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The objective of the study was to determine the main causes of osteoporosis in chronic kidney disease, chronic obstructive pulmonary disease, pulmonary sarcoidosis and understand how the disease develops in these conditions. Materials and Methods. To study the mechanisms of developing secondary osteoporosis, a literature review was conducted. Results. Secondary forms of osteoporosis account for approximately 15-20% of reported cases and result mainly from concomitant diseases or from using drugs that have a negative effect on bone tissue. Despite its inert and stable appearance, bone tissue is a metabolically active, continuously renewing system. Throughout life, it continuously undergoes remodeling cycles involving the two main processes: the first one is called bone resorption and involves the breakdown of old bone followed by the destruction and removal of both the mineral substance and the organic matrix from resorption sites; the second one is called new bone formation and involves bone matrix synthesis and its subsequent mineralization. The imbalance between these two processes, the predominance of bone resorption over bone formation, is the key link in the pathogenesis of osteoporosis. Such an imbalance reflects the impairment of the major mechanisms of systemic hormonal and local (cytokine) regulation of cellular activity and occurs in secondary osteoporosis. Conclusions. To date, at the stage of providing medical care to patients with chronic bronchopulmonary diseases and chronic kidney disease, inadequate attention is paid to timely diagnosis and treatment of concomitant osteoporosis. The latter often develops as a secondary condition due to systemic inflammation, severe hypoxia, low physical activity, taking inhaled and systemic glucocorticoids. Its signs are not clinically apparent; hence, it is referred to as the ‘silent epidemic. Since osteoporosis has no pathognomonic symptoms and its clinical presentation is rather vague, in patients with chronic bronchopulmonary diseases and chronic kidney disease, its early diagnosis by determining mineral bone density is recommended to prevent the development of severe complications, including low-energy fractures.

The Coronavirus disease 2019 (COVID-19) outbreak turned out the greatest pandemic for decades. It challenged enormously the global health system, forcing it to adjust to the new realities. We aimed to analyze articles covering COVID-19 papers in the rheumatological field and outline emerging topics raising within this frame. We applied the bibliometric database Scopus for our literature search and conducted it on the 5th of June using the following keywords: “rheumatic” OR “rheumatology” OR “rheumatoid arthritis” OR “systemic lupus erythematosus” OR “myositis” OR “systemic sclerosis” OR “vasculitis” OR “arthritis” OR “ankylosing spondylitis” AND “COVID-19”. We analyzed all selected articles according to various aspects: type of document, authorship, journal, citations score, rheumatology field, country of origin, language, and keywords. With the help of the software tool VOSviewer version 1.6.15, we have built the visualizing network of authors and keywords co-occurrence. The measurement of the social impact of articles was made using Altmetric data. This study included 1430 retrieved articles with open access mostly. The top five journals in this field were Annals of the Rheumatic Diseases (n = 65), Rheumatology International (n = 51), Clinical Rheumatology (n = 50), Lancet Rheumatology (n = 50), and Frontiers In Immunology (n = 33). Most studies originate from countries with a high incidence of COVID-19 among the general population (the USA—387; Italy—268; UK—184; France—114; Germany—110; India—98 and Spain—96, China—94, Canada—73 Turkey—66). Original Articles (42.1%) were the most common articles’ type, following by Letters (24.4%), Reviews (21.7%), Notes (6%), Editorials (4.8%), Erratum (1%). According to the citations scores, articles dedicated to the clinical course of COVID-19 in patients with rheumatic diseases were of the highest importance for the scientific rheumatologic community. Rheumatoid arthritis (n = 527), systemic lupus erythematosus (n = 393), vasculitis (n = 267), myositis (n = 71), systemic sclerosis (n = 68), and psoriatic arthritis (n = 68) were the most widely discussed rheumatic diseases in the view of COVID-19. The analysis of Altmetric and citations scores revealed a moderate correlation between them. This article provides a comprehensive bibliometric and altmetric analysis of COVID-19 related articles in the rheumatology field and summarizes data about features of rheumatology service in the time of the pandemic.

Objective To assess non-inferiority of s.c. to i.v. CT-P13 in RA. Methods Patients with active RA and inadequate response to MTX participated in this phase I/III double-blind study at 76 sites. Patients received CT-P13 i.v. 3 mg/kg [week (W) 0 and W2] before randomization (1:1) at W6 to CT-P13 s.c. via pre-filled syringe (PFS) 120 mg biweekly until W28, or CT-P13 i.v. 3 mg/kg every 8 weeks until W22. Randomization was stratified by country, W2 serum CRP and W6 body weight. From W30, all patients received CT-P13 s.c. In a usability sub-study, patients received CT-P13 s.c. via auto-injector (W46–54) then PFS (W56–64). The primary endpoint was change (decrease) from baseline in disease activity score in 28 joints (DAS28)-CRP at W22 (non-inferiority margin: −0.6). Results Of 357 patients enrolled, 343 were randomized to CT-P13 s.c. (n = 167) or CT-P13 i.v. (n = 176) at W6. The least-squares mean change (decrease) from baseline (standard error) in DAS28-CRP at W22 was 2.21 (0.22) for CT-P13 s.c. (n = 162) and 1.94 (0.21) for CT-P13 i.v. [n = 168; difference 0.27 (95% CI: 0.02, 0.52)], establishing non-inferiority. Efficacy findings were similar between arms at W54. Safety was similar between arms throughout: 92 (54.8%; CT-P13 s.c.) and 117 (66.9%; CT-P13 i.v.) patients experienced treatment-emergent adverse events (from W6). There were no treatment-related deaths or new safety findings. Usability was similar for CT-P13 s.c. via auto-injector or PFS. Conclusion CT-P13 s.c. was non-inferior to CT-P13 i.v. in active RA. The convenience of s.c. administration could benefit patients. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT03147248.

