The clinical introduction of biological agents (BAs) is one of the most significant advances in rheumatology in recent decades. At the same time, the cost of this treatment is very high; the development of methods for predicting the results of proposed therapy may therefore be of great interest. A number of studies are under way, which determine a response to BAs. Publications dealing with this problem are very heterogeneous: the data obtained in different populations, as well as different studies and criteria for evaluating the efficiency of therapy are used. The specific features of the course of the disease, the constitutional parameters of a patient, genetic factors, and the presence of comorbidity or concomitant therapy are considered as potential predictors of the efficacy of BAs. It is not inconceivable that the optimal result can be obtained from a comprehensive assessment of these factors.

Invasive mycoses are becoming a more relevant problem in modern rheumatology. There are difficulties in the lifetime diagnosis and treatment of mycoses in patients with rheumatic diseases. The significance of this issue increases considerably due to the active clinical introduction of biological agents. The paper provides general information on the clinical presentation, diagnosis, and therapy of the most common mycoses.

Objective: to evaluate the efficacy of tocilizumab (TCZ) versus tofacitinib (TOFA) in patients with severe and moderate rheumatoid arthritis (RA) who have not previously received methotrexate (MTX). Material and methods. A systematic search for studies dealing with the evaluation of the efficacy of TCZ and TOFA was made in accordance with the provisions of the instruction «Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)». Indirect comparison of two Function and ORAL Start randomized clinical trials was done, as described by Н.C. Buchera. The trials were comparable in their design and in the baseline characteristics of patients. The efficiency of pharmacotherapy for early RA was evaluated based on the ACR20/50/70 response rates in MTX-naive patients from three endpoints. Results. The indirect comparison of TOFA and TCZ (A MTX general control) after 52 weeks of treatment in MT-naive patients with severe and moderate RA indicated that the use of TOFA 5 mg twice daily and TCZ 8 mg/kg showed no difference in ACR20, ACR50, and ACR70 response rates. Nevertheless, there was a tendency to the greater efficiency of TOFA (5 mg twice daily) than that of TCZ (8 mg/kg). The indirect comparison of TOFA (10 mg twice daily) and TCZ (8 mg/kg) established that TCZ therapy was associated with the lower response rate for ACR50 (by 37%): the relative risk (RR) was 0.63; 95% confidence interval (CI), 0.44–0.90 and for ACR70 (by 51%): RR, 0.49; 95% CI, 0.29–0.83 as compared with TOFA therapy. Conclusion. The indirect comparisons confirmed that monotherapy with TOFA (10 mg twice daily) produced a more pronounced antiinflammatory effect than that with TCZ in MTX-naive patients with early severe and moderate RA of less than one year's duration. There were no statistically significant differences in ACR response rates between the TOFA (5 mg twice daily) and TCZ (8 mg/kg) groups.

Objective: to show the characteristics of teaching this area of clinical medicine in the context of new knowledge and to identify ways of introducing new data into teaching practice by the example of development of the concept of spondyloarthritis (SpA). Material and methods. At Stage 1, by using the keywords: spondyloarthritis, ankylosing spondylitis, psoriatic arthritis, rehabilitation care, and Bechterew's disease, the articles published in January 1951 to January 2017 were sought in the electronic resources PubMed, MedLine, and e-library. The fundamental aspects of the pathogenesis, diagnosis, and treatment of SpA, which need to be introduced into a pedagogical process, were assessed. At Stage 2, by using the analyzed data, the authors proposed to optimize the teaching of the SpA concept in the clinical presentations of visceral diseases. Results. Analysis of the data available in the literature could determine the key points of the new concept of SpA and the ways of its introduction into teaching practice at medical universities and during postgraduate training of physicians.

