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BackgroundInterstitial lung disease (ILD) is one of the most relevant extra-articular manifestations of rheumatic diseases resulting in a substantial increase in morbidity and mortality. High-resolution computed tomography (HRCT), which is the current gold standard for diagnosis and evolutionary control, is problematic owing to ionizing radiation, cost, and accessibility. In the last decade, the use of lung ultrasound (LUS) in clinical medicine has increased. LUS is an accurate tool for the diagnosis of pneumonia, pneumothorax, acute pulmonary edema, and pleural effusion. LUS may also be useful in detection of ILD by the evaluation of B-lines, the sonographic hallmark of the interstitial syndrome.ObjectivesTo compare semi-quantitative scores of B lines in patients with rheumatic disease with different intensity of lung fibrosis.Methods50 pts with ILD of rheumatic disease such as: vasculitis n=11 (mean age 40.7± 9.1, fem 5); dermatomyositis (DM), anti-synthetase syndrome (ASS), polymyositis (PM) n=20, (mean age 48.7± 11.9, fem 13); rheumatoid arthritis (RA) n=9 (mean age 56.5± 6.3, fem 7); Sjogren’s syndrome (SSj) n=9 (mean age 59.6± 12.3, fem 8). To determine the intensity of fibrosis of ILD we used a limited/extensive classification for disease extent, integrating HRCT observation. According this scheme pts were divided into 2 groups: group 1 included 33 pts had “limited” lung disease (lung lesions less than 20%) and the group 2 included 17 pts had “extensive” lung disease (lung lesions greater than 20%). LUS examination protocol that include the anterior, lateral, and/or posterior thorax have been suggested The B-lines score denoting the extension of ILD was calculated by summing the number of B-lines on a total of 58 scanning sites. In each patient ULC score was obtained by summing the number of comets detected as previously recommended. The data were collected in protocols for statistical testing. Other data collected including biological results (high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR)).Resultsthe mean score of B-lines in each groups were: vasculitis (n=11) 21,4 ±12,6; (DM, PM, ASS) (n=20) 41,3±20.8; RA (n=9) 56.5±6.3; SSj (n=9) 59 ± 11.8. The mean score of B-lines in groups pts with different intensity of fibrosis are presented in Table 1.Table 1.Groupsmean score of B-linesAnterior chest Mean score of B-linesPosterior chest Mean score of B-linesLimited (n=33)22±146.6 ±7.1 5 [1;10]15.4±13.4Extensive (n=17)61.3±27.424.2±12.536.4±22.4PThe correlations in Table 1 may confirm the connection of B-lines score and extensity of ILD association with rheumatic disease. The mean score of ULCs determined in all 50 pts didn’t correlate with dates of ESR (R = 0,188, p>0.05) and hsCRP (R= -0,07, p>0.05).ConclusionIn Russian cohorts presence of LUS score is associates with more severe ILD. Echographic examination of the lung allows evaluating the severity of lung fibrosis and can be used as an additional simple and available method to assess the ILD of rheumatic disease, but we couldn’t find correlation with hsCRP and ESR.Disclosure of InterestsNone declared

BackgroundHRCT is the gold standard for confirming ILD.However,the role of HRCT for estimating the effectiveness of therapy is not determined in full.ObjectivesTo assess the dynamics of X-ray changes and PFTs during IST in pts with SSc and different prevalence of ILD according to HRCT.MethodsThe study included 37 pts with signs of ILD(the average age-53.1±11.5 yrs,the ratio of m/w- ¼, d/l–1/1.8,the SSc-duration-10.9±9 yrs).For all pts at the time of inclusion in the study and after an average of 34±2.3 months were studied FVC,DLC and HRCT.The pts received IST during the follow-up period.The ILD dynamics was assessed as follows:improvement,deterioration and no dynamics.The analysis of HRCT data was conducted at 5 levels.The severity of changes by type of ground-glass,reticular changes,traction bronchiectasis,and honeycombs were evaluated(0–3 points).The dynamics of X-ray changes and PFTs was separately assessed in pts with the prevalence of interstitial changes up to 20%(group A,n=23) and more than 20%(group B,n=14) of the total area of lung tissue.ResultsIn the general group during the IST CT-improvement was noticed in 13(34.2%),deterioration–in 9(24.3%) pts.There was no dynamics