to the Research Institute of Rheumatology, Russian Academy of Medical Sciences, in 2006-2008 for chronic (a history of at least 3 months, but not more than 3 years) low back (LB) and/or thoracic portion (TP) pains without significant X-ray signs of sacroiliitis. In addition of pelvis X-ray study, goal-seeking collection of history data, and examination, sacroiliac joint (SJ) magnetic resonance imaging (MRI) (1,5 Tesla, Magnetom Symphony (Siemens)) was performed and HLA-B27 and erythrocyte sedimentation rate were determined in all the patients. X-ray and MRI of vertebral portions with pains being observed were, if needed, carried out. The diagnosis of axSPA was established in the detection of inflammatory LB and/or TP pains that met the criteria described by A. Calin et al., in the presence of MRI signs of sacroiliitis and/or spondylitis with no evidence for another interpretation of back pain. Pelvis X-ray films were assessed by two rheumatologists; MRI scans were estimated by a rheumatologist and a radiodiagnostician. The MRI diagnosis of sacroiliitis was made if there was one T2-FS medullary edema (ME) area (on at least two consecutive slices) or two areas or more (on at least one slice) in the SJ subchondral or periarticular regions. The MRI diagnosis of spondylitis was established if there was one T2-FS ME area (on at least two consecutive slices) or more (on at least one slice) in the vertebral bodies or posterior vertebral structures. The ESSG criteria or the criteria proposed by B. Amor et al. were used for the diagnosis of undifferentiated SA. Results. Early axSPA was diagnosed in 39 patients (a study group). A control group consisted of other 39 patients with chronic LB and/or TP pain without MRI signs of sacroiliitis and spondylitis. The patients' median age in these groups was 25 and 23 years; the median duration of back pain was 12 and 20 months; HLA-B27 was detected in 94,9 and 43,6% of the patients, respectively. The sensitivity of the first variant of the ASAS criteria was 84,6% and its specificity was 100%. These of the second variant of the ASAS criteria were 94,9 and 84,7%, respectively. With the consecutive use of the first variant of the ASAS criteria for early SPA, then their second variant, their sensitivity was as high as 100%. LB pain only was observed in 76,9% of patients with axSPA, 20% of them having wandering pains in the buttocks. In the control patients, LB pain was also predominant (71,7%). The sensitivity and specificity of the criteria proposed by M. Rudwaleit et al. and the ASAS (J. Siper et al.) were 89,7 and 85,7%; 89,7 and 100%, respectively. There were no statistical differences in the sensitivity of individual criteria. The specificity of the ASAS criteria was significantly higher than that of the criteria described by A. Calin (p=0,0000; double Fisher's test). Conclusion. With the consecutive use of the first variant of the ASAS criteria for early SPA, then their second variant, their sensitivity was as high as 100%. It is more preferential to use the criteria described by М. Rudwaleit et al. or the 2009 new criteria by the ASAS working group. The valuable symptom of inflammatory pain is wandering buttock pain, the specificity of which in patients with early axSPA was 100%.

Objective: To define reasons for late diagnosis of ankylosing spondylitis (AS) in the outpatient setting.
patients aged 18 years or older with the valid diagnosis of AS being first established in their life. Results. The outpatient diagnosis of AS is made 8,1±6,0 years, on average, after the occurrence of the first symptoms of the disease. In 75% of cases, the onset of AS begins with inflammatory back pain. The most common diagnosis made in patients is vertebral osteochondrosis before AS is diagnosed in the outpatient practice. Conclusion. The reasons for late diagnosis of AS are the pattern of the disease at its onset and diagnostic errors.

