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Rheumatology Science and Practice

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Vol 61, No 4 (2023)
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FRONTIERS

397-420 1612
Abstract

Two fundamental pathologic processes are central to the spectrum of chronic inflammation mechanisms: autoimmunity and autoinflammation. Autoimmunity and autoinflammation are mutually potent pathologic processes; their development is considered within the framework of the “immunoinflammatory” continuum, reflecting the close relationship between innate and acquired types of immune response. Autoimmunity is the leading mechanism of pathogenesis of a large group of chronic inflammatory human diseases, defined as autoimmune diseases, the frequency of which in the population exceeds 10%. Advances in molecular biology, pharmacogenetics and bioinformatics have created prerequisites for individualization of therapy of autoimmune rheumatic diseases within the concept of personalized medicine. The study of immunopathogenesis mechanisms, improvement of diagnostics, deciphering the nature of molecular taxonomy, development of approaches to prevention and personalized therapy of human autoimmune diseases is among the priority directions of medicine of the 21st century.

К 100-ЛЕТИЮ СО ДНЯ РОЖДЕНИЯ АКАДЕМИКА РАН В.А. НАСОНОВОЙ

INTERNATIONAL AND RUSSIAN GUIDELINES FOR THE TREATMENT OF RHEUMATIC DISEASES

435-449 3290
Abstract

Rheumatoid arthritis (RA) is the most frequent immunoinflammatory (autoimmune) rheumatic disease characterized by chronic erosive arthritis and systemic damage to internal organs. The data obtained in the course of basic research on deciphering the mechanisms of action of methotrexate (MT) and the materials of numerous randomized placebocontrolled trials, observational studies and national registries have strengthened the position of MT as the “gold standard” of RA pharmacotherapy and a key component of the “Treatment to Target” strategy. This was the basis for the development of new recommendations of the Association of Rheumatologists of Russia (ARR) concerning the use of MT in RA, according to which MT is considered as the drug of “choice” for induction and maintenance of remission in patients with early and advanced RA, including those who need combination therapy of MT with glucocorticoids, standard Disease-Modifying Antirheumatic Drugs (DMARDs), biologics and targeted synthetic DMARDs. Special attention is paid to the safety of MT therapy and the impact of MT on comorbid pathology associated with cardiovascular complications and interstitial lung disease. Implementation of the ARR recommendations into clinical practice will reduce the risk of disability and improve life prognosis in patients with RA.

PROBLEMS OF RHEUMATOLOGY DURING THE 2019 CORONAVIRUS PANDEMIC

450-457 517
Abstract

During the three years that have passed since the beginning of the COVID-19 pandemic, many new fundamental and medical problems have been discovered regarding the relationship between the viral infection and many common chronic non- infectious diseases. Among the latter, an important position is occupied by immuno-inflammatory rheumatic diseases (IIRD), which include rheumatoid arthritis (RA). To date, there is no doubt that patients with RA are at risk for SARS-CoV-2 infection, a severe course of infection that necessitates hospitalization and death. The article presents current data on the course and outcomes of COVID-19 in patients with RA. The literature and own data on postcovid syndrome in this group of patients are presented. The necessity of vaccination against SARS-CoV-2 in patients with IIRD, including those with RA, was substantiated. The prospects for further study of the features of COVID-19 in patients with RA are outlined.

PROGRESS IN RHEUMATOLOGY IN THE XXI CENTURY

458-465 1224
Abstract

The article is dedicated to a new actual problem in rheumatology: vasculitis and vasculitis-like manifestations in monogenic autoinflammatory syndromes in adult. The features of the clinical course of the rarely diagnosed VEXAS syndrome, as well as the SAVI and COPA syndromes, which sometimes occur in adults, are considered. Promising directions of future treatment are discussed.

YOUNG SCIENTISTS FORUM

466-474 654
Abstract

Systemic sclerosis (SSc) is one of the most severe systemic rheumatic diseases, characterized by the development of progressive skin fibrosis and damage to internal organs, accompanied by a decrease in the quality of life and high mortality. The treatment of SSc remains a difficult clinical task due to the complex pathogenesis. Nowadays therapy is complex and based on the dominant clinical and pathogenetic phenotype of SSc. However, standard therapy have limited potential to radically improve the prognosis of SSc, and often their use can lead to the development of intolerance and adverse events. In this connection, it remains relevant to study and introduce new approaches for the treatment of SSc, one of which is anti-B-cell therapy. Based on the data on the key role of B cells in the regulation of inflammatory and fibrotic processes in SSc, rituximab (chimeric monoclonal antibody to B-lymphocyte surface receptors – CD20) is increasingly being studied and used in clinical practice for the treatment of this disease. This review collects and analyzes data on the efficacy, safety and impact of rituximab on various manifestations of SSc.

