Spondyloarthritis (SpA) is a group of rheumatic diseases that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA) and a number of other diseases. SpA lead to a significant social problem, since it is a common pathology that debuts mainly at a young age, significantly impairing the ability to work and the ability to social contacts of the most active part of the population. For all the main types of chronic progressive SpA, biological agents (biologics) are of great importance in patients with persistent activity despite standard treatment, especially in the case of predominantly axial involvement, since in this case it is actually the only option for effective treatment, in addition to the constant use of non-steroidal anti-inflammatory drugs (NSAIDs). Over the past decade, interleukin-17A (IL-17A) inhibitors have taken the first place in therapy of SpA, because, according to modern ideas about pathogenesis, IL-17A may be a key target for therapeutic intervention in SpA. In terms of ensuring availability for Russian patients with SpA, it is of particular importance to the introduction of the original medication from the group of IL-17A inhibitors Netakimab (NTK). This review presents data from randomized clinical trials of NTK phases I, II and III in AS and PsA also post-registration observational studies of phase IV, including analysis of subpopulations of patients of special interest, in particular, patients with psoriatic spondylitis. NTK demonstrated high effectiveness in the treatment of SpA both in randomized clinical trials and in clinical practice. The drug is characterized by a rapid onset of clinical action and persistent maintenance of the achieved improvement, a complex effect on various manifestations of the disease, is able to have a structure-modifying effect and slow down the progression of both the erosive process and osteoproliferation. The safety profile of NTK is generally typical for the entire group of IL-17 inhibitors. The drug has low immunogenicity, which allows us to count on the possibility of many years of effective use. Resolutions of expert councils on the use of NTK in AS and PsA support the inclusion of this drug in clinical guidelines.

Reduction in tumor necrosis factor (αTNF) and interleukin-6 (IL-6) activities is a widely utilized strategy for the treatment of rheumatoid arthritis (RA) with a high success rate. Despite both schemes targeting the deprivation of inflammatory reactions caused by the excessive activity of cytokines, their mechanisms of action and the final output are still unequal. This was a comparative longitudinal study that lasted for 24 weeks and aimed to find the answer to why the two schemes of therapy can pass out of proportion in attitude of their efficiency. What are the differences in metabolic and proteomic responses among patients who were being treated by either the anti-TNF or anti-IL-6 strategy? We found increased levels of immunoglobulins A and G (more than 2-fold in anti-IL-6 and more than 4-5-fold in anti-TNF groups) at the final stage (24 weeks) of monitoring but the most profound increase was determined for µ-chains of immunoglobulins in both groups of study. Metabolomic changes displayed main alterations with regard to arginine metabolism and collagen maintenance, where arginine increased 8.86-fold (p < 0.001) in anti-TNF and 5.71-fold (p < 0.05) in anti-IL-6 groups but patients treated by the anti-TNF scheme suffered a higher depletion of arginine before the start of therapy. Some indicators of matrix and bone tissue degradation also increased 4-hydroxyproline (4-HP) more than 6-fold (p < 0.001) in anti-TNF and more than 2-fold (p < 0.05) in the anti-IL-6 group, but the growth dynamics in the anti-IL6 group was delayed (gradually raised at week 24) compared to the anti-TNF group (raised at week 12) following a smooth reduction. The ELISA analysis of IL-6 and TNFα concentration in the study population supported proteomic and metabolomic data. A positive correlation between ΔCDAI and ΔDAS28 indicators and ESR and CRP was established for the majority of patients after 24 weeks of treatment where ESR and CRP reduced by 20% and 40% finally, respectively. A regression model using the Forest Plot was estimated to elucidate the impact of the most significant clinical, biochemical, and anthropometric indicators for the evaluation of differences between considered anti-TNF and anti-IL-6 schemes of therapy.

The below case of the development of reactive arthritis against the background of coinfection of Chlamydia trachomatis and Chlamydia pneumoniae is interesting by the features of the clinical picture, the duration of the course, the complexity of diagnosis, laboratory observation, and a comprehensive approach to therapy. Reactive arthritis belongs to the group of seronegative spondyloarthritis, has a variety of symptoms with damage to various organs and systems. All patients have pathology of peripheral joints and/or axial skeleton. The disease is immuno-inflammatory in nature, may follow an infection of the genitourinary or digestive tract. A special role in the development of urogenic reactive arthritis is assigned to Chlamydia trachomatis. Less often, reactive arthritis is caused by C. pneumoniae. In the case of persistent infection, non-simultaneous development or low expression of symptoms, the diagnosis of reactive arthritis is difficult, and in about one case out of five, the disease becomes chronic. Predisposition to severe course of reactive arthritis may cause the presence of HLA-B27 antigen in the patient. It can be assumed that coinfection of two varieties of chlamydia (C. pneumoniae and C. trachomatis) can act synergistically, increasing the risk of developing reactive arthritis. The available data on the effectiveness of the complex of antibacterial anti-chlamydia drugs, own experience of the lymphotropic method of administration, has been successfully used in the complex treatment of the patient.