The paper gives the experience of the V.A. Nasonova Research Institute of Rheumatology in identifying and managing patients with familial Mediterranean fever (FMF). Objective: to describe the features of the disease in patients with FMF in Russia and to compare them with the data obtained in the study of Turkish and Armenian populations with a high incidence of this disease. Patients and methods. The investigation enrolled 23 patients with a documented diagnosis of FMF who met the Turkish pediatric criteria (F. Yalcinkaya et al.) and/or the criteria described by A. Livnech et al. and had two identical mutations (homozygosity) or two different mutations (compound heterozygosity) in the MEFV gene. Among the patients there were 9 men and 14 women. The age of the patients at the time of treatment was 4.5 to 36 years. Their age at onset of FMF was 2 months to 15 years (mean age, 3.2±2.3 years). Results. The examination established that 18 (78.3%) patients were Armenians, 3 were representatives of the North Caucasus peoples (a Darghin woman, an Avar man, and an Ingush/Kabardian man), a man from mixed (Greek/Georgian) marriage, and a Russian woman whose ancestors were Armenian and Jewish. The most common manifestation of FMF were recurrent episodes of fever (22; 95.7%); abdominal pain with fever ranked second (19; 82.6%), followed by chest pain (11; 47.8%), locomotor apparatus lesion (16; 69.6%), and skin lesions (7; 30.4%). The episodes were accompanied by increased levels of acutephase markers in 100% of the patients. There were a high proportion of patients, in whom FMF was concurrent with other rheumatic and autoinflammatory diseases (juvenile chronic arthritis, chronic recurrent multifocal osteomyelitis, and acute rheumatic fever) (7; 30.4%). Twenty-two (95.6%) patients received colchicine; the tumor necrosis factor inhibitor etanercept was prescribed in 2 (8.7%) patients with comorbidity; there was a pronounced therapeutic effect. Conclusion. Although the majority of our patients were Armenians, the disease was also identified in those belonging to the peoples of the North Caucasus and Transcaucasia and in one Russian female patient. There has generally been a fairly typical picture of the disease. The considerable frequency of joint damage and the high proportion of patients with comorbid rheumatic diseases have engaged our attention. From a diagnostic point of view, of importance is the elevated level of acutephase markers during a disease attack, which in combination with the clinical and ethnic characteristics of patients allows the diagnosis of FMF to be suspected.

Autoinflammatory diseases (AIDs) are a group of rare disorders characterized by persistent or recurrent inflammation caused by the hyperactivation of mediators and innate immune cells (neutrophils, monocytes/macrophages). The paper describes the authors' own case of NLRP12-associated AIDs and the efficiency of canakinumab therapy and reviews a series of cases of the similar disease, which are given in the literature.

The rheumatic manifestations of endocrine diseases are well-known. The endocrine system has a complex effect on the structure and function of musculoskeletal tissues. The symptoms of locomotor apparatus injuries often come to the forefront in the clinical picture of an endocrine disease. It is therefore important to put endocrine diseases, including hypothyroidism, arthropathy, myopathy, etc., in a range of differential diagnoses of musculoskeletal system lesions. It should be remembered that changes in the locomotor system are able to partially or completely regress when endocrine disorders are adequately and long compensated for. The paper describes a clinical case in which, despite an obvious diversity of the typical clinical presentations of hypothyroidism, the main complaint was pain in the joints and muscles. In this connection, the female patient was initially misdiagnosed. This could be avoided if there was alertness to endocrine arthropathies and myopathies.

Erythema nodosum (EN) is the most common form of panniculitis that is a reactive process caused by a wide variety of etiological factors. The problems with the differential diagnosis of this abnormality have not lost its relevance. The paper deals with a clinical case of recurrent EN concurrent with an immunological phenomenon (positivity for rheumatoid factor and antimitochondrial antibodies), long-lasting asymptomatic splenomegaly, and subsequently developed primary myelofibrosis. To ascertain the cause of secondary EN often causes difficulties in real clinical practice.

Weber–Christian disease is a rare form of lobular panniculitis characterized by painful subcutaneous nodules on the trunk and limbs commonly concurrent with systemic manifestations and a tendency to relapse. Known are only sporadic cases of a long-term (more than 5-year) followup of patients with Weber–Christian disease. For this reason, there are neither prognostic criteria for the disease no proven conventional treatment option now. The paper describes a clinical case of a female patient with a verified diagnosis of Weber–Christian disease who has a sustained subclinical remission due to low-dose prednisone use and basic antirecurrent therapy.

Helicobacter pylori is the most common human infection. H. pylori is known to cause chronic gastritis and gastric and duodenal ulcers. However, the H. pylori-host interaction is not confined to the gastric mucosa, the mechanism responsible for the adaptation of this bacterium to the living conditions in the human body, can cause systemic immune imbalance, provoking various autoimmune reactions. The paper considers the investigations demonstrating the possible role of H. pylori as a trigger or aggravating factor in rheumatic diseases, such as rheumatoid arthritis (RA), Sjögren's syndrome and disease, systemic lupus erythematosus, and progressive systemic sclerosis. The relationship between H. pylori and autoimmune diseases is confirmed by the higher frequency of more aggressive strains of this microorganism in rheumatic diseases. There are also clinical trials showing the positive impact of H. pylori eradication on RA activity.

