The paper considers current views on the mechanisms for the development and progression of osteoarthritis (OA) and gives the definition of the disease. It describes the processes underlying aging and OA at the molecular and cellular level, with emphasis on the role of chronic nonspecific inflammation. The possible mechanisms of chronic age-related inflammation (inflammaging), the mainstay of which is systemic aging of the immune system, are characterized. On the basis of the data available in the literature, it is concluded that aging and OA have common intracellular transcription cascades and pathophysiological mechanisms: chronic nonspecific inflammation and metabolic disorders are substantially implicated in the pathogenesis of these conditions. Metabolic and structural changes occurring in the cartilage and other tissues of the locomotor apparatus with aging are noted to serve as a favorable platform for the further development and progression of OA.

Tofacitinib (TOFA), a representative of a new class of targeted synthetic disease-modifying antirheumatic drugs (s-DMARD), is a promising drug for treating rheumatoid arthritis (RA) and other immune inflammatory diseases.

Objective: to evaluate the efficiency and safety of therapy with TOFA in combination with methotrexate (MTX) and other s-DMARDs in real clinical practice in patients with active RA and previous ineffective therapy.

Patients and methods. A 6-month Russian multicenter study of function and quality of life enrolled 101 patients with resistant RA: 18 men and 83 women; mean age, 51.03±11.28 years; mean disease duration, 105.4±81.43 months; rheumatoid factor-positive individuals (89.1%); and anticyclic citrullinated peptide antibody-positive ones (74.7%). 93 (92,1%) of these patients completed a 24-week study. TOFA was used as both second-line drug (after failure of therapy with s-DMARD) (n=74) and as a third-line drug (after failure of therapy with s-DMARDs and biological agents (BAs) (n=74). The tools RAPID3, HAQ, and EQ-5D were used to determine disease outcomes from a patient's assessment.

Results. All the three tools demonstrated significant positive changes at 3–6 months following therapy initiation. RAPID3 scores for the status of a patient achieving a low disease activity or remission coincided with the mean DAS28-ESR and SDAI scores in 60% and 68% of cases, respectively. The achievement rates of the minimally clinically significant improvement (ΔHAQ≥0.22) and functional remission (HAQ≤0.5) at 6 months of TOFA therapy were 79.6 and 30.1%, respectively. The mean change value in EQ-5D scores over 6 months was -0.162±0.21. There were no significant between the groups of patients who used TOFA as a second- or third-line agent in the majority of indicators, except EQ-5D scores at 6 months.

Conclusions. The results of our multicenter study using considerable Russian material confirmed the pronounced positive effect of TOFA used as a second-line agent (after s-DMARD failure) and a third-line agent (after s-DMARD and BA failure) on patients' assessment of disease activity, functional ability in daily life, and quality of life.

Objective: to study the prevalence of psoriatic arthritis (PsA) and comorbidities in a hospital cohort of patients with severe psoriasis (PsO).

Patients and methods. Case history data were retrospectively analyzed in 592 patients with PsO (348 men and 244 women; mean age, 49.2±0.6 years; mean PsO duration, 11.8±0.6 years; mean Psoriasis Area and Severity Index (PASI), 49.4±0.5 scores) who had been treated at the Branch of the V.G. Korolenko Clinic, Moscow Research and Practical Center of Dermatovenereology and Cosmetology, in 2010 to 2011. The diagnosis of comorbidities was confirmed by medical specialists in accordance with the ICD-10 code; the rate and pattern (%) of comorbidities were analyzed.

Results. Out of the 592 patients with PsO, 503 (85.1%) were found to have comorbidities. Diseases of the cardiovascular system (CVS)
(I00–I199) were recorded in the majority (61.6%) of the patients. PsA (L40.5, M07.0–M07.3) was detected in 39.4% of the examinees. Other diseases of the skeletomuscular system unassociated with psoriasis (M00–M99) were present in 27.6% of the patients. Diseases of the gastrointestinal tract (GIT) and hepatobiliary system (K00–K93, B15–B19) were found in 47.5% of the patients. Endocrine diseases, nutritional and metabolic disorders (E00–E90), particularly diabetes mellitus, thyroid diseases, and obesity, were diagnosed in 12.2, 24, and 88% of the patients with PsO, respectively. 13.9% of the patients with PsO had urinary tract diseases, among them there was chronic pyelonephritis (N20), kidney cysts (N28.1), urolithiasis (Q61), prostate diseases (N11) in 73, 71, 47, and 27% of cases, respectively.

Conclusion. Most patients with severe PsO were observed to have comorbidity, primarily diseases of the locomotor apparatus, CVS, and GIT. PsA was recorded in more than one third of patients. Comorbidity was identified in 36% of the patients with PsO.

Gout is a severe metabolic disease with a wide range of comorbidities. The specific features of gout should be evaluated to optimize medical control over the disease.

Objective: to study clinical trends for gout in Irkutsk over time (2007–2016).

Patients and methods. Examinations were made in two patient groups: Group 1 (n=467) during 2007 and Group 2 (n=252) during 2016. The groups were matched for gender, age, and mean disease duration.

Results. There was an increase in the prevalence of gout among able-bodied patients, in the rate of late gout diagnosis, and in the cases of chronic tophaceous gout and concomitant diseases. The number of patients continuously taking allopurinol reduced.

Conclusion. The reasons for negative clinical trends for gout can be late diagnosis and insufficient medical supervision.

The level of vascular endothelial growth factor (VEGF) and the assessment of synovial vascularization can reflect the intensity of angiogenic processes that are an important step in the initiation and chronicity of rheumatoid arthritis (RA).

Objective: to study the blood level of VEGF and to assess the degree of synovial vascularization in patients with RA depending on the duration of the disease and the degree of its activity and on the level of anti-cyclic citrullinated peptide (anti-CCP) antibodies.

Patients and methods. A total of 173 patients (women, 85%; men, 15%; mean age, 47.7±10.22 years; mean disease duration, 3.82±3.43 years) diagnosed with RA underwent Doppler ultrasonography of the hand joints with assessment of the intensity of synovial vascularization and determination of blood VEGF concentrations by enzyme immunoassay (BCM Diagnostic, Canada).

Results. In patients with RA duration less than 2 years, the blood level of VEGF was 30% higher and the synovial vascularization scored 3 was 4 times more common than in those with longer RA durations. In RA patients with high disease activity, blood VEGF concentrations were 2 times higher and the synovial vascularization scored 3 was observed 6 times more often than in those with low RA activity. In patients with the blood level of anti-CCP antibodies over 60 U/ml was 1.5-fold higher and the synovial vascularization score of 2–3 was twice more frequently than in those who were lowly positive for anti-CCP antibodies. High VEGF levels and synovial hypervascularization may be markers for the severe clinical course of RA and for its high progression rate, as well as for the development of early joint destruction.

Rheumatoid arthritis (RA), which affects about 1% of the adult population mostly in old age, has specific clinical features at the onset in elderly and senile people. The paper describes two clinical cases that are demonstrative as the rare variant of RA onset at old age (86 years). In one case, the female patient was observed to have an acute onset, polyarthritis with sharp pains, obvious exudative phenomena, with significant functional limitation, and a relatively rapid course of the pathological process with high immunological activity. The other patient showed, on the contrary, a gradual onset of the disease with the minimal clinical and immunological manifestations and a rapid progressive joint destruction. Both patients were found to have several concomitant diseases, which corresponds to the comorbidity data given by different authors in elderly patients, including those with RA. The specific feature of the described clinical cases is the disease onset at 86 years; therefore during hospitalization, there was a differential diagnosis of articular syndrome in the presence of this age-related cancer that was ruled out by examination.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of pathogenetic therapy for acute and chronic pain associated with rheumatic diseases. It would seem that NSAIDs are well studied: their pharmacological properties are known; the fields of their applications, the efficacy of the drugs in treating various diseases and pathological conditions, possible adverse reactions (ARs), and methods for their prevention have been identified. Nevertheless, this drug group has so far remained one of the most debated topics in the international medical literature. Debates continue about the therapeutic value of NSAIDs, the ratio of their therapeutic potential and the risk of complications, and the expediency of their long use in a number of nosological entities. There are constantly reports of new studies that modify the existing view on many aspects of using NSAIDs in real clinical practice. The paper gives a brief overview of some of the most interesting and significant works on NSAIDs, which appeared in the world medical press in the past 2016.

The involvement of the spine in psoriatic arthritis (PsA) is observed in a large number of cases; however, a unified approach to solving this problem has not yet been formed. Criteria for the diagnosis of psoriatic spondylitis have not been clearly defined; internationally accepted definitions for this concept are absent; criteria for a PsA exacerbation and remission have not been formulated with regard to spondylitis. The specialists of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis) have no their own recommendations for the treatment of axial involvement in PsA now. The therapeutic tactics used in the treatment of axial spondylitis and ankylosing spondylitis is borrowed in this area. The involvement of the spine calls for further investigation.

