Giant cell arteritis (GCA) characterized by the paradoxical discrepancy between the high effectiveness of glucocorticoid (GCs) in the short term and the increase in signs associated with the persistence of inflammatory activity and the accumulation of organ damage induced by GCs in the long term, which indicates the need for the use of therapy, primarily in the direction of optimizing the use of GCs. New opportunities for pharmacotherapy of GCA are associated with the use of monoclonal antibodies (mAbs) that block the activity of cytokines involved in the immunopathogenesis of IMIRDs. Among pharmacological “targets”, interleukin (IL) 6, as well as IL-17, attracts special attention. Currently, several mAbs specific for IL-17 have been developed. The article summarizes data regarding the pathogenetic significance of IL-17 in GCA and the prospects for pharmacotherapy of GCA using mAbs to IL-17.

The question about the peculiarities of the course of rheumatoid arthritis in different age periods was raised in the literature repeatedly and the answer depended on the period of development of rheumatology and was not unambiguous. The course of age-specific features of the initial stages of disease development has also been studied (although less frequently). At the same time, the issues of age-related features of as yet untreated early rheumatoid arthritis have not been previously presented in the literature studied by the authors. This article gives a brief overview of the problem and discusses the findings.The aim of the present study was the comparative study of the characteristics of untreated early rheumatoid arthritis with early (18–49 years) and late (50 years and older) onset.The material was represented by 292 patients with rheumatoid arthritis with disease duration from 1 to 12 months from the disease onset, entered into the All-Russian Register of Patients with Inflammatory Arthritis “OREL” in the period from January 01, 2012 to December 31, 2018 with the results of examination at the time of the first examination. All patients were naïve to treatment with basal (synthetic, biological or other targeted) drugs and systemic glucocorticoid therapy. In 141 patients, the disease started at a younger age, group 1 (18–49 years), and in 151, at an older age (50 years or older), group 2.Methods. Disease activity (according to DAS-28 index), radiological stage – (according to Steinbroker, modified), functional disorders – according to functional class, immunological characteristic and additional immunological characteristic (rheumatoid factor, cyclic citrullinated peptide antibodies) and other parameters were estimated in accordance to requirements of current national rheumatoid arthritis classification. The results of the study indicate that the disease in older age is characterized by more pronounced inflammatory, destructive changes in relation to the joint apparatus and functional disorders than the onset of rheumatoid arthritis at a young age.

Background. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, characterized by erosive arthritis (synovitis) and systemic inflammation. Janus kinase (JAK) inhibitors (JAKi) are small molecules that block major signal pathways of many cytokines a growth factors, associated with RA. Identification of patients sensitive to JAKi before treatment could significantly improve therapy outcomes. Currently it is not possible to predict JAKi efficacy in every patient, while some patients are non-responsive to the drug, other develop adverse effects. JAKi effect in RA patients has been recently associated with alterations in mitochondrial function and ATP production. Therefore, we hypothesized that baseline metabolic status of RA patients prior to drug administration can predict the therapeutic outcome.Objective: to investigate the predictive value of baseline expression of genes involved in energy generation in the blood of RA patients, for treatment response to JAKi.Patients and methods. We examined peripheral blood of 28 RA patients aged 52.2±15.6 years, average disease duration 3.5 years (range 0.6–19), treated with Tofacitinib (TOFA, 5–10 mg twice a day) during three months and 26 healthy age-matched control subjects. Clinical response was assessed by disease activity score (DAS28-ESR), immunological status by measurements of serum levels of anti-citrullinated protein antibodies (ACPA), rheumatoid factor (RF), and C-reactive protein (CRP). Gene expression was assessed in peripheral blood cells by realtime reverse-transcription polymerase chain reaction (RT-PCR). At baseline all patients had Steinbrocker radiographic stage II–III. Most patients (85.7%) were ACPA and RF positive. Thirteen patients had medium, others – high RA activity.Results and discussion. JAKi treatment significantly decreased the inflammatory disease activity according to DAS28. At the end of the study 17 patients demonstrated moderate disease activity (3.2<DAS28<5.1), 4 patients retained high disease activity while 7, attained remission (DAS28 <2.6). Disease remission, achieved on TOFA treatment, was accompanied by significant decrease in CRP and the number of swollen and tender joints. ESR values were not changed significantly. Gene expression analysis revealed that RA patients, which attained clinical remission after TOFA treatment, demonstrated significantly lower baseline expression of genes associated with glycolysis (pyruvate kinase, PKM2) and oxidative phosphorylation (succinate dehydrogenase, SDHB) compared to other examined RA patients, but higher expression of the abovementioned genes compared to control subjects. Moreover, RA patients who attained clinical remission demonstrated a trend to increase of these gene expressions within follow-up period, while in the rest of patients these gene expression was tending to downregulate.Conclusion. Clinical remission in RA patients treated with JAKi is associated with significantly lower baseline expression of genes associated with energy generation pathways (PKM2 and SDHB) compared to other examined subjects.

Mutations and polymorphisms of the genes whose products are involved in the formation of extracellular matrix components can lead to the development of specific changes in the connective tissue of the eye in primary open-angle glaucoma (POAG). Understanding the nature of connective tissue pathology and its manifestations at the system level contributes to the development of specific markers of early detection and a personalized approach to the prevention and treatment of POAG.PURPOSE:To study the associations between systemic manifestations of undifferentiated connective tissue dysplasia (uCTD) and the development of POAG based on clinical and molecular genetic studies.MATERIAL AND METHODS:The observational study was conducted in the period from 2008 to 2021 (12 full years) and included retrospective data analysis of up to 15 years. The study involved 60 people with «suspected glaucoma» diagnosis and burdened heredity, who were divided into groups according to the severity of phenotypic signs of uCTD (on the T.I. Kadurina scale), as well as 15 people with «glaucoma» diagnosis whose morphological and immunohistochemical studies of the sclera were analyzed retrospectively. The comparison group consisted of 64 relatively healthy individuals. All patients underwent clinical-anamnestic, molecular-genetic, standard and special ophthalmological studies.RESULTS:Significant associations were revealed between the development of POAG, and the presence of clinical and phenotypic manifestations of uCTD, carriage of the GT genotype and the T allele of the rs8136803 (TIMP3) polymorphism, the AG genotype and the A allele of the rs652438 polymorphism (MMP12), the GA genotype and the A allele of the rs3825942 polymorphism (LOXL1).CONCLUSION:The specific features of preclinical morphofunctional changes and glaucoma progression can be determined by a hereditary predisposition to the pathology of the connective tissue of the eye. Testing of clinical-phenotypic and molecular-genetic signs of uCTD in patients with suspected glaucoma is promising in preclinical diagnosis, prognosis, and personalized approach to prevention and treatment.

Objective: to analyze the results of tofacitinib (TOFA) therapy in real clinical practice according to the All-Russian Arthritis Registry (OREL). Subjects and methods. The OREL Registry included 347 patients (286 (82%) women and 61 (18%) men) with rheumatoid arthritis (RA) who initiated TOFA therapy. The male:female ratio was 1:4.7. The patients’ median age at onset of the disease was 42 years; its duration was 8 years. Most of the patients included in the registry had extended- (n=171 (52%)) or late- (n=148 (45%)) stage of RA. Results and discussion. Prior to initiation of TOFA therapy, RA activity according to DAS28 was high and moderate in 91 (64.5%) and 40 (28.4%) patients, respectively; the median DAS28 value was 5.5 [4.6; 6.2]; SDAI – 30.5 [21.4; 42.9], and CDAI – 28.2 [20.0; 37.1]. The use of TOFA was accompanied by significant decrease of disease activity. After 12 weeks, high RA activity was persistent in 32 (22.7%) patients; the number of patients with moderate activity increased to 77 (54.6%), that of those with low activity rose to 15 (10.6%); remission was observed in 17 (12.1%) patients. 216 (62.6%) and 76 (22%) patients received TOFA as first- and second-line therapy, respectively. TOFA was most frequently prescribed when tumor necrosis factor-á inhibitors (19.6%), rituximab (7.8%), tocilizumab (4.3%), and abatacept (5.2%) were insufficiently effective or poorly tolerated. Conclusion. The results of using TOFA in real clinical practice may suggest that the drug has high efficacy in patients with RA. TOFA can be used at a dose of 5 or 10 mg twice daily as both alone and in combination with disease-modifying anti-rheumatic drugs. TOFA showed similar efficacy in patients who had earlier taken biological agents and in those who had not.

The paper presents three cohorts of patients with early rheumatoid arthritis (RA) who fell ill at 50 years or older and had a disease duration of 1.5 months to 1 year. To establish its diagnosis, the investigators used classification criteria for each cohort of its period: 1) the 1958 American Rheumatism Association (ARA) criteria; 2) the 1987 ARA criteria, and 3) the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria. Along with a change in the criteria, diagnostic methods were improved in this period. Many qualitative laboratory parameters were replaced with their quantitative equivalent; new disease markers (including anti-cyclic citrullinated peptide antibodies) emerged; imaging methods were improved; treatment policies were changed, and targeted biological agents and numerous analogs of the original drugs appeared.Conflicting opinions about the course of RA in older age groups have repeatedly been published in the literature. In the period when the 1958 classification criteria were applied, the opinion that RA has a relatively favorable course was prevalent. Later on, when a more rigid approach to diagnosing RA was applied, there were more and more specialists who considered it to be a severe disease. In this study, the authors try to answer the question of whether the course of the disease changed in the older age groups at the earliest possible date after its onset, by comparing the three cohorts of patients. The findings are discussed.

The article presents 3 cohorts with early rheumatoid arthritis in patients aged 50 years and older with a disease duration from 1.5 months to 1 year. To establish a diagnosis, the classification criteria of its period were applied to each of the cohorts: to the 1st - the 1958 ARA criteria, to the 2nd – the 1987 ARA criteria, to the 3rd - the 2010 ACR / EULAR criteria. Along with changes in the criteria diagnostic methods improved, many qualitative laboratory indicators were replaced by a quantitative equivalent; new disease markers (including ACPA), improved imaging methods, changed treatment strategies, genetically engineered drugs, numerous analogues of the original drugs appeared. Сonflicting opinions about the course of RA in older age periods have been published in the literature consistently. During application of the 1958 classification criteria, the prevailing opinion was that these patients had a more favorable course; as a more hardline approach to RA diagnosing appeared, a growing number of supporters of its more severe course appeared. In the research the author tries to answer the question whether the course of the disease in the older age groups has changed at the earliest time from its beginning by comparing three cohorts of different time periods. The data obtained are discussed.

Objective: to analyze therapy with rituximab (RTM) in real clinical practice according to the data available in OREL registry of patients with active rheumatoid arthritis (RA).Subjects and methods. The analysis included 349 patients. All the patients received RTM: 340 – the original drug (MabThera®) and 9 – the biosimilar Acellbia®. 263 patients (75.4%) received RTM in combination with disease-modifying anti-rheumatic drugs (DMARDs) and 86 (24.6%) – RTM as monotherapy.Results and discussion. Of the 349 patients included in the analysis, 272 (77.9%) patients received RTM as the first biologic agent (BA) (263 patients were treated with the original drug and 9 – with the biosimilar) and 77 (22.1%) patients had previously used the BA. The majority of patients (n=205 (58.7%)) received three or more; 109 (31.2%) patients – one, and 35 (10%) – two RTM courses of RTM therapy. RTM caused a significant reduction in disease activity just after the first therapy course and in the levels of acute-phase reactants (C-reactive protein (CRP) and ESR); after the fifth therapy course, median CRP concentration decreased by 1.4 times and amounted to 7 [1.2; 17.9] mg/l and that of ESR reduced by 1.8 times and was 10 [5; 20] mm/hr (p<0.05).Conclusion. The analysis of RTM therapy in RA patients in real clinical practice demonstrated that in most cases RTM was given as the first BA, in combination with DMARDs, the main agent of which was methotrexate. The use of RTM was accompanied by a significant reduction in disease activity and in the serum levels of acute-phase reactants and autoantibodies.

The paper considers the evolution of knowledge of polymyalgia rheumatica (PR) since 1888 and presents dynamics in the creation of a unified terminology. It characterizes the diagnostic development process, by using the criteria by H.A. Bird et al. 1979, J.G. Jones and B.L. Hazleman 1981 (UK), T.Y. Chuang, G.G. Hunder et al. 1982 (USA), M. Nabunaga et al. 1989 (Japan), and L.A. Healey 1984 (USA) as an example. The author scrutinizes the validation of these criteria in different countries and then the process of developing international classification criteria for PR (under the auspices of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR), by validating the new classification and previously existing diagnostic criteria.

Rheumatoid nodules (RNs) are one of the most common extra-articular manifestations of rheumatoid arthritis (RA), but are rarely located in lung tissue. The development of extra-articular (systemic) manifestations of RA is associated with the high levels of rheumatoid factor and anticyclic citrullinated peptide antibodies. The specific features of the course of RNs in lung tissue are their frequent occurrence with minimally pronounced joint inflammatory changes or remission. In rare cases, RNs are prone to disintegration and suppuration, which may be complicated by the formation of small caverns, hemoptysis, and, if located subpleurally, pneumothorax. In addition, there are publications on the possible relationship of the formation of RNs and their accelerated development to the administration of immunosuppressive drugs (methotrexate, tocilizumab, D-penicillamine, gold salts, leflunomide, infliximab, and other TNF-α inhibitors) and on the association of pulmonary RNs with methotrexate treatment. The paper describes a clinical case of a female patient with RA-systemic sclerosis overlap syndrome and RN formation in lung tissue early at disease onset when the DAS28 target level for RA has been achieved. The atypical outline of a pulmonary nodule has required a differential diagnostic search. The results of imaging RNs in the lung and their dynamics are shown. The given data are discussed.

Objective: to assess whether adalimumab (AD) can be gradually discontinued during continuous methotrexate (MTX) use in patients with early rheumatoid arthritis (ERA).Subjects and methods. Within the REMARCA (the Russian study of methotrexate and biological agents in early active arthritis) study, the investigators examined 20 patients (17 women and 3 men; median age, 51 [41.5; 56] years) with ERA (disease duration, 10 [5.5; 20] months; DAS28, 5.17 [4.37; 6.51]; 85% of the patients were seropositive for rheumatoid factor and 85% for anti-cyclic citrullinated peptide antibodies.Results and discussion. All the patients received subcutaneous MTX 25 mg/week. Twelve weeks after beginning therapy with MTX, due to its inefficiency, ADA was added according to the standard scheme. At week 24, the median DAS28 was 3.0 [1.65; 3.73]; 85% of the patients achieved remission or low disease activity. After 3 months of ADA therapy, high or moderate disease activity remained in 3 (15%) patients; median DAS28 was 4.4 [4.3; 6.1]; the drug was discontinued in them due to ineffective therapy. After 12-month follow-up, low DAS28 scores were observed in 5 (29.4%), DAS28 remission was in 12 (70.6%) of the 17 patients who continued ADA treatment; after 24 months, all the 17 patients were noted to have remission. After achieving sustained remission (≥ 6-month duration during ADA therapy), there was a carefully controlled reduction (titration) in the dose of ADA with its complete discontinuation, by maintaining remission at 36-month follow-up; the median DAS28 was 1.6 [1.4; 2.2]. During ADA treatment, one female patient developed pustular psoriasis and therefore the drug was discontinued at 24-month follow-up during the period of sustained remission. Other serious adverse events and tuberculosis cases were not recorded.Conclusion. Thus, the results of the study are indicative of the high clinical efficiency of the therapy. After ADA discontinuation, sustained remission can be maintained in patients with ERA and if they took biological agents early.

The lecture presents an update on the epidemiology, pathogenesis, clinical manifestations, diagnosis, differential diagnosis, and treatment stages of polymyalgia rheumatica, a chronic inflammatory disease of unknown etiology, which affects older people.----Authors of the article «Rheumatic polimyalgia», published in the section «Program of continuous post-graduate education of therapists» in journal «Scientific-practical rheumatology» No 2 (V 56)2018 Satybaldyev А.M et al. present their apologies for unpremeditated using for educational purposes of illustrative material on page 217 (Fig. 1) from the article by BlockmansD. Positronemission tomography and magnetic resonance imaging. In: Polymyalgia Rheumatica and Giant Cell Arteritis, Chapter 8.OxfordUniversity press. EdBh. DasguptaandCh. Dejaco; 2016:63-71 and on page 220 (Fig 2) from the article by M. Jiang,S. Navanathan“Crowned dens syndrome: a rare cause of neck pain and fever”Med J Aust 2017; 206 (5):199 || http://doi.org/10.5694/mja16.01077 Published online: 20 March 2017.

П р о г р а м м а н е п р е р ы в н о г о п о с л е д и п л о м н о г о о б р а з о в а н и я в р а ч е й

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.

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.

The paper presents the materials of the Russian Arthritis Registry (OREL) that includes 3276 patients from 11 Russian Federation's largest research-and-practical centers situated in Moscow, Saint Petersburg, Novosibirsk, Kazan, Tula, Yaroslavl, Tyumen. It discusses the main goals of setting up registries, compares the results of an analysis of the data available in the Russian Registry OREL and registries of European countries and the USA. The findings suggest that there is non-uniform information on clinical, laboratory, and instrumental parameters in the national registers of a numberof European countries and the USA. According to its basic characteristics, the Russian Registry OREL compares favorably with a number of other registries in the completeness of data collection, which allows a general idea of rheumatoid arthritis (RA) patients in Russia. For further development of the OREL Registry, it is necessary to concentrate our attention on the following main areas: to improve the quality of filling out documents; to follow-up patients receiving different RA therapy regimens according to the guidelines of the Association of Rheumatologists of Russia for the treatment of RA; to conduct in-depth studies of comorbidity, primarily depressive disorders; to analyze adverse reactions that make RA therapy difficult; to actively use modules for patients' self-rating of their condition; to develop nursing care, etc.

New international guidelines for the diagnosis and treatment of systemic vasculitis involving large vessels, which had resulted from the systematic generalization of current scientific achievements and clinical experience, were published in 2015. The experts of the French Large Vessel Vasculitis Study Group have elaborated 15 recommendations covering a wide range of problems of giant cell arteritis; the European League Against Rheumatism and the American College of Rheumatology have presented 9 recommendations for the management of polymyalgia rheumatica. The purpose of this paper is to provide common characteristics of the main points of the new guidelines, by discussing some controversial issues.

The article describes the All-Russian Registry of Rheumatoid Arthritis (RA) Patients launched in 2011Р2012 as an Internet-based project. The Registry aims at updating the record system of RA patients and providing reliable information on real clinical practice to improve healthcare. The aims, structure, and software of the Registry, as well as its interrelations with other registries, are described. A scheme of the interplay between healthcare facilities and the Russian Association of Rheumatologists during their work with the All-Russian Registry of Rheumatoid Arthritis Patients is proposed.