The paper presents the main provisions of the updated 2019 EULAR/ERA-EDTA guidelines for the lupus nephritis (LN) therapy, which have been prepared by an international group of rheumatologists, nephrologists, morphologists, and pediatricians. Part 2 of the article discusses additional therapy, monitoring, and prognosis for LN, and the management of patients with end-stage renal failure and antiphospholipid syndrome. Attention is paid to the problem of LN and pregnancy, as well as to the management of pediatric patients with kidney damage.

Increasing attention in rheumatology is today paid to the detection of diseases at the earliest possible (preclinical) stages, which can contribute to a more favorable response to therapy. The preclinical period of a systemic autoimmune reaction is assumed to be related to dysregulation of immune interactions with the synanthropic microflora. A sequencing method was used to study deviations in the diversity of the gut microflora in patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, a number of unresolved issues remain, since the emphasis has been on the cataloguing of the microorganisms present and on the identification of correlations between microbial species and diseases. The main difference in future microbiome research in patients with immune-mediated inflammatory diseases should be a closer examination of the functions of microbiota components, and not just their description. Long-term studies with the collection of intestinal microbiome samples are required at several time intervals: before disease-modifying antirheumatic drug therapy and during ineffective therapy. Such studies will contribute to the development of new diagnostic and therapeutic interventions. Until they are completed, it is untimely to recommend microbiome analysis as a diagnostic or prognostic tool for the management of rheumatic diseases in clinical practice.

Seropositive juvenile rheumatoid arthritis (JRA) is the rarest subtype of juvenile idiopathic arthritis (JIA) that is the equivalent of RA in adults and is manifested mainly by a symmetric polyarticular lesion, rapid structural disease progression with the formation of intraarticular erosions, the presence of positive rheumatoid factor (RF), and/or anti-cyclic citrullinated peptide (CCP) antibodies.

Objective: to analyze demographic, clinical, and laboratory features of seropositive JRA and drug therapy according to a retrospective 10-year study.

Patients and methods. The retrospective study enrolled patients diagnosed with seropositive JRA confirmed according to the ILAR classification, who were treated at the Childhood Rheumatology Department, V.A. Nasonova Research Institute of Rheumatology, from 2010 to 2020. Demographic indicators, data from clinical, laboratory, and instrumental examinations, and performed therapy were assessed.

Results and discussion. The investigation enrolled 70 patients, amounting to 6.5% of the total number of patients with all clinical types of JIA. Among them, there was a great preponderance of girls (88.6%); the ratio of boys to girls was 1:7.8. The median age of onset of JRA was 12.2 [7.0; 14.0] years; the median duration of disease at diagnosis verification was 6 [4; 12] months; the median number of active joints at diagnosis of JRA was 16.5 [10.75; 23.25]; oligoarthritis was identified in 11.2% of patients at disease onset (within the first 6 months). During the first year of the disease, radiographic Stages II, III, and IV were defined in 42.9, 50, and 7.1%, respectively. Positive RF was found in 94.3% of patients; there was positivity for anti-CCP antibodies in 78.6%, a combination of positivity for RF and anti-CCP antibodies in 72.9%; only positive anti-CCR antibodies were seen in 5.7%. The median ESR at diagnosis verification was 29 [19.75; 44.5] mm/h; that of CRP was 15.0 [6.9; 34.4] mg/l. The extra-articular manifestations of the disease were found in 18 patients (25.7% of the total number of patients): fever in 5 (7.2%); lymphadenopathy in 17 (24.3%); lung damage in 3 (4.3%); rheumatoid nodules in 2 (2.9%); pericarditis in 1 (1.4%) patient, and uveitis in 1 (1.4%). Sjögren's syndrome was diagnosed in 25.7% of patients; autoimmune thyroiditis in 8.6%. A family history of autoimmune diseases was recorded in 22.8%. Nonsteroidal anti-inflammatory drugs and glucocorticoids were used in 97.1 and 48.6% of patients; respectively; the patients received synthetic disease-modifying antirheumatic drugs (sDMARDs): only methotrexate (MTX) [n=55 (78.6%)], sequentially 2 sDMARDs [n=10 (14.3%)], 3 sDMARDs [n=5 (7.1%)]; biological agents (BAs) [n=66 (94.2%)]. During the first year of the disease, Biological therapy was initiated because of the rapid progression of the erosive process in 78.6% of patients. 64.3% of children took one BA, 18.6 and 7.1% received two and three BAs, respectively. Abatacept (ABC) as the first BA was used most often (45.7%). The reasons for revision of therapy were its secondary inefficiency in most cases and serious adverse reactions in 4 patients (ABC- and infliximab-related infusion reactions in 2 cases and conversion of tubercular tests in 2). The differences in the anti-CCP antibody detection rate were statistically insignificant in the group that used only one BA effectively long and in the group that needed to switch to another BA. When choosing a BA, preference was given to tocilizumab or rituximab (RTM) in patients with seropositive JRA in the presence of systemic manifestations, and high clinical and laboratory activities and to RTM or ABC in those with detected Sjögren's syndrome.