in 15(40.5%)pts.ParametersAll group (n=37)рGroup А (n=23)рGroup В (n=14)рРBetween groups А and Вpoint “1”point “2”point “1”point “2”point “1”point “2”Negative CT-dynamics, n/%9/24.34/17.45/35.70.008Positive CT-dynamics, n/%13/34.26/42.97/30.40.06Mean CT-score, points (M±σ)9.6±8.29.4±8.30.74.1±3.90.518.07±5.618.1±6.11р1=0.000038р2=0.000001“Ground-glass” score, points (M±σ)5.1±3.34.95±3.30.61.9±2.6 (median-0 [0;3])1.3±2.1(median-0 [0;2])0.125.4±2.64.6±3.20.3р1=0.018р2=0.013Reticular changes score, points (M±σ)7.4±3.77±3.40.42.6±2.42.7±2.30.77.9±2.47.6±1.980.3р1=0.0007р2=0.0004Traction bronchiectasis index, points (M±σ)1.67±2.3 (median-0 [0;3])2.0±2.6(median-1 [0;3])0.020.5±1.2 (median-0 [0;0])0.7±1.3(median-0 [0;1])0.17.8±2.07.6±2.00.7р1=0.000000р2=0.000000FVC, % of proper values (M±σ)94.2±19.594.6±16192±18.991.9±19.60.9589.2±21.590.3±14.20.23р1=0.7р2=0.8DCL, % of proper values (M±σ)57.3±20.257.9±20.70.660.6±19.662.6±19.10.347.6±11.445.2±13.50.22р1=0.13р2=0.02* Between groups А and В. Point “1”–at the time of inclusion in the study; point “2”–at the time of the last examination.On average,values of FVC and DLC remained stable.None of the pts with improvement of HRCT showed a deterioration of FVC.Among pts with the X-ray picture deterioration,in 2 cases,there was a decrease in FVC by 5% or more;in other cases,indicator stabilized.The mean CT score did not change during the therapy.In group B,the total CT score and the average score of ground-glass,reticular changes,and traction bronchiectasis were significantly higher.Changes by type of “honeycombs” were mainly revealed in group B.During the IST,positive X-ray was detected in 6(42.9%) pts of group A, in 7(30.4%) pts of group B(p=0.06),and negative X-ray dynamics–in 4(17.4%) pts of group A, in 5(35.7%) pts of group B(p>0.05).During the IST,the mean values of DLC and FVC did not significantly change in both groups.ConclusionSemi-quantitative evaluation according to HRCT in pts with SSc-ILD did not reveal any dynamics in the total score of structural changes during IST,which coincided with stable indices of PFTs.Pts with less common pulmonary involvement during therapy were more likely to demonstrate positive CT-dynamics. With an increase in the prevalence of ILD,signs of fibrosis increased.Most pts had unidirectional dynamics of values of FVC and CT-changes,which confirmed the possibility of effective use of HRCT to assess the conducted therapy.Disclosure of InterestsNone declared

BackgroundRituximab (RTX) has shown itself as an effective option in treatment of interstitial lung disease associated with systemic sclerosis (ILD-SSc). However, there is not enough data on the effect of rituximab biosimilars in patients (pts) with SSc. Biosimilars could reduce price and increase pts access to expensive, but more efficient biologic therapy. The RTX biosimilar Acellbia (ACB) was registered in Russian Federation for all indications consistent with RTX.ObjectivesTo study changes of lung function and skin fibrosis in pts with ILD-SSc on ACB therapy in comparison with original RTX (Mabthera (MBT) during 1 year of follow-up.MethodsThis prospective study included 62 pts received RTX as an addition to previous therapy, when it was ineffective. The mean follow-up period was 12.9±2.2 months. 31 pts received MBT (group 1) and 31 pts received ACB (group 2). All pts had ILD. In group 1 the mean age was 42.2±12.3 years, female-25 pts (81%), the diffuse cutaneous subset of the disease had 21 pts (68%). The mean disease duration was 5.3±3.5years. 91% of pts were positive for ANA and 77% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 11.2±3.9 mg/day, immunosupressants (IS) at inclusion received 39% of them. The cumulative mean dose of RTX was 1.5±0.5g. In group 2 the mean age was 48.7±11.3 years, female-23 pts (74%), the diffuse cutaneous subset of the disease had 16 pts (52%). The mean disease duration was 6.2±7.1years. 