Systemic sclerosis (SSc) is a chronic progressive autoimmune disease characterized by immune inflammation, vasculopathy, and fibrosis. There are still numerous uncertainties in the understanding of disease initiation and progression. Pulmonary involvement in SSc, and particularly pulmonary fibrosis, is critical for all organ systems affections in this disease. This review is aimed to describe and analyze new findings in the pathophysiology of SSc-associated pulmonary involvement and to explore perspective diagnostic and therapeutic strategies. A myriad of cellular interactions is explored in the dynamics of progressive interstitial lung disease (ILD) and pulmonary hypertension (PH) in SSc. The role of exosomes, microvesicles, and apoptotic bodies is examined and the impact of micro and long non-coding RNAs, DNA methylation, and histone modification in SSc is discussed.

The objective of the research was to evaluate the risk of the development of chronic kidney disease: glomerulonephritis with nephrotic syndrome by antigens of blood groups of AB0 and Rhesus (Rh) systems. Material and methods. We examined 119 patients (76 men and 43 women) with chronic kidney disease: primary glomerulonephritis with nephrotic syndrome. The mean age of the patients was 39.65±14.16 years. The patients underwent a puncture biopsy of the kidney to verify the morphological form of the disease. A survey of 1428 healthy individuals was conducted to determine the populational distribution of blood groups phenotypes of AB0 and Rh systems. Results. Greater probability of the development of chronic kidney disease: glomerulonephritis with nephrotic syndrome was observed in carriers of 0 Rh+ and AB Rh+ antigens. The fact was interesting that carriers of phenotype 0 Rh– were registered much less of ten in patients than in healthy individuals. This may indicate some resistance to the disease in such individuals. Greater predisposition to the development of chronic kidney disease: glomerulonephritis with nephrotic syndrome was observed in Rh-positive women with blood groups0 (χ2=6.98; р=0.008) and АВ (φ=2.32; р=0.010). The chance of the studied pathology development in Rh-positive women versus Rh-negative was in 2.19 times higher than the same ratio in men. The highest chance to contract the pathology was in Rh-positive women with groups AB and 0 versus B, in 4.49 and 4.34 times more than men, respectively. Conclusions. Men with phenotypes A Rh– and B Rh– versus 0 Rh–, women with phenotypes AB Rh+ and 0 Rh+ versus A Rh+ and B Rh+ have the highest risk to contract the disease. Individuals of both genders with groups 0 Rh–and B Rh+ may be resistant to the development of the disease.

The objective of the work was to determine the possibility of drug correction of endothelial dysfunction, structural changes in peripheral arteries and the synthesis of end products of nitric oxide metabolism by the use of a combination of roflumilast and quercetin in the baseline therapy. In contrast to the baseline, the use of integrated therapy was followed in 6 months by a probable increase in the initial rate by 18.76 % (0.61 ± 0.04) m/s to (0.75 ± 0.04) m/s (t = 2.47; P < 0.05) and a probable decrease in the initial diameter of the brachial artery to (3.69 ± 0.29) mm (t = 2.49; P < 0.05). Patients of the experimental group have shown a significant increase in mean values of EDVD at the end of in-patient treatment and after 6 months of intensive supportive therapy (t = 2.17; Р < 0.05). The appointment of complex therapy after 6 months showed an increase in concentration in the blood of metabolites of NO in 1,3 times to (10.35 ± 1.89) μmol/l (t = 1.00; P > 0.1) at normal (12.05 ± 2.11) μmol/l. In patients of the index group after six months of the background therapy, IMT index has appeared in 1.07 times lower than the input data and has not reached the level of the control group. The IMT index for patients in the experimental group was considerably lower than the index before treatment (t = 0.31; P > 0.1). Application of complex therapy in patients with severe chronic obstructive pulmonary disease in the exacerbation phase in combination with stable coronary heart disease, stable angina pectoris I–II FK contributes to the restoration of endothelial function, improves structural changes in the peripheral arteries and has a stimulating effect on the synthesis of nitric oxide.

Granulomatosis with polyangiitis (GPA) is an orphan disease with multifaceted clinical presentations and delayed diagnosis. Given the risks of delayed diagnosis and treatment, improving clinicians' awareness of atypical course of this disease is critically important. The aim of this report is to analyze a case of delayed diagnosis of GPA in view of similar publications. We analyzed articles retrieved from Scopus and MEDLINE/PubMed. The following keywords were used: "granulomatosis with polyangiitis", "Wegener granulomatosis", and "diagnostic errors". All case studies that fulfilled the Chapel Hill Consensus Conference and the American College of Rheumatology GPA criteria were retrieved. We report a 71-year-old female patient with a facial defect in the nasal region, nasal congestion, and serosanguineous discharge. Her final diagnosis of GPA was reached after a series of incorrect diagnoses in the past 40 years. A deforming facial lesion developed during this period of uncertainty and absence of appropriate treatment. This patient presented with atypical features of laboratory and instrumental examinations. Anti-neutrophil cytoplasmic antibodies (ANCA) were negative, while rheumatoid factor (RF; 46.3 IU/mL) and anti-citrullinated protein antibody (ACPA; 25.6 IU/mL) were elevated. The histological analysis of the nasal mucous membrane specimen did not indicate definite signs of vasculitis. However, it revealed a granuloma with aggregation of macrophages and massive infiltration of lymphocytes, ruling out previous diagnosis of carcinoma. We analyzed delayed diagnosis of GPA in our patient in the context of 12 previously reported similar cases of limited form of GPA. We emphasize the importance of histological examination for differential diagnosis of GPA.