Conclusion. Seropositive JRA is a rare subtype of JIA that has an initially unfavorable course. Most patients require early aggressive therapy, including MTX and a BA due to the rapid progression of erosive arthritis. The presence of systemic manifestations and/or Sjögren's syndrome plays a defining role in choosing a specific BA. The presence of anti-CCP antibodies does not affect the selection or change of a BA.

The goal of psoriatic arthritis (PsA) therapy is to achieve remission or minimal disease activity (MDA). According to the EULAR guidelines, synthetic disease-modifying antirheumatic drugs (sDMARDs), methotrexate (MTX) in particular, are first-line therapy for PsA.

Objective: to study the rate of MDA achievement after initiation of sDMARD therapy in patients with early- and late-stage PsA and the efficacy of oral and parenteral MTX.

Patients and methods. The investigation enrolled 253 patients (93 men and 160 women) diagnosed with PsA who met the appropriate 2006 CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria and were recorded in the All-Russian PsA Registry. The median (Me) age was 47 (Min 20 – Max 82) years. All the patients took sDMARDs: MTX (n=211) that was received orally (as tablets) (n=102) and parenterally (n=109); leflunomide (n=7); sulfasalazine (n=24); apremilast (n=10); and tofacitinib (n=1). According to the disease duration at sDMARD treatment initiation, the patients were divided into two groups. Group 1 included 165 patients with an early PsA duration of less than 2 years and Group 2 consisted of 88 patients with a disease duration of >2 years. The efficiency of oral and parenteral MTX was evaluated in 182 patients (68 men and 114 women). Every 6 months, the patients underwent a standard rheumatology examination that included PsA activity assessment. The efficiency of MTX therapy was evaluated from MDA achievement (5 out of the 7 criteria) in the patients.

Results and discussion. After sDMARD prescription, MDA was achieved in 39 (24%) of the 165 patients with early PsA and in 4 (5%) of the 88 long-term patients. The patients who started sDMARD at an early stage of the disease were significantly more likely to achieve MDA than those with late-stage PsA (odds ratio (OR) 6.5; 95% confidence interval (CI) 2.2–18.9). At 11 years after sDMARD therapy initiation, the cumulative MDA achievement rate in the patients with late-stage disease was 5% (p<0.05). MDA was achieved by 16.5% of the 182 patients receiving oral or subcutaneous MTX. MDA was observed in 25 (31%) patients who received parenteral MTX and in only 5 (5%) patients who took oral MTX. The patients who received parenteral MTX were significantly more likely to achieve MDA than those who took oral MTX as tablets (OR 8.8; 95% CI 3.2–24.3). Following 27-month parenteral MTX therapy, the cumulative rate of MDA achievement was 48%, whereas after oral MTX treatment, that was 7% (p<0.05). In the patients who achieved MDA, the mean dose of parenteral MTX was 17 mg/week, and in those who failed, that was 15 mg/week. The mean dose of oral MTX was 15 mg/week, regardless of MDA achievement.

Conclusion. The administration of sDMARD at an early stage of PsA lasting less than 2 years allows MDA to be achieved significantly more often and faster than at later stages of the disease. Among sDMARDs, preference is mostly given to the use of MTX in real clinical practice; the treatment with the latter enables 16.5% of patients to achieve MDA. Parenteral MTX significantly enhances the efficiency of therapy and can achieve MDA in almost one third (31%) of patients.