88% of pts were positive for ANA, 36% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 10.6±4.5mg/day, IS at inclusion received 42% of them. The cumulative mean dose of RTX was 1.4±0.5g. The results are presented in the form of mean values and standard deviations, delta(Δ)-difference between the baseline parameter and follow up point, median, lower quartile and upper quartile.ResultsThere was an improvement of all evaluated parameters in both groups: decrease of Rodnan skin score (mRSS) and activity index(EScSG-AI), increase of forced vital capacity % predicted (FVC), diffusion capacity for carbon monoxide % predicted (DLCO) and 6-minute walk distance (Table 1). Both groups managed to reduce the mean dose of prednisolone. B-lymphocyte depletion persisted in both groups. When we compared changes (Δ) of the parameters between groups - no significant difference was obtained (Table 1).Table 1.Changes of the main parameters at RXT therapy in delta (Δ); median; lower quartile; upper quartile.ParametersGroup 1Pfor Group 1 (between baseline and follow-up point)Group 2Pfor Group 2 (between baseline and follow-up point)Pbetween group 1 and 2Δ mRSS4.7±5.6[2; 0; 10]0.00014.3±4.1[3; 0; 8]0.0001NSΔ FVC, % pred4.9±5.6[5.8; 1.8; 7.8]0.00014.7±5.5[3.1; 0.9; 7]0.0002NSΔ DLCO, % pred2.3±5.1[1.4; -0.6; 5.5]0.032.5±3.8[2; 0.8; 4.9]0.001NSΔ Activity Index (EScSG-AI)2±1.9[2; 0; 3.5]0.00011.8±1.5[2; 1; 2]0.0001NSΔ B-lymphocyte, absolute count0,221±0,16[0.185; 0.09; 0.33]0.00010,216±0,17[0.135; 0.09; 0.34]0.0001NSΔ 6-minute walk distance, m60.4±67.5[42.5; 10; 91]0.00855.1±42.6[52.5; 13; 90]0.0003NSΔ Prednisolone, mg/day2.03±2.1[2.5; 0; 5]0.00062.1±2.7[2.5; 0; 5]0.0004NSCumulative mean dose of RTX, g, M±σ1.5±0.5-1.4±0.5-NSConclusionOur prospective study showed the similar effectiveness of АСB in comparison with MBT in ILD-SSc. There was a significant improvement of lung function tests and decrease of skin fibrosis. RTX has been shown the positive effect even at low doses (less than 2 g). ACB has shown a good efficacy for therapy ILD-SSc, but studies with a large number of patients are required.Disclosure of InterestsNone declared

BackgroundRituximab (RTX) is considered as one of the effective options for the treatment of interstitial lung disease associated with systemic sclerosis (ILD-SSc) [1]. Factors that affect the effect of RTX therapy are not well investigated.ObjectivesTo evaluate associations of clinical parameters of the disease with response to RTX therapy in patients with ILD-SSc.MethodsThis prospective study included 102 patients with ILD- SSc, 86 (84%) of them were women. The mean age was 47.6±12.9 years, mean disease duration 6.2±5.5 years. The mean follow-up period was 12.9±2.1 months. The diffuse cutaneous subset of the disease had 55 pts (54%). 69 (68%) pts were positive for antitopoisomerase-1 antibody (anti-Topo-1). All pts received prednisolone at a dose of 11.3±4.5 mg/day. 49 (68%) subjects were exposed to immunosupressants (IS) at baseline. Subjects were categorized as having improvement if baseline forced vital capacity (FVC % predicted) increased by > 5% [2]. Stabilization was defined as a change in FVC of < 5 % and a decrease of > 5% in FVC as worsened ILD-SSc. Out of the 102 patients who started treatment with RTM, 46 pts (45%, group I) fulfilled the improvement criteria during follow-up. A total of 34 patients (33%) stabilized and 21 (20%,, group 2) worsened during follow-up. We compared patients of groups 1 and 2 and performed the statistical analysis, including the linear regression analysis.ResultsFor the age, baseline diffusing capacity for carbon monoxide (DLCO % of predicted), anti-Topo-1 level, activity index (EScSG-AI) and mean dose of prednisolone there were no differences (all p > 0.05) between the two groups. There was a significant differences between the different response groups in a higher percentage of men (13% in group 1 vs 27% in group 2), patients with a limited form of the disease (40 vs 55%), an initially lower Rodnan skin score (median 10 (4;16) and 6 (4;9) and with ΔmRss of 0 (-1; 2) and 2 (0; 8), р=0,02), lower frequency of anti-Topo-1 (50 vs. 74%) and a higher frequency of prescribing IS before inclusion in the study (68 vs. 38%). Worsened pts initially had a higher FVC (88.8±18.1 vs 74.1±19.8, p=0.01) and DLCO (53.6±19.3 vs. 46.8±17.2, p>0.05), but received the lowest cumulative mean dose of RTX (1.2±0.5 vs 1.9±0.6, p=0.001). The linear regression analysis revealed a number of parameters associated with worsening of FVC (with a sensitivity of 75% and a specificity of 91%). These parameters included a limited subset of the disease (odds ratio (OR) 6.374, 0.83-48.8, p=0.068), increased activity index (OR 2.04, 0.19-4.18, p=0.046) and the presence of arthritis (OR 1.39, 0.08-23.19, p=0.82) at the end of the study. The