Objective To evaluate fenebrutinib, an oral and highly selective noncovalent inhibitor of Bruton's tyrosine kinase (BTK), in patients with active rheumatoid arthritis (RA). Methods Patients with RA and an inadequate response to methotrexate (MTX) (cohort 1; n = 480) were randomized to receive fenebrutinib (50 mg once daily, 150 mg once daily, or 200 mg twice daily), adalimumab (40 mg every other week), or placebo. Patients with RA and an inadequate response to tumor necrosis factor inhibitors (cohort 2; n = 98) received fenebrutinib (200 mg twice daily) or placebo. Both cohorts continued MTX therapy. Results In cohort 1, the percentages of patients in whom American College of Rheumatology 50% improvement criteria (ACR50) was achieved at week 12 were similar in the fenebrutinib 50 mg once daily and placebo groups, and were higher in the fenebrutinib 150 mg once daily group (28%) and 200 mg twice daily group (35%) than in the placebo group (15%) (P = 0.016 and P = 0.0003, respectively). Fenebrutinib 200 mg twice daily and adalimumab (36%) were comparable (P = 0.81). In cohort 2, ACR50 was achieved in more patients receiving fenebrutinib 200 mg twice daily (25%) than placebo (12%) (P = 0.072). The most common adverse events in the fenebrutinib groups included nausea, headache, anemia, and upper respiratory tract infections. Fenebrutinib had significant effects on myeloid and B cell biomarkers (CCL4 and rheumatoid factor). Fenebrutinib and adalimumab caused overlapping as well as distinct changes in B cell and myeloid biomarkers. Conclusion Fenebrutinib demonstrates efficacy comparable to adalimumab in patients with an inadequate response to MTX, and safety consistent with existing immunomodulatory therapies for RA. These data support targeting both B and myeloid cells via this novel mechanism for potential efficacy in the treatment of RA.

ObjectivesEfficacy, safety and immunogenicity results from the phase III study of SB2, a biosimilar of reference infliximab (INF), were previously reported through 54 weeks. This transition period compared results in patients with rheumatoid arthritis (RA) who switched from INF to SB2 with those in patients who maintained treatment with INF or SB2.MethodsPatients with moderate to severe RA despite methotrexate treatment were randomised (1:1) to receive SB2 or INF at weeks 0, 2 and 6 and every 8 weeks thereafter until week 46. At week 54, patients previously receiving INF were rerandomised (1:1) to switch to SB2 (INF/SB2 (n=94)) or to continue on INF (INF/INF (n=101)) up to week 70. Patients previously receiving SB2 continued on SB2 (SB2/SB2 (n=201)) up to week 70. Efficacy, safety and immunogenicity were assessed up to week 78.ResultsEfficacy was sustained and comparable across treatment groups. American College of Rheumatology (ACR) 20 responses between weeks 54 and 78 ranged from 63.5% to 72.3% with INF/SB2, 66.3%%–69.4% with INF/INF and 65.6%–68.3% with SB2/SB2. Treatment-emergent adverse events during this time occurred in 36.2%, 35.6% and 40.3%, respectively, and infusion-related reactions in 3.2%, 2.0% and 3.5%. Among patients who were negative for antidrug antibodies (ADA) up to week 54, newly developed ADAs were reported in 14.6%, 14.9% and 14.1% of the INF/SB2, INF/INF and SB2/SB2 groups, respectively.ConclusionsThe efficacy, safety and immunogenicity profiles remained comparable among the INF/SB2, INF/INF and SB2/SB2 groups up to week 78, with no treatment-emergent issues or clinically relevant immunogenicity after switching from INF to SB2.Trial registration numberNCT01936181; EudraCT number: 2012-005733-37.

Rheumatology in Ukraine is based on established research and clinical infrastructure that enable the integration with regional and global societies. This article overviews current state of Ukrainian rheumatology, important steps toward expanding clinical settings, and opportunities for strengthening cooperation of local rheumatologists and patients with rheumatic diseases with related international societies. The main achievements and some challenges encountered by the Association of Rheumatologists of Ukraine are outlined. The Association supports continuing medical education of local specialists and explores options for advancing research and publishing in rheumatology. One of the main challenges still remains the creation of registries of patients with rheumatic diseases and expansion of activities of public societies with interest in combating rheumatic diseases. The issue of inadequate access to immunobiological therapies is also highlighted.