Objective: to estimate the high and very high Frax® 10-year probabilities of fractures in patients with systemic sclerosis (SSc) to assess the need for anti-osteoporotic treatment.

Patients and methods. The investigation enrolled 136 SSc patients (110 women and 26 men; mean age, 59.3±7.5 years). The patients underwent a questionnaire survey, by calculating the risk of major fractures with the FRAX® algorithm and dual-energy X-ray densitometry (DXA) of the lumbar spine and proximal femur.

Results and discussion. There was a very high risk of fractures in 41.2% of the examinees, a high risk in 10.3%, and a low risk in 48.5%. Osteoporosis (OP) in at least one area was detected in 41.2% of the patients. Among the persons with a low risk of fractures, OP was diagnosed in 18.2%, whereas 10.6% had a history of fractures. A total of 65.4% of SSc patients needed anti-osteoporotic treatment.

Conclusion. According to the comprehensive assessment, OP treatment and fracture prevention were indicated for 65.4% of SSc patients. The FRAX® algorithm is less informative in males who need therapy than in females.

Objective: to study clinical presentation, course variants and complications of Takayasu arteritis (AT) in Kyrgyz patients.

Patients and methods. 75 Kyrgyz patients with a definite diagnosis of AT were included in the study, most of them were women (93.3%). The median age was 33 [23; 40] years, the median duration of the disease was 7 [3.0; 13.0] years. The anatomical type of vascular lesions was determined using the angiographic classification of R. Moriwaki et al., the AT activity – according to the BVAS index, the clinical stage of AT – using the R. Jefferson classification, the severity and prognosis of the disease – according to the K. Ishikawa classification. Highly sensitivity CRP (hsCRP) was assessed in 44 (58.67%) patients, interleukin 6 (IL6) – in 26 (34.7%). Instrumental procedures included duplex Doppler ultrasonography of peripheral arteries and contrast-enhanced computed pan aortography.

Results and discussion. The mean age of AT onset was 24.4±9.4 years. The majority of patients had V anatomical type of vascular lesions (61.3%), vascular stage (89.3%), severe stenosis (54.7%) with predominant affection of the brachiocephalic trunk (68%), common carotid arteries (53.7 %) and renal (52%) arteries. Most patients (82.7%) at the time of inclusion in the study had a severe exacerbation of AT according to the BVAS index. An increase in hsCRP level was seen in 66% of cases, IL6 – in 31%. At the onset of AT, 20% of patients had fever, general weakness, weight loss, myalgia and/or arthralgia. 43% of patients had ≥2 complications. The clinical manifestations of AT were mainly characterized by cardiovascular pathology (77.3%) with the formation of relative aortic valve insufficiency (AVI) (93.1%) and kidney damage (57.3%) with the development of renovascular arterial hypertension (91%). At the first visit, more than one third of patients (37.3%) had irreversible damage, accompanied in half of them by AVI degree II or III.

Conclusion. Young women predominated among Kyrgyz patients with AT. Most of the patients had anatomical type V AT (61.3%), vascular stage (89.3%), severe stenosis (54.7%), affection of the brachiocephalic trunk (68%), common carotid (57.3%) and renal (52%) arteries. Severe exacerbation of the disease was observed in 82.7% of patients. The presence of ≥2 complications worsened the prognosis of AT. The clinical manifestations of AT were characterized mainly by cardiovascular pathology (77.3%) and kidney damage (57.3%). In more than one third of patients (37.3%) AT was diagnosed late.

The diagnosis of coxitis remains one of the most difficult problems in the management of patients with axial spondyloarthritis (axSpA). In Russia, almost every two patients with axSpA were found to have hip joint (HJ) damage. However, until a certain time, there have been no methods to estimate the rate of progression of radiographic HJ changes in clinical practice. We have previously developed a formula for calculating the rate of coxitis progression, which simplifies the assessment of radiographic HJ changes and allows a physician to make a timely decision about changing therapy if rapidly progressing coxitis is detected.

Objective: to estimate the rate of radiological progression of coxitis during a 24-month follow-up of patients with early axSpA.

