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The efficacy and safety of levilimab (LVL) in patients with active rheumatoid arthritis (RA) has been confirmed in controlled clinical trials. This article presents the results of a preliminary analysis of a non-interventional observational study of LVL in RA patients. Objective: to evaluate the efficacy and safety of LVL in the treatment of patients with RA in real-world clinical practice. Materials and methods. The HELIOS study is a retrospective-prospective, multicenter, non-interventional study of retention rate of LVL therapy and the safety of LVL in patients with RA in real-world clinical practice. Patients received medical care, including LVL, according to routine clinical practice for the treatment of RA and Russian instructions for medical use of the drug. This article presents the results of an analysis of the efficacy and safety of LVL after 12 and 24 weeks of treatment. Efficacy was assessed using the DAS28-CRP/ESR, SDAI, CDAI and patient assessment of pain, fatigue and morning stiffness according to VAS (0–100 mm). Results and discussion. 524 patients from 42 medical centers in the Russian Federation were enrolled in the study from June 2022 to November 2023. The majority of patients were female (83.2 %) and the mean age of patients was 53 years. A statistically significant decrease in DAS28-CRP/ESR, SDAI, CDAI, patient assessment of pain, fatigue and morning stiffness (VAS) was observed after 12 and 24 weeks of treatment, regardless of previous treatment with biologics or Jak inhibitors (JAKi). LVL was well tolerated by patients, the most frequently reported adverse events were infections, changes in peripheral blood and laboratory abnormalities characteristic of treatment with IL-6R inhibitors. Conclusion. In real-world clinical practice, LVL has been shown to be highly effective and well tolerated in patients with RA when prescribed as the first biologic disease-modifying antirheaumatic drus (bDMARD) and after switching from other bDMARDs or JAKi.

Background. Netakimab has shown high efficacy in controlled clinical trials in the treatment of patients with ankylosing spondylitis (AS). This article presents results of an observational study of netakimab using in routine clinical practice.Methods. Patients were recruited for the study from August 2020 to December 2021 at 23 centers in the Russian Federation. The study included patients who were prescribed netakimab therapy before enrollment, so clinical and medical history data for the first visit were entered retrospectively, and following visits at weeks 12, 24 and 52 of therapy were collected within the study. Drug survival rate has been calculated according to Kaplan – Meier analysis.Results. The study included 137 patients (93 men and 14 women) with AS. The average age of patients was 42.3 (±11.9) years, 34.3% of patients had previously received therapy with genetically engineered biologic drugs, mainly tumor necrosis factor inhibitors. At the end of the analyzed period (52 weeks of therapy), 90.4% [95% CI: 85.4–95.7] of patients continued treatment with netakimab. The BASDAI and ASDAS-CRP showed statistically significant decreases in scores from baseline at all time points. Netakimab was well tolerated by patients; adverse effects (AEs), related to therapy according to the investigator’s opinion, were reported in 7 (5.1%) patients. 2 patients stopped taking netakimab due to AEs: terminal ileitis and chronic colitis.Conclusions. In real-world clinical practice, netakimab demonstrated high retention rates, a favorable safety profile, and sustained efficacy throughout the first year of therapy.

The article presents the relevance of the problem of postmenopausal osteoporosis (OP) in modern medicine, due to the social and economic consequences of fractures. The pathogenetic mechanisms of its formation are highlighted, indicating that during postmenopausal women amid estrogen deficiency, there is a violation of bone remodeling processes with increased bone resorption and decreased bone formation. Modern recommendations of the pathogenetic therapy of OP are presented, in which it is noted that the drugs of the first choice are drugs of the bisphosphonate class (BF). The ability of BF to suppress the pathological resorption of bone tissue and stimulate bone formation determines their therapeutic effect in OP. One of the drugs of the BF class is alendronate. In the treatment with alendronate, the processes of resorption by osteoclasts are suppressed and the processes of bone metabolism are restored to the premenopausal level, microarchitectural disturbances and bone loss are prevented. It has been demonstrated that the processes of bone metabolism remain stable during prolonged treatment with alendronate for 10 years, while the accumulation of the drug in the bone does not lead to excessive suppression of bone metabolism, but rather remains at the premenopausal level. The data of international and Russian randomized placebo-controlled trials (RCTs) are presented, which indicate the high effectiveness of alendronate at a dose of 70 mg 1 time / week in the treatment of primary OP in postmenopausal women: it had a positive effect on bone mineral density (BMD), reduced pain and, as a result, reduced the restriction of physical activity of patients. Quite good tolerability of the drug was noted, side effects in the treatment group were comparable to those in the placebo group. An analysis of the action of alenadronate shows that it has an aftereffect within a 12-month period after the end of treatment in relation to the BMD of the spine.

