The All-Russian public organization «The Association of Rheumatologists of Russia» (ARR) is in the forefront of the history and present-day activity of Russian rheumatology. In 1928, the Committee on Rheumatism and Control was set up, which was essentially the predecessor to All-USSR (1964) and All-Russian (1987) research societies of rheumatologists, which were succeeded by ARR (1991). Today ARR is one of the largest and influential public health organizations in Russia, the activity of which has been able to sustain and strengthen a rheumatology service in the country and to train a highly experienced professional community rendering care for patients with rheumatic diseases. Innovative biological agents that could substantially improve treatment results have been recently designed. However, cardinal prognosis improvement is associated not only with the introduction of the innovative medicines, but also with the improvement of early-iagnosis-based pharmacotherapy strategy that determines the possible initiation of very early (a window of opportunity) active tightly controlled anti-inflammatory therapy whose goal is to maximally achieve active remission (to treat to target). ARR jointly
with European rheumatologists has been engaged in this international initiative shortly since its creation in 2010. Further training of rheumatologists has been one of the main tasks of ARR at all times. ARR has proposed a learningthrough-life model of continuing medical education, by involving rheumatologists at full-term and on-line advanced training cycles, seminars, schools, conferences, meetings, and congresses. At the website of the V.A. Nasonova Research Institute of Rheumatology there is a portal of education programs in rheumatology, which is available to all rheumatologists of the country. Today ARR unites not only rheumatologists, but also physicians of related professions: cardiologists, gastroenterologists, aftercare specialists, traumatologists/orthopedists, endocrinologists, neurologists, and psychiatrists. In the past decade, the All-Russian society of disabled people «Nadezhda (Hope) Association» has joined ARR in implementing its measures.

Rheumatoid arthritis (RA) generally starts at the age when many women have already become mothers; however, it may occur in childhood or adolescence. Furthermore, there has been recently a women’s tendency to plan pregnacy for a more mature age, which necessitates a discussion about gestation in this disease. Investigation of mechanisms pregnancy can influence the development of RA both in the gestation and long-term periods is of important theoretical and practical value. The results of these investigations may be used to develop new treatments for RA and management tactics for patients during pregnancy and lactation. The  aper gives the data available in the literature on fertility in RA, impact of pregnancy on its activity and that of RA on the course and outcomes of gestation, as well as current ideas on lactation and use of oral contraceptives in RA. Particular attention is given to drug therapy in pregnant and breastfeeding women with RA: groups of anti-rheumatic drugs are considered in detail in relation to the safety of or a potential risk from their use. A therapeutic algorithm and recommendations for pregnancy planning and a follow-up of patients with RA during gestation are proposed.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are able to effectively control the major symptoms of rheumatic diseases and widely used in real clinical practice. However, they may cause serious gastrointestinal (GI) and cardiovascular (CV) events. The prevention of these events is based on the estimation of whether risk factors (RFs) are present.

Objective: to estimate the presence of RFs in patients needing NSAIDs.

Subjects and methods. A cross-sectional epidemiological survey was performed, during which 2021 physicians from 9 CIS countries questioned for 2 weeks at least 10 patients needing NSAIDs. The inclusion criterion was severe musculoskeletal pain (>40 mm on a 100-mm visual analogue scale (VAS)) or use of NSAIDs at the examination. Data were obtained on 21,185 patients (57.5% women and 42.5% men) (mean age 50.5±14.1 years) who had predominantly dorsalgia (56.6%) and osteoarthritis (23.5%). The mean pain value was 62.2±25.2 mm.

Results. 1.7, 11.3, and 25.3% of patients had history of gastrointestinal bleeding, ulcer, or dyspepsia, respectively; people over 65 years of age constituted 16.8%; those who took low-dose aspirin (LDA) – 20.0%. The total number of patients at high risk for GI events was 29.0%. There were also common CV RFs: myocardial infarction or stroke (7.8%), coronary heart disease (17.8%), hypertension (37.7%), and diabetes mellitus (8.1%). The total number of patients at high risk for CV events (without SCOR assessment) was 23.0%. Many high-risk patients who has already used NSAIDs received no effective prevention. Thus, 62.2% of the patients at high GI risk took gastroprotective drugs; 53.2% of those at high CV risk used LDA.