Objective: To assess the informative value of parotid gland (PG) biopsy in the diagnosis of sarcoidosis.
Subjects and methods. PG biopsy was made in 15 patients (4 males and 11 females) with a presumptive diagnosis of sarcoidosis. The patients were grouped by the presence of PG enlargement.
Results. By taking into account clinicoinstrumental data and found morphological changes, three (20%) and 12 (80%) patients were diagnosed as having multifocal fibrosclerosis and sarcoidosis, respectively. PG biopsy could establish a histologically verified diagnosis in 100% of cases (that of sarcoidosis (50%) and multifocal fibrosclerosis (50%) in the enlarged PG group (n=6)); sarcoidosis was diagnosed in 67% of cases in the non-enlarged PG group (n=9). Epithelioid cell granulomas were detectable in 100 and 50% of the patients with sarcoidosis in its active (n=6) and remission (n=6) phases, respectively. Conclusion. PG biopsy is of high diagnostic value and may be used in the diagnosis of sarcoidosis.

Objective: To study the incidence of vascular disorders and to estimate their contribution to the severity and prognosis of Behcet's disease (BD). Subjects and methods. Ninety-five patients with evident BD, followed up at Research Institute of Rheumatology, Russian Academy of Medical Sciences, in the January 2006 to October 2009, were examined. Their mean age was 29,7 years; malefemale ratio was 3,7. The onset of the disease was chiefly at the age of 21-30 years in 36,8% of the patients.
Vascular pathology was evaluated by the following techniques: vascular duplex scanning; brain magnetic resonance imaging in the mode of venosinusography, contrast-enhancement chest computed tomography, chest and abdominal angiography. The data were statistically processed by the programs Statistica 6.0 (Statsoft, USA) and EpiInfo 5.0 recommended by the WHO. Parametric and non-parametric statistical methods were used.
Results. Vascular diseases were diagnosed in 26,3% of the patients. The venous bed was mainly involved (88%), the proportion of patients with arterial pathology was 12%. Vascular death occurred in 2 men aged 20 and 18 years due to pulmonary artery rupture aneurysm and brain sagittal sinus thrombosis.
Assessment of an association of vascular disorders with other clinical manifestations of BD revealed their correlation with erythema nodosum and epididymitis. The risk for vascular events in erythema nodosum was 5 times greater (OR=5,03; 95% CI 1,54-17,41), the risk was higher in men than that in women (OR=7,11; 95% CI 1,83-30,02 versus OR=2,15; 95% CI 0,16-61,38). The male vascular risk is associated with epididymitis (OR=6,71; 95% CI 1,25-39,89). In erythema nodosum concurrent with epididymitis, the relative vascular risk was increased up to 21; 95% CI 2,15-503,94.
Conclusion. Vascular disorders in BD were diagnosed in one fourth of the patients, mainly in young male patients. Severe thromboses with the development of chronic venous insignificance, Budd-Chiari syndrome, pulmonary and iliac artery aneurysms, and arterial thromboses were observed in male patients only. Vascular events were associated with erythema nodosum and epididymitis; in these concomitances, the vascular risk was substantially increased. Vascular death rates were 2,2%.

Objective: To evaluate the time course of changes in the symptoms of rheumatoid arthritis (RA) and its activity index during tight control in routine clinical practice.
Subjects and methods. One hundred and twelve Khabarovsk outpatients with the valid (by the American College of Rheumatology (ACR) criteria) diagnosis of RA (88 females and 24 males; their mean age 37,8±1,9 years) were followed up. The patients were divided into 2 groups: 1) those who had been followed up once every 3-4 months by a rheumatologist in real clinical practice for 2 years; 2) those who were tightly controlled (estimation of the number of swollen and tender joints and general conditions, pain scores by the visual analogue
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scale, erythrocyte sedimentation rate, by calculating the disease activity score (DAS) 28 and functional index by the Health Assessment Questionnaire (HAQ)) by an investigating rheumatologist once monthly. The significance of differences between the groups was estimated by Student's t-test (a significant difference at p<0,05).
Results. In Group 1, 32,8% of the patients achieved the permissible activity (< second-degree) of RA during 2 years. Remission was recorded in 8.6% of cases. The HAQ functional activity failed to achieve the goal level (1,8±0,4 and 1,7±0,8 following 12 and 24 months, respectively. In the tight control group 2 (n = 54), remission was observed in 47 (87%) patients: induced remission in 17 (31,5%) cases and remission during therapy in 30 (55,6%) patients. The decrease rates for all clinical parameters of RA were much higher in Group 2. Changes were noted by just month 3; a significant improvement was achieved by month 6 (p<0,05) and this difference was obvious by months 12 and 24 (p<0,01 and p<0,001).
Conclusion. Thus, tight control provides a greater opportunity to make timely and adequately correct treatment, by applying the DAS 28 and HAQ score, remission or decreased RA activity is achieved more rapidly.

Heavy economic expenses for treatment with genetic engineering biologicals (GEB) in patients with rheumatoid arthritis (RA) determine what strategies are most optimal in terms of both their clinical efficiency and economic constituent should be sought for. Objective: To define the most optimal strategies to use tocilizumab and TNF-α inhibitors in a Russian population of patients with different duration of RA.
Material and methods. The investigation was based on the cost-benefit analysis using imitation simulation. Modeling relied on the relationship of RA mortality to a patient's functional status rated by the health assessment questionnaire (HAQ). A model was constructed, which simulated the progression of functional incompetence in RA patients seeking medical advice in health care facilities of Russia. Five variants of the model were developed to simulate the sequence of changing the basic anti-inflammatory drugs (BAIDs), including the incorporation of tocilizumab or a TNF-α inhibitor. The first strategy that ignored the use of BAIDs involved palliative therapy alone, by
simulating a gradual disease progression, and that was used to obtain data for comparison of results (reference). The second strategy estimated the sequence of BAID changes in the following order: methotrexate (MT) → leflunomide (LF) → sulfasalazine (SS) → azathioprine → palliative therapy. This strategy was also considered to obtain data for comparison of results. The third strategy comprised the use of tocilizumab or a TNF-α inhibitor after determining the resistance or intolerance of MT therapy. The fourth strategy assumed the use of tocilizumab or a TNF-α inhibitor after determining the resistance or intolerance of MT and LF therapy. The fifth strategy envisaged the use of tocilizumab or a TNF-α inhibitor after determining the resistance or intolerance of MT, LF, and SS therapy. The possibility that a combination of BAIDs and MT might be used and the impact of RA duration on lower HAQ scores were taken into account. Direct and indirect costs were calculated in terms of social aspects, their relationship to HAQ scores being derived. The cost of TNF-α inhibitors was taken as that of adalimumab. The model simulated the participation of 10,000 patients in each sequences. The prediction horizon was 10 years. The age of patients and the initial distribution of HAQ scores were taken from the results of the RAISER epidemiological survey. Results. The least additional cost per quality-adjusted life year (QALY) was when GEB was used after 3 synthetic BAIDs, no significant difference being found in the cost of tocilizumab and that of a TNF-αinhibitor. The additional cost for a TNF-α inhibitor used after 3 BAIDs in relatively early RA was about 500,000 rubles; that for tocilizumab was slightly higher - 560,000 rubles. The cost increased with the duration of RA and when the moment of using GEB approached that of discontinuation of the first synthetic BAID - MT. The administration of tocilizumab after MT turned out to be cost-effective in patients with relatively late RA - the cost per QALY was 845,000. The use of synthetic BAIDS was in terms of cost-based effectiveness was most optimal - about 40,000 rubles per QALY. The availability of additional agents permits the choice of the most optimal strategy for the use of GEB.
Conclusion. The application of the imitation simulation technique demonstrated that the strategy of using GEB after several synthetic BAIDs in patients with the least duration of the disease is most optimal in the context of cost-based efficiency. In this regard, no great difference was found in the use of tocilizumab or TNF-α inhibitors

The paper provides a detailed description of a rare case of rheumatoid arthritis concurrent with Sjogren's syndrome, MALT lymphoma of the parotid gland, and multiple myeloma. It presents a review of literature