The Association of Rheumatologists of Russia (ARR) is one of the largest and most influential public medical organizations in Russia, whose activities have allowed us to preserve and strengthen the rheumatology service in the country, train highly qualified personnel, and work productively and successfully for the benefit of our patients. Today we celebrate the 60th Anniversary of the ARR, we remember the history, the stages of a long journey and our achievements.

Gout has the richest history of all rheumatic diseases. The name of this most ancient of the described diseases of the musculoskeletal system for a long time not only determined the fact of damage to the joints, but was also synonymous with severe pain. Although the disease itself is much older than humanity and dates back to prehistoric times, it was with the advent of man on Earth that gout began to influence the historical process and became an integral part of it. Since ancient times, it was noticed that famous kings, emperors, generals, admirals and philosophers, musicians and artists, scientists and writers often suffered from gout. The cause of the disease was seen in a sedentary lifestyle, overeating, and abuse of wine with significant mental stress. And now it is difficult to imagine our world without this disease, which is so closely intertwined with the history of humanity.

Autoimmunity is a pathological process associated with a violation of immunological tolerance to normal structural components of the body (autoantigens), associated with the predominance of active (adaptive) immunity and manifested by hyperproduction of autoantibodies. Systemic autoimmune rheumatic diseases (SARDs) are among the most common and severe nosological forms of this pathology associated with autoimmunity. Problems of pharmacotherapy of SARDs are the subject of intensive research. At the beginning of the 21st century, more than 20 biologic agents were developed for the treatment of rheumatoid arthritis – monoclonal antibodies (mAbs) and recombinant proteins that control inflammation associated with the overproduction of “pro-inflammatory” cytokines, the use of which has dramatically improved the results of pharmacotherapy. However, much less research has been devoted to studying the possibilities of pharmacotherapy aimed at selective suppression of the “autoimmune” component of the pathogenesis of SADRs associated with uncontrolled activation of B cells and restoration of immunological tolerance to autoantigens. In the spectrum of drugs whose mechanism of action is associated with the suppression of pathological activation of B cells, the leading place is occupied by rituximab (RTM). It is noteworthy that 20 years ago (2004), a group of researchers led by prof. J.C. Edwards first demonstrated the effectiveness of RTM in patients with RA, which was soon successfully repositioned to treat a wide range of SARDs. A major achievement in the pharmacotherapy of SARDs is associated with the use of CAR (сhimeric antigen receptor) T cell therapy, developed for the treatment of refractory hematological tumors. The main component of CART-cells is a genetically engineered T-cell receptor that recognizes the target antigen without the participation of the major histocompatibility complex. Although limited, extremely impressive data regarding high remission rates have been obtained by adapting CD19 CART-cell therapy to treat patients with severe systemic lupus erythematosus (SLE) and other SARDs refractory to standard immunosuppressive medications. The article discusses the results of the use of CART-cell therapy in SLE and other SARDs and prospects for further research.

Gout manifests as acute arthritis attacks, the frequency of which varies and is unpredictable.

The aim of this study was to identify factors associated with the frequency of arthritis attacks in patients with gout who have not received urate-lowering therapy (ULT).

Materials and methods. A retrospective cohort study included 116 patients (6 females, 110 males) with gout, with a mean age of 50.1±12.05 years, who were not receiving ULT. The frequency of arthritis attacks in the past year and the presence of subcutaneous tophi were evaluated. Analyzed factors included alcohol consumption, smoking, body mass index (BMI), blood pressure values, comorbidities, diuretic use, and laboratory tests, including serum levels of glucose, creatinine, creatine phosphokinase (CPK), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), uric acid (UA), C-reactive protein (CRP), and estimated glomerular filtration rate (eGFR).

Results. The mean disease duration was 9.2 [3.9; 15.8] years. The average number of arthritis attacks per year was 5 [2; 6], with ≥4 arthritis attacks per year observed in 40% of patients, and subcutaneous tophi present in 33.6%. A weak positive correlation was found between the frequency of exacerbations and systolic blood pressure (p<0.001), serum GGT levels (p<0.001), CPK levels (p=0.120), and serum CRP levels (p=0.040). Serum UA levels correlated only with the presence of subcutaneous tophi (p=0.017), but not with the frequency of arthritis attacks (p=0.972). OR >4 attacks of arthritis was significant for: presence of heredity for gout – 1.955 (95% CI: 1.224–3.121; p<0.05); presence of tophi – 1.746 (95% CI: 1.161–2.626; p=0.007); alcohol consumption – 2.656 (95% CI: 1.766–3.994; p<0.001); in the presence of a sUA level ≥540 µmol/l – 1.586 (95% CI: 1.041–2.416; p=0.031). Diuretics users had attacks more frequently (р<0,001).

Conclusion. The frequency of arthritis attacks in untreated gout patients may be associated with the presence of subcutaneous tophi, systolic blood pressure values, serum GGT, uric acid levels (when >540 µmol/L), diuretic use, and alcohol consumption.

Aim – to study the clinical manifestations of rheumatoid arthritis (RA) and the spectrum of concomitant diseases, depending on the level of hepcidin in patients with high inflammatory activity.

Material and methods. The analysis included 78 patients (48.9±15.5 years) with RA, disease duration of 108 [48; 204] months. All patients were diagnosed with high or medium inflammatory activity of the disease (DAS28-ESR (Disease Activity Score 28 with erythrocyte sedimentation rate detection – 5.2). Indicators of iron metabolism, levels of hepcidin and interleukin 6 were determined. Three subgroups of patients were identified: subgroup I – with serum hepcidin levels below the reference values (less than 40 pg/ml); subgroup II – with hepcidin levels within the reference values (40–120 pg/ml); subgroup III – patients with high hepcidin levels (more than 120 pg/ml).

Results. It was found that in RA with high inflammatory activity, regardless of the hemoglobin level, disorders in iron metabolism were noted in 83% of cases. Reduced serum hepcidin levels were diagnosed in 40% of cases (subgroup I), on average, very high hepcidin values were detected in every second (n=34; subgroup III). The main clinical manifestations of RA, DAS28 activity and duration of the disease were comparable in all three subgroups. The largest number of concomitant diseases were diagnosed in RA patients with high levels of hepcidin. Chronic obstructive pulmonary disease (26%), endocrine pathology – 22% (diabetes mellitus, thyroid diseases, obesity), chronic kidney disease (21%) and cardiovascular disease (60%) were significantly more common (p<0.05). With iron deficiency, the most common pathology was gastrointestinal tract damage – 35% (erosive gastritis, peptic ulcer of the stomach and duodenum, etc.), the second most common was pathology of the cardiovascular system (32%). In the same subgroup, one in ten had a change of two classes of bDMARDs/tsDMARDs by the time of the study.

Conclusion. The results of this study illustrate the need for further study of the pathogenetic pathways of iron metabolism disorders in order to form scientifically sound approaches to personalized treatment of a wide range of immunoinflammatory rheumatic diseases, including RA.

According to the World Health Organization (WHO), worldwide, annual influenza epidemics lead to approximately 3–5 million cases of severe forms of the disease and 250–500 thousand deaths. The problem of the course and outcomes of influenza is also relevant for patients with immunoinflammatory rheumatic diseases, including spondyloarthritis (SpA). However, data on the immunogenicity, efficacy and safety of influenza vaccines in patients with SpA are limited.

The aim of the work was to study the immunogenicity, efficacy and safety of the trivalent inactivated influenza split vaccine in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA), observed at the V.A. Nasonova Research Institute of Rheumatology.

Materials and methods. 94 people were included in the study: 28 patients with AS, 14 patients with PsA, 52 patients in control group (СG) without immunoinflammatory rheumatic diseases. Vaccination with a trivalent inactivated influenza split vaccine was carried out over three consecutive epidemic seasons: 2020–2021, 2021–2022, 2022–2023. The majority of patients (71,4%) received immunosuppressive therapy. The trivalent inactivated influenza split vaccine was administered in an amount of 1 dose (0.5 ml) intramuscularly against the background of anti-rheumatic therapy, regardless of the activity of the main IVR. The level of antibodies (AT) of class G to hemagglutinin (HA) of influenza A (H1N1), A (H3N2) and B viruses was determined using enzyme immunoassay systems manufactured by PPDP LLC (St. Petersburg, Russian Federation) before vaccination, 1–3 (on average, 1,6±0,8) and 6 months after it. The clinical efficacy and safety of trivalent inactivated influenza split vaccine were also evaluated, including the effect on the activity of AS and PsA according to the dynamics of BASDAI and DAPSA indices.

Results. At the second and third visits after vaccination the level of AT, determined in units of optical density, to HA of influenza A (H1N1), A (H3N2) and B was significantly higher compared to baseline values. During follow-up, influenza or flu-like disease according to WHO criteria were absent in 37 patients. In general, there was no negative effect of vaccination on the activity of the underlying disease. The frequency of postvaccinal reactions in patients and in СG was comparable.

Conclusions. The obtained results of the study indicate sufficient immunogenicity, clinical efficacy and safety of trivalent inactivated influenza split vaccine in patients with AS and PsA.

Aim – to evaluate myeloid-derived suppressor cell (MDSC) subset counts and their suppressor potential in axial spondyloarthritis (axSpA) patients, as well as to analyze changes in the studied parameters in biological therapy (BT).

Materials and methods. The study included 50 axSpA patients receiving 1st line therapy (non-steroidal anti-inflammatory drugs ±sulfasalazine/methotrexate) and 44 ageand sex-related healthy donors. Eight patients were initiated with BT (TNFαor IL-17 inhibitors). Peripheral blood granulocytic (G-MDSC), monocytic (M-MDSC) MDSCs, early-stage differentiation MDSCs (E-MDSC), and inhibitory molecule expression (PDL1, Arg-1, and IDO) were evaluated by flow cytometry.

Results. The axSpA patients were characterized by increased G-MDSC counts (р<0.01), particularly manifested with high disease activity. Axial manifestation was associated with a combination of increased G-MDSC and E-MDSC numbers (р<0.05). The extra-axial group showed an isolated increase in G-MDSC (р<0.05), whereas coxitis was associated with an increase in both G-MDSC and M-MDSC (р<0.05). Low activity was associated with an isolated M-MDSC increase (р=0.045). Patients had reduced expression of majority of the studied suppressor molecules in MDSCs. Axial manifestation was characterized by a decreased expression of PDL1 and IDO in G-MDSCs and E-MDSCs (р<0.05), as well as Arg-1 in E-MDSCs and M-MDSCs (р<0.05). Patients with extra-axial manifestations (including coxitis) exhibited the most significant reduction in the expression of all three inhibitory molecules in M-MDSCs. High activity was associated with a decrease in PDL1+ G-MDSCs and E-MDSCs (р<0.05), as well as Arg-1and IDO-expressing M-MDSCs (р<0.05). In low disease activity, most of the analyzed parameters did not differ significantly from donor values, with the exception of a reduced Arg-1+ M-MDSC frequency (р=0.04). BT reduced G-MDSC counts in 75% of patients to levels comparable to those of healthy donors.

Conclusion. Despite the reduced suppressor potential of MDSCs, patients undergoing first-line therapy with high activity demonstrated increased G-MDSC counts, while low activity axSpA was characterized by an isolated increase in M-MDSCs. The BT administration blocked G-MDSC accumulation.

Juvenile idiopathic arthritis (JIA) is characterized by a high risk of joint destruction, extra-articular changes, and rapidly progressive disability. The CHAQ (Childhood Health Assessment Questionnaire) questionnaire and X-ray are often used to assess functional impairment and the degree of irreversible damage, but both methods have limitations. The Juvenile Arthritis Damage Index (JADI) has been developed to comprehensively assess the biological prognosis of JIA, which includes articular (JADI-A) and extra-articular (JADI-E) damage evaluation. The use of the JADI may be an effective tool for predicting and monitoring the effectiveness of JIA therapy in real clinical practice conditions.

The aim – to identify correlations of the JADI index with features of clinical manifestations in patients with non-systemic variants of JIA who had no experience with biologic therapy (B) and to evaluate the impact of lesions defined through the JADI damage index value on predicting response to B.

Methods. This open prospective study included 150 children with non-systemic JIA variants with no history of biologic therapy. The mean age was 12.2±4.6 years, 60% were girls. 112 patients were examined in dynamics after 6 or 12 months from the beginning of B therapy. Clinical and anamnestic evaluations, including detailed assessment of joint status and JADI-A and JADI-E scores, were performed on all patients.

Results. The study found that 50% of patients had damage on the JADI score, with 43% having JADI-A+ and 23% having JADI-E+. Both articular and extra-articular damage were present in 15% (n=23) of children. Among those with JADI-A, flexion contractures of the knee joints were most frequently noted in 39%, elbow joints in 28%, and limitation of movement in the cervical spine in 26%. Extra-articular injuries were more frequently presented as avascular necrosis of bones, confirmed by imaging methods (41%), and a significant difference in limb length was observed in 35% of patients. The presence of articular changes was significantly associated with positivity for antinuclear antibody , rheumatoid factor, and anticyclic citrullinated peptide, as well as the absence of enthesitis, elevated erythrocyte sedimentation rate and С-reactive protein, high clinical activity, Juvenile Arthritis Disease Activity Score, CHAQ values, a history of glucocorticoid therapy, and low adherence to treatment. Polyarticular onset involving small hand joints and a tendency for rapid contracture formation were also associated with positive JADI-A values. The onset of polyarthritis with involvement of the small joints of the hands and a tendency to fast contracture formation were also associated with JADI-A positivity. As a result of therapy with B prescribed in routine clinical practice, the vast majority of patients achieved stable status without signs of damage or the value of the damage index remained unchanged. In 26 (23%) patients, JADI-A scores improved with complete resolution of contractures or increased amplitude of joint movement. In 10 (9%) cases there was progression of the lesions with no established correlation with the choice of a specific drug, including 6 (5%) children with irreversible changes despite the use of targeted therapy.

Conclusions. The JADI index is a useful and accessible tool for clinical assessment of articular and extra-articular lesions, reflecting the prognosis of JIA and an objective indicator of therapy efficacy.

The aim of the study – Is to evaluate the effectiveness and safety of the use of a functional unloading orthosis with the possibility of varus–valgus correction (FUOVVC) in patients with stage III osteoarthritis of the knee joint.

Materials and methods. The study involved 10 patients with stage III osteoarthritis of the knee joint who underwent outpatient treatment at the V.A. Nasonova Federal State Medical University of the Russian Academy of Medical Sciences. All patients used the FUOVVC for 3 months. To evaluate the results, pain intensity was determined using a visual analog scale (VAS) and knee joint function according to the knee injury and osteoarthritis KOOS (Knee injury and Osteoarthritis Outcome Score) questionnaire before using the orthosis, after 1 and 3 months. Additionally, the assessment of VAS was carried out immediately after fixation of the orthosis on the knee joint.

Results. The median age of the patients was 63.5 [55.0; 74.0] years, body mass index – 29.9 [27.9; 34.0] kg/m², pain according to VAS baseline – 40.0 [40.0; 60.0] mm, pain according to VAS 1 hour after the start of the use of The median age of the patients was 63.5 [55.0; 74.0] years, body mass index – 29.9 [27.9; 34.0] kg/m², pain according to VAS baseline – 40.0 [40.0; 60.0] mm, pain according to VAS 1 hour after the start of the use of FUOVVC – 25.0 [10.0; 30.0] mm, pain according to VAS after 1 month – 10.0 [0.0; 20.0] mm, VAS after 3 months – 10.0 [0.0; 20.0] mm. The median score according to the KOOS questionnaire was initially 41.5 [38.0; 50.0], after 1 month – 61.0 [53.0; 63.0], after 3 months – 63.5 [58.0; 64.0]. None of the patients had any adverse events when wearing the FUOVVC. – 25.0 [10.0; 30.0] mm, pain according to VAS after 1 month – 10.0 [0.0; 20.0] mm, VAS after 3 months – 10.0 [0.0; 20.0] mm. The median score according to the KOOS questionnaire was initially 41.5 [38.0; 50.0], after 1 month – 61.0 [53.0; 63.0], after 3 months – 63.5 [58.0; 64.0]. None of the patients had any adverse events when wearing the FUOVVC.

Obstetric pathology (pregnancy loss at different gestational ages; premature delivery of morphologically normal foetus due to pre-/eclampsia or placental insufficiency), along with thrombotic complications are the main clinical manifestations of antiphospholipid syndrome (APS). Among arterial thromboses in APS, cerebral vascular thromboses in the form of strokes or transient ischaemic attacks. Patients with APS have a well known increased risk of thrombosis associated with pregnancy or conditions accompanied by hyperestrogenemia. More than half of thrombotic complications in women with APS occur during gestation or hyperestrogenemia. Most studies of pregnancy in APS have focused on women with recurrent fetal loss, and data on pregnancy outcomes in patients with other clinical phenotypes of APS, such as thrombotic APS, are limited. We present a case report of a patient with reliable thrombotic APS (with recurrent ischaemic cerebral circulatory disorders) and highly positive levels of antiphosphrolipid antibodies with a favourable pregnancy outcome.