The paper presents the materials of the Russian Arthritis Registry (OREL) that includes 3276 patients from 11 Russian Federation's largest research-and-practical centers situated in Moscow, Saint Petersburg, Novosibirsk, Kazan, Tula, Yaroslavl, Tyumen. It discusses the main goals of setting up registries, compares the results of an analysis of the data available in the Russian Registry OREL and registries of European countries and the USA. The findings suggest that there is non-uniform information on clinical, laboratory, and instrumental parameters in the national registers of a number
of European countries and the USA. According to its basic characteristics, the Russian Registry OREL compares favorably with a number of other registries in the completeness of data collection, which allows a general idea of rheumatoid arthritis (RA) patients in Russia. For further development of the OREL Registry, it is necessary to concentrate our attention on the following main areas: to improve the quality of filling out documents; to follow-up patients receiving different RA therapy regimens according to the guidelines of the Association of Rheumatologists of Russia for the treatment of RA; to conduct in-depth studies of comorbidity, primarily depressive disorders; to analyze adverse reactions that make RA therapy difficult; to actively use modules for patients' self-rating of their condition; to develop nursing care, etc.

Subclinical inflammation detected by ultrasonography (USG) promotes the progression of joint injury in patients with rheumatoid arthritis (RA). Performed studies ambiguously assess the association of disease activity indices with the Doppler ultrasonic signs of synovitis and the serum concentration of cytokines in patents with RA.

Subjects and methods. Thirty-eight patients with early RA, who were followed up within the framework of the REMARCA program, were examined. All the patients' therapy was started with subcutaneous methotrexate (MTX) with its rapid dose escalation up to 20–30 mg/week and assessment of the achievement of the treatment goal (low disease activity or remission) every 3 months according to the reason why a decision had been made to add biological agents to the therapy. Clinical and standard laboratory parameters with calculated disease activity indices (DAS28, CDAI, SDAI) were analyzed immediately before and 12, 24, and 48 weeks after treatment. Blood cytokine concentrations were determined by the xMAP multiplex technology before and then 12 and 24 weeks after therapy. USG of 8 joint areas of the hands and feet was undertaken prior to and then 12, 24, and 48 weeks following treatment. Gray-scale synovial hypertrophy and synovial power Doppler (PD) signals were rated for each joint area (0 to 3 scores).

Results and discussion. During the drug therapy, all the patients showed improvement with a reduction in activity indices (DAS28, SDAI, CDAI; p < 0.001) and PD signals (p < 0.05). After 12 months of therapy, the ultrasonic signs of remission were found in 4 (21%) patients with clinical remission, amounting to 11% of all the patients included in the study. In a group of patients with active inflammation persisting after 48 weeks of therapy, the basal concentration of interleukin-6 (IL-6) was significantly higher than that in a group without signs of inflammation (p = 0.025). There was a trend for higher tumor necrosis factor-α (TNF-α) levels in the persistent inflammation group (p = 0.06); however, following 24 weeks, the concentration of TNF-α in the patients with persistent synovitis was significantly higher than in those without the latter (p = 0.045). The baseline level of IL-6 as a prognostic factor showed satisfactory sensitivity (71%) and specificity (67%) for a cut-off value of 46.02 pg/ml (p < 0.025). The TNF-α level of ≤51.79 pg/mg achieved after 6 months was associated with the absence of active inflammation, as evidenced by PD with 64% sensitivity and 62.5% specificity (p < 0.046). The predictive value of DAS28 following 24 weeks (3.26) was lower than that of IL-6. Thus, PD USG of hand and foot joints is a sensitive and specific method to assess RA activity. The association of the basal level of IL-6 (and TNF-α to a lesser extent) with ultrasonic changes after 48 weeks of therapy may suggest that PD USG can more accurately characterize inflammation activity than can the disease activity indices.

T helper type 17 (Th17) cell-mediated reactions can be implicated in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitides (SV) (ANCA-SV). The relationship of clinical parameters to the serum levels of interleukin-23 (IL-23) that is involved in a Th17 response and the impact of therapy on this factor were studied in patients with ANCA-SV.

Objective: to study serum IL-23 concentrations in patients having varying ANCA-SV activities and different induction treatment regimens as compared to healthy donors.

