Rheumatic diseases of juxta-articular soft tissues (RDJAST) (tendinitis, tenosynovitis, bursitis, etc.) are one of the most common causes of disability and one the most common reasons for seeking medical advice. To manage patients with RDJAST is an important part of practising rheumatologists’ work. But unfortunately, the issues of diagnosis and therapy of this pathology have been relatively rarely discussed on the pages of Russian medical journals and at the scientific congresses and conferences of rheumatologists in recent years. This review is to refresh physicians’
interest in this problem. Part 1 of this review briefly considers the general issues relating to the epidemiology, pathogenesis, and diagnosis of RDJAST of the upper extremity, such as rotator cuff tendinitis, lateral and medial epicondylitis, stenosing flexor tenosynovitis, de Quervain’s syndrome, and carpal tunnel syndrome.

The interleukin (IL)-1β inhibitor canakinumab may be effective in relieving an acute gout attack and in preventing an arthritis exacerbation. However, there are insufficient data on the use of this agent to abolish and prevent arthritis in patients who are resistant to another anti-inflammatory therapy.

Objective: to evaluate the efficacy of the interleukin (IL)-1β inhibitor canakinumab in patients with chronic tophaceous gout, who are resistant to traditional anti-inflammatory therapy, in order to abolish arthritis and to prevent its exacerbations when adjusting the optimal dose of allopurinol.

Subjects and methods. An open-labeled prospective study was conducted in 20 patients (mean age, 54.5±12.7 years) with chronic tophaceous gout. Serum uric acid (UA) levels were 486.3±135.2 μmol/l. The inclusion criteria were crystal-verified gout; arthritis affecting more than 5 joints; inefficacy of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids (GCs), or colchicine when used for over a month; more than 4 arthritis attacks during year. The exclusion criteria were Stage ≥3 chronic kidney disease, infectious diseases. All the patents received a single subcutaneous injection of canakinumab 150 mg. NSAIDs and/or colchicine was discontinued a day before the injection. The number of swollen and tender joints and visual analogue scale (VAS) pain intensity were estimated before and 14 and 120 days after the injection; SF-36v1 and HAQ changes were assessed before and 120 days after the injection. 14 days after the injection, all the patients were given allopurinol, the dosage of which was individually adjusted, by starting on 100 mg/day and subsequently increasing by 100 mg/day
every 2 weeks (not more than 800 mg/day) until the goal UA level (<360 μmol/l) was reached.

Results. 14 days after canakinumab injection, arthritis was abolished in 8 (40%) patients and 3 patients needed to continue NSAID therapy. Following 14 days of the injection, there was a decline in the number of swollen joints from 12 [5; 16] to 3 [0; 4] (р<0.001), that of tender joints from 10 [1; 25] to 4 [0; 15], VAS pain from 60 to 24 [10; 30] mm, and high-sensitivity serum C-reactive protein from 29 [1.8; 168] to 7.6 [0.2; 41] mg/l. After 120 days, the decline in the indicators remained in the majority of the patients; there were significant improvements in physical component summary (PCS) from 39±6.9 to 44.5±9.4 (р=0.04), mental component summary (MCS) from 52.6±7.6 to 55.6±8.2 (р=0.01); HAQ scores decreased from 1 [0.1; 1.5] to 0.7 [0; 0.9] (р=0.049). No attacks of arthritis were observed in 10 patients. Seven and
3 patients had 1 and 2 arthritis attacks, respectively. 17 (85%) patients achieved the goal serum UA level; the latter was <300 μmol/l in 12 (60%) patients. Median allopurinol dosage was 400 [300; 600] mg/day. By the completion of the study, 4 (20%) patients required continued NSAID therapy.

Conclusion. The use of canakinumab in patients with severe gout, who are resistant to therapy with NSAIDs, colchicine, and GCs, is an effective method to treat arthritis and to prevent acute arthritis attacks during allopurinol therapy. The administration of high-dose allopurinol causes a target reduction in serum UA levels in most patents.

Objective: to evaluate the osteoclastogenesis regulatory system – osteoprotegerin/receptor activator of nuclear factor-κβ ligand (OPG/RANKL) system – in men with different clinical types of ankylosing spondylitis (AS).

Subjects and methods. The osteoclastogenesis regulatory system was studied in 60 men, including 40 patients diagnosed with AS complying with the 1984 New York criteria and 20 men without AS. RANKL, a major stimulant of osteoclastogenesis, and OPG, a decoy receptor that binds RANKL and, accordingly, blocks osteoclastogenesis, were investigated.

Results. It was shown that in the patients with AS, RANKL concentrations were normal and the content of OPG and OPG/RANKL ratio proved to be significantly higher than those in the men without AS. The highest OPG concentrations were recorded in patients with the axial form of this disease, its moderate activity and early X-ray stage. No relationship was found between the level of RANKL and the clinical characteristics of AS; however, there was a tendency to a slight increase in its concentration in patients with extraskeletal manifestations of AS, its high activity, high functional class, and late X-ray stage.

Conclusion. The considerable increase in OPG levels and OPG/RANKL ratio was ascertained to be associated to the fact that 94% of the patients with late-stage AS characterized by the presence of numerous syndesmophytes. These changes must be compensatory in response to modestly increased RANKL level and enhanced bone resorption.

The Russian Federation has not got sufficient experience with tofacitinib (TOFA) in patients with rheumatoid arthritis (RA) so far; in this connection, all follow-ups using this drug in real clinical practice are of particular interest.

Objective: to evaluate the efficancy and safety of TOFA in an open-label noncomparative trial of RA patients who have failed to achieve low disease activity or remission in compliance with the EULAR criteria after standard disease-modifying therapy and who have been previously untreated with drugs from a group of biological agents.

Subjects and methods. Five patients (4 women and 1 men, whose age was 45 to 58 years (mean age 53 years)) with a valid diagnosis of RA were followed up. All the patients had an advanced clinical stage of RA with erosive arthritis (X-ray Stage III), predominantly involving the minor hand joints. Seropositive and seronegative (for rheumatoid factor (RF)) RA was diagnosed in 4 and 1 patients, respectively. At the inclusion into the study, the patients received disease-modifying antirheumatic drugs. Due to the remaining disease activity, all the patients were given TOFA in a dose of 5 mg twice daily (10 mg/day); moreover, 4 patients received its monotherapy (1 because of intolerability and 3 because of noncompliance); 1 female patient took a combination of TOFA and methotrexate (MT) in a dose of 10 mg/week. Two patients continued to use methylprednisolone 4 mg/day (that had been long taken) in combination with TOFA. The duration of TOFA therapy was 3 months.

Results. TOFA 10 mg/day showed high therapeutic efficacy and good tolerability. Three-month disease-modifying therapy with TOFA
(4 patients) and its combination with MT (1 patient) resulted in a considerable reduction in DAS28 scores and a significant clinical improvement in ACR 20/50/70 responses. Positive clinical changes were associated with a reduction in the blood level of immune markers (C-reactive protein and RF) up to the seroconversion phenomenon in one female patient.

Conclusion. The findings allow TOFA to be recommended for the treatment of RA in case of the inefficiency of standard disease-modifying agents or contraindications to their use.

Methotrexate or leflunomide is used as a first-line synthetic disease-modifying anti-rheumatic drug in the therapy of rheumatoid arthritis (RA). In 2011, the Russian Federation registered and since it has been successfully using leflunomide**.

Objective: to evaluate the efficacy and tolerability of leflunomide** used to treat RA in routine clinical practice.

Subjects and methods.The investigation enrolled patients with varying duration of RA that met the 1987 classification criteria. The patients were followed up in 33 healthcare facilities of Russia from March 2013 to October 2014. A total of 235 patients were randomized; the data of 196 patients were statistically processed. The mean age of the patients was 52.4±11.8 years; the mean duration of the disease was 75.4±69.1 months. The disease activity estimated by DAS28 and CDAI were 5.5±1.2 and 35.1±14.3 scores, respectively. 105 and 57 patients had X-ray Stages II and III disease, respectively. 80.1% of the patients were positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. According to the instruction of its use, leflunomide was administered in a dose of 100 mg/day during the first 3 days and then in that of 20 mg/day. When adverse reactions (ARs) occurred, it was recommended that the daily dose of the drug was decreased to 10 mg. The patients were examined before and 1, 3, and 6 months after treatment. The investigators measured the number of tender joints (NTJ) and that of swollen joints (NSJ), and visual analog scale (VAS) pain intensity, performed a laboratory examination involving clinical blood test, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), in patients during their visits to physicians. The disease activity was assessed with DAS28 and CDAI and ARs were recorded.