Conclusion. A large number of patients needing active analgesic therapy have a serious risk for drug-induced complications. This limits the possibility of using NSAIDs and determines the need for effective prevention or use of alternative methods for analgesia.

To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilities of its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care.

Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT) and biological agents (BA) when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA) who have risk factors for a poor prognosis.

Subjects and methods.The results of the REMARCA (Russian InvEstigation of MethotrexAte and biologicals in eaRly aCtive inflammatory Arthritis) trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%); anti-cyclic citrullinated peptide antibody positivity (89.2%). Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months)); 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months)). In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission) was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA) (a tumor necrosis factor inhibitor or abatacept). If the former was insufficiently effective, it was substituted for a BA from another class.

Results. Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7%) patients; a BA was given to 81 (62.3%) patients. Following 6 and 12 months, low activity or remission according to SDAI was observed significantly more frequently in the patients who continued subcutaneous MT monotherapy than in those who received combined therapy with MT and BA. The similar results were obtained by using DAS28 and CDAI to assess a trend in disease activity. After 6- and 12-month follow-up, there was a significantly more marked decline of tender joint count, SDAI and CDAI in early RA than in advanced-stage RA; at 12 months, SDAI remission rate was 45.7% and 28.3%, respectively (p=0.047).

Conclusion. The treat-to-target strategy should be used in real clinical practice and can yield spectacular results. Active therapy with subcutaneous MT with its rapid dose escalation to the maximally tolerable dose allows identification of a considerable group of patients (38%) with a good response to MT monotherapy

The data on the efficacy of rituximab (RTM) in systemic manifestations of primary Sjogren's syndrome (PSS) are limited by single trials.

Objective: to evaluate the efficacy of RTM in patients with the systemic manifestations of PSS.

Subjects and methods. RTM therapy was performed in 24 patients with the systemic manifestations of PSS. The mean dose of a RTM for induction therapy cycle was 2±0.3 g. Nine patients received RTM monotherapy and 12 were treated with RTM in combination with cyclophosphan. A complete clinical response was defined as complete disappearance of pre-treatment clinical manifestations; a partial one was interpreted as more than 50% improvements in some signs or cessation of half of the existing signs. A complete immunological response implied normalization of a low baseline C4 level, disappearance of cryoglobulinemia and monoclonal immunoglobulins in serum and/or their light chains in urine; a partial one meant normalization or cessation of more than half of the initial signs. The remaining cases were regarded as no treatment response. A recurrence was considered to be the reoccurrence of at least one pretreatment sign during a 3-month or more follow-up.

Results. At 3 months after RTM therapy, a complete or partial clinical response was observed in 71.4% (15/21) and 19% (4/21) of cases, respectively. A complete or partial immunological response was obtained in 50% (10/20) and 25 (5/20) of the patients, respectively. At 6 months, a clinical and immunological recurrence was noted in 25% (5/20) and 33% (6/18) of the patients, respectively. There was a reduction in median ESSDAI from 8 (7–10) (median, 25th and 75th percentiles) to 3 (2–4) at 3–6 months (p<0.001). After RTM therapy, medium serum BAFF concentrations
in 9 patients decreased from 1.71 (0.66–2.73) to 0.68 (0.62–2.58) ng/ml (normal value <0.8 ng/ml).

Conclusion. RTM shows good efficacy in treating systemic forms of PSS.

Objective: to assess the relationship of the efficiency of adalimumab (ADA) therapy in early rheumatoid arthritis (RA) with the serum level of the drug and with the presence of antibody (Ab) to it.

Subjects and methods. Serum concentration of ADA and Ab against it (μg/ml) were measured using an enzyme immunoassay in 25 patients with early RA before, 12 and 24 weeks after beginning of the therapy. All patients received the disease-modifying antirheumatic drug methotrexate and ADA 40 mg subcutaneously every other week. ADA was the first biological agent for all patients.