risk of worsening of FVC was associated with an initially elevated level of creatine phosphokinase (OR 1.02, 0.1-0.84, p=0.054) and a decrease of glomerular filtration rate according to EPI (OR = 1.075,1.0-1.14, p=0.022). In patients initially receiving IS, the OR was 9.85, 1.154-84.066, p=0.033). The highest OR =19.6 (2.4; 156, p=0.005)] was associated with the cumulative mean dose of RTX.ConclusionIn this study 45% of the pts improved, one third stabilized, and one fifth worsened over a one-year period. On multivariate analysis, limited scleroderma subsets (dcSSc vs lcSSc), increased activity index, the presence of arthritis at the end of the study, cumulative mean dose of RTX (References[1]Fernández-Codina A, et.al. Arthritis Rheumatol.2018;70:1820-182[2]Kafaja S, et.al. Am J Respir Crit Care Med. 2018 Mar 1;197(5):644-652Disclosure of InterestsLidia P. Ananyeva Speakers bureau: Yes, Consultant of: Yes, Grant/research support from: Yes, Liudmila Garzanova Speakers bureau: Yes, Svetlana Glukhova: None declared, Oxana Desinova Speakers bureau: Yes, Consultant of: Yes, Olga Koneva Speakers bureau: Yes, Consultant of: Yes, Grant/research support from: Yes, Mayya Starovoytova Speakers bureau: Yes, Paid instructor for: Yes, Consultant of: Yes, Rushana Shayakhmetova: None declared, Olga Ovsyannikova: None declared

BackgroundInterstitial lung disease (ILD) is one of the most common and severe manifestations of connective tissue diseases, such as systemic scleroderma (SSc), dermato- and polymyositis (DM/PM), mixed connective tissue disease (MCTD), etc.ObjectivesTo compare the course and outcomes of ILD in SSD, MCTD and DM/PM, immunoinflammatory myopathies (IIM) after three years of follow-up.MethodsThe SSc group consisted of 82 patients, the IIM group – 61 patients, and the MCTD group – 20 patients. In all the studied groups, women predominated. The oldest patients were found in the IIM group, and the average age was 51±12.88 years. The duration of the disease varied from 0.5 to 18.5 years. A longer course of the disease was observed among patients with MCTD, the median was 10.6 (6.9; 18.5) years. When assessing the initial parameters of lung function tests, significantly lower values of FVC and DCL were recorded in the IIM group (on average, 82±21.5 and 51.1±16.2, respectively), and higher values in the MCTD group (95.4± 20 and 67.5±15). All patients took GCs, the highest doses were taken by patients with IIM. The great majority of patients received immunosuppressants, of which 100% of patients were in the MCTD group.ResultsDespite the fact that the indices of FVC and DСL in the SSc group were initially lower (on average 91.8±19.1 and 59.2±19.5, respectively) than in the MCTD group. The dynamics of Δ FVC over three years against the background of ongoing therapy was discordant: Δ FVC in the SSc group significantly increased [0.6 (-8; 4.9)], in the MCTD group, it decreased [-5.7 (-10.3; 10.9)]. The mean value of DCL over the follow-up period remained practically the same; the dynamics between the groups was also discordant: it slightly increased in patients with SSc [1.1 (-3.8; 4.6)] and decreased in patients with MCTD [-1.6 (-11.2; 12.6)]. FEV1 decreased in both SSD and MCTD groups, but the alterations were not significant.In the group of patients with IIM during the follow-up period, there was a significant increase in the mean values of Δ DCL, FVC and FEV1 [9.8 (4-16), 13.9 (3.2-28.5), 10.2 (2-26.8)].ConclusionTherefore, due to the study, positive dynamics in lung function in patients with ILD was noticed in the IIM group, stabilization of the pathological process and the absence of progression in the SSc group were achieved, and, despite the initially higher values of FVC and DCL, negative dynamics was detected in the group of patients with MCTD. It is likely that the positive dynamics of lung function in patients with IIM is due not only to an improvement in the condition of the lungs, but also to an increase in muscle strength. A peculiarity of the group of patients with IIM is the high frequency of intake of rituximab in this group (40 patients).Disclosure of InterestsNone declared