ORIGINAL RESEARCH

475-484 329
Abstract

The aim of the study was to investigate the dynamics of clinical and laboratory parameters of inflammatory disease activity and cytokines in patients with rheumatoid arthritis (RA) against the background of olokizumab (OKZ) treatment.
Materials and methods. Ten patients with a reliable diagnosis of RA were examined: patients’ age was 46.00 (30.00; 60.00) years, duration of disease was 9.0 (3.0; 12,0) years. All patients had moderate to high disease activity: DAS28-ESR (Disease Activity Score 28 with Erythrocyte Sedimentation Rate) – 513 (4.34; 5,80); CDAI (Clinical Disease Activity Index) – 30.00 (24.00; 35.00); SDAI (Simplified Disease Activity Index) – 31.86 (24.36; 38.59). All patients were treated with OKZ at a dose of 64 mg subcutaneously every 4 weeks on the background of therapy with methotrexate, leflunomide, nonsteroidal anti-inflammatory drugs, and glucocorticoids. Observations were performed before treatment and after 3, 6 months of therapy. Serum levels of 15 cytokines: interleukin (IL) 1β, IL-4, IL-6, tumor necrosis factor α (TNF-α), interferon (INF) γ, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, sCD40L, – were examined using multiplex xMAR technology.
Results. After 3 and 6 months of OKZ therapy, there was a significant decrease in DAS28-ESR of 3.53 (2.83; 4.26) and 3.48 (2.8; 4.10); CDAI – 11.00 (6.0; 16.00) and 10.0 (5.0; 15.0); SDAI – 10.0 (5.0; 15.0) and 10.17 (7.02; 15.02); C-reactive protein (CRP) concentrations (initial – 14.30 (7.00; 24.70) mg/l, after 3 months – 0.70 (0.40; 0.90) mg/l and after 6 months – 0.65 (0.20; 3.00) mg/l). After 3 months of treatment we found an increase in IL-6 concentration (initial – 1.89 (1.61; 2.33) pg/ml and 89.98 (35.09; 165.84) pg/ml; p<0.01), after 6 months – its level decreased to 44.88 (5.25; 80.90) pg/ml without reaching, however, the initial values (p<0.05). Against the background of OCZ, after 3 months of treatment there was an increase in IL-25 concentration (p<0.01), and after 6 months of therapy – TNF-α (p<0.05).
Conclusion. The use of OKZ leads to an increase in the concentration of total IL-6 in the blood serum of RA patients, while the clinical and laboratory activity of the disease decreases.