BackgroundWith the advent of medications with different mechanisms of action in the treatment of rheumatoid arthritis (RA), clinicians face the challenge of personalizing the approach to the treatment of RA patients. One of the steps in this direction is to identify predictors of the effectiveness of the therapy. This work is devoted to the identification of predictors of the therapy effectiveness with the blocker of T cells co-stimulation - abatacept (ABA).ObjectivesSearch for clinical and immunological predictors of the effectiveness of ABA therapy.Methods91 patients were included in the study, most of them women, with high disease activity of RA (DAS28=5.1±1.0, SDAI=28±13.4, CDAI=25±12) and failure of previous biologics (51, 6%) and DMARDs (100%). Moreover, in 20% (n=18) of patients the inefficiency more than 2 biologics were recorded. The average duration of the disease was 3.0 (1.4–12) years, most patients were positive for RF 72.5%, ACCP 77%, AMCV 86%. In 44 patients the levels of RF, ACCP, AMCV and MMP-3 were assessed after 24 weeks of ABA therapy. In 36 patients enzyme-linked immunoassay was used to measure serum concentrations of biomarkers IL-1β, IL-6, IL-17AF, TNF-α, VEGF-A, IP-10, YKL-40 at baseline and after 24 weeks of ABA therapy. The effectiveness of therapy was assessed according to the EULAR criteria. ABA IV infusions were performed according to the standard schedule. Methods of parametric and non-parametric statistics were used in statistical analysis.ResultsABA treatment led to a significant decrease of disease activity assessed by DAS28, SDAI, CDAI starting from 3 months of therapy (p<0.05). More than half of the patients were in remission and had low disease activity according to the DAS28 (65.7%, n=35) after 48 weeks of treatment. After 48 weeks, the highest percentage of patients with RA remission was registered by the DAS28 (37.4%, n=20), the lowest — SDAI (21.6%, n=11). After 24 weeks of therapy, ABA led to a significant decrease in the serum levels of IL-6 from 2.4 [1.1 - 6,4] to 1.29 [0.9-2.2] pg/ml, (p=0.0006), IP-10 from 21 [12,9-49,8] to 14 [7.5-28] pg/ml, (p=0.007) and matrix metalloproteinase 3 (MMP3) from 30.1 [13-82] pg/ml to 10 [7.4-55] pg/ml, (p = 0.0003). A decrease in the serum level of IL-6 significantly correlated with a decrease in the DAS28 and SDAI (r=0.5 and r=0.479, p<0.05), IP-10 with DAS28 (r=0.326, p<0.05). Initially, the serum level of TNF-α was significantly lower in patients who achieved low disease activity by the SDAI (72.6%, n=37) after 48 weeks of therapy, compared with the rest. On the contrary, a significantly higher level of IP-10 before treatment was recorded in patients with a good response according to the EULAR criteria (39%, n=29) after 48 weeks of ABA treatment (Figure 1). The ROC-analysis revealed that an initially high concentration of TNF-α may indicate with 71% sensitivity and 77% specificity about the possible ineffectiveness of ABA therapy after 48 weeks of treatment, the area under the curve was 0.7, 95% CI (0.5– 0.9). In patients initially positive for AMCV, low RA activity by SDAI was significantly more often registered after 24 (p=0.04) and 48 weeks. (p=0.01). 89% (n=34) of AMCV-positive patients achieved low disease activity after 48 weeks therapy by the SDAI and CDAI. It is noteworthy that a cohort of patients with insufficient effect after 48 weeks consisted entirely of AMCV-negative patients.ConclusionABA therapy led to a significant decrease in disease activity according to the main indices (DAS28, SDAI, CDAI). During ABA treatment, there was a decrease of important immunoinflammatory markers - IL-6, IP-10, MMP-3. AMCV positivity is significantly associated with higher efficacy of ABA therapy. Also, a high basal concentration of TNF-α could use as a predictor of possible failure of ABA therapy, and a high initial level of IP-10, on the contrary, indicates the possible efficacy of ABA therapy.ReferencesNoneDisclosure of InterestsNone declared

Урогенный реактивный артрит — заболевание из группы серонегативных артритов, известных как спондилоартропатии. Симптомокомплекс характеризуется поражением различных органов и систем, включая поражение мочеполовых органов, кожи, слизистых оболочек, костно-суставной системы, сердца, глаз. С учетом полиорганной патологии, возникающей зачастую неодномоментно, лечение проводится симптоматически, что увеличивает со временем риск хронизации и развития осложнений, наиболее тяжелым из которых является ревматологическая патология. Приводим клиническое наблюдение пациента в возрасте 38 лет с жалобами при поступлении на наличие высыпаний, ощущение скованности и «затекания» в ночное и утреннее время, подтвержденным диагнозом урогенного реактивного артрита, развившегося на фоне хламидийного уретропростатита, с многоплановыми проявлениями и различными исходами на фоне проведенной комплексной терапии (с излечением хламидийного уретропростатита) со стороны органов и систем, в том числе инструментально зафиксированным положительным сдвигом в проводящей системе сердца и переходом урогенного реактивного артрита в болезнь Бехтерева. Случай представляет собой яркую иллюстрацию мультидисциплинарной проблемы и интересен для практических врачей разных специальностей: дерматовенерологов, ревматологов, офтальмологов, кардиологов, терапевтов, реабилитологов, семейных врачей.

A strategic approach is crucial to the management of patients with osteoarthritis (OA). It should be based on the current understanding of the pathogenesis of OA as an inflammatory disease. A review of current clinical guidelines for the management of patients with OA shows significant differences in the evaluation of pharmacological approach, especially the place of symptomatic slow-acting drugs for osteoarthritis, (SYSADOA) and a certain consensus in relation to non-pharmacological methods (primarily exercise, patient education, body weight control, various physiotherapy methods, orthotics and massage/manual therapy). It should also be taken into account the international “treat to target” recommendations, the main idea of which is careful regular monitoring of the patient’s condition and adaptation of treatment tactics depending on the response to treatment. Based on the analysis of literature data and their own clinical experience, the authors developed an algorithm for the strategy of complex therapy of OA, including the following steps: 1) pain control (2-4 weeks), 2) inflammation control (4-6 weeks); 3) control over cartilage degradation (6 weeks – 12 months). For each stage, a specific combination of systemic pharmacotherapy (non-steroidal anti-inflammatory drugs, SYSADOA), intra-articular administration of glucocorticoids and hyaluronic acid, exercises and magnetotherapy (pulsed electromagnetic field) was proposed. A staged comprehensive strategy for the treatment of patients with OA should help to achieve control over the symptoms, while minimizing the duration of NSAIDs and avoiding polypharmacy, and further achievement of inhibition of structural progression.