BackgroundImmunosuppressants (IS) is considered as a drug of choice for the treatment of interstitial lung disease (ILD) in the patients with systemic sclerosis (SSc). However, the IS use leads to rather limited and transient improvement of the pulmonary fibrosis. In this context the search for novel, more efficacious agents have been continued, such as attracting much attention rituximab (RTM).ObjectivesTo compare the dynamics of pulmonary function parameters and skin fibrosis in patients with SSc associated with ILD, who received RTM and IS for 3 years in real clinical practice.Methods158 pts with the SSс-ILD were enrolled into the study. All pts received low- and moderate-dose glucocorticoids regimens. Group A (n=100) received IS’s (31/31% mycophenolate mofetil, 27/27% cyclophosphamide, 15/15% methotrexate; 27/27% other drugs; the patient’s average age was 49.5±12.2 years, with female proportion 87%; SSc duration 8.6±7.2 years; diffused/localized forms 1/ 2.8). Group B (n=58) received RTM a total dose 3.0±1.2 g, 22 patients received RTM in combination with ISs (11/19% mycophenolate mofetil, 11/19% cyclophosphamide; average age 48.0±13.2 years, female proportion 86%, SSc duration 6.4±4.9 years, diffused/localized forms 1.5/1). The therapy duration in both groups was 36 months. The time courses of forced vital capacity (FVC), diffusive lung capacity (DLC), modified skin count (mRss, points), activity index (EScSG, points), HAQ were assessed in the study.ResultsIn Groups A and B the therapy was associated with significant decrease in mRss and stabilization of the diffusive lung capacity. During the follow-up period in Groups A no change of the other studied parameters was observed.In Groups B the therapy was associated with significant decrease in HAQ and EScSG.Evaluation of FVC time course in Group B revealed significant FVC increase with median increment about 5.6%. In Group B 10% FVC increase was found in the third of the patients thus exceeding respective parameter in Group B (16%). The patient percentage with FVC decrease by ≥10% in group B was less common compared to group A.During RTM therapy it was possible to significantly reduce the dose of glucocorticoids.RTM and immunosuppressants administration for 36 months in the patients with SSc and ILD effectively alleviated skin induration and stabilized DLCO.Table 1.ParametersGroup Аn=100Group Вn=58рFVC1 M ± SD95.2±17.0Р=0.376.8±20.7P=0.0003FVC1 M ± SD96.5±18.983.8±22.2Δ FVC %, SD’S [25%’S; 75%’S]-0.7 [-5.8; 7,9]5.6 [-1.9;14.8]0.008DLCO 1, M ± SD62.6±19.9Р=0.0846.4±18.3P=0.6DLCO 2, M ± SD60.1±17.447.1±17.6Δ DLCO %-1.7 [-5.9;3.3]1.25 [-4; 7.05]0.15mRss, 1 M ± SD5.6±5.3P=0.00311.3±10.2P=0.000013mRss, 2 M ± SD4.3±3.75.5±4.8Δ mRss, SD’S [25%’S; 75%’S]0 [-2;0]-3 [-11;0]0.000031HAQ10.86±0.5P=0.91.14±0.8P=0.01HAQ20.86±0.60.9±0.8EScSG 1, M ± SD1.64±1.2P=0.42.6±P=0.0005EScSG 2,M ± SD1.8±1.31.4±Dose of glucocorticoids 1, mg8.8±4.8P=0.1611.4±4.0P=0.002Dose of glucocorticoids 2, mg8.1±3.79.1±2.9FVC increment by ≥10%, n/%16/1617/29.30.04FVC decrement by ≥10% n/%14/144/6.70.18DLCO increment by ≥10%, n/%6/65/8.60.5DLCO decrement by ≥10% n/%14/145/8.60.31 = before treatment, 2 = after treatment; M ± SD = mean value and standard deviation; * = significant difference between the vales measured before and after the treatmentConclusionOnly RTM significantly improved FVC and the patient’s quality of life and decreased of the activity index. RTM demonstrated a steroid-saving effect. The study findings substantiate potential use of RTM as a first-line agent for the treatment ILD progressive phenotype in SSc. The immunosuppressants use as a single-agent therapy is more preferable in patients with less pronounced ILD.Disclosure of InterestsNone declared

BackgroundDecrease of immunoglobulin G (IgG) could often be observed during rutuximab (RTX) therapy in systemic sclerosis (SSc) and other autoimmune diseases. Lower lever of IgG could be associated with an increased risk of secondary infectious complications. However, there are very few data on changes of IgG in SSc during long-term RTX therapy.ObjectivesTo evaluate changes of Ig G and the frequency of infectious adverse events (AE) in SSc patients (pts) on RTX therapy during long-term follow-up.MethodsOur prospective study included 78 pts with SSc received RTX therapy. The mean follow-up period was 50.2±23 months. The mean age was 48.2±13.7 years, female-64 pts (82%), the diffuse cutaneous subset of the disease had 48 pts (62%), limited - 24 (31%), overlap - 6 (7%). The mean disease duration was 5.4±3.4 years. 