Subjects and methods. Enzyme immunoassay was used to investigate IL-23 concentrations in 40 patients with ANCA-SV [median age, 44 years (20 to 65 years); female/male ratio, 1.11] and 8 healthy donors [median age, 47 years (21 to 66 years); female/male ratio, 1.67]. ANCA-SV was classified as granulomatosis with polyangiitis in 23 patients, as microscopic polyangiitis in 14, and as eosinophilic granulomatosis with polyangiitis in 3. Examinations were made in 26 patients with ANCA-SV in active stage and in 28 in remission (induced with rituximab in 22 of the 28 patients). The association was analyzed between IL-23 concentrations and disease activity, as well as clinical features of ANCA-SV.

Results and discussion. Significantly elevated serum IL-23 concentrations were noted only in the untreated patients at the onset of ANCA-SV as compared to the healthy donors (median 41.9 and 13.1 pg/ml, respectively; p < 0.05). Both immunosuppressive and anti-B-cell therapy persistently decreased serum IL-23 concentrations (to 5.2–88 pg/ml).

Conclusion. Further investigation of IL-23 and functionally related cytokines in ANCA-SV is promising

Interleukin-1β (IL-1β) is a potential stimulant of bone resorption. IL-1β receptor antagonist (IL-1RA) is a natural inhibitor of the biological effects of IL-1β.

Objective: to study the frequency distribution of polymorphisms in the IL-1β and IL-1RA genes and their association with bone mineral density (BMD) in women with primary osteoporosis (OP).

Subjects and methods. The distribution of genotype frequency of IL-1β (-511C/T) polymorphism and that of IL-1RA 511C/T polymorphism that is associated with the number of variable tandem repeats (VTR), were investigated in 254 women with OP and 214 healthy women.

Results and discussion. IL-1β (-511C/T) genotype carriers were encountered somewhat more frequently among the patients with OP (53.0%) than in the control group (43.4%); however, the differences were insignificant. In these carriers, the risk of OP was 1.5-fold higher than that in those of other genotypes (odds ratio, 1.49; confidence interval, 1.02–2.18; p = 0.041). The patients who were IL-1β T allele (CT- and TT-genotype) carriers had a significantly lower spine (LI–IV) BMD than those who had not this allele (CC-genotype; p = 0.011). The patients and the controls showed no differences in the frequency distribution of IL-1RA gene polymorphism associated with the number of VTR. In the OP group, the carriers of the rare genotype A1A3 in the IL-1RA gene (3.1%) had significantly higher femoral neck BMD (0.698±0.064 g/cm2) than those of the А1А1, А1А2 and А2А2 genotypes (0.613±0.078; 0.607±0.082. and 0.615±0.064 g/cm2; р = 0.003, р = 0.003, and р = 0.002, respectively).

Conclusion. IL-1β (-511C/T) polymorphism is associated with lower spine BMD and IL-1RA A1A3 genotype polymorphism is related to higher femoral neck BMD.

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.

The paper considers the prevalence, pattern, and clinical features of mental disorders (MDs) that are characteristic of patients with immune-mediated inflammatory rheumatic diseases (RDs). It discusses in detail risk factors for MDs, their pathogenesis, association with inflammatory activity, and major clinical symptoms of RD. Particular emphasis is placed on the diagnosis and treatment of MDs in patients with RDs in primary health care facilities and at rheumatology hospitals.

Rheumatoid arthritis (RA) is a systemic autoimmune rheumatic disease characterized by chronic inflammation of the synovial membrane of joints and by a wide spectrum of extra-articular (systemic) manifestations, with the pathological T cell activation that plays a key role in the pathogenesis of this disease. Therefore, the design of abatacept (ABC) that selectively inhibits T cell costimulation occupies a special place among various approaches to the pathogenetic therapy of RA. The review gives novel evidence for the efficacy and safety of its subcutaneous formulation and discusses its mechanism of action in suppressing the synthesis of autoantibodies and in restoring normal regulatory T cell function,
etc. Mechanisms for the synergic action of ABC and methotrexate for RA and prospects for personified medicine in rheumatology are specially considered using the drug as an example.