Background Comorbidities cardiovascular disease such as arterial hypertension (AH) are common in people with gout and complicate its management and disease outcomes. Objectives Our purpose was to evaluate the effect of AH on the severity of gout. Methods We included data of 286 male patients with gout: median (Ме) age 51.2 [interquartile range (IR) 42.8;59.4] years (ys), disease duration – Ме 6.2 [IR 3.8;12.1] ys, number of joints involved during disease course – Ме 7 [IR 4;12], subcutaneous tophi – in 35% pts, intraosseous tophi – in 44% pts. All pts underwent standard clinical examination. AH was defined using by 2018 ESC/ESH Guidelines for the management of arterial hypertension criteria: elevated blood pressure (BP) (systolic BP≥140 or diastolic BP≥90 mm Hg or treatment for hypertension). Results AH was found in 244 out of the 286 pts (85 %). AH was diagnosed before gout in 129 (52.9%) pts, and after gout - in 115 (47.1%) pts. The 1 st degree of AH was found in 27 (11%), the 2 nd degree – in 62 (25%), the 3 rd degree – in 155 (64%) pts. AH developed at a younger age in patients with 3 rd degree AH compared to patients with 2 nd and 3 rd degree AH, but did not reach statistical significance. Patients with 3 rd degree of AH had longer gout and AH duration compared to patients with 1 st and 2 nd degree of AH. They had higher prevalence of subcutaneous and intraosseous tofuses, nephrolithiasis compared with the 1 st and 2 nd degree of AH, p<0.05 (Table 1). Table 1. Parameters Grade 1 hypertension Grade 2 hypertension Grade 3 hypertension Age of gout onset,ys 41.6[34.4; 53.5] 39.6[35.6; 48.0]• 44.1[36.9; 52.6] Age of AH onset,ys 44.9[37.4; 55.4] 43.6[36.9; 49.9] 40.4[29.9; 49.9] Gout duration,ys 3.8[1.6; 5.8] 5.6[3.8; 13.5] 8.0[4.8; 14.6]* AH duration,ys 0.1[0; 2.0] 3.3[0.2; 9.8] 11.3[4.7; 22.8]* Number of joints involved,n 4.0[2.0; 6.0] 7.0[4.0; 10.0] 9,0[5,0; 14.0]* Subcutaneous tophi,% 4(14.8%) 16(26%) 69(44.5%)* Intraosseous tophi,% 5(18.5%) 29(47%) 83(53.5%)* Nephrolithiasis,% 16(59%) 34(55%) 124(80%)* Data are presented in median values and IR (unless otherwise noted), •p<0,05 reliability of differences for trend, *p<0,05 compared vs group 3 (Mann -Whitney). AH preceded the development of gout in 26% pts with 1 st degree of AH, in 42% pts with 2 nd degree of AH, in 62% pts with 3 rd degree of AH. Conclusion Hypertension preceded the development of gout in 62% patients with 3 rd degree of AH. They had a more severe course of gout compared to patients with 1 st and 2 nd degree of AH. It can be assumed that an earlier onset of AH is a risk factor for severe courses of gout. Disclosure of Interests None declared

Background Despite the high efficacy of rheumatoid arthritis (RA) therapy, in routine clinical practice, clinicians face questions about the choice of a second biologics, as well as the possibility of biologics monotherapy. Therefore, the specialties of biologics use in these categories of patients are of great clinical interest. This work is devoted to the study of the effectiveness of abatacept (ABA) therapy in biologic-naïve and biologic-experienced patients and in the subgroup of ABA monotherapy. Objectives To evaluate the effectiveness of ABA therapy between biologic-naïve and patients who had experienced an inadequate response to biological agents and in the subgroup of ABA monotherapy. Methods We prospectively enrolled and followed 91 patients with high RA activity (SDAI=28±13.4, CDAI=25±12) and an inadequate response of conventional synthetic DMARDs (mainly methotrexate, 70.3%) and biologics (mainly TNF-α blockers, 93%) were included in the study. Most of the patients were middle-aged (49±13.5), positive for RF (72.5%) and ACCP (77%) with moderate functional impairment - 1.4 (0.9-2). Patients were divided into two groups: biologic-naïve (48.4%, n=44) and biologic-experienced patients (51.6%, n=47). 18% (n=17) of patients had a history of an inadequate response of 2 or more biologics. The ABA monotherapy group (13%, n=12) was assessed separately. ABA were administered IV, 10 mg/kg according to the standard scheme. The evaluation of the effectiveness of the therapy was carried out according to the EULAR/ACR 2011 criteria using the intention-to-treat approach and SDAI, CDAI and the functional state using the HAQ. Results ABA led to a significant (p<0.05) decrease in RA activity after 3 months of ABA therapy in all groups. After 6 months of treatment, there was a tendency towards an increase in the number of patients who achieved remission and low RA activity in the group of biologic-naïve patients, which continued to 12 months of therapy. So, after 6 months and 12 months in the group of biologic-naïve patients, the frequency of remission and low disease activity was 71% (n=25) and 76% (n=19) by SDAI, 75.6% (n=28) and 81.5% (n=24) by CDAI, respectively. Whereas, in the group of biologic-experienced patients - SDAI - 61.8% (n=21) and 69.2% (n=18), CDAI - 64.8% (n=22) and 77.8% (n=21), respectively. However, these differences didn’t reach significance. Similar results were obtained according to the EULAR criteria: after 12 months of treatment, the percentage of patients with a good response in both groups did not differ, 38% (n=14) in biologic-naïve and 38.4% (n=15) in biologic-experienced patients. ABA significantly improved functional status of patients, after 12 months the median HAQ of biologic-naïve and biologic-experienced patients were 0.7 (0.2–0.8) and 1.18 (0.7–1.6), respectively. More biologic-naïve patients achieved functional remission by HAQ after 6 and 12 months compared with biologic-experienced patients: 67% (n=23) vs. 33% (n=17), 62.5% (n=11) vs. 37.5% (n=9), respectively, but these differences didn’t reach significance. In the ABA monotherapy group after 6 months treatment, a good response by EULAR criteria was achieved in 10% (n=1) patients, while in the group of ABA+csDMARDs therapy in 43.5%, p=0.04. After 12 months the trend towards a more pronounced response in the combination therapy group persisted (11%, n=1 and 42%, n=28, respectively), but no significant differences were obtained. Conclusion Abatacept has shown significant improvement clinical and functional status in all studied groups. There were no significant differences in response to ABA therapy between biologic-naïve and biologic-experienced patients. ABA monotherapy were significantly worse compared with the combination therapy of ABA and csDMARDs after 6 months. After 12th month observation, this tendency continued, but no significant differences were achieved. This is probably due to the small number of patients on ABA monotherapy and, as a result, to the insufficient statistical representativeness of the sample. Disclosure of Interests None declared

Instrumental physiotherapeutic treatment using portable devices is optimal for patients with rheumatic diseases due to the devices' greater accessibility. However, there are still issues concerning the efficacy of physical factors generated by portable equipment in osteoarthritis (OA), mostly due to the limited evidence.OBJECTIVE:To study the efficacy and safety of long-term use of the portable magnet therapy device ALMAG+ (Almag Active) in knee OA (KOA).MATERIALS AND METHODS:A double-blind, randomized, placebo-controlled, prospective, 55-week clinical trial of the medical device was conducted. The study included patients with primary and secondary (associated with immunoinflammatory rheumatic diseases) KOA stages I-III according to Kellgren-Lawrence diagnosed using generally accepted criteria (R. Altman et al., 1986). Enrollment of patients with secondary KOA was allowed given that the remission or low disease activity was achieved. During the study patients had to receive steady drug therapy. No intra-articular injections of glucocorticosteroids, hyaluronic acid, PRP, and physiotherapy procedures for knees (electrotherapy, shockwave therapy, heat therapy, hydrotherapy, peloid therapy) were allowed three months or less before the enrollment and throughout the study. According to the approved protocol, 77 patients (mean age 52.73±12.97 years) from two research centers participated in the study: 32 (41.6%) were males, and 45 (58.4%) were females. Primary KOA occurred in 41 (52%) patients, 36 (46.8%) patients had secondary KOA (associated with rheumatoid arthritis, ankylosing spondylitis, Sjögren's disease, psoriatic arthritis, systemic lupus erythematosus, or diffuse scleroderma). All patients received NSAIDs as a concomitant therapy, 24.7% received diacerein, 28.6% received disease-modifying anti-rheumatic drugs, 2.6% received methylprednisolone up to 8 mg/day, and 9% received biologic therapy. After randomization, 40 (52%) patients received placebo treatments (Group 1) and 37 (48%) received active treatments (Group 2). Both groups were comparable in the main parameters. The proportion of smokers was higher in Group 2, but the difference was not statistically significant. During the 55-week follow-up, three courses of 18 daily home magnet therapy procedures each were performed.RESULTS:In both groups, starting from week 5 of the study, an improvement of pain on movement and at rest according to VAS compared to the baseline (p<0.01 at all assessment time points) was observed, which can be explained by a pronounced placebo effect, often observed in OA. The improvement of pain at rest was more prominent in Group 2 vs. Group 1 at Week 21 (p=0.038) and Week 55 (p=0.017) of the study, probably due to the anti-inflammatory effect. The overall WOMAC index score was also lower in Group 2 vs. Group 1 at Weeks 21 and 55 (p=0.03 at both time points). The mean articular cartilage thickness, determined by ultrasound, reduced in Group 1 and remained practically unchanged in Group 2 (p=0.011). No adverse events associated with the use of the ALMAG+ (Almag Active) device, according to the attending physician, and no exacerbations of immunoinflammatory rheumatic diseases during the study period were reported.CONCLUSION:The results of a double-blind, placebo-controlled study of magnet therapy using a portable device demonstrated analgesic, anti-inflammatory, and structure-modifying effects of this type of physiotherapeutic treatment. No adverse events and exacerbations of rheumatic diseases associated with the study treatment have been reported.

Background: Prognosis of the need for in-hospital treatment in patients suffered with COVID-19 is crucial to optimize the use of medical resources. Risk factors of hospitalization due to COVID-19 are not sufficiently studied in patients with rheumatic diseases (RD). Objectives: To reveal factors associated with the risk of hospitalization of patients with RD due to SARS-CoV-2 (COVID-19) infection. Methods: We analyzed data based on the preliminary results of the patients registry from the ongoing project “Patient’s Opinion on Covid-19 in Rheumatic Diseases (POPCORD)”. The registry contains data collected directly from Russian-speaking patients with different RD who completed a special questionnaire, located on the website https://revmo-covid.ru/ . The questionnaire includes information on whether the patient had COVID-19 and related information, as well as information on rheumatic disease and its treatment. Results: 1050 patients (92% from Russian Federation, 8% from other locations) completed the survey - 93% females, mean age 40,28±11,26 (M±SD, median 38 [32;48]), BMI 24,52±5,38 (median 23,42 [21;27]), disease duration 7,91±8,46 (median 5,00 [2;11]). Diagnoses reported: rheumatoid arthritis (49%), ankylosing spondylitis (14%), systemic lupus erythematosus (13%), psoriatic arthritis (6%), Sjogren’s disease (5%), systemic sclerosis (3%), other (10%). 51% of respondents indicated concomitant conditions: arterial hypertension (19%), obesity (15%), kidney disease (11%), cardiovascular disease (7%), liver disease (6%), IBD (5%), other lung diseases, including ILD (5%). 96% of patients reported constant intake of antirheumatic drugs: steroids (37%), NSAIDs (46%), hydroxychloroquine (22%), csDMARDs (66%), bDMARDs (17%), tsDMARDs (2%). 344 (31,8%) patients reported COVID-19 or suspected SASR-CoV2 viral pneumonia, 282 (84,4%) were treated as outpatients, 52 (15,6%) were hospitalized. Relatives or physicians reported 3 cases of death related to COVID-19 (0,9% of total mortality, 5,8% of in-hospital mortality). Table 1 contains odds ratios for the main factors, related to hospitalization, based on the results of the survey. Analysis of the survey participants’ parameters (patients’ characteristics, treatments etc.) did not reveal any significant variables, related to increased risk of hospitalization. No increased risk related to any groups of anti-rheumatic drugs or any particular medications was found either. Risk of hospitalization was significantly lower in patients with ankylosing spondylitis. Table 1. Factors, related to hospitalization due to COVID-19 in patients with RD. Factor OR [95% CI] p Age ≥50 y.o. 2,12 [1,14;3,94] 0,99 Age ≥65 y.o. 9,04 [2,10;38,98] 1,00 Female 1,73 [0,70;4,25] 0,92 Body mass index ≥35 2,09 [0,71;6,10] 0,88 Current smoking 0,47 [0,11;2,06] 0,24 Smoking in the past 1,43 [0,83;2,48] 0,92 Diagnosis of ankylosing spondylitis 0,25 [0,06;1,05] 0,02 Comorbid conditions: •Diabetes mellitus 3,39 [1,07;10,77] 0,99 •Cardiovascular disease 1,91 [0,72;5,08] 0,94 •Asthma 5,42 [1,07;27,61] 0,99 •COPD 0,42 [0,05;3,26] 0,34 •Kidney disease 1,57 [0,71;3,50] 0,91 •Liver disease 0,90 [0,26;3,18] 0,57 •Neurological disorders 5,42 [0,75;39,36] 0,99 •No concomitant conditions 0,70 [0,40;1,25] 0,14 Therapy: •Oral steroids 1,37 [0,82;2,29] 0,91 •NSAIDs 1,12 [0,67;1,87] 0,72 •Traditional DMARDs 1,39 [0,89;2,17] 0,94 •Biologic DMARDs 1,15 [0,55;2,43] 0,72 •Targeted synthetic DMARDs (JAK-inhibitors, apremilast) 3,25 [0,75;14,03] 0,97 Level of concern about COVID-19: •Low level / no concern about COVID-19 0,57 [0,28;1,17] 0,08 •Medium level of concern 0,60 [0,28;1,28] 0,12 •High level of concern 1,69 [1,03;2,76] 0,99 Conclusion: Survey of patients with RD did not show significantly increased risk for hospitalization due to COVID-19 in relation with specific diagnosis, any anti-rheumatic medications, as well as comorbid conditions and main patient characteristics. Diagnosis of ankylosing spondylitis related to significantly lower risk of hospitalization. Acknowledgements: Dr Anna S Misiyuk from V.A. Nasonova Institute of Rheumatology, Moscow, Russia. The COVID-19 Russian patient experience survey is conducted on behalf of Russian Rheumatology Association “Nadezhda”. The project was partially granted by BIOCAD. Disclosure of Interests: None declared

Background:The course of new coronavirus infection in patients with rheumatic diseases (RD) undergoing treatment with biological and targeted drugs is still poorly understood.Objectives:To study outcomes of COVID-19 in patients with RD receiving treatment biological and targeted synthetic DMARDs.Methods:We studied cases of COVID-19 in patients with RD, included in “Moscow regional registry of patients with rheumatic diseases receiving treatment with biological and targeted synthetic drugs” – observational cohort, started in 2018. A total number of patients, included in the registry, is 1048 at December 2020.Results:By January 2021, 44 known cases of COVID-19 were registered among patients included in the registry (4,2%). This group included 29 (65,9%) females, 15 (34,1%) males, with mean age 45,09±12,7 (median 47,0 [34,0; 57,0]) y.o. The vast majority of patients had rheumatoid arthritis (19, 43,2%) and ankylosing spondylitis (19, 43,2%), there were 3 (6,8%) patients with psoriatic arthritis, and one patient each (2,3%) with systemic lupus erythematosus, systemic sclerosis, and ANCA-vasculitis. Before COVID-19, 20 (45,5%) patients received TNF inhibitors (adalimumab, infliximab, etanercept, certolizumab, golimumab), 7 (15,9%) – IL-6 receptor inhibitors (tocilizumab, sarilumab), 7 (15,9%) – rituximab (period between last infusion and COVID-19 was 1-4 months), 5 (11,4%) – sekukinumab, 2 (4,5%) – tofacitinib, and one patient each (2,3%) received abatacept and ustekinumab. Also, 22 (50%) received methotrexate, 4 (9,1%) – leflunomide, 3 (6,8%) - mycophenolate mofetil, 1 (2,3%) – sulfasalazine; 12 (27,3%) took oral steroids. COVID-19 presented as mild disease in 23 (52,3%) patients, and 21 (47,7%) had viral interstitial pneumonia verified by computed tomography. 16 (36,4%) patients were hospitalized, only one patient underwent artificial lung ventilation. We found no significant associations between particular diagnosis and treatment on the one hand, and hospitalization for COVID-19 on the other hand. For treatment of COVID-19, two (4,5%) patients did not receive any medications, and the rest of patients received antiviral and antibacterial therapy according to standardized protocol. In addition, corticosteroids were administered for COVID-19 in 15 (34,1%) patients, mainly (12 cases) in hospital, and two (4,5%) patients in hospital were treated by tocilizumab. The outcome in all cases was favorable, all patients successfully recovered from the new coronavirus infection.Conclusion:In this observational study, we found no association between biologic and targeted therapy for rheumatic diseases and severe course of new coronavirus infection, as well as with the need for hospitalization for COVID-19. The outcome of COVID-19 was favorable in all patients receiving treatment with biological and targeted synthetic drugs for rheumatic diseases.Disclosure of Interests:None declared

Rheumatic diseases are a major medical and social problem. The mechanisms' variety of these diseases' development requires different approaches: the strategies of drug and non-drug therapy in modern rheumatology are designed to be complemented to each other. The most relevant treatment of rheumatic conditions is the method of pulsed magnetic fields because the sensitivity of biological tissues to them is the highest one.OBJECTIVE:To evaluate the efficiency and safety of the ALMAG + magnetic therapy device in the treatment of osteoarthritis of the knee joints».MATERIAL AND METHODS:The article presents preliminary data of a double-blind, placebo-controlled study «Evaluation of the efficacy and safety of the ALMAG + magnetic therapy device in the treatment of osteoarthritis of the knee joints». The study includes 70 patients (25 men, 45 women) of which 34 (48.6%) are patients with primary osteoarthritis (OA) of the knee joints (OAKS) and 36 (51.4%) are with secondary knee OA (on the background of immunoinflammatory rheumatic diseases). The patients were randomely divided into 2 groups: the main group (active devices) with 34 (48.6%) patients and the control group (placebo devices) - 36 (51.4%) patients. Patients of the main and control groups were comparable in all main parameters. During the study, the patients underwent 3 courses of treatment with the ALMAG + apparatus or with a placebo apparatus during the year. The preliminary analysis includes data on 58 patients who underwent at least 2 courses of therapy (28 patients from the main group and 30 from the control group).RESULTS:Pain at rest decreased in the main group by 4.0±2.9 mm, in the control group - by 1.07±2.21 mm (p=0.420), after the second course - by 5.13±3.4 and 1.81±2.19 mm (p=0.406), respectively. In the main group, the total WOMAC index decreased after the 1st course of physiotherapy from 24.0±14.9 to 20.25±14.31 mm (p=0.038), after the 2nd course it slightly increased - to 22.96±14.8 mm (p=0.314), in the control group the WOMAC index did not change statistically significantly: it decreased after the 1st course from 26.3±21.9 to 24.6±20.83 mm (p=0.112), after the 2nd course it increased to 27.04±21.9 mm (p=0.088).CONCLUSION:Thus, the use of the ALMAG + apparatus at home contributed to a decrease in pain at rest and a significant decrease in the WOMAC index in patients with primary and secondary OA of the knee joints. Pulsed magnetotherapy did not cause adverse events or exacerbation of immunoinflammatory diseases.

Background: YKL-40 (chitinase-3-like 1 protein, human cartilage glycoprotein 39) is one of the major proteins secreted locally in the arthritic joint by activated macrophages, chondrocytes, synoviocytes and neutrophils, YKL-40 an important marker for inflammation, cartilage remodelling and synovial hyperplasia is recognized as a possible auto-antigen in rheumatoid arthritis (RA). Objectives: The aims of the study were to determine the serum level of YKL-40 in early RA and investigate his relationship with biomarkers of disease activity and joint destruction. Methods: We studied 22 patients with early RA (ACR/EULAR 2010 classification criteria); 4 males, 18 females; median and interquartile range (25th—75th percentile) of age 55,0 (43,0-64,0) years, disease duration 7,0 (5,0-11,0) months, DAS28 4,9 (4,3-5,8); 86% IgM rheumatoid factor (IgM RF) +; 91% anti-cyclic citrullinated peptide antibody (anti-CCP) +. All patients were treated with methotrexate (MTX). Three (14 %) patients received low oral doses of steroids and intra-articular injections. The control group included 22 healthy donors (HC). Radiographs were scored according to the van der Heijde-modified Sharp score. YKL-40, matrix metalloproteinase-3 (MMP-3), anti-CCP were detected using commercially available enzyme-linked immunosorbent assays (ELISA). The serum levels of IgM RF, C-reactive protein (CRP), serum amyloid A (SAA) were measured by immunonephelometry. Results: RA patients had significantly higher serum level of YKL-40 than HC (92,1; 68,5-153,1 pg/ml vs 54,0; 41,7-83,2 pg/ml, p<0.01). Serum YKL-40 concentration was positively correlated with DAS 28 (r=0,5; p<0,05), erythrocyte sedimentation rate (ESR) (r=0,5; p<0,05), CRP (r=0,8; p<0,05), SAA (r=0,6; p<0,05) and MMP-3 (r = 0,6; p<0,05). We found no relationship between the level of YKL-40 and articular radiographic changes. Conclusion: Elevated serum concentration of YKL-40 in early RA is associated with clinical and laboratory indicators of disease inflammatory activity and increased level of MMP-3 - an immunological marker of joint destruction. Disclosure of Interests: Elena Aleksandrova: None declared, Alexander Novikov: None declared, Elena Luchikhina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Consultant of: Abbvie, Biocad, Sanofi, Celgene, Dmitriy Karateev Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Lilly, Bayer, Paid instructor for: Abbvie, Pfizer, Biocad, Sanofi, Novartis, Lilly, Galina Lukina Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Paid instructor for: Abbvie, Biocad, Sanofi, Celgene