There is evidence that insufficient intake of antioxidants may increase the risk of autoimmune inflammatory diseases, including rheumatoid arthritis (RA). Also, lower plasma concentrations of antioxidant vitamins can be a sign of their heavy expenditure to suppress inflammatory processes in the preclinical stage of RA. This article provides an overview of modern studies that have assessed a relationship between the incidence of RA and serum levels or dietary intake of vitamins A, E, C and beta-carotene. Case-control studies have revealed that α-tocopherol and β-cryptoxanthin have a protective effect and their high plasma levels are associated with the decreased incidence of RA. An inverse relationship has been also found between the dietary intake of carotenoids and vitamin C and the risk of RA. At the same time, larger prospective cohort studies have failed to confirm the relationship between the levels of consumption of the major antioxidant vitamins and the risk of RA. The currently available data on the role of antioxidant vitamins in the development of RA remains controversial. Conceivably, sufficient intake of the vitamins has no self-protective activity against RA, but serves as a marker for a healthier lifestyle that lowers the risk of many diseases, including autoimmune disorders.

Osteoarthritis (OA) is one of the most common diseases of the musculoskeletal system, affecting mainly people of old age. The management of OA requires combined therapy using pharmaceutical and nonpharmacological modalities, including hyaluronic acid (HA). Hylans are highmolecular-weight (HMW) HA derivatives. The use of hylans results in reducing pain and stiffness and in improving functional activity. Their efficacy is comparable with that of lowmolecular-weight HA. Intraarticular injection of HMW HA derivatives is safe and effective for treating OA.

The paper reviews the literature regarding the use of procalcitonin (PCT) as a marker providing a differential diagnosis between diffuse connective tissue diseases, active systemic vasculitis, and manifestations of systemic bacterial infection. The discriminatory significance of PCT in most cases varies from 0.1 to 0.5 ng/ml. At the same time it has been found that the level of PCT in some forms of systemic vasculitis (adultonset Still's disease, macrophage activation syndrome) may correspond to that in systemic bacterial infections. In this connection, the role of PCT should not be absolutized; it may serve only as a great help using the current methods for X-ray, microbiological, and laboratory investigation. The diagnostic value of PCT in these clinical situations can be enhanced by the combined determination of its blood levels and the severity of organ dysfunction in accordance with the Sepsis-related Organ Failure Assessment (SOFA) scale.

Are high cyclooxygenase-2 (COX-2) selectivity and the absence of its impact on COX-1 the most important benefit of coxibs? Based on the classical concepts that nonsteroidal anti-inflammatory drugs (NSAIDs) are implicated in the pathogenesis of the most well-known complication – NSAID gastropathy, this must be so. Indeed, the development of gastrointestinal tract (GIT) diseases associated with NSAID use is mainly related to the blockade of COX-1 and to the decreased synthesis of cytoprotective prostaglandins. However, the clinical experience with etoricoxib, one of the most selective coxibs, casts doubt on this fact. There are well-known data of the MEDAL study, which show the equal rate of gastrointestinal bleeding in patients receiving etoricoxib and diclofenac. At the same time, moderately selective NSAIDs that include very popular meloxicam demonstrate a good tolerability and a low risk for GIT complications. A network meta-analysis of 36 studies covering a total of 112,351 patients indicates that there are no significant differences in the incidence of complicated and uncomplicated ulcers in patients receiving coxibs (a group analysis) and moderately selective NSAIDs (meloxicam, nabumetone, and etodolac). It is important that meloxicam demonstrates not only the low total frequency of GIT complications, but a quite moderate (as compared with diclofenac and etoricoxib) risk for cardiovascular and renal complications, which determines its benefit when used in real clinical practice.

The detection of anti-cyclic citrullinated peptide (anti-CCP) antibodies plays a diagnostic and statistical predictive role in rheumatoid arthritis (RA). The decreased concentration of anti-CCP antibodies or their seroconversion is observed for not all groups of anti-inflammatory drugs. Seropositivity for anti-CCP antibodies is a predictor of the higher efficacy of abatacept (ABC). The possibility of seroconversion of anti-CCP antibodies, like rheumatoid factor, during treatment with ABC is associated with the more pronounced suppression of clinical symptoms of RA activity and progressive joint destruction, with remission achievement in a large proportion of patients.

On November 26, 2016, Moscow hosted an Interdisciplinary Council of Russian Experts in Dermatology and Rheumatology, which discussed the unsolved problems and new possibilities of therapy for psoriasis (Ps) and psoriatic arthritis (PsA). The meeting was attended by leading experts in rheumatology and dermatology. The experts analyzed data, including the foreign guidelines relating to the new representative of a class of small molecule compounds, apremilast (registered in the Russian Federation in 2016) in order to determine the place of the drug in algorithms for treatment of moderate and severe Ps and PsA. They came to the following conclusions: the use of apremilast extends the existing possibilities for treating Ps and PsA; the drug can be administered to patients with moderate-to-severe plaque Ps or active PsA in case of the insufficiently efficiency or intolerance of previous therapy with disease-modifying antirheumatic drugs or contraindications to their use. Apremilast may be recommended in patients with concomitant diseases; it is appropriate to carry out a pharmaco-economic analysis and to get experience with apremilast in the healthcare facilities of the Russian Federation.