Results. The patients were divided into the following groups: those with a serum ADA level of <2.85 (Group 1, n=7) and ≥2.85 (Group 2, n=13). After 24 weeks of treatment, Group 1 showed higher disease activity (DAS was 4.5 [3.3; 4.9]) and levels of acute-phase reactants (ESR, 44 [18; 57] mm/hr; C-reactive protein (CRP), 10.1 [4.9; 34.5] mg/ml) than Group 2 (3.5 [2.9; 3.9], 15.0 [6.0; 17.0] mm/hr, 1.9 [0.75; 6.7] mg/ml, respectively; p<0.05). Also, after
24 weeks of therapy, there was a negative correlation of ADA level and DAS28 (r=-0.46; p=0.04), CRP (r=-0.54;p=0.02) and ESR (r=-0.5; p=0.02). Anti-ADA Ab were found in 3 and 2 patients after 12 and 24 weeks, respectively. After 24 weeks of therapy, all
patients with anti-ADA Ab exhibited no clinical effect. There were few unresponsive patients (11%) among those without anti-ADA Ab.

Conclusion. In patients with early RA treated with ADA, its low serum level (<2.85 μg/ml) is associated with the higher clinical and laboratory measures of disease activity. After 12–24 weeks of ADA therapy, 10–12.5% of patients are found to have Ab to the drug and its production is associated with lower efficacy.

Objective: to reveal neurogenic mechanisms in the pathogenesis of chronic pain syndrome in rheumatoid arthritis (RA) and knee osteoarthritis (OA) in order to develop individualized pharmacotherapy.

Subjects and methods. One hundred and eighty-three patients with RA and 80 with knee OA were examined. By using the neuropathic pain diagnostic questionnaire (DN4), all the patients were divided into 2 groups with and without a neuropathic pain component (NPC).

Results. NPC was found in 43% of the patients with RA and it was connected with involvement of the peripheral somatosensory system. In RA, NPC was common in older patients with longer disease duration, higher X-ray stage, and severe functional insufficiency. 30% of patients with knee OA also had NPC, however the signs of nervous system involvement were absent. In OA, NPC was associated with hyperalgesia, higher pain intensity, more marked joint dysfunction on the WOMAC, and anxiety.

Discussion. This investigation revealed a mixed pattern of chronic pain syndrome in patients with RA and knee OA; some patients were found to have a NPC in the presence of predominantly a nociceptive component

Objective: to estimate the prevalence of psoriatic arthritis (PsA) and the pattern of osteoarticular injury in psoriatic patients according to the data of the PEST (Psoriasis Epidemiology Screening Tool) questionnaire.

Subjects and methods. The trial included 80 psoriatic patients who had sought for dermatological and rheumatological advice (35 men and 45 women); mean age 43.06±1.71 years; psoriatic skin damage area (PSDA) 9.83±2.63%; and psoriasis area severity index (PASI) 12.05±3.23; dermatology life quality index (DQLI) 8.57±0.94. Answers to 6 questions about nail psoriasis in the PEST questionnaire were rated; each positive answer corresponded to 1; PEST ≥3 or <3 is indicative of the presence or absence of psoriasis, respectively. All patients, irrespectively of PEST value, were examined by a rheumatologist and underwent a standard clinicoinstrumental examination. The CASPAR criteria were considered to be a gold standard of PsA diagnosis.

Results. 53 (66.2%) patients had PEST≥3; the CASPAR criteria confirmed PsA in 40 (75.4%) of them. 27 (33.8%) patients had PEST<3; in 13 (48%) of them, fulfilled CASPAR criteria. PsA was first diagnosed in 30 (56.6%) of the 53 patients. Thus, PsA was identified in 53 (66.2%) of the 80 patients; another rheumatic disease (RD), such as dermatomyositis, rheumatic polymyalgia, osteoarthritis, ankylosing spondylitis, reactive arthritis, rheumatoid arthritis (RA), gout, etc., was found in 10 (12.5%); a concurrence of RDs (RA and gout) in 3 (3.7%); RD was absent in 14 (17.5%) cases. The disease duration was <1 year in 17 (34%) of the 53 patients with PsA, 1 to 2 years in 16 (32%), 2 to 3 years in 11 (22%), and ≥3 years in 9 (18%). Nail psoriasis was detected in 55 (70%) patients. It was found in 38 (71.7%) patients with PsA and in 17 without this disease. In patients with PsA, PSDA averaged 7.23±2.24%; PASI 11.69±1.94; DQLI 7.71±0.17, respectively; in those without PsA 11.44±2.78%, 14.94±4.29, and 8.96±1.74, respectively. No significant differences of these parameters were found.

Conclusion. Thus, in psoriasis, there may be any RD, chiefly PsA with common nail involvement. The PEST questionnaire reveals PsA at its early stage in the majority of cases; however, its isolated use is not sufficient to establish accurate diagnosis and rheumatologic clinicoinstrumental examination is necessary.

The epidemiological characteristics of osteoporotic fractures in Russia have been inadequately studied.

Objective: to estimate the incidence rate of osteoporotic fractures in the old age groups of an urban population in the Middle Urals.

Subjects and methods. The survey was performed in Pervouralsk, a typical industrial town in the Middle Urals, with a total of 160,860 people, including 54,189 dwellers over 50 years of age (20,746 men and 33,443 women), which amounted to 33.7% of the general population of the town. The survey covered its residents aged 50 years and over who had fractures of the proximal hip (FPH), distal forearm (FDF), distal shin, ribs, or surgical neck of the humerus
between 1 January 2008 and 31 December 2009. Statistical analysis was made applying the programs Biostatistics, Microsoft Excell 2007, and MedCalc (demo-version). The findings were processed using parametric and nonparametric statistical methods.

Results. During two years, 1371 fractures, including FPH, FDF, fractures of the humerus, distal shin, and ribs, were registered in the examined sample of persons aged 50 years and over from Pervouralsk. 383 (27.9%) of these fractures occurred in men and 988 (72.1%) in women. The incidence rate of all fractures was 1265.0 per 100,000 inhabitants aged 50 years and over (1,477.1 for women and 923.1 for men). FDF were more common in women, the incidence was 787.9 cases per 100,000 population; costal fractures – in men (386.7 per 100,000). The investigation has shown that certain types of fractures are predominant in the oldest age groups. Thus, the incidence rate of FDF and fractures of the distal shin decreases while that of FPH and fractures of the humerus increases
with age, which is likely to be due to several causes: an age-related decline in bone mass; an increase in the frequency of falls with age; muscle weakness and movement discoordination, which alter the mechanism of fall and increase the risk of femoral and humeral fractures.

The lecture gives basic information about psoriatic arthritis (PsA), a chronic inflammatory disease of the joints, spine, and enthesises from a group of spondyloarthritis. It describes the epidemiology of the disease and considers current ideas on its pathogenesis and factors influencing the development of PsA in psoriatic patients. The classification and clinical forms of PsA are presented. The major clinical manifestations of the disease are indicated to include peripheral arthritis, enthesitis, dactylitis, and spondylitis. The diagnosis of the disease is noted to be established on the basis of its detected typical clinical and radiological signs, by applying the CASPAR criteria. A dermatologist, rheumatologist, and general practitioner screen PsA, by actively detecting complaints, characteristic clinical and radiological signs of damage to the joints, and/or spine, and/or enthesises and by using screening questionnaires. There are data that patients with PsA are observed to be at higher risk for a number of diseases type 2 diabetes mellitus hypertension, coronary heart disease, obesity, metabolic syndrome, inflammatory bowel diseases, etc. The aim of current pharmacotherapy for PsA is to achieve remission or minimal activity of clinical manifestations of the disease, to delay or prevent its X-ray progression, to increase survival, to improve quality of life in patients, and to reduce the risk of comorbidities. The paper considers groups of medicines used to treat the disease, among other issues, information about biological agents (BA) registered in the Russian Federation for the treatment of PsA. Most patients are mentioned to show a good response to this therapy option just 3–6 months after treatment initiation; however, some of them develop primary inefficiency. In this case, switching one BA to another is recommended. Some patients using a BA develop secondary treatment inefficiency, which is firstly due to the appearance of neutralizing antibodies and to the decrease of blood drug concentrations. Concurrent methotrexate therapy is noted to improve adherence to BA therapy in patients with PsA.

Infectious diseases still remain a serious social and medical problem. The importance of comorbid infections in rheumatology has increased substantially in recent years, particularly due to the clinical introduction of biologicals. The investigation and active use of different vaccines are one of the ways to solve the above problem. This review considers the issues concerning the use of vaccines against influenza, infections caused by pneumococci, herpesviruses, human papillomavirus, and hepatitis B virus in rheumatology patients. It discusses the safety and immunogenicity of vaccination associated with the prevention of airway infections as the most common cause of a poor outcome in rheumatic diseases. The main areas of future investigations in the problem under consideration are defined.

The paper gives the data currently available in the literature on the impact of biological agents (BA) on bone mineral density, metabolism, and remodeling in rheumatoid arthritis (RA). These agents, by virtue of their high efficacy, are widely used to treat patients with RA. Since localized and generalized bone resorption and destruction play a prominent role in its pathogenesis, an investigation of the effect of BA on bone may be of essential interest. Activated osteoclastogenesis occurs because of an interaction between the immune and bone systems under the influence of different proinflammatory cytokines. The inhibition of the latter has been ascertained to not only reduce joint inflammation, but also to prevent localized and generalized osteoporosis. This review discusses the results of these trials and the issues of further investigations.

The paper discusses the apparent rhetorical question whether psoriatic arthritis is psoriatic. Based on the data available in the literature and logical considerations, it has been suggested that accepted view may be contrary to fact.

The major goals of the EUSTAR (EULAR Scleroderma Trials And Research group) are to coordinate and centralize systemic sclerosis (SS) researches in Europe, to reach a consensus in the standards of evidence-based medicine for patient management, to enhance treatment efficacy, and to improve quality of life in patients and prognosis. Under the aegis of the EUSTAR, more than 100 centers have combined their efforts to solve basic research problems, to study the clinical aspects of the disease, and to conduct clinical trials. The major task of their activities has been to follow-up and timely treat SS patients examined according to a standard protocol, and to accumulate information in the unified European database that includes more than 10,000 patients now. The V.A. Nasonova Research Institute of Rheumatology has formed a cohort of 220 patients with SS, of whom 90–100 persons are annually followed up.
The main joint projects implemented have shown the present-day course of SS, studied the causes of death, and characteristics of patient subgroups (juvenile scleroderma, SS in the elderly, damage of the lung, heart, gastrointestinal tract, etc.). New diagnostic criteria for SS and an algorithm for its very early, preclinical diagnosis have been proposed. An analysis of the first 3656 patents with SS has revealed the major clinical characteristics of its diffuse and limited forms at the present stage. Pooled patient data have been used in international multicenter projects whose results are given in joint publications. The results of EUSTAR projects with the participation of the V.A. Nasonova Research Institute of Rheumatology are covered in 28 articles. Analysis of the results of EULAR/EUSTAR researches gives grounds to hold that the early diagnosis and timely detection of visceral injuries and the use of current therapy standards may assist in improving the quality of life of patients as well as in reducing the severity of SS and its mortality rates.

The 15th annual European Congress of Rheumatology took place in Paris in June 2014. Its program was extremely diverse and included a discussion of new data pertinent to the diagnosis and treatment of the most common rheumatic diseases and problems of their etiology and pathogenesis, personified therapy, and many others. The Congress focused on the problems of early rheumatoid arthritis (RA). A number of papers concerned the efficiency and safety of different therapy regimens for RA at its onset, the discontinuation of biological therapy after achievement of remission, and the maintenance of drug-free RA remission. The Congress discussed new results of the tREACH trial comparing three treatment regimens for early inflammatory arthritis: combined therapy with methotrexate (MT), sulfasalazine, and hydroxychloroquine in conjunction with intramuscular glucocorticoids (GC); combined therapy with these drugs in conjunction with oral GC; and MT monotherapy with oral GC. A large number of reports dealt with the use of tumor necrosis factor-α inhibitors, the evaluation of their immunogenicity, and the
analysis of reasons for therapy discontinuation and adverse reactions. Some aspects of therapy with disease-difying antirheumatic drugs were discussed. A number of reports concerned the application of novel laboratory biomarkers for RA.
Thus, sufficiently many new data that will be able to optimize therapy for common rheumatic disease, such as RA, were presented at the Congress.