Background:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is now in the spotlight of the medical community. Obtaining the most complete data on COVID-19 in the rheumatic diseases (RD) is an urgent task, and the data received directly from patients seems to be is extremely important.Objectives:To study the factors, associated with the possibility of COVID-19 in patients with RDs.Methods:We conduct COVID-19 Russian rheumatology patient experience survey to create a registry of “Patient’s Opinion on Covid-19 in Rheumatic Diseases (POPCORD)”. This ongoing project is based on the data collected directly from Russian-speaking patients with different RDs who fill out a special questionnaire via the https://revmo-covid.ru/. The questionnaire was developed by the national patient organization – Russian Rheumatology Association “Nadezhda” in collaboration with Moscow regional rheumatology center and department of rheumatology of Moscow Regional Research and clinical institute n.a. M.F. Vladimirsky (MONIKI). The anonymous questionnaire includes information on whether the patient had COVID-19, as well as information on rheumatic disease, its treatment, and information on social distancing and compliance with other anti-epidemic measures.Results:At the moment, 1050 patients (92% from Russia, 8% from other countries) completed the survey, including residents of 74 regions of Russia, most of them from Moscow (20%), Moscow region (8%) and St. Petersburg (8%). In total, there were 93% females, with mean age 40,28±11,26 (M±SD, median 38 [32;48]), BMI 24,52±5,38 (median 23,42 [21;27]), disease duration 7,91±8,46 (median 5,00 [2;11]). The main diagnoses reported: rheumatoid arthritis (49%), ankylosing spondylitis (14%), systemic lupus erythematosus (13%), psoriatic arthritis (6%), Sjogren’s disease (5%), systemic sclerosis (3%), other (10%). 344 (31,8%) patients reported COVID-19 or suspected SASR-CoV-2 viral pneumonia. Relatives or physicians reported 3 cases of death related to COVID-19. The most important results of the survey presented in Table 1.Table 1.Main results of the patients survey, n=1050.ItemResults (n, %)p, chi-squareNo COVID-19/ pneumonia reported (n=716)COVID-19/ pneumonia (n=334)Smoking status0,003•Current smoker118, 16,5%25, 7,5%•Never smoke359, 50,1%199, 59,6%•Quit smoking239, 33,4%110, 32,9%Vaccination during last 3 years against Influenza, Pneumococcus and others0,265•No531, 74,2%236, 70,7%•Yes185, 25,8%98, 29,3%Social distancing0,003•I avoid crowds and large gatherings of people412, 57,5%172, 51,5%•Self-isolation219, 30,6%96, 28,7%•No social distancing85, 11,9%66, 19,9%Hygiene0,031•wearing a mask, hand washing/ using a sanitizer, gloves etc.705, 98,5%321, 96,1%•nothing11, 1,5%13, 3,9%Withdrawal of anti-rheumatic medication last weeks for fear of infection<0,001•Yes124, 17,3%104, 31,1%•No592, 82,7%230, 68,9%Possible contacts with COVID-19 infected persons<0,001•Yes203, 28,4%205, 61,4%•No299, 41,8%65, 19,5%•Don’t know214, 29,9%64, 19,1%Conclusion:According to patient-reported data, lack of adherence to social distancing and hygienic measures, higher possibility of contacts with infected persons, as well as withdrawal of anti-rheumatic medication for fear of infection and smoking status were the factors, significantly associated with the possibility of COVID-19/viral pneumonia in patients with rheumatic diseases.Acknowledgements:Dr Anna S Misiyuk from V.A. Nasonova Institute of Rheumatology, Moscow, Russia.The COVID-19 Russian patient experience survey is conducted on behalf of Russian Rheumatology Association “Nadezhda”. The project was partially granted by BIOCAD.Disclosure of Interests:None declared

Objectives. RA patients who fail to respond to MTX can receive biologic dMARDs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and its association with clinical response to bDMARDs. Methods. The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-lg (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood. Results. TTV was measured in 95 patients (INF, n =23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5 x 10(4) copies/ml [c/ml; interquartile range (IQR) 0-7.5 x 10(5)] after 3 months. TTV levels at month 3 were associated with the Simplified Disease Activity Index (SDAI) (P = 0 .03) and the Clinical Disease Activity Index (CDAI) response (P = 0 .026) at month 6. A TTV cut-off level of 1.2 x 10(6) c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of an 85% reduction in SDAI at month 6. Conclusion. Our data suggest that TTV levels increase upon TNF, CD20 and costimulation blockade and are associated with the clinical response to bDMARDs in RA patients.

Treatment of osteoarticular pathology with an alternating electromagnetic field (AEMF) is used today as a promising, non-invasive and safe strategy of physiotherapy. It has been shown that the action of alternating electromagnetic fields on the musculoskeletal system triggers signaling cascades that effectively contribute to the restoration of bone and articular tissue. The pathophysiological mechanisms underlying the cellular and subcellular effects of stimulation by an alternating electromagnetic field during the restoration of bone and articular tissue are considered. It was pointed out the several key signaling pathways involved in the restoration of bone and articular tissue under the influence of electromagnetic fields with an analysis of the potential for therapeutic application of electromagnetic fields alone or in combination with other available therapies.

The treatment of immuno-inflammatory rheumatic diseases has advanced significantly in recent decades due to development of biological medications, which, however, are not without some weak points. They include immunogenicity, parenteral administration, and potentially insufficient stability of the composition of the drug. Great hopes are related to a relatively new class of targeted synthetic immunomodulatory drugs, currently represented in rheumatology by JAK kinase inhibitors (tofacitinib, baricitinib, upadacitinib) and phosphodiesterase 4 inhibitor (apremilast). The most actively developed group is JAK inhibitors that influence one of the most important signal pathway of immune system. This family includes 4 subtypes: JAK1, JAK2, JAK3 и tyrosine-kinase2 (TYK2). JAK-kinases selectively aggregate with cytoplasmic domains of different cytokine receptors, activation of which includes intracellular signal pathway JAK-STAT (Signal Transducer and Activator of Transcription). STAT proteins are responsible for transduction of the signals from more than 50 cytokines, hormones and growth factors that regulate key processes of survival, proliferation and differentiation of immune cells. The greatest practical experience achieved on tofacitinib. This medication approved inRussiafor several indications: rheumatoid arthritis, psoriatic arthritis, psoriasis, ulcerative colitis. Clinical trials of III phase of ORAL series in rheumatoid arthritis and OPAL series in psoriatic arthritis showed high efficacy of Tofacitinib in different clinical situations. In Russian strategic trial REMARKA after treatment with Tofacitinib very fast improvement of the signs of activity was observed, 68,8% patients achieved low disease activity or remission at 6th month of follow-up. Russian open multi-center observational study of Tofacitinib in 101 patients with rheumatoid arthritis and insufficient efficacy of basic and biologic drugs showed achievement of low disease activity or remission in 60% patients, as well as significant improvement of quality of life with a very low frequency of withdrawals due to adverse events (less than 2%).