Patients and methods. Examinations were made in 38 patients (20 women and 18 men) who had been followed up for at least 2 years without radiographic and ultrasound signs of HJ joint involvement. The patients' mean age was 28.8±5.5 years; the disease duration was 22.7±15.7 months. HLA-B27 was positive in 35 (92%) patients. The summary stage of radiographic coxitis (ssRC) was used to assess HJ damage; the previously developed formula was applied to estimate the rate of radiological progression of coxitis (R-rpC).

Results and discussion. The median cervical-capsular distance (CCD) was 5.2 mm at baseline and 4.9 mm at 2 years (p7 mm increase in the CCD. The mean ssRC was 0.34±0.75 scores at base line, 0.86±0.78 scores at 1 year; and this indicator increased up to 1.24±1.36 scores at 2 years (p=0.004). During 2 years of follow-up, there was no coxitis progression (the difference between ssRC2 and ssRC1 was 0) in 24 (63%) patients; ΔssRC increased by 1 score in 5 (13%); by 2 scores in 6 (16%), and by 4 scores in 3 (8%). On patient inclusion to the investigation, R-rpC averaged 0.5 (it was conventionally assumed that patients had no signs of HJ damage at the disease onset (ssRC=0). During therapy for the underlying disease, the mean R-rpC was 0.3 and 0.2 score/year within the first and second years, respectively. The mean R-rpC in the ΔssRC >0 group was as many as 0.85 score/year at one-year follow-up and 0.53 score/year at two-year follow-up.

Conclusion. The developed procedure for estimating the progression of coxitis using ssRC is easy to use and can identify patients at high risk for coxitis progression.

Objective: to evaluate the efficacy and safety of glycosaminoglycan-peptide complex (GPC, Rumalon) used in patients with knee osteoarthritis (OA) and comorbidities (hypertension and/or type 2 diabetes mellitus (T2DM).

Patients and methods: A 10-month multicenter (13 centers from 10 subjects of the Russian Federation) prospective study included 179 patients with Stages II–III primary tibiofemoral knee OA and comorbidity, a walking pain intensity of ≥40 mm on a visual analogue scale (VAS), and a need for nonsteroidal anti-inflammatory drugs (for at least 30 days in the previous 3 months). The efficiency of treatment was evaluated from the changes in VAS scores for knee pain intensity during walking, the overall WOMAC score and scores of its individual indicators, laboratory parameters, and ultrasound data. All the patients received 2 cycles of GPC treatment with 25 injections, by following the manufacturer's instructions.

Results and discussion. Even at 2 months after starting the treatment, there was a statistically significant reduction in pain during walking from 60 (50–69) to 40 (27–53.5) mm on the VAS (p< 0.05), which persisted during the follow-up period. A similar pattern was found when assessing the WOMAC index and its components. The drug demonstrated an anti-inflammatory effect: a decrease in the number of patients with synovitis from 55.7 to 39.2% (p=0.02), the level of high-sensitivity C-reactive protein (hsCRP) from 3.2 (1.3–6.2) to 2.6 (1.2–5.7) mg/l (p< 0.05). GPC was ascertained to have a safety profile.

Conclusion. The data of this study confirm the good therapeutic effect and safety of GPC Rumalon in knee OA patients with hypertension and/or T2DM. The drug is shown to have a rapid analgesic and anti-inflammatory effect, as well as a positive influence on all clinical manifestations of OA.

Objective: to evaluate the efficacy and safety of Alflutop (the bioactive concentrate from small sea fish) in patients aged 75 years and older with knee osteoarthritis (OA). Patients and methods. The investigation enrolled 38 patients aged 75 years and older with knee OA (according to the American College of Rheumatology (ACR) criteria, 1986), Kellgren–Lawrence grades II–III, ≥40 mm pain visual analogue scale (VAS), who required continuous non-steroidal anti-inflammatory drug (NSAID) use. All the patients received Alflutop in the standard regimen: a 1-ml intramuscular injection daily for 20 days. The dynamics of pain during movement was assessed using the VAS scale, the WOMAC, and the EQ-5D questionnaire. Comorbidity was determined according to the Charlson comorbidity index, polypharmacy, and the safety of therapy in all the patients. The investigation duration was 8 weeks.