The article discusses the participation of interleukin-6 (IL6) in the formation of pathogenetic mechanisms of immuno-inflammatory diseases (IID). IL6 is one of the central cytokine in progressive IID. The biological activity of IL6 is determined by its ability to activate target genes that regulate differentiation, apoptosis and proliferation of immunocompetent cells. The immune-inflammatory effects of IL6 include regulation of the acute phase reaction, differentiation of immune cells, switching from innate to adaptive type of immune response (activation of T-helper 17 (Th17) cells and T-follicular Th-cells, suppression of the formation of T-regulatory cells, synthesis antibodies by B cells), stimulation of hematopoiesis (maturation of myeloid progenitors and megakaryocytes, leading to neutrophilia and thrombocytosis), neoangiogenesis, osteoclast-mediated bone remodeling. Currently, the use of a humanized monoclonal antibody to the IL-6α receptor (tocilizumab) is one of the most promising directions in the treatment of rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, large arterial vasculitis – aortoarteritis, temporal arteritis. The use of tocilizumab is included in the draft recommendations for the treatment of IID in conditions of coronavirus disease 2019 (COVID-19) developed by the All-Russian public organization “Association of Rheumatologists of Russia”. The presented data from international and domestic studies, as well as our own clinical experience, suggest that Tocilizumab (Actemra) is a highly effective and safe genetic engineering biological drug (GEBD) in the treatment of IID, and its use leads to a decrease in clinical and immunological activity and helps to improve life prognosis both when appointing as a first-line GEBD therapy and in case of ineffectiveness of other biological drugs and basic anti-inflammatory drugs in this category of patients.

The beginning of the 21st century was marked by a simultaneous changes in view on pathogenesis, diagnostics and treatment of axial spondyloarthritis (axSpA). Anti-TNFα inhibitors were the first biologics prescribed in axSpA. 20 year after the biological treatment was first prescribed we have enough data to understand their long-term efficacy.The aim of this study is to evaluate the long-term efficacy of etanercept in patients with axial spondyloarthritis based on data published in periodicals and clinical practice.Patients and methods. An analysis of publications from medical database and data from the St. Petersburg register of patients with rheumatic diseases (n=68) was performed to assess the effectiveness of etanercept in axSpA treatment in the long-term perspectives. Descriptive statistics methods were used.Results. In clinical studies and in real word practice, etanercept has shown high efficiency in reducing clinical, laboratory and visual manifestations of non-radiographic and radiographic axial spondyloarthritis at early and advanced stages of their development.Conclusions. In the long term, the use of etanercept is associated with an increasing slowdown in structural progression while maintaining a stable clinical and laboratory improvement. Discontinuation of treatment in the majority of patients leads to exacerbation of axSpA. At the same time, the low immunogenicity of etanercept allows the resumption of axSpA treatment with a high probability of re-achieving the lost effect with a low probability of secondary ineffectiveness or anaphylaxis.

α1-Antitrypsin (α1-AT) deficiency is a common genetic disorder characterized by low serum α1-AT levels and a clinical manifestation of pulmonary emphysema and liver disease. In addition to its classical manifestations, α1-AT deficiency frequently accompanies granulomatosis with polyangiitis (GPA); in this case the role of α1-AT deficiency in the clinical course of GPA has not been defined. Objective: to estimate the prevalence of pathological α1-AT phenotypes in GPA and other systemic vasculitides (SV) and to determinate their impact on the clinical course of GPA. Subjects and methods. The investigation enrolled 86 patients with SV, including GPA (n=47), microscopic polyangiitis (MPA) (n=16), eosinophilic granulomatosis with polyangiitis (EGPA) (n=12), and polyarteritis nodosa (PAN) (n=11). A control group included 46 healthy donors. Isoelectric focusing was used to phenotype α1-AT in blood samples and its concentrations were determined. The phenotypes of α1-AT were compared with the overall SV activity index using the Birmingham Vasculitis Activity Score (BVAS), the vasculitis damage index (VDI), the nature of an organ lesion, and the markers of immune inflammation (proteinase 3-antineutrophil cytoplasmic antibodies, total IgG, and C3 and C4 fractions of the complement system). Results and discussion. Pathological α1-AT phenotypes were detected in 17% (8/47) of the patients with GPA, 6.25% (1/16) of those with MPA and absent in EGPA and PAN. Patients with GPA had PiZZ (n=1), PiMZ (n=4), PiMF (n=2), and PiMS (n=1) phenotypes; those with MPA had a PiMS-phenotype. The detection of a pathological α1-AT phenotype in patients with GPA was characterized by the high values of BVAS and VDI (p

The deficiency of alpha-1 protease inhibitor, or alpha-1-antitrypsin (A1AT), predisposes to chronic lung diseases and extrapulmonary pathology. Besides classical manifestations, such as pulmonary emphysema and liver disease, alpha-1-antitrypsin deficiency (A1ATD) is also known to be associated with granulomatosis with polyangiitis (GPA or Wegener’s granulomatosis). The aim of our study was to evaluate the frequency of allelic isoforms of A1AT and their clinical significance among GPA patients. Detailed clinical information, including Birmingham Vasculitis Activity Score (BVAS), incidence of lung involvement, anti-proteinase 3 (PR3) antibodies concentrations, and other laboratory data were collected in 38 GPA patients. We also studied serum samples obtained from 46 healthy donors. In all collected samples A1AT phenotyping by isoelectrofocusing (IEF) and turbidimetric A1AT measurement were performed. Abnormal A1AT variants were found in 18.4% (7/38) of cases: 1 ZZ, 4 MZ, 2 MF, and only 1 MZ in control group (2%). The mean A1AT concentration in samples with atypical A1AT phenotypes was significantly lower (P=0.0038) than in normal A1AT phenotype. We found that patients with abnormal A1AT phenotypes had significantly higher vasculitis activity (BVAS) as well as anti-PR3 antibodies concentration. We conclude that A1AT deficiency should be considered in all patients with GPA.