Background: Pulsed electromagnetic field (PEMF) therapy is widely used in different areas of medicine. There are a lot of portable PEMF therapeutic devices on the market around the world. Nevertheless, the role of PEMF in treatment of rheumatic conditions is not clear. Current evidence is of low and very low quality. Objectives: To study efficacy and safety of PEMF therapy in primary and secondary osteoarthritis (OA) of the knee in controlled clinical trial. Methods: This abstract presents the preliminary results of an ongoing double-blind placebo-controlled trial of PEMF portable therapeutic device “ALMAG+” (Certificate EN ISO 13485:2012+AC:2012 reg.-No 44221 117836, Yelatma Instrument-Making Enterprise, Russian Federation, Reg. Num.: 3007075140). The device is intended for physiotherapeutic treatment and rehabilitation with a low-frequency low-intensity PEMF in medical institutions, as well as at home after the recommendation of a doctor. Patients with primary and secondary (as a part of inflammatory rheumatic disease) OA of knee with Kellgren-Lawrence Grade I-III included in the study (in patients with inflammatory conditions disease activity should be minimal on stable drug therapy). Three courses of PEMF of 20 procedures for 1 year planned in active treatment group and placebo (inactive device) group of 35 patients each. Efficacy is evaluated by pain VAS, WOMAC, Lequesne index, and quality of life studied using SF-36, EuroQoL 5D tools. Instrumental control with knee ultrasound and MRI investigations will be performed. The study protocol was approved by local Ethical Committee. Results: To date 23 patients (7 males, 16 females, age 54,6±11,2 years, primary knee OA – 16 pts, RA- 6 pts, AS – 1 pt) completed 1 st course of PEMF. Table presents differences (Δ) in the main clinical parameters in active treatment and placebo device groups. No significant difference in ESR or CRP levels was found. No treatment-related adverse events has been reported. Table. Differences (Δ) in the main clinical parameters after a 1 st course of PEMF. Parameter Active device (n=11) Placebo device (n=12) p Δ VAS pain in movement 15 [0; 38,5] 5 [1,25; 10,5] 0,053 Δ VAS pain in rest 10 [0; 34] 1 [0; 2,75] 0,043 Δ WOMAC 3 [2; 10] 2 [0; 4,5] 0,174 Δ Lequesne index 3 [0; 4] 1 [0,25; 2,5] 0,258 Conclusion: In this preliminary analysis pulsed electromagnetic field (PEMF) therapy showed significant impact on pain in rest in knee OA after one course of procedures. References: Negm A, Lorbergs A, Macintyre NJ. Efficacy of low frequency pulsed subsensory threshold electrical stimulation vs placebo on pain and physical function in people with knee osteoarthritis: systematic review with meta-analysis. Osteoarthritis Cartilage. 2013 Sep;21(9):1281-9. doi: 10.1016/j.joca.2013.06.015 Disclosure of Interests: Dmitry Karateev Consultant of: Abbvie, Pfizer, Biocad, Sanofi, Novartis, Lilly, Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Lilly, Bayer, Alexandra Makevnina Speakers bureau: Sanofi, Aminat Tangieva: None declared, Elena Luchikhina Consultant of: Abbvie, Biocad, Sanofi, Celgene, Speakers bureau: Abbvie, Roche, Pfizer, Biocad, MSD, Sanofi, Johnson & Johnson, Glaxo, UCB, Celgene, Novartis, Hava Hamhoeva: None declared

Background: The COVID-19 pandemic is seriously affecting the society and economy of many countries, including the Russian Federation. Identifying of the major risk factors for an unfavorable outcome could help save lives and reduce the disease burden. Until now, no results of the studies on this issue based on the Russian clinical material have been published. Aim: To evaluate the effects of comorbidities on the outcome (discharge or hospital death rates) in patients hospitalized with a diagnosis of COVID-19. Materials and methods : We analyzed a database of 13,585 patients who were treated in 66 hospitals functioning under the obligatory health insurance system of the Moscow Region, with a final diagnosis of COVID-19, virus identified (ICD 10 code U07.1) from April 1, 2020 to June 23, 2020 (53.7% women, 46.3% men, mean (± SD) age 56.5 ± 14.9 years (median 57 [46; 67])). In all patients, the diagnosis of COVID-19 was confirmed by polymerase chain reaction (PCR) for the SARS-CoV-2 virus in nasopharyngeal or oropharyngeal swabs. 93.8% of the patients showed signs of interstitial viral pneumonia (87.9% confirmed by computed tomography of the lungs, 5.9% by standard chest X-ray). All patients received the standard treatment according to the Temporary Guidelines on prevention, diagnosis and treatment of the new coronavirus infection (COVID-19), version 7 (03.06.2020)” from the Ministry of Health of the Russian Federation. 1518 (11.2%) patients had at least one comorbid condition, the most frequent being arterial hypertension (AH), ischemic heart disease (IHD), and diabetes mellitus (DM). In 71 female patients, COVID-19 occurred during pregnancy. By June 23, 2020, 10761 (79.2%) patients have been discharged from hospitals with recovery, improvement, or stabilization (the latter was considered a conditionally favorable outcome). 1246 patients died, that transfers into the in-hospital death rates of about 9.2% (unfavorable outcome). The rest of 1578 (11.6%) patients continued their treatment, or were transferred to other medical units for the continuation of care. The comparative analysis included patients (total, n = 12,007) with favorable (n = 10,761) and unfavorable (n = 1246) inpatient outcomes. The age-adjusted Charlson index was used to quantify the severity of comorbidity. Results: In the patients without any comorbidity, the in-hospital death rate was 9.4%. At least one comorbidity increased the incidence of unfavorable outcome to 13.9% (p 3 was associated with a more than 2-fold increase in the in-hospital death rates (25.2%, p < 0.001). Conclusion: Comorbidity is one of the drivers in the prognosis of in-hospital death rates in patients with COVID-19. However, it should be considered in the context of the patient age-related characteristics. The Charlson Age-Adjusted Comorbidity Index is a useful tool for assessment of the COVID-19 prognosis. The prognosis should be considered serious at a score of 3 or more.