Background CT-P13 subcutaneous (SC) formulation showed comparable efficacy and safety with CT-P13 intravenous (IV) formulation in rheumatoid arthritis (RA)1 and Crohn’s disease2 preliminary studies (Part 1). Objectives The purpose of this study was to demonstrate non-inferiority (NI) of efficacy and compare safety profiles of CT-P13 SC to CT-P13 IV in RA patients over 30 weeks of Part 2. Methods In this randomized, controlled, double blinded, phase I/III study, RA patients received CT-P13 IV 3 mg/kg at Weeks 0 and 2 and were randomized at Week 6 to receive CT-P13 SC 120 mg every 2 weeks or CT-P13 IV 3 mg/kg every 8 weeks. From Week 30, all patients received CT-P13 SC 120 mg every 2 weeks. The primary efficacy endpoint, change of DAS28 (C-reactive protein [CRP]) from baseline to Week 22, was analyzed by using an analysis of covariance (ANCOVA). Non-inferiority is to be concluded if the lower bound of the 95% CI for the treatment difference in the change of DAS28 (CRP) from baseline to Week 22 is greater than the pre-specified NI margin of -0.6. Results A total of 362 patients were enrolled, of whom 348 were randomly assigned at Week 6 into 2 treatment arms in a 1:1 ratio (169 and 179 patients in SC 120 mg and IV 3 mg/kg arms, respectively). The mean change of DAS28 (CRP) from baseline to Week 22 was similar between the arms. The lower limit of two-sided 95% CI (0.03) was greater than the pre-specified NI margin (-0.6) which indicated NI of SC 120 mg compared to IV 3 mg/kg (Table 1). Additional efficacy including ACR responses were similar between two treatment arms up to Week 22 with slightly higher response rate trend observed in SC 120 mg arm at Week 30 (Figure 1). The safety profiles which occurred after study drug administration at Week 6 in SC 120 mg arm were generally comparable to IV 3 mg/kg arm. All of injection site reactions were grade 1 or 2 in intensity. Majority of administration-related reactions (ARRs) were grade 1 or 2 in intensity except 1 patient in IV 3 mg/kg arm who experienced grade 3 ARR and was withdrawn from the study due to this event (Table 2). Conclusion The study demonstrated NI of efficacy for CT-P13 SC to the CT-P13 IV. Also, CT-P13 SC showed similar efficacy and safety profiles to CT-P13 IV up to Week 30. CT-P13 SC could provide a favorable benefit to patients with an alternative convenient way of administration. References [1] Westhovens R, et al. Annals of the Rheumatic Diseases 2018;77(-):315 (suppl2) [2] Schreiber, S, et al. Gastroenterology2018;154(6):S-1371 Disclosure of Interests Rene Westhovens Grant/research support from: Bristol-Myers Squibb, Consultant for: Celltrion, Galapagos-Gilead, Piotr Wiland Speakers bureau: Novartis, Pfizer, Abbvie, Gedeon-Richter, Lilly, Roche and Sandoz, Marek Zawadzki Grant/research support from: Celltrion, Inc., Delina Ivanova Grant/research support from: Celltrion, Inc, PPD, Quintiles, Egis Pharmaceuticals, and Pfizer., Alfredo Berrocal Grant/research support from: Celltrion, Inc., Elias Chalouhi Grant/research support from: Celltrion, Inc., Eva Balazs Grant/research support from: Celltrion, Inc., Consultant for: Merck and Amgen, Sergii Shevchuk: None declared, Larisa Eliseeva Grant/research support from: Celltrion, Inc., Mykola Stanislavchuk Grant/research support from: AstraZeneca, Celltrion, Galapagos, Genentech, GlaxoSmithKline, Human Genome, Lilly, MedImmune, Pfizer, Roche and UCB, Roman Yatsyshyn Grant/research support from: Celltrion, Inc., SangJoon Lee Shareholder of: Celltrion, Inc., Employee of: Celltrion, Inc., JeeHye Suh Employee of: Celltrion, Inc., SeulGi Lee Employee of: Celltrion, Inc., Yunah Kim Employee of: Celltrion, Inc., DaeHyun Yoo Grant/research support from: Celltrion, Inc., Consultant for: Celltrion, Inc.

Background: Patients with rheumatoid arthritis (RA) have an early development of endothelial dysfunction, an increase of the atherogenicity index (AI), and a high risk of fatal cardiovascular events. The presence of arterial hypertension (AH) in patients with RA accelerates the process of early atherogenesis and increases the risk of fatal cardiovascular events. Objectives: To evaluate the dynamics of lipid profile changes in patients with RA in combination with AH. Methods: It was examined 47 patients with RA in combination with AH (by all patients was discovered IIstage/2degree of AH). The age of the patients ranged from 18 to 72 years. Among the surveyed group dominated men (41 patients). All patients were assessed for the levels of total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides (TG), high density lipoprotein (HDL), AI (AI = TC – HDL/LDL), antibodies to modified citrulline vimentin (anti-MCV), rheumatoid factor (RF), C-reactive protein (CRP) before treatment. All patients were also assessed for the risk of death for 10 years by the SCORE scale (> 15% - very high risk, 10-14% high, 5-3% - moderate, Results: Due to the obtained data, it can be asserted, that in patients with seronegative RA the moderate risk by SCORE was prevalent, and among seropositive RA patients– high risk. The high level of anti-MCV titres was directly corelated with the risk of the death by SCORE (p > 0,05, r = 0,64). We found that patients with RA and AH had relatively low levels of TC (5,82 ± 2,21 mmol/L) and LDL (2,82 ± 0,81 mmol/L), but the AI in these patients was 4,42 ± 0,68. It was measured the correlation between the levels of LDL and the activity of the inflammatory process DAS28, the level of CRP and the duration of RA (r = 0,56, p Conclusion: 1. Seropositivity, high activity and anamnesis of RA for more than 10 years are the factors, that are associated with high risk of fatal cardiovascular events. 2. In patients with RA in combination with AH, serum lipid levels have paradoxical ratio, resulting in lower levels of TC and LDL associated with an increased risk of cardiovascular events (”lipid paradox”). 3. The presence of high anti-MCV titres serves as a prognostically unfavorable feature of the course of RA and AH, since its association with a high risk of fatal cardiovascular events. Disclosure of Interests: None declared

To present a case of prostate involvement (PI) in granulomatosis polyangiitis (GPA) and analyse related published reports. We employed the following keywords for retrieving reports indexed by MEDLINE/PubMed and/or Scopus: “granulomatosis with polyangiitis”, “Wegener granulomatosis” and “prostate involvement”. Additional searches were performed through Google Scholar and HINARI. All cases that fulfilled the American College of Rheumatology criteria for GPA, standards of Chapel Hill Consensus Conference, and did not match with exclusion criteria were analysed and summarised. A 35-year-old man presented with complaints of stuffy nose, difficulty breathing through the nose, swelling and pain in the left half of the nose, low-grade fever, and discomfort. The nasal mucosal biopsy did not reveal any specific changes. During the inpatient treatment, he developed eye redness, tearing, dysuria, and decreased urinary stream. Prostate-specific antigen (PSA) was elevated (2.81 μg/L; normal values ≤ 1.4 μg/L for males below 40 years). Prostate biopsy findings were consistent with diagnosis of GPA, which was confirmed by detecting elevated anti-PR3 antibodies (4.1 IU; normal values

Background:Systemic sclerosis (SSc) is a heterogeneous autoimmune pathology, which detailed pathogenetic mechanisms of initiation and progression still require further investigations. It could be achieved with implementation of reliable experimental modeling techniques.Objectives:This study was aimed to determine the state of oxidant/antioxidant system, dysregulation of collagen synthesis in laboratory animals and evaluate effectiveness of the considered model of SSc induction.Methods:Thirty adult Wistar rats (220-240 g) were included in the study. The experimental group consisted of 20 animals, which received 3 subcutaneous injections of 0.5 ml of 5% sodium hypochlorite solution (NaClO) with an active chlorine concentration of 190 g / dm3 for 6 consecutive weeks. The control group consisted of 10 rats injected with isotonic solution according to the previously described scheme.Results:The level of catalase in the experimental group was lower than in the control 9.69 ± 0.67 g / l and 11.1 ± 0.87 g / l respectively (p = 0.002). Protein oxidative modification (POM) products were higher in the experimental group (0.0722 ± 0.023 vs 0.0527 ± 0.023, p = 0.014). Malondialdehyde (MDA) was also higher in the experimental group compared to the control (4.30 ± 0.26 and 3.85 ± 0.23, respectively, p = 0.010). The concentration of oxyproline in the serum of laboratory animals subjected to repeated administration of NaClO was significantly higher compared to the control group (34.03 ± 5.01 and 33.23 ± 2.40, p = 0.020).Conclusion:As a result of the use of NaClO for the reproduction of SSc in laboratory animals, there is a violation of oxidative-antioxidant homeostasis and increased fibrotic processes. These changes are comparable with those in SSc patients, which makes this modeling technique a promising tool for a detailed investigation of SSc pathogenesis.Disclosure of Interests:None declared

Background:The Coronavirus disease 2019 (COVID-19) outbreak spread rapidly among the whole world, becoming the greatest pandemic for the decades. It triggered the enormous challenges for the global health system, forcing doctors and patients to adapt to new realities and the field of rheumatology was not an exclusion.Objectives:The aim of this study was to analyze articles covering interconnection between COVID-19 and rheumatic diseases; to investigate the common features of papers in this category and indicate the most influential among them; to determine which rheumatic nosologies were most represented.Methods:For retrieving of literature data, we applied the bibliometric database Scopus and conducted our search on 12th of January using following keywords: “rheumatoid arthritis” OR “systemic lupus erythematosus” OR “systemic sclerosis” OR “vasculitis” OR “myositis” OR “rheumatology” AND “COVID-19”. All selected articles were analyzed according to various aspects: type of document, authorship, journal, citations score, rheumatology field, country of origin, language, and keywords. We have built the visualizing keywords network (Figure 1) with the help of software tool VOSviewer version 1.6.15 (the minimum keyword occurrence threshold was set at 5).Figure 1.Results:A total of 844 literature items were obtained. After screening of title, abstract and keywords we excluded 106 records as they were not emphasized the rheumatological perspective on COVID-19 and as a result were inapplicable for this study. The 738 retrieved articles were mostly (86.8%) open access publications. The top five journals that contributed most to the coverage of this topic were: Annals Of The Rheumatic Diseases (n=59), Clinical Rheumatology (n=41), Lancet Rheumatology (n=24), Arthritis And Rheumatology (n=20) and Rheumatology International (n=19). The origin of most studies was not surprisingly from those countries, which belong to the top ten according to the total cases of COVID-19 [1] (USA – 167; Italy – 148; UK – 76; India – 60 and Spain – 58). Most items were written in English but articles in German (n=12), Spanish (n=11), Russian (n=5) and Chinese (n=2) could also be found. Analyzed studies were designed in the form of Original Articles (41.2%), Reviews (23.7%), Letters (21.8), Notes (6.9%), Editorials (5.1%). According to the citations scores, articles of highest interest were dedicated to clinical course of COVID-19 in patients with autoimmune pathologies. The other highly cited studies were about cytokine storm and perspective usage of biological drugs for severe cases of COVID-19. Our analysis of keywords showed that the most widely discussed rheumatic disease in the view of COVID-19 was systemic lupus erythematosus (n=188), followed by vasculitis (n=132), rheumatoid arthritis (n=90), systemic sclerosis (n=32) and psoriatic arthritis (24). The liveliest discussion about disease-modifying antirheumatic drugs in COVID-19 revolved around hydroxychloroquine (n=305), corticosteroids (n=161), tocilizumab (n=83), methotrexate (n=46) and anakinra (n=34).Conclusion:As far as we know, it is the first bibliometric overview of studies dedicated to interrelation between COVID-19 and rheumatic pathology. The high number of open access items contributes to the increase of research visibility in this emergently developing research field and facilitates the process of scientific data sharing. The conducting of bibliographic studies may provide a valuable guide through this area of knowledge.References:[1]https://www.worldometers.info/coronavirus/ Accessed on January 12, 2021Disclosure of Interests:None declared.

Background:Systemic sclerosis (SSc) - is an autoimmune connective tissue disease, which crucial role is played by inflammation and fibrosis development. This pathology is characterized by multiple symptoms that occur due to alterations of the vascular wall, limited or widespread fibrosis of the dermis and visceral organs, dysregulation of cellular and humoral immunity, followed by the formation of autoantibodies specific to the structures of the organism. Although external manifestations of SSc certainly lead to a decrease in the functional activity and patient’s quality of life up to disability, the real danger is a violation of the functions of the internal organs and systems.Objectives:The aim of our study was to determine changes in the morphological structure of lung interstitial tissue at the subcellular level of the structural organization, which were achieved by modeling of this autoimmune pathology in laboratory animals.Methods:The main concept of modeling process was based on the previously described method of SSc induction [1,2] however with some differences from original model. Into the study were involved 30 pubescent Wistar rats (220-240g) who underwent a three times a week subcutaneous administration of 0.5ml of 5% sodium hypochlorite (NaClO) solution with active chlorine concentration of 190 g/dm3for 6 weeks in a row; control group (20 rats) that received injections with an equal volume of sterile saline solution. After 8 weeks from the beginning of the experiment animals were sacrificed under thiopental anesthesia, lung tissue specimens were obtained, fixed alternately in 2.5% glutaraldehyde and in 1% solution of osmium tetroxide. After dehydration, the material was embedded in Epon-Araldite. Sections were obtained on an ultramicrotome (Tesla BS-490) magnification x9600 was performed on high-resolution microscope (PEM-125K).Results:The ultrastructural study of lung specimens reviled the fibroblasts with high amounts of collagen fibers in the interstitial tissue of the alveoli wall. Fibroblast nuclei were characterized by irregular shape and numerous invaginations of the nuclear envelope and marginal aggregation of chromatin granules. Fig. 1 depicts the fragment of the alveolar wall of the lungs of white Wistar rats in 8 weeks after the start of the experiment. On the Fig. 1 could be distinguished the lumen of the alveoli (1), fibroblast (2) with increased quantity of collagen fibers (3) and a peripheral part of alveolocyte I type (4).Figure 1.Conclusion:The current findings confirm the efficacy of NaСlO chemical model of reproduction of interstitial lung tissue involvement within SSc pathogenesis; this model could contribute to the further investigation of peculiarities of autoimmune origin interstitial lung disease (ILD).References:[1]Servettaz A, Goulvestre C, Kavian N, Nicc, C, Guilpain P, Chéreau C, Batteux F. Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse. The Journal of Immunology. 2009; 182(9), 5855-5864.[2]Batteux F, Kavian N, Servettaz A. New insights on chemically induced animal models of systemic sclerosis. Current opinion in rheumatology. 2011; 23(6), 511-518.Disclosure of Interests:None declared

Background Secondary sarcopenia may be caused by low physical activity, eating disorders, chronic inflammation. In patients with rheumatoid arthritis (RA), sarcopenia co-occurs with osteoporosis as well as obesity and, in most cases, both osteoporosis and obesity co-occur with sarcopenia. Therefore, 3 phenotypes of sarcopenia can be identified: sarco-osteoporosis, sarcopenic obesity, osteosarcopenic obesity. Objectives The aim of the research was to study the features of sarcopenia and her phenotypes in patients with RA. There were examined 40 women with stage II-III RA, Rtg stage II-III, functional limitation stage II. The patients average age was 40.7±2.25 years. Methods The algorithm for diagnosing phenotypes of sarcopenia recommended by the European Working Group on Sarcopenia in Older People (2009) was used. Body mass index was determined. Dynamometry (the measurement of hand-grip strength using handgrip dynamometer) was performed and the evaluation of physical fitness. S erum levels of leptin and creatine phosphokinase MM (CPK MM) fraction were determined. The dual-energy X-ray absorbtiometry DEXA (tocalculate a T-score) was performed Results According to the results of laboratory tests and methods of evaluating functional muscle disorders, 87.5% of patients were diagnosed with sarcopenia. The mean values of dynamometry were within 18.3±0.7 kg being significantly lower as compared to healthy individuals – 28.3±0.5 kg. After the evaluation of physical fitness, the average score was 7.9±0.7, while in healthy individuals, it was 11.3±0.4. The mean CPK MM concentration was 175±2.34 U/L, while in healthy individuals, it was 144±3.5 U/L. The average T-score were within the limits (– 1,83±0,17) SD and was significantly lower than in healthy (−0,56±0,10) SD. After conducting studies in 17 patients were diagnosed with osteosarcopenic obesity in 11 – sarco-osteoporosis, 7 – sarcopenic obesity, 5 patients sarcopenia has not been diagnosed. Conclusions RA leads to muscle metabolism disorders which result in the development of secondary sarcopenia. Therefore, a high-protein diet, physical exercise, namely aerobic exercise (swimming, cycling) and medical preparations that improve muscle metabolism should be included in therapeutic measures and preparations of calcium. Disclosure of Interest None declared

ObjectivesTo compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy.MethodsThis is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence.Results584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was −1.88% (95% CI −10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF.ConclusionsSB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF.Trial registration numberNCT01936181.

Background Lesion of the cardiovascular system is associated with uncontrolled inflammation and immune defects in patients with Rheumatoid Arthritis (RA). There is an evidence of the close pathogenetic connection between rheumatoid inflammation and accelerated development of atherosclerosis. The first sing of atherosclerosis is endothelial dysfunction (ED). Objectives Evaluate the effectiveness of NO donators (4,2% solution of arginine hydrochloride and L-arginine aspartate) in the correction of lipid and ED in patients with RA and secondary Raynaud9s syndrome (RS). Methods 68 patients with RA were examined. All patients were divided into 2 groups: (37 people with RA in combination with secondary RS) received basic therapy of RA (methotrexate 10–15 mg/wk.), antiplatelet and vasodilatory drugs; II group (31 people – RA in combination with secondary RS) got similar therapy plus NO donators (4,2% solution of arginine hydrochloride and L-arginine aspartate). The examination was carried out at the patient9s admission to the hospital and the hospital and 3 months after the beginning of treatment. Endothelial function was assessed by determining the flow-mediated vasodilation of brachial artery (FMD), levels of endothelin-1, rheumatoid factor (RF), C-reactive protein (CRP), lipid profile (total cholesterol – TC, low density lipoprotein – LDL, high-densitylipoprotein – HDL and triglycerides – TG), index of intima/media (IM) and atherogenic index (AI). Results Levels of TC, LDL, AI and MI indexes were significantly higher than the norm in 2 compared groups before the treatment and 3 months after its start (p Conclusions 1.There is a lack of flow-mediated vasodilation of brachial artery in patients with RA and secondary RS, which can indicate a dysregulation of endothelial function. 2. The level of CRP is increased in patients with RA and secondary RS and is associated with the risk of hyperlipemia and atherosclerosis. 3. The usage of NO donators (4,2% solution of arginine hydrochloride and L-arginine aspartate) in the treatment of RA with secondary RS significantly reduces the levels of IA and IM index, the level of atherogenic lipoprotein fractions (TC, LDL and TG) and decreases the severity of ED, which leads to minimizing the risk of atherogenesis and its complications. References Kuryliszyn-Moskal A, Klimiuk PA, Sierakowski S, Ciolkiewicz M. A study on vascular endothelial growth factor and endothelin-1 in patients withextra-articular involvement of rheumatoid arthritis // ClinRheumatol. 2006 May; 25 (3): 314–9. Disclosure of Interest None declared

Objectives SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage. Methods In this phase III, double-blind, parallel-group, multicentre study, patients with moderate to severe RA despite MTX were randomized (1:1) to receive 3 mg/kg of either SB2 or INF at 0, 2, 6 and every 8 weeks thereafter. Dose escalation by 1.5 mg/kg up to a maximum dose of 7.5 mg/kg was allowed after week 30. Efficacy, safety and immunogenicity were measured at each visit up to week 54. Radiographic damage evaluated by modified total Sharp score was measured at baseline and week 54. Results A total of 584 patients were randomized to receive SB2 (n = 291) or INF (n = 293). The rate of radiographic progression was comparable between SB2 and INF (mean modified total Sharp score difference: SB2, 0.38; INF, 0.37) at 1 year. ACR responses, 28-joint DAS, Clinical Disease Activity Index and Simplified Disease Activity Index were comparable between SB2 and INF up to week 54. The incidence of treatment-emergent adverse events and anti-drug antibodies were comparable between treatment groups. Such comparable trends of efficacy, safety and immunogenicity were consistent from baseline up to 54 weeks. The pattern of dose increment was also comparable between SB2 and INF. Conclusion SB2 maintained similar efficacy, safety and immunogenicity with INF up to 54 weeks in patients with moderate to severe RA. Radiographic progression was comparable at 1 year. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov; NCT01936181) and EudraCT (https://www.clinicaltrialsregister.eu; 2012-005733-37).

Background SB2 is developed as a biosimilar of the infliximab reference product (INF). The 30-week and 54-week results of Phase III study have been reported1,2. Objectives To evaluate the safety, immunogenicity, and efficacy in patients with RA who transitioned from INF to SB2 vs maintained INF and who continued to receive SB2 after Week 54 up to Week 78. Methods This study is a randomised, double-blind phase III transition study. Patients with moderate to severe RA were randomised in a 1:1 ratio to receive either SB2 or INF at Weeks 0, 2, 6, and then every 8 weeks thereafter until week 46. At Week 54, patients previously receiving INF were re-randomised in a 1:1 ratio to either receive SB2 (INF/SB2) or continue INF (INF/INF) up to week 70; patients receiving SB2 continued to receive SB2 (SB2/SB2) up to Week 70. Safety, immunogenicity and efficacy were assessed up to week 78. Results At Week 54, 94 patients from INF were transitioned to SB2 (INF/SB2), 101 patients from INF continued to receive INF (INF/INF), and 201 patients from SB2 continued to receive SB2 (SB2/SB2). The safety profile during the transition period was comparable between INF/SB2, INF/INF, and SB2/SB2. The incidence of adverse events during the transition period was 36.2% in INF/SB2, 35.6% in INF/INF, and 40.3% in SB2/SB2. The incidence of infusion related reaction during the transition period was 3.2%, 2.0%, and 3.5%, respectively. Among the patients with overall negative anti-drug antibodies (ADA) results up to Week 54, ADAs were newly developed in 14.6% (6/41) in INF/SB2, 14.9% (7/47) in INF/INF, and 14.1% (11/78) in SB2/SB2. The efficacy was sustained and comparable between the treatment groups. Conclusions The safety, immunogenicity, and efficacy profiles remained comparable between the INF/SB2, INF/INF, and SB2/SB2 up to Week 78, revealing that there were no treatment emergent issues or clinically relevant immunogenicity after switching from INF to SB2. References Choe JY et al. Ann Rheum Dis. 2015–207764 [Epub ahead of print] Choe JY et al. Arthritis Rheumatol. 2015; 67 (suppl 10), 2056 Disclosure of Interest J. S. Smolen Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glazo, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB, J.-Y. Choe Grant/research support from: Samsung Bioepis, Consultant for: Samsung Bioepis, N. Prodanovic Grant/research support from: Samsung Bioepis, J. Niebrzydowski Grant/research support from: Samsung Bioepis, I. Staykov Grant/research support from: Samsung Bioepis, E. Dokoupilova Grant/research support from: Samsung Bioepis, A. Baranauskaite Grant/research support from: AbbVie, Samsung Bioepis, R. Yatsyshyn Grant/research support from: Samsung Bioepis, M. Mekic Grant/research support from: Samsung Bioepis, W. Porawska Grant/research support from: Samsung Bioepis, H. Ciferska Grant/research support from: Samsung Bioepis, K. Jedrychowicz-Rosiak Grant/research support from: Samsung Bioepis, A. Zielinska Grant/research support from: Samsung Bioepis, J. Choi Employee of: Samsung Bioepis, Y. H. Rho Employee of: Samsung Bioepis

Background CT-P13 is a biosimilar product of infliximab (INX). Data up to week 30 has been reported at EULAR 2012.1 Objectives To compare the efficacy and safety of CT-P13 and INX in active rheumatoid arthritis (RA) patients up to week 54. Methods Patients with active RA (1987 ACR criteria) and inadequate response to methotrexate (MTX) were randomised (1:1) to receive either CT-P13 (3mg/kg) or INX (3mg/kg) at weeks 0, 2, 6 and then every 8 weeks up to week 54 in combination with MTX (12.5–25mg/week). Results Of 606 patients randomised at baseline, 457 patients were treated up to week 54. At week 54, ACR20 was highly similar between groups (CT-P13, 57.0% [172/302]; INX, 52.0% [158/304]; 95% CI: -0.03–0.13). ACR50 and ACR70 scores were also comparable between groups (CT-P13, 33.1% and 16.2%; INX, 31.6% and 15.1%, respectively). In the CT-P13 and INX groups respectively, 26.4% and 27.8% of patients reached remission with DAS28-CRP; additionally, 14.3% and 14.8% reached low disease activity compared to approximately 80% high disease activity in both groups at baseline. The proportion of patients testing positive for anti-drug antibodies (ADAs) was comparable between CT-P13 (52.3%) and INX (49.5%). More patients with negative ADA results achieved ACR20 responses (CT-P13, 73.9%; INX, 67.2%) compared with patients with positive results (CT-P13, 53.2%; INX, 48.1%). Total Sharp scores at baseline and week 54 were comparable (CT-P13, 104.6 and 70.4; INX, 103.6 and 73.0). Cmax of CT-P13 or INX at all doses ranged from 66.1µg/mL–112.2µg/mL and 60.3µg/mL–104.5µg/mL, respectively. The safety profiles of CT-P13 and INX were also comparable (table). Conclusions CT-P13 showed comparable efficacy and PKs to those of INX up to week 54. CT-P13 was well tolerated with a safety profile comparable to that of INX up to week 54. References Yoo D et al. A randomized, double-blind, phase 3 study demonstrates clinical equivalence of CT-P13 to infliximab when co-administered with methotrexate in patients with active rheumatoid arthritis. Ann Rheum Dis 2012;71(Suppl 3):359. Disclosure of Interest D. H. Yoo Consultant for: CELLTRION Inc., A. Racewicz Grant/research support from: CELLTRION Inc., J. Brzezicki Grant/research support from: CELLTRION Inc., R. Yatsyshyn Grant/research support from: CELLTRION Inc., E. Tobias Arteaga Grant/research support from: CELLTRION Inc., A. Baranauskaite Grant/research support from: CELLTRION Inc., C. Abud-Mendoza Grant/research support from: CELLTRION Inc., S. Navarra Grant/research support from: CELLTRION Inc., Consultant for: Pfizer Ltd., Speakers bureau: CELLTRION Inc., R. Eullaran Grant/research support from: CELLTRION Inc., V. Kadinov Grant/research support from: CELLTRION Inc., I. Goecke Sariego Grant/research support from: CELLTRION Inc., P. Byrne Grant/research support from: CELLTRION Inc., W. Park Consultant for: CELLTRION Inc., S. J. Lee Consultant for: CELLTRION Inc., Employee of: CELLTRION Inc., H. U. Kim Employee of: CELLTRION Inc., U. Muller-Ladner Speakers bureau: CELLTRION Inc.

Background CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®). The aim of this study was to compare the 54-week efficacy, immunogenicity, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of CT-P13 and RP in patients with active rheumatoid arthritis (RA). Methods In this multinational phase III double-blind study, patients with active RA and an inadequate response to methotrexate (MTX) were randomized (1:1) to receive CT-P13 (3 mg/kg) or RP (3 mg/kg) at weeks 0, 2, 6 and then every 8 weeks to week 54 in combination with MTX (12.5–25 mg/week). Efficacy endpoints included American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates, Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), European League Against Rheumatism (EULAR) response rates, patient-reported outcomes and joint damage progression. Immunogenicity, safety and PK/PD outcomes were also assessed. Results Of 606 randomized patients, 455 (CT-P13 233, RP 222) were treated up to week 54. At week 54, ACR20 response rate was highly similar between groups (CT-P13 74.7 %, RP 71.3 %). ACR50 and ACR70 response rates were also comparable between groups (CT-P13 43.6 % and 21.3 %, respectively; RP 43.1 % and 19.9 %, respectively). DAS28, SDAI and CDAI decreased from baseline to week 54 to a similar extent with CT-P13 and RP. Radiographic progression measured by Sharp scores as modified by van der Heijde was also comparable. With both treatments, patient assessments of pain, disease activity and physical ability, as well as mean scores on the Medical Outcomes Study Short Form Health Survey (SF-36), improved markedly at week 14 and remained stable thereafter up to week 54. The proportion of patients positive for antidrug antibodies at week 54 was similar between the two groups: 41.1 % and 36.0 % with CT-P13 and RP, respectively. CT-P13 was well tolerated and had a similar safety profile to RP. PK/PD results were also comparable between CT-P13 and RP. Conclusions CT-P13 and RP were comparable in terms of efficacy (including radiographic progression), immunogenicity and PK/PD up to week 54. The safety profile of CT-P13 was also similar to that of RP. Trial registration ClinicalTrials.gov identifier: NCT01217086. Registered 4 Oct 2010. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-0981-6) contains supplementary material, which is available to authorized users.