92% of pts were positive for ANA and 71% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 11.8±4.1 mg/day, immunosupressants at inclusion received 40% of them. The IgG was evaluated over the periods: at baseline (point 0), 12-18 mo (point 1), 24-60 mo (point 2) and 66-84 mo (point 3) after initiation of RTX therapy. IgG levels was measured using ELISA. Normal IgG reference values ranged within 7.0-16.0 g/l. AE were assessed and recorded by a physician at a hospital immediately after the infusion of RTX, then by patient reported outcome during the observation period. Severe AE were defined as those that required hospitalization for more than 24 hours and life-threatening situations. The results are presented in the form of mean values and standard deviations.ResultsThere was a significant decrease of IgG during RTX therapy (Table 1). However, the level of IgG remained within normal limits. Initially lower level of IgG had 6 pts (8%). And further at point 1 there was 12 pts (15%) with decrease of IgG below normal limits, at point 2 - 12 pts (15%) and at point 3 - 5 pts (6%). When we compared the level of IgG between point 2 and 3 - no significant differences were found.Table 1.Changes of IgG level during RTX treatment.ParametersPoint 0 (n=78)Point 1(n=78)Point 2(n=76)Point 3(n=27)PPoint 0-1PPoint 0-2PPoint 0-3IgG, g/l, M±σ12.3±4.210.6±3.49.6±2.89.6±2.60.00010.00010.01Cumulative mean dose of RTX, g, M±σ-1.8±0.53.9±1.34.8±2.1---AE was evaluated over the period of 335.4 patient-years (PY). Infectious AE were reported in 34 patients (44%), the overall frequency was 10.2/100 PY (95% Confidence Interval (CI) 7.1-13.8). No serious opportunistic infections were reported. The highest frequency of infectious AE was observed in the first 2-6 months after the first infusion of RTX, however these were mainly mild AE (82%). The frequency of serious infections was 1.8/100 PY (95% CI 0.7-3.8). There was a decrease of infectious AE in the follow-up period (4.4/100 PY, 95% CI 2.5-7.2 – at period from 24 month of RTX therapy).ConclusionIn our study, a significant decrease of IgG was noted in SSc pts during the first 5 years of RTX therapy, but later its level stabilized and remained within normal limits. A decrease of IgG in the first year after the initiation of RTX therapy was accompanied by an increase in the frequency of infectious AE. However, with an increase of the cumulative dose of RTX, there was no increase in infectious AE. Monitoring of IgG levels may be useful for SSc pts on RTX therapy for early identification of the risk for developing infectious complications.Disclosure of InterestsNone declared

BackgroundSystemic sclerosis (SSc) is a complex disease having an incidence of 1-2 cases per 100,000. In SSc, inflammation leads to organ failure due to severe fibrosis of the skin and internal organs. At late stages, this disease is characterized by a profound decline in the quality of life and premature death [1]. The course of SSc is often one of progressive damage to multiple organs including the skin, joints, heart, lungs, gastrointestinal tract and kidneys. The scleroderma clinical trials consortium damage index (SCTC-DI): a new instrument to quantify organ damage in systemic sclerosis [2].ObjectivesTo use the scleroderma clinical trials consortium damage index (SCTC-DI) for pts with systemic sclerosis and highlight pts with different disease severity in Russian cohort patients.MethodsData from 96 patients with systemic sclerosis (mean age was 51,3±12,2; 63% have limited subset of the disease; 88% were female) all fulfilling the ACR criteria for SSc. Functional lung tests, high-resolution CT (HRCT), echocardiography, SSc activity (by the European Scleroderma Study Group (EScSG) activity index), HAQ, SHAQ, the six minute walk test (6MWT), scleroderma clinical trials consortium damage index (SCTC-DI) were evaluated. Total scores of SCTC-DI were categorized into groups (low damage scoreResultspts were divided into 3 groups in depend on total score of SCTC-DI. 77pts (80%) were into group 1 (with low damage score); 17 pts (18%) were into group 2 (with moderate damage score) and 2 pts (2%) were into group 3 (with high damage score). Baseline characteristics of the groups are presented in Table 1Table 1.parametersGroup1(n=77) (M±SD)Group2 (n=17)(M±SD)Group3 (n=2)(M±SD)PAge (months)51.7±12.354.1±12.247±11.3>0.05SSc formsLim43 (55%)12 (70%)1 (50%)>0.05Gender: fem69 (88%)14 (82%)2 (100%)Duration of dis.