Joint hypermobility syndrome (JHS) is a disease characterized by symptoms of locomotor system involvement in the absence of obvious systemic rheumatic diseases (RDs). JHS accompanied by the symptomatology of RDs should be distinguished from isolated joint hypermobility, in which there are no complaints even in cases of its generalized manifestations and the patients feel virtually healthy. The paper provides an overview of the literature on the JHS. It gives diagnostic criteria for JHS (the Brighton criteria encompasses the Beighton score) and the clinical manifestation of damages to the locomotor apparatus, visceral organs, and skin in this syndrome. Autonomic nervous system dysfunction as a possible manifestation of JHS and its impact on the daily life of patients are discussed. Attention is paid to the prevention and treatment of JHS.

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, spine, and entheses, which is associated with psoriasis. The pathological process is localized mainly in the tissues of the locomotor system and leads to the development of erosive arthritis, intra-articular osteolysis, and spondyloarthritis. Nonsteroidal anti-inflammatory drugs, glucocorticoids, disease-modifying antirheumatic drugs (DMARDs), biological agents (BAs), and targeted synthetic drugs (or signaling pathway blockers) are used to treat PsA. The latter group of drugs includes apremilast, a phosphodiesterase 4 inhibitor. Recent data of controlled studies suggest that apremilast is effective and safe in treating psoriasis and PsA. Prospects for the use of apremilast in PsA are associated with the possibility of giving the drug to patients because of the inefficacy of DMARDs or BAs.

Widespread osteoarthritis (OA) and high related disability rates determine not only the medical, but also socioeconomic significance of this disease. In recent years there has been a tendency to increase the incidence of OA. According to the current concepts, inflammation plays a leading role in the development of chronic pain in OA, which requires adequate anti-inflammatory therapy. There are data on the diverse mechanisms of action of the nonsteroidal anti-inflammatory drug (NSAID) nimesulide and results from clinical trials and metaanalyses, which confirm its efficacy and good tolerability. Several clinical trials covering 22,938 patients with OA have indicated that the overall frequency of adverse reactions (AR) from nimesulide is 8.2%. There is evidence on the efficacy and good tolerability of topical NSAIDs, as well as combination drugs containing glucosamine sulfate and chondroitin sulfate, the use of which together with oral drugs enhances the efficiency of treatment without increasing the risk of ARs.

Objective: clinical and economic analysis of including of secukinumab (SEC) in the essential drug list (EDL) and Federal Reimbursement (ONLS) to ensure the availability of the drug to patients with ankylosing spondylitis (AS) at the expense of health. Material and methods. A budget impact analysis was used. Only cost of drugs was taken into account. Adalimumab (ADA) and infliximab (INF) were used for comparison. Basing on the calculated number of patients treated with these drugs in 2016 from the budget of health care system impact on 3-years budgets of State Guarantee Program (SGP) and ONLS was analyzed. The analysis scenario was based on the replacement of ADA and INF with SEC. Results. Expenditure of a 3-year therapy cycle with SEC amounted to 1.703 million rubles, which was 41.6% less than that with ADA (2.917 million rubles) and 57.7% less than that with INF (4.022 million rubles) in the same period. The budget impact analysis to estimate the cost of SGP demonstrated that the use of SEC during a 3-year period would result in a reduction in expenses by 51.2% (saving of 3.8 billion rubles). When SEC is used within the ONLS, its cost during 3 years will be reduced by 51.9% (savings of 1.9 billion rubles). Conclusion. The inclusion of SEC in EDL and ONLS is appropriately and economically justified, as it enables a substantial reduction in the expenditure of health care budgets to treat patients with AS and to maintain the clinical effectiveness of therapy.

The expert forum on pain treatment for rheumatic diseases was held in Voronezh on February 22, 2017. The meeting was chaired by Professor L.I. Alekseeva, MD, Head, Department of Metabolic Bone and Joint Diseases with Osteoporosis Prevention Center, V.A. Nasonova Research Institute of Rheumatology. The aim of this meeting was to discuss new evidence on the pharmacological methods of pain control in rheumatologic practice, in particular, current ideas on the role of nonsteroidal anti-inflammatory drugs.