485-492 979
Abstract

Introduction. The possibilities of modern therapy for systemic sclerosis (SSc) remains limited, since most of the used drugs do not have a diseasemodifying effect. This encourages the study of new approaches that potentially affect the fundamental pathological processes underlying the disease. One example is anti-B cell therapy, in particular rituximab (RTX). Until now RTX do not have a registration for the treatment of SSc, but there is a large positive experience of its use, which is reflected in recent meta-analyses and clinical recommendations. Complicated and expensive methods for obtaining genetically engineered biological preparations have contributed to the emergence of more accessible biosimilars, one of which is the RTX biosimilar, Acellbia (Biocad, Russian Federation). The “biosimilar” versions of RTX might reduce the cost of therapy and increase patients accessibility to this treatment option. The RTX biosimilar Acellbia (ACB) has received approval in Russian Federation in 2014 for all indications held by reference RTX (including rheumatoid arthritis and ANCA-associated vasculitis).
The aim of this study was to investigate the efficacy and safety of Acellbia in patients with systemic sclerosis.
Material and methods. Our prospective uncontrolled study included 20 patients (14 women) aged 50±14 years, with a disease duration of 3.5±2.7 years. Indications for the prescribing of ACB were high disease activity and the presence of risk factors for progression. All patients had radiological signs of interstitial lung disease, 13 (65%) were positive for antibodies to topoisomerase 1. None of the patients had previously been treated with biological therapy. All patients received glucocorticoids in low doses and 15 (75%) patients were not on concomitant immunosuppressants during the study. ACB was administered in doses of 2 g (two doses of 1 g with a weekly interval) at inclusion of the study and after 6–8 months according to the same scheme, cumulative dose – 4 g. An assessment of basic measurements was obtained at baseline (Point 0), before the second course (after 7.2±1.7 mo, Point 1) and at the end of follow-up (13.4±1.6 mo, Point 2). The results are presented in the form of mean values and standard deviations.
Results. There was a positive effect on the main manifestations of the disease, which accompanied by stable depletion of CD19+ B lymphocytes in the peripheral blood. At the intermediate assessment (between points 0–1), no significant changes were observed, with the exception of the skin score. At the end of the study, most of the parameters showed a significant improvement between points 0–2. The activity of the disease (EScSG-AI) decreased, and the skin score decreased from 12.8±11 to 6.2±5.6 (p=0.002). The forced vital capacity (% of predicted) increased from 89±18.2 to 98.26±16.13% (p=0.0002), and the diffusion capacity of the lungs (% of predicted) increased from 56.8±15.7 to 61.9±17.2% (p<0.019). A significant decrease in CRP, antitopoisomerase-1 antibodies, as well as IgG (from 12.6±2.6 to 10.2±2.2 g/l) was noted. Repopulation to normal level of B lymphocytes did not occur in any case, and complete depletion of B lymphocytes at the end of the study was maintained in 83% of patients (15 of 18). The quality of life questionnaire SHAQ improved (p=0.0001), and the average dose of prednisolone was reduced from 11.0±2.7 to 9.4±2.3 mg/day (p=0.03). Positive changes according to HRCT was evident in 9 (45%) patients due to a decrease in ground glass opacity. The frequency and spectrum of adverse events (AEs) corresponded to those already known for RTX. Of the 20 patients who received 2 courses of ACB, two withdrew from the evaluation at Point 2 due to pregnancy (1) and lung cancer (1). A total of 11 (55%) AEs were reported in 9 (45%) patients, most of them were classified as mild. Infectious complications developed in 7 (35%) patients: respiratory infections of the upper respiratory tract (4), positivity in the TB skin test (2), otitis (1), cystitis (1) and cholecystitis (1). One patient developed calf vein thrombosis and lung cancer was diagnosed in one case.
Conclusion. Our data suggest that Acellbia could be used for the treatment of SSc. A short-term, prospective, uncontrolled study showed good efficacy and acceptable safety of the ACB biosimilar in SSc. A significant decrease of skin fibrosis and improvement of lung functions have been proven. The clinical effect of ACB manifested by the 6th month from the start of therapy and reached its maximum one year after its initiation. Due to the positive efficacy of ACB, it can be prescribed for the patients with SSc with ineffectiveness and/or intolerance to immunosuppressants, and could be considered as a first-line therapy. Our data should be confirmed by the results of controlled clinical trials.

493-500 412
Abstract

Objective – to analyze whether axial psoriatic arthritis (axPsA) patients meet classification criteria for axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS).
Subjects and methods. 104 patients (66 men and 38 women) with PsA according to CASPAR criteria were examined, all patients had back pain. Patients were evaluated for presence of inflammatory back pain (IBP) by ASAS criteria. Back pain not meeting the ASAS criteria was taken to be chronic back (chrBP). Patients underwent hands, feet and pelvis, cervical spine and lumbar spine X-rays. Erosions, osteolysis, and periarticular osteo-proliferative lesions were evaluated. Radiographically significant sacroiliitis (r-sSI) was defined as bilateral grade ≥2 or unilateral grade ≥3. 19 patients without r-sSI underwent sacroiliac joints MRI. 93 patients underwent HLA B27 examination. The number of patients who met the criteria for axSpA (ASAS) and the modified New York (mNY) criteria for AS was determined.
Results. IBP was identified in 67 (64.4%), chrBP in 37 (35.6%) patients; 31 (29.8%) patients were of advanced age (over 40) at the onset of IBP/chrBP; 57 (58.8%) cases had r-sSI; 6 (31.6%) patients had MRI-SI; syndesmophytes were detected in 57 (58.8%) cases. Among 40 patients without r-sSI, 19 (47.5%) had syndesmophytes. In 38 (39.2%) out of 97 patients r-sSI was detected along with syndesmophytes, while 19 (19.6%) out of 97 patients had isolated r-sSI without spondylitis, and 19 (19.6%) out of 97 patients had isolated syndesmophytes without r-sSI. HLA B27 was present in 28 (30.1%) cases. 51 (55.4%) patients met criteria for axSpA. 41 (44.6%) patients didn’t meet criteria for axSpA, however 27 (65.9%) of them had syndesmophytes. 48 (48.5%) PsA patients met mNY criteria for AS.Among these patients a set of specific features was revealed: 18 (37.5%) had no IBP, 18 (37.5%) were of advanced age (over 40) at the onset of IBP/ chrBP, 34 (70.8%) had dactylitis, 38 (79.2%) – erosive polyarthritis, 23 (48.8%) – periarticular osteo-proliferative lesions, 14 (30.2%) – osteolysis, 23 (48,9%) – “chunky” non-marginal syndesmophytes, 40 (82,6%) – nail psoriasis, 28 (66,6%) patients were HLA-B27 negative.
Conclusion. 45% of axPsA patients don’t meet criteria for axSpA. Characteristic features have been identified to differentiate axPsA from AS.

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