(years)8.9±7.612.4±7.115±7>0.05HAQ0.83±0.681.14±0.6531.62>0.05SHAQ1.174±0.7041.3±0.761.5>0.056MWT412±170358±187108>0.05EScSG1.81±1.442.14±1.440.5>0.05hsCRPMED[25;75‰]6.63±14.82.93 [1.2;5.62]3.7±2.5720.7±18.1>0.05ESRMED[25;75‰]16.7±21.412 [7;19]20±31.614 [12;23]71.5±92.6.871.5 [6;137]>0.05PAP34.7±10.838±13.140±19.75>0.05Left ventriculi infection fraction69.9±7.366.7±5.764.5±3.5>0.05FVC97.3±14.6864.7±17.343.3±5.8Gr1 vsGr2Gr1vs Gr3pDLco60.9±1636.4±9.5.344.3Gr1 vsGr2pFEV196.8±14.966.3±20.146.7±7.2Gr1 vsGr2Gr1vs Gr3pWe didn’t find a lot of significant differences in between groups, but it could be noted that group 3 was younger and the severity of the parameters increased in groups moderate and high damage. We found that mean value of FVC, DLco and FEV1 were significant increased in group1.Conclusionthe pts with moderate and high damage scores of SCTC-DI had worse clinical and instrumental characteristics than pts with low damage score. We could try to use scores of SCTC-DI as measures of SSc severity.References[1]Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med (2009) 360(19):1989–2003. 10.1056/NEJMra0806188[2]Ferdowsi N, Huq M, et al. Development and validation of the Scleroderma Clinical Trial Consortium Damage index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis. Ann Rheum Dis 2019;0:1–10. doi:10.1136/annrheumdis-2018-214764.Disclosure of InterestsNone declared

BackgroundHRCT is the gold standard for confirming the presence of ILD. According to the literature data,there is an association between the prevalence of pulmonary involvement and the severity of PFTs.However,it remains unclear whether the nature of interstitial changes affects the degree of PFTs.ObjectivesTo study the clinical significance of various X-ray symptoms in SSc-ILD during long-term follow-up.MethodsThe study included 37 pts with a SSc-ILD(average age-53.1±11.5 yrs, m/w- ¼, and d/l–1/1.8, SSc duration-10.9±9 yrs).For all pts at the time of inclusion in the study and after an average of 34±2.3 months,there were examined FVC,DLC,HRCT.All pts received immunosuppressive therapy(IST). The analysis of HRCT data was conducted at 5 levels.The severity of changes by type of ground-glass,reticular changes,traction bronchiectases,and honeycombs were evaluated(0–3 points).The dynamics of X-ray changes and PFTs was assessed in the general group and in pts with the prevalence of ILD up to 20%(group A,n=23) and more than 20%(group B, n=14).ResultsAt the time of inclusion in the study,the total CT score of ILD on average for the group was 9.6±8.2.FVC was normal(94±19.5%);a moderate decrease in DLC was detected(57.3±20.2%).The prevalence of ILD significantly correlated only with the DLC(R=-0.35, pWhen included in the study,reticular changes were most often observed(the score was 4.6±3.5).Alterations by type of ground-glass were somewhat less common(the score was 3.2±3.1).The score of traction bronchiectases was 1.68±2.3.Changes by type of honeycombs were found in only 5 patients,of which only 1 patient was from the group A.Against the background of IST,values of FVC and DLC remained stable in the group as well as in the groups A and B,and the total CT score did not change.In patients of the group B,both the total CT score and the average score of ground-glass and reticular changes,and traction bronchiectases score were significantly higher.To assess the clinical significance of various X-ray symptoms,a correlation analysis of the total score of each of them with the PFTs data in groups A and B was executed.Table 1.Correlation DLC with CT scoreGroup AGroup BpDLCCT scoreRDLCCT scoreRDLC1 with total CT score 160.6±19.64.5±4.4-0.547.6±11.418.1±5.6-0.35DLC2 with total CT score 262.6±19.14.1±3.9-0.5745.2±13.518.1±6.1-0.47DLC1 with reticular changes score 160.6±19.62.6±2.4-0.4447.6±11.47.9±2.4-0.43DLC2 with reticular changes score 262.6±19.12.7±2.3-0.4645.2±13.57.6±1.98-0.51DLC1 with bronchiectases score 160.6±19.60.5±1.2 (median-0 [0;0])-0.5447.6±11.47.8±2.0-0.49DLC2 with bronchiectases score 262.6±19.10.7±1.3(median-0 [0;1])-0.645.2±13.57.6±2.0-0.56DLC1 with honeycomb score 1-47.6±11.41.3±2.3 (median-0 [0;1])-0.34DLC2 with honeycomb score 2-45.2±13.51.7±3.3(median-0 [0;1])-0.34“1”–at the time of inclusion in the study “2”–at the time of the last examination.No