The review highlights the impact of obesity on the development, progression, and severity of osteoarthritis (OA) and discusses treatments for obesity in this disease. Weight loss in obese patients with OA is shown to lead to a reduction in clinical manifestations. Despite a great deal of performed investigations of the impact of non-drug therapy for obesity (diet, physical activity), their results are contradictory and call for further investigation

The paper analyzes the data available in the literature on the mechanisms of action of certolizumab pegol (CZP), a new tumor necrosis factor-α (TNF-α) inhibitor for the treatment of active psoriatic arthritis (PsA). It describes the unique molecular structure of the drug and its mechanism of action and shows that CZP effectively inhibits TNF-α, without inducing cell apoptosis, and has also low immunogenicity. The results of the RAPID-PsA clinical trial of CZP are discussed. Treatment with CZP at different doses promptly suppresses the manifestations of both arthritis and psoriasis. There is evidence that CZP therapy prevents joint erosion formation in patients with active disease in particular. It is concluded that CZP is a promising drug to treat active PsA; however, it is necessary to conduct further fundamental and clinical studies of this class of drugs against certain cytokines.

One of the most menacing complications of large joint total endoprosthesis (TE) in patients with rheumatic diseases (RD) is the development of periprosthetic infection (PI), progression of which may give rise not only to limb loss, but also death. At the same time, early diagnosis and adequate surgical care make it possible not only to arrest the infectious process, but also to preserve an implanted joint.

Objective: to define criteria for the diagnosis, prevention, and treatment of PI after hip and knee joint (HJ and KJ) TE in patients with RD.

Subjects and methods. In 2009 to 2013, 654 KJ and 549 HJ TE was performed in the V.A. Nasonova Research Institute
of Rheumatology performed KJ (n = 654) and HJ (n = 549) joint ERs.
Results and discussion. PI developed in 12 (3.63%) and 8 (2.95%) patients after KJ and HJ ER, respectively. Early, delayed, and late PI was seen in 11, 6, and 3 patients, respectively. Eleven patients with early PI underwent joint revision/ debridement with preservation of an endoprosthesis and replacement of HJ endoprosthetic inserts and heads. The operations were completed with the collagen hemobiotics being left in the wound and its drainage. Systemic antibiotic therapy was used for 4–6 weeks. No recurrent infection was observed in 9 cases. Two patients underwent
resurgery, by setting suction-irrigation systems. Nine patients with delayed or late PI had the following operations: A single-stage revision operation (the endoprosthesis was removed and a new one was implanted) was performed in two cases of stable endoprosthetic components and accurately verified low-virulent microorganisms susceptible to certain antibiotics. It was imperative to use cement with an antibiotic, collagen hemobiotics, and systemic antibiotic therapy for 6 weeks. The other 7 patients with unstable endoprosthetic components underwent two-stage revision: Stage 1, endoprosthetic removal and antibiotic-loaded spacer implantation; 6-12 weeks after postoperative wound healing, 6 patients underwent Stage 2, removal of the spacer and implantation of a new endoprosthesis. Following Stage 1, one female patient developed generalized infection and, because of her advanced age and comorbidities, underwent amputation followed by exoprosthetic replacement.

Conclusion. The practical application of the current diagnostic criteria allowed to reveal early slowly progressive PI, perform early surgical treatment without endoprosthetic removal in 11 patients, and prevent recurrent infection in 81.8% of the patients. The described treatment policy for PI turned out to be effective and prevented recurrent infection in 70% of the patients during 1 to 5 years.

The paper analyzes the main problems associated with randomized controlled studies in medical rehabilitation: patient selection; use of simulation devices as placebo; standardization of methods; blinding procedure. It presents methodological considerations for improving the quality of studies.

The paper describes a female patient who had a concurrence of the signs of juvenile idiopathic arthritis (JIA) and chronic recurrent multifocal osteomyelitis (CRMO). The latter was also diagnosed in her mother and brother. There is reason to suggest that CHMO and JIA may be a clinical reflection of identical pathology turning out to be the overlap syndromes of a single autoinflammatory disease. When making a differential diagnosis if there are cases of atypical JIA without signs of autoimmune diseases, CRMO is well to bear in mind.