Results and discussion. On day 21 of Alflutop therapy, there was a statistically significant reduction in pain, stiffness, and functional insufficiency according to the WOMAC index (p< 0.001) and improvements in quality of life as shown by the EQ-5D questionnaire (p< 0.001); on day 56, the number of NSAID intake days decreased (p=0.005). The findings suggest that there is a high level of comorbidity in the majority (94.7%) of patients. The mean number of drugs taken was 5.0±1.5, which indicates the presence of polypharmacy. No serious or severe adverse events were recorded.

Conclusion. The results of the investigation showed the statistically significant efficacy and safety of Alflutop in patients with knee OA in the elderly group.

Autologous hematopoietic stem cell transplantation (auto-HSCT) is presently the only disease-modifying strategy for the treatment of systemic sclerosis (SSs) that has Level A evidence, the effectiveness of which has been proven in three controlled clinical trials: ASSIST, ASTIS, and SCOT. Despite the positive results obtained with the use of this treatment option, the issues related to its tolerability and safety remain unresolved. The complications caused by obvious immunosuppression and higher frequency of infections are the main causes of death after autoHSCT for autoimmune diseases and occur mainly in the first month after treatment. Overall, the studies performed confirm the overall assessment of auto-HSCT as an effective and relatively safe treatment for severe SSs.

Effective pain control is one of the first and most important challenges in medical practice. Non-steroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of treatment for acute and chronic inflammatory pain syndromes. Of particular interest is a group of patients with a low risk of cardiovascular development and a low to moderate risk of gastrointestinal complications, for whom any NSAID may be recommended. Their choice may depend on the duration and severity of the inflammatory process. The most high analgesic potential have non-selective inhibitors of cyclooxygenase – diclofenac and ketoprofen. Modern technologies give great opportunities for modifying the active substance of NSAIDs and improvement of the drug dosage form in order to hasten their effects and enhance analgesic and anti-inflammatory effect of drugs. In the new form of diclofenac (Dialrapid sachet), sodium salt was replaced by potassium salt, which provided a high rate of both absorption of the active substance and action, comparable to that with intramuscular administration of the drug. It also expanded the possibilities of its use for acute pain and relapses of pain relief in exacerbation of chronic inflammatory diseases. The inclusion of lysine salt significantly changed the pharmacodynamics of ketoprofen. Unlike conventional ketoprofen, its lysine salts (Artrozilen and OKИ) are fast-dissolving compounds with neutral pH that do not irritate the mucous membrane of the gastrointestinal tract, which makes them suitable for long-term treatment of chronic inflammatory pain syndromes.

Enthesitis is a common clinical feature of spondyloarthritis (SpA), characterized by inflammation of the tendon or ligament attachment site to a bone or joint capsule. The importance of detecting enthesitis for the diagnosis of SpA is confirmed by its inclusion in the classification criteria for psoriatic arthritis (PsA) – CASPAR – and in the classification criteria for SpA of the international group for the study of spondyloarthritis – ASAS. Enthesitis may be the first clinical sign of SpA, as well as the leading symptom that significantly influences the therapeutic choice. Enthesitis occurs in 30–50% of patients with SpA and is associated with high disease activity, more severe pain and worse quality of life. The frequency of enthesitis detected by ultrasound in patients with PsA is approximately 4 times higher than in patients with ankylosing spondylitis and is associated with the severity of the disease. The review presents current data on the pathophysiology, diagnosis and treatment of enthesitis. Recent studies emphasize the role of imaging methods for the diagnosis of enthesitis due to their higher sensitivity and specificity compared to clinical examination. There is very limited information on the effect of synthetic disease-modifying antirheumatic drugs on enthesitis, while targeted drugs and biologic therapy have shown high efficacy in its treatment compared to placebo. Preliminary evidence suggests that targeting interleukin (IL) 17 or IL12/23 may be more effective in enthesises inflammation suppression than tumor necrosis factor α inhibition.