Results. Six-month therapy reduced the mean NSJ from 10.9 to 7.5%, NTJ from 12.3 to 8.9, VAS pain intensity from 64.1 to 39.3 mm, on average, ESR from 37.04 to 23.6 mm/hr, and CRP from 27.8 to 12.35 mg/l. By 6 months of therapy, low and moderate RA activities estimated by DAS28 were noted in 70.9% of cases and those by CDAI in 61.2%. No serious ARs were detected during the study.

Conclusion. The findings suggest that leflunomide shows a good clinical efficacy and tolerability.

To control musculoskeletal pain (MSP) is an important component of combination treatment for systemic inflammatory rheumatic diseases, such as rheumatoid arthritis and spondyloarthritis, and a major area of therapy for osteoarthritis and nonspecific back pain. Pain development is associated with a number of pathogenetic mechanisms: local involvement; involvement of the elements of the ligamentous apparatus; chronic muscle tension; biomechanical disorders; dysfunction of the nociceptive system. This necessitates a comprehensive approach during analgesic therapy, with combined use of drugs having a different mechanism of analgesic action. This review considers the targets of pharmacotherapy for MSP and the main groups of medications that may affect them. The paper proposes an analgesic treatment algorithm based on the diagnosis of individual elements of the pathogenesis of chronic MSP and on the successive assessment of treatment results.

The paper analyzes the data available in the literature on the mechanisms of action of ustekinumab (UST), a new medication to treat activepsoriatic arthritis (PsA) and psoriasis. UST is a human IgG1κ monoclonal antibody (mAb). The mechanism of action of the drug is described; UST is shown to effectively neutralize interleukin 12- (IL12) and IL-23-mediated responses in humans, but not to affect the immune response mediated by cytokines or cellular activity. The paper considers the results of clinical trials of UST used to treat psoriasis and psoriatic arthritis, among them there are PSUMMIT-1 and 2 which included 615 patients with active PsA. Long-term treatment with UST is noted to exhibit an increasing clinical efficacy. At week 52 of treatment, all the patients are shown to have 58% ACR20 responses, 34.2% ACR50 responses, 19.6% ACR70 responses, and 69% PASI75 responses. There is evidence that UST therapy slows down joint radiographic progression in patients with active PsA. Trends in the body mass index (BMI) of psoriatic patients treated with UST are comparatively analyzed; at this time the use of the drug contributes to a significantly smaller increase in BMI than that the other mAb-based drug infliximab, which is relevant in patients with PsA, whose obesity lowers the clinical effect of anticytokine therapy. It is concluded that the results of UST administration confirm successful targeted therapy with mAb-based drugs that effectively reduce the severity of clinical manifestations in psoriasis and psoriatic arthritis presumably through local changes in the expression of cytokines in the skin or synovium; however, but it is necessary to perform further fundamental studies and clinical trials of this class of drugs aimed at blocking the biological effects of certain cytokines.

The review presents the data available in the literature on the rate of hypovitaminosis D in systemic lupus erythematosus (SLE), analyzes the associations between the clinical and laboratory parameters of the disease and the levels of vitamin D, and considers the possibilities of the therapeutic use of its metabolites.
Vitamin D deficiency is a very common pathological condition that creates prerequisites for the development of a wide range of diseases. The low serum level of vitamin D may be associated with insufficient solar exposure, genetic predisposition (vitamin D receptor polymorphism), and alimentary factors and may accompany autoimmune diseases. The very recently revealed immunomodulatory properties of vitamin D are of interest with respect to the possible implication of this hormone in the pathogenesis of autoimmune (including rheumatic) diseases. A number of investigators propose to regard vitamin D as a modifying environmental factor involved in the development of autoimmune diseases. There is evidence for the association of low serum 25(ОН)D levels with a risk for some rheumatic diseases (primarily rheumatoid arthritis and SLE), their activity, severity, and prognosis, which calls for further investigation. The antiresorptive, anti-inflammatory, and immunomodulatory effects of vitamin D metabolites substantiate that the latter should be used in combination with traditional disease-modifying agents to treat
chronic inflammatory diseases.

The main goal of osteoarthritis (OA) treatment is to perform rational analgesic and anti-inflammatory therapy, to slow down the progression of the disease, and to preserve quality of life in patients. The performance of analgesic therapy in the elderly is impeded by the presence of a concomitant disease, primarily that of the cardiovascular system and gastrointestinal tract. A group of experts has elaborated the algorithm for managing OA patients, which tracks a careful approach to using nonsteroidal anti-inflammatory drugs and confirms the efficacy of slow-acting agents (chondroitin sulfate (CS) and glucosamine) and intraarticular hyaluronate. The experts have concluded that the use of symptomatic slow-acting drugs for the treatment of OA (SYSADOA), if need be, in combination with short-term paracetanol cycles as basic therapy for this condition is safer and more effective. The 2003 EULAR guidelines identify CS and glucosamine as chondroprotectors. Many studies have shown that CS and glucosamine have a moderate or significant effect on joint pain syndrome and functional mobility in OA; they are safe and characterized by minimal side effects. Long-term qualitative randomized controlled trials have demonstrated that CS and glucosamine are able to slow down the progression of joint space narrowing in OA. It is also shown that the use of a combination of glucosamine and CS allows cartilage loss to be prevented.

Many patients with rheumatoid arthritis (RA) continue symptomatic treatment with anesthetics despite the progress in treating this disease, which is associated with improved methods for its early diagnosis and pathogenetic therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain a main class of analgesics used in RA. NSAIDs are an important component of RA treatment and should be administered in all cases of joint pain. Their administration at disease onset and in undifferentiated arthritis when carrying out a diagnostic search and selecting a concept of use of disease-modifying antirheumatic drugs (DMARDs) is of basic importance. NSAID therapy reduces patients’ distress and quality of life before DMARDs show their activity, considerably reduce disease activity, and relieve pain. This review considers the important aspects of using NSAIDs in RA. Nimesulide is one of the most popular NSAID representatives; its advantages and disadvantages are shown; particular emphasis is placed on its safety. Analysis of the data available in the literature has shown that the hepatotoxicity of nimesulide is not higher than that of many other representatives of the NSAID class. Although the fact that nimesulide may be responsible for menacing cardiovascular events is being investigated, none of the recent large trials of nimesulide has recorded a significant increase in the rate of cardiovascular events during its long-term use.

The paper reviews the literature on the treatment of chronic diseases of the locomotor apparatus. In arthrological diseases, pain is most commonly chronic and has a different genesis, mainly inflammatory, as well as mechanical, vascular, neurogenic, and psychosomatic, which requires continuous, at times long-term, therapy to improve quality of life in patients. Requirements for long-term drug therapy that can reduce the degree of inflammation and pain are determined by the magnitude of the analgesic and anti-inflammatory effect and safety of drugs. Mostly elderly age, the presence of comorbidities, and the need for attendant treatment complicate anti-inflammatory and analgesic therapy in these patients. It is shown that the representative of a class of selective cyclooxygenase-2 inhibitors meloxicam is as effective as classical nonsteroidal anti-inflammatory drugs (NSAIDs), but it is much well tolerated by elderly patients in particular. There is information on the efficacy and safety of meloxicam, as evidenced by researches and real clinical practice. The paper shows the higher safety of meloxicam having an efficacy equal to that of nonselective NSAIDs, its low frequency of gastrointestinal complications, which is comparable with that of celecoxib, and no cardiotoxicity. It also gives clinical and experimental findings suggesting that meloxicam has no negative effect on the cartilage.

EU Registries Forum Meeting took place 2–3 March 2015 in Chantilly, France. Leading experts in the field participated in the forum. Registers
not only of Western Europe but also of Russia, USA, Canada and Japan were presented at the meeting. The most important directions of development of modern registers of patients with rheumatic diseases are the inclusion of comprehensive data on the process of care in practice, the integration of the data of registers in different countries, the active collection of information on the application of the new anti-rheumatic drugs