significant correlation between the score of X-ray signs and values of FVC was detected. DLC significantly inversely correlated with the total score of each HRCT symptom, with the exception of ground-glass.At the same time,strength of the correlation was approximately the same for reticular changes, bronchiectases, and honeycombs in both groups.ConclusionThe severity of the alveolar-capillary membrane functional disorders is primarily due to the prevalence of fibrotic changes.The variant of fibrotic changes has no significant importance.Changes by type of ground-glass to a lesser extent affect the degree of reduction in DLC.The best surrogate indicator reflecting the prevalence of interstitial changes was DLC.Disclosure of InterestsNone declared

BackgroundNowadays ILD is one of the most common manifestations of systemic rheumatic diseases and one of the leading cause of death of patients.ObjectivesTo assess the course and outcomes of interstitial lung disease (ILD) in mixed connective tissue disease (MCTD) based on lung function after three years of follow-up.MethodsThe study included 20 patients with MCTD associated with ILD. The diagnosis was set according to Kasukawa criteria (1987). There were 19 (95%) women and 1 (5%) men; average age was 44.73±15.26 years; mean disease duration was 13.7±9 years. All patients took glucocorticoids (GCs) and immunosuppressants (IS); the average dose of prednisone was 10.2±5mg. To identify and assess the dynamics of ILD, there was used high-resolution computed tomography (HRCT). Their lung function was assessed by data obtained due to spirometry (in particular, forced vital capacity, FVC) and diffusing capacity of the lungs (DCL); Doppler echocardiography was also conducted.ResultsIn the group of patients with MCTD there was a chronic course of the disease with a gradual addition of symptoms, musculoskeletal pathology prevailed. After three-year follow-up period there was a decrease in clinical manifestations (arthritis, myositis, proximal muscle weakness). Functional capacities of the lungs and heart did not deteriorate. DCL remained stable 67.5±15 and 66.9±13.8, respectively. Systolic pulmonary artery pressure also remained stable (31.4±4.5 and 32.8±5.2, respectively), indirectly indicating the absence of progression in pulmonary involvement. These positive alterations were the basis for reducing the daily dose of GCs in some patients. The reduction in dose of GCs was small but statistically significant (8.64±4.58 and 7.86±3.33, respectively, p=0.007). There was a trend towards a decrease in dose of prednisone (from 10.2±5 to 8±4,5, respectively). However, these data were not clinically significant.ConclusionDue to the study,there were no significant changes in the main indicators in patients with MCTD. All indicators remained stable, indicating the absence of clinically significant progression of lung damage on the background of therapy with GCs and IS. There was no significant change in the daily dose of GCs, but there was a decreasetendencyDisclosure of InterestsNone declared

BackgroundSystemic sclerosis (SSc) is a multiorgan disease wherein the pathogenic processes of inflammation, vasculopathy and fibrosis lead to multiple disease manifestations. The course of SSc is often one of progressive damage to multiple organs including the skin, joints, heart, lungs, gastrointestinal tract and kidneys. The scleroderma clinical trials consortium damage index (SCTC-DI): a new instrument to quantify organ damage in systemic sclerosis [1].ObjectivesTo assess the scleroderma clinical trials consortium damage index (SCTC-DI) in patients with systemic sclerosis in Russian cohort patients.MethodsData from 104 patients with systemic sclerosis (mean age was 51,7±12,5;64% have limited subset of the disease; 88% were female) all fulfilling the ACR criteria for SSc. Functional lung tests, high-resolution CT (HRCT), echocardiography, SSc activity (by the European Scleroderma Study Group (EScSG) activity index), HAQ, SHAQ, the six minute walk test (6MWT), scleroderma clinical trials consortium damage index (SCTC-DI) were evaluated. Other data collected including biological results (high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR). Statistical analysis: descriptive data are presented as means (±SD) or medians (with interquartile range [IQR]) for continuous variