Cryopyrin-associated periodic syndromes (CAPS) are the most prominent representatives of monogenic autoinflammatory diseases (AIDs). They are characterized by a concurrence of fever, rash, and other symptoms that are accompanied by disabling or life-threatening complications. Based on the current guidelines for the management of patients with AIDs and on their own experience, the authors have elaborated a diagnostic algorithm for CAPS, which can optimize their differential diagnosis with systemic juvenile arthritis and other AIDs and the early use of effective therapy and management tactics. Interleukin-1 inhibitors are target agents, by which one can monitor activity and prevent complications. The given algorithm will be able to improve the timely diagnosis of CAPS and to optimize treat-to-target treatment and management in patients.

Data on the clinical course and treatment of such as the severe disease systemic lupus erythematosus (SLE), are virtually lacking in Russia.

Objective: to evaluate the clinical presentations of the disease and its treatment in adult patients with active SLE in the cities of three post-Soviet countries (Russia, Ukraine, and Kazakhstan) in the ESSENCE study.

Patients and methods. This paper concerns Russian patients. The data of clinical cases of 232 patients who were followed up in 6 centers (Moscow, Saint Petersburg, Voronezh, Yekaterinburg, Kursk, and Yaroslavl) were studied. The demographic and clinical characteristics of the patients, SLE activity, laboratory and instrumental findings, treatment, and consumed healthcare resources were assessed.

Results. The demographic characteristics of patients with SLE were generally comparable to those in other international studies. However, the Russian patients were 4–10 years younger and their SLE duration was 3–7 shorter; the majority of patients were noted to have a severe course of the disease. The level of SLE activity was higher in the patients of our study. There were frequent hospitalizations and unplanned visits to a physician because of exacerbations. The Russian patients who had repeatedly sought medical advice had obvious and severe SLE complications. The disease remained with great probability undiagnosed or misdiagnosed in a sufficiently large number of patients. There were pitfalls in the treatment of SLE: less than half of the patients received antimalarial drugs; nearly 100% took glucocorticoids; nonsteroidal anti-inflammatory drugs were used rarely. The ESSENCE study can form a view of the clinical picture of SLE in Russia. These findings may help to plan healthcare resources in our country.

Despite the advances in the therapy of rheumatoid arthritis (RA), which are associated with the use of biological anti-rheumatic drugs, the problem
of effective treatment of RA is not still solved. Inclusion of new methods in treatment strategies, in particular the so-called «small mole

cules», i.e. synthetic compounds acting on intracellular signaling pathways, such as Tofacitinib (TOFA) approved for use in rheumatologic practice, is very important.

Objective: to evaluate the efficacy and safety of therapy with TOFA in combination with synthetic disease-modifying anti-rheumatic drugs (s-DMARDs), primarily methotrexate (MTX) in in patients with active RA in real clinical practice.

Subjects and methods. This ongoing open-label trial is a part of the scientific program «Russian Investigation of Methotrexate and Biologics in Early Active Inflammatory Arthritis» (REMARCA) that explores the possibility of adapting the «treat-to-target» strategy in real prac-tice in Russia. The study included RA patients with moderate to high disease activity despite treatment with MTX or other DMARDs. A total of 41 patients with RA were included (8 males, 33 females; mean age 52.6±14.2 years, disease duration 47.2±49.7 months, 82.9% RF+ and 80.5% anti-CCP+,DAS28-ESR 5.45±0.95, SDAI 30.2±12.2). All the patients had previously received s-DMARDs; 12 (29.3%) patients also had biological DMARDs (1 to 4 biologics). Oral TOFA 5 mg in combination with MTX or leflunomide was administered twice daily to 40 and 1 patients, respectively, with the possibility of increasing the dose up to 10 mg BID. To date, 37 and 12 patients received TOFA for 3 and 6 months, respectively.

Results. TOFA was used as a second-line drug (after s-DMARDs failure) in 29 (70.7%), as a third line drug (after s-DMARDs and biologics failure) in 12 (29.3%) patients. The dose was escalated to 10 mg BID in 13 (31.2%) patients, on the average, 11.2±1.7 weeks after treatment initiation. TOFA was not discontinued in the reporting period. There was a significant reduction in disease activity following just 4 weeks of TOFA therapy. At 3 months, 27% of patients achieved low disease activity (LDA) by the SDAI; 29.7% had SDAI remission; 35% had HAQ ≤0.5; at 6 months, LDA, SDAI remission, had HAQ ≤0.5 were seen in 41.7, 41.7, and 67%, respectively. There were no significant differences in the suppression of RA activity depending on whether second- or third-line TOFA therapy was performed. There were no serious adverse events (SAEs) or serious infections.

Conclusions. Second- and third-line TOFA therapy allows the majority of patients to quickly achieve the T2T goals (56.7 and 83.4% of patients at 3 and 6 months, respectively), so the drug can be quite successfully «integrated» into the T2T strategy along with biologics. The drug effectively inhibits granulomatous inflammation (by the example of rheumatoid nodules) and shows a sufficient safety (no SAEs).

Objective: to investigate the relationship between some signs of hereditary connective tissue disorders (HCTDs) as a Marfanoid appearance (MA) and the risk of atrial fibrillation (AF) in female patients with osteoporosis (OP).

Subjects and methods. In 2014–2015, the investigation enrolled consecutively 104 women aged 58 to 70 years (mean age, 64.7±3.8 years) who had a verified diagnosis of primary OP and a body mass index of ≤25.0 kg/m2. The entries in the outpatient medical records and in the automated information system «Polyclinic» were retrospectively analyzed to divide the patients into 2 groups according to the sign of the documented diagnosis of AF. A study group consisted of 53 women (mean age, 65.6±5.2 years) with AF and OP; a control group included 38 patients (mean age, 64.9±4.7 years) with OP without AF; a control group comprised 38 patients (mean age, 65.1±3.9 years) without OP and AF. Anthropometric and phenotypical parameters and cardiovascular visceral signs were analyzed; the levels of transforming growth factor-β1 (TGFβ1) and interleukin (IL) 1β and 6 in the serum and those of deoxypyridinoline (DPD) in the urine were measured.

Results. Analysis of the phenotypical signs of HCTDs in the patients with OP has shown that those with OP and AF have external signs of dysmorphogenesis and meet the criteria of MA. Statistically significant correlations were found between the frequency of MA signs and the magnitude of all cardiac morphometric parameters and the visceral signs of HCTDs in the study group. The serum levels of IL-1β, IL-6, and TGFβ1 in these patients were significantly higher than in the comparison and control groups. There was also a high correlation between the signs of MA and the content of DPD in the study group.

Conclusion. The patients with OP and AF was found to have a statistically significant correlation of the phenotypical signs of dysmorphogenesis with the frequency of visceral signs of HCTD, the morphofunctional parameters of the heart, and the high concentration of cytokines and DPD. It may be suggested that there exists a genetically determined mechanism of connective tissue dysembryogenesis in OP, which is associated with the risk of AF.

Objective: to investigate the relationship between coronary artery calcification (CAC) and osteopenic syndrome in men with coronary heart disease (CHD).

Subjects and methods. A total of 102 men aged 51 to 75 years (mean age 61 (55; 65) years) with verified CHD were examined. Bone mineral density (BMD) and its T-score of LI–IV and femoral neck were determined by dual-energy X-ray absorptiometry. According to the T-score, the men were divided into 3 groups: 1) 33 (32.4%) patients with osteoporosis (OP) (T-score <-2.5); 2) 48 (47.0%) patients with osteopenia (OSP) (T-score -1 to -2.5) and 3) 21 (20.6%) examinees with normal BMD (NBMD) (T-score ≥-1). In all the patients, CAC was quantified by multislice spiral computed tomography. The investigators calculated CA calcium scores by the Agatston method and rated the extent of calcification: none (0), minimal (1–10), mild (11–100), moderate (101–400), or severe (>400).

Results and discussion. Severe CAC was detected in 57.8% of the men; moderate CAC was in 25.5%; mild CAC was in 6.9; minimal CAC was in 2.0%; and none CAC was in 7.8%. In the OP group, the majority (69.7%) of the patients had severe CAC; 15.1% had moderate CAC, 6.1% had mild CAC; 3.0% had minimal CAC; CAC was undetected in 6.1% of cases. In the OSP group, there was severe CAC in 60.4%, moderate CAC in 33.3%, mild CAC in 4.2%, and minimal CAC in 2.1%. The patients without CAC were absent in this group. In the NBMD group, 33.3% of the examinees were recorded to have severe CAC; 23.8% had moderate CAC; 14.3% had mild CAC; CAC was undetected in 28.6%. Minimal CAC was also undetected in the patients of this group. There was a preponderance of patients with severe CAC in all the groups of those identified by the T-score. The extent of CAC was significantly lower in the NBMD group than in the OSP group (p<0.05). CAC was significantly more frequently absent in the NBMD group than in the low BMD group (p<0.05). There was an inverse correlation between Agatston CAC scores and T-scores of the femoral neck (r=-0.25; p=0.01), T-scores of LI–IV (r=-20; p=0.04), and the BMD of the femoral neck (r=0.23; p=0.02) and LI–IV (r=-0.19; p=0.04). Low BMD was associated with severe CAC, which lends credence to the relationship between vascular wall calcification and osteopenic syndrome in the men with CHD.

Objective: to investigate the clinical efficacy and cardiovascular safety of the combined symptomatic slow-acting drug glucosamine and chondroitin sulfate in patients with osteoarthritis (OA) and hypertension.

Subjects and methods. The investigation enrolled 44 patients (a female:male ratio of 40:4) aged 54.5±7.4 years with knee OA (duration, 6.4±1.54 years). The patients were blindly randomized into two groups: 1) those who received antihypertensive therapy, teraflex (chondroitin sulfate 400 mg and glucosamine sulfate 500 mg) with/without acetaminophen; 2) those who had antihypertensive therapy and acetaminophen. At baseline and 3 and 6 months after treatment, the investigators assessed a change in the degree of OA by the WOMAC and Lequesne indices, the treatment efficiency evaluated by a physician and a patient using a visual analogue scale, and cardiovascular safety (during the first and last visits) through examination of the antithrombogenic properties of the vascular wall and arterial stiffness.

Results. All the patients taking teraflex for 6 months were observed to have a positive effect manifesting as a substantial reduction in WOMAC and Lequesne indices, pain syndrome, and needs for analgesics compared to both the baseline level and parameters in the patients receiving acetaminophen only. Teraflex therapy showed an increase in the fibrinolytic activity of the vascular wall. A more obvious fall in augmentation index and pulse wave velocity was seen in OA and AG patients receiving antihypertensive therapy and teraflex.

Conclusion. Group 1 displayed not only reductions in pain syndrome and needs for analgesics, but also no blood pressure destabilization. They also had lower endothelial dysfunction manifesting as enhanced fibrinolytic activity of the vascular wall, decreased brachial and aortic augmentation indices, and lower pulse wave velocity.

The goal of therapy for rheumatoid arthritis (RA) is to suppress inflammation, to prevent or delay destructive changes in the joints, and to normalize functions during the longest monitoring of the course of RA. The data of randomized controlled trials and national registries are of great importance to a clinician. The paper reviews the literature data characterizing the long-term results of RA therapy with the tumor necrosis factor-α inhibitor golimumab (GLM) and patient compliance with the therapy. Treatment with GLM at the registered subcutaneous dose of 50 mg once every 4 weeks gives rise to an effect in the vast majority of patients regardless of the type of previous ineffective therapy, the dose of concurrently administered methotrexate, the number of previous ineffective disease-modifying antirheumatic drugs, and the use and nonuse of glucocorticoids. GLM is characterized by a long-term (as long as 5 years) effect with suppressed progression of destruction, functional recovery, and satisfactory tolerability with no additional risk for adverse events as the therapy is continued.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat pain syndrome in acute and chronic diseases of various genesis, which are accompanied by pain and inflammation. However, the use of NSAIDs is partially limited by their adverse reactions (ARs), so great attention has been recently given to the safety of NSAIDs and to the elaboration of guidelines for their administration. Therapy with NSAIDs requires that a physician should be aware of not only the mechanism of their action, but also the possible ARs, as well as their risk factors and ways of correction. It is emphasized that NSAIDs should be prescribed in terms of the possible risk of complications in different organs and tissues. The review considers the gastrointestinal, renal, and cardiac safety of NSAIDs, such as the extensively used drug meloxicam in particular. Meloxicam is as effective as nonselective NSAIDs, but due to the primary inhibition of cyclooxygenase-2, it has also a better safety profile: when it is used, there are rare gastrointestinal complications and a low cardiovascular risk that is chiefly represented by a vascular component, which makes possible to use it with caution in patients at cardiovascular risk. The results of numerous investigations show that meloxicam has a good efficacy/safety ratio and noticeable analgesic and anti-inflammatory effects, which makes it the drug of choice for the treatment of a wide range of rheumatic diseases and acute and chronic diseases of the joint and spinal column. It is pointed out that there is a need for further clinical trials of the safety of meloxicam to specify individual mechanisms of its cardiotoxicity.

The article presents review of literature dedicated to the contemporary view on the cellular-molecular mechanisms of the bone remodeling and pathogenesis of the osteoporosis. The discovery of the cytokine RANKL-RANK-OPG system and significant role of the cathepsin K in process bone remodeling has made progress in understanding the mechanisms development disease and possible to development drugs of the new generation – denosumab, a fully human RANKL monoclonal antibody and inhibitor cathepsin K odanacatib that inhibits of the bone resorption.

The current recommendations for the pharmacotherapy of osteoarthritis (OA) primarily focus on analgesics and main concern is with the use of paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs). Intraarticular injections of first of all hyaluronic acid (HA) preparations that have proven to be effective in clinical practice are a promising treatment for OA. By taking into account the favorable safety profile of HA preparations, it may be suggested that these injections may be an acceptable alternative to NSAIDs or successfully used in combination with the latter. There have been recently the recommendations for the administration of HA preparations in OA treatment, which characterize the current practice of HA use for OA and had been prepared by a group of experts from 5 European countries. The experts consider that there is today rather solid evidence to demonstrate the efficacy of HA in mild and moderately severe knee OA; moreover, its effect is clinically significant in such patients. In the authors’ view, topical HA therapy should be a compulsory component of treatment for knee OA, since the alternative possibilities of therapy for this disease are limited. Although the optimal effect of HA is observed when it is applied in the early stage of OA, this treatment may be also useful in its late stage. HA should be regarded as an adjunct method that must be applied if surgery cannot be performed in these patients.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a main tool used in real clinical practice to relieve acute pain and to control major symptoms in chronic diseases of the joint and spinal column. They are effective and easy-to-use; however, they may cause adverse reactions (ARs) that require careful monitoring and effective prevention. The current concept of the safe use of NSAIDs is aimed at maximally reducing both gastrointestinal and cardiovascular events. Clinical trials and population-based studies have revealed that among all NSAIDs (other than aspirin), naproxen is associated with the least cardiovascular risk. This drug that belongs to traditional (nonselective) NSAIDs (n-NSAIDs) has been commonly used in clinical practice for more than 40 years and gained physicians’ confidence worldwide as a reliable analgesic and anti-inflammatory agent. The therapeutic potential of naproxen has been proven in a great variety of diseases and abnormalities: from acute injuries to Bechterew’s disease. When using naproxen, like other n-NSAIDs, it should be borne in mind that gastrointestinal ARs may develop. However, this risk may be substantially decreased by the administration of proton pump inhibitors, such as pantoprazole. This review presents basic investigations that have studied the efficacy and safety of naproxen.

The paper reviews literature on locomotor apparatus injury in inflammatory bowel disease (IBD). It describes the types of joint and spinal column involvement in ulcerative colitis (UC) and Crohn’s disease (CD). The ratio of onset to the activity of IBD and articular syndrome is estimated. The most common type of articular syndrome is peripheral arthritis that involves mainly the knee and ankle joints and that is associated with IBD activity in most cases. Unlike peripheral arthritis, the course of axial spondyloarthritis manifesting as isolated sacroiliitis and ankylosing spondylitis (AS) is unrelated to IBD activity. There is evidence on isolated sacroiliitis that is rather common asymptomatic, that is diagnosed late, and that is a finding in a number of patients during examination. The paper provides the clinical and instrumental characteristics of AS in IBDand points to the similarity of their clinical manifestations and radiographic changes with those in idiopathic AS. It also describes the picture of enthesitis with emphasis on the systemic extra-articular manifestations of IBD, which are associated with articular syndrome (erythema nodosum and uveitis) in a number of cases. Radiographic changes in peripheral joints and spinal column are characterized in different types of locomotor apparatus injury in patients with IBD. There are data available in the literature on the treatment of articular syndrome in patients with UC and CD. It is noted that there is a need for a differentiated approach to treating peripheral arthritis and axial skeleton involvement; the role of nonsteroidal anti-inflammatory drugs, sulfasalazine, and biological agents in the treatment of articular syndrome in IBD is assessed. It is indicated that IBD patients having rheumatic manifestations should be followed up jointly by a gastroenterologist and a rheumatologist.

The review gives data on the safety of nimesulide used for the treatment of chronic joint diseases. The first-line treatment at its any stage for joint diseases is nonsteroidal anti-inflammatory drugs (NSAIDs). Questions have recently arisen of the safety of nimesulide; however, epidemiological findings and clinical experience confirm a positive benefit/risk profile of nimesulide in the treatment of acute pain. The International Consensus Meeting (Vienna, 2014) noted that the risk of severe adverse hepatic NSAID reactions was low and the rate of liver damage associated with nimesulide was completely similar to that observed with other NSAIDs. There are data available in the literature on the rate of serious adverse liver reactions to different NSAIDs and paracetamol. The rate of such reactions to all NSAIDs per million patientyears was 1.55 and that to nimesulide was 1.88. The members of the International Consensus Group concluded that nimesulide, if properly used, remained a valuable and safe drug for the treatment of various conditions, characterized by the presence of acute inflammatory pain, by virtue of the rapid onset of analgesic action and an evidence-based positive benefit/risk profile. The long successful experience with nimesulide in our country suggests that the agent may be successfully used to treat chronic and acute pain (including dysmenorrhea) in a daily dose of 200 mg/day. The safety profile of the drug is quite satisfactorily for all adverse reactions typical of NSAIDs, including its negative effect on the liver.