The paper reviews the data available in the literature on the mechanisms of action of platelet-rich plasma (PRP) and the experience of its use in patients with rheumatoid arthritis (RA). It defines the place of PRP in the systemic and local therapy of RA. The chemical composition of PRP and the structure of the platelet organelles included in it are described. An estimate is made for procedures to prepare platelet-rich plasma containing different concentrations of key growth factors, such as platelet-derived growth factor (PDGF), transforming growth factor α (TGFα), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), and epidermal growth factor (EGF). The variants of PRP classifications, which take into account differences in the composition and levels of the growth factors, are considered. The experience with intra-articular injections of autologous plasma products in patients with RA and synovitis is analyzed. These findings lead to the conclusion that PRP therapy can be an effective tool to relieve inflammation and to stimulate local reparative processes in damaged joint tissues in patients with RA. Further study of the possibilities of using this method of therapy and the formation of a PRPtherapy protocol for patients with rheumatoid arthritis will provide effective personalized care to these patients.

This review describes a case of atraumatic avascular necrosis in the foot and ankle in a patient with systemic sclerosis who did not receive corticosteroid therapy. Both avascular necrosis and systemic sclerosis are uncommon disease entities. This case demonstrates that vasculitis and secondary vasoconstriction in the pathogenesis of systemic sclerosis are important risk factors for the development of avascular necrosis of the foot and ankle. Therefore, if these patients develop chronic foot and ankle pain, avascular necrosis should be included in the differential diagnosis, even if they do not receive corticosteroids. For the diagnosis and follow-up of avascular necrosis MRI remains the gold standard. Thus, MRI should be used to diagnose avascular necrosis in an early stage. Level of Clinical Evidence: 4.

We presented two clinical cases with clinical manifestations of antiphospholipid syndrome (APS) and ankylosing spondylitis (AS). The peculiarity of these cases is the onset of diseases in childhood, as well as the presence of not only extra-skeletal manifestations, but also complications or manifestations of other pathology. In the first case, it was thrombosis of the superficial veins of the lower limbs with the development of postthrombotic syndrome. In the second case, aortic valve defect, as a result of aortitis with a dilatation of the ascending aorta, which led to aortic valve replacement and its subsequent dysfunction because of thrombosis of the valve prosthesis. The frequency of detection of antiphospholipid antibodies (aPL), APS and thrombosis in AS is discussed. The role of tumor necrosis factor α (TNFα) inhibitors in the induction of aPL synthesis and the development of APS in patients with AS is considered either. Separately, we discussed the role of TNFα inhibitors, which are the main drugs in the treatment of ankylosing spondylitis, in the induction of aPL synthesis and the development of APS. Data on the occurrence of aPL, the reasons for the development of thrombosis in APS and the role of TNFα inhibitors remains incomplete. Perhaps the combination of APS and AS is an underestimated problem, and the information available in the literature does not reflect the real numbers. It is obvious that further research is needed to improve the treatment of patients with AS with thrombosis.

Currently, in patients with systemic lupus erythematosus (SLE) increasing attention is paid to the ovarian reserve evaluation, which can serve as one of the markers of a favorable response to therapy and pregnancy planning. For this purpose, anti-Mullerian hormone (AMH) is considered as the most sensitive marker, that reflect the continuous growth of small follicles. The article presents data on the relationship of serum hormone levels with age, ethnicity, body weight, disease activity, and therapy. We present clinical cases of three women of childbearing age with SLE, different duration of the disease and cumulative dose of disease-modifying antirheumatic drugs in whom the level of AMH in the blood serum was measured.

The article discusses the treatment of patients with primary generalized osteoarthritis (OA), a common joint lesion of different localization. Clinical guidelines are presented that provide guidance on various drug and non-drug approaches in the treatment of primary generalized OA. In accordance with the modern understanding of the pathogenesis of OA, the role of inflammation and the influence of various pro-inflammatory factors, the priority of anti-inflammatory therapy, primarily non-steroidal anti-inflammatory drugs (NSAIDs), is justified. A clinical case of a 5-year observation of a patient with primary generalized OA and low compliance to treatment with symptom-modifying slowacting drugs is described. For articular syndrome exacerbations etoricoxib (Kostarox®) was mainly used as an analgesic and anti-inflammatory agent at a dose of 60 mg / day for 7–14 days with a good effect. Due to self-isolation and inability to visit a doctor during COVID-19 pandemic, the patient took etoricoxib for a long time (up to 200 days) for severe neck- and backpain relief, the duration of some courses was up to3 months. We discuss the possibility of etoricoxib use not only in the «on demand» mode, but also for a long time – until the effect is achieved.

Objective: to evaluate the economic impact of the use of various biologic disease-modifying antirheumatic drugs (bDMARDs) from the group of inhibitors of interleukins (iIL) 12/23 and iIL17 in adult patients with psoriatic arthritis (PsA) with insufficient response to therapy with TNFα inhibitors (TNFα inhibitors).

Patients and methods. A Microsoft Excel model has been developed, it allows to calculate the average cost of treatment of 1 patient with PsA who needs a second-line bDMARD from the iIL12/23 or iIL17 group. Only direct medical costs (drug costs) were considered. Cost minimization analysis and budget impact analysis were carried out.

Results and discussion. The results of a network meta-analysis demonstrate no statistically significant differences in efficacy and safety between ixekizumab (IXE) and secukinumab (SEC) and superiority SEC over ustekinumab when used in adult patients with active PsA with insufficient response to or intolerance of previous therapy with synthetic disease-modifying antirheumatic drugs or TNFα inhibitors. The analysis of cost minimization showed that the total cost of 1 patient managing for 1 year using IXE is 26% lower than treatment with SEC: on a 2 year horizon, the difference is 27%. Analysis of the impact on the budget revealed that on the horizon of 1 year the simulated distribution will lead to budget savings of 16,796,131 rubles, which will allow additional treatment of 17 patients with IXE, after 2 years the budget savings will amount to 39,289,373 rubles, which will allow to treat additionally 52 patients. The sensitivity analysis confirmed the robustness of the study results.

Conclusion. Thus, in adult patients with PsA requiring second-line bDMARDs, the use of IXE is more effective than the use of SEC and provides reduction in direct medical costs. The use of IXE will not have a significant impact on costs under the State Guarantee Program, but it can increase the availability of bDMARDs in patients with active PsA who have not responded to the previous therapy, without increasing the budget.

Objective: to conduct a cost-effectiveness study of major biologic disease-modifying antirheumatic drugs (bDMARDs) used for the treatment of ankylosing spondylitis (AS) in Russian health care system with the focus on the new effective drug netakimab (NTK).

Patients and methods. Based on the available meta-analysis, a Markov model for therapy was constructed using reference drugs. Then, based on the simulation results, a Cost-Effectiveness Analysis (CEA) and a Budget Impact Analysis (BIA) were carried out. The robustness of the result has been confirmed by several sensitivity analyzes.

Results and discussion. NTK showed an advantage in CEA, including the cases when the direct costs of therapy were lower for the reference drug (which shows the greater efficacy of NTK). According to the BIA, the extension of NTK administration in naive patients was consistently associated with a decrease in the budgetary burden. Sensitivity analyzes confirmed the robustness of the result.

Conclusion. NTK has clinical and economic advantage in the treatment of AS, it is attractive in terms of both patient's and health care benefit in general. More extensive use of NTK can save more than 5 billion RUB.

A systematic analysis of 37 post-genomic osteoarthritis (OA) studies (genomics, transcriptomics, proteomics, metabolomics) allowed to isolate 483 genes and corresponding proteins, their levels and activity disturbances are involved in the pathogenesis of the disease. These proteins can be conditionally subdivided into three groups: 1) structural proteins of connective tissue (CT); 2) proteins that support the activity of CT growth factors; 3) proteins that promote CT remodeling and degradation, as well as proteins associated with the regulation of inflammation (cellular response to tumor necrosis factor α, interleukin 1, bacterial lipopolysaccharides, NF-κB activation, etc.). It is important to note the epigenetic effects (DNA hypomethylation) associated with the pathogenesis of OA, which indicates the need for the use of vitamins group B in the therapy. Chondroprotectors (symptomatic slow-acting drugs) – chondroitin sulfate (CS) and glucosamine sulfate (GS), – in addition to reducing inflammation through inhibition of NF-κB and lipopolysaccharide receptors (Toll-receptors), also contribute to an increase in the expression of genes for structural CT proteins, CT growth factors and modulate the activity of CT remodeling and degradation proteins. These effects of CS/GS allowed to describe the complex mechanisms of the pathogenetic action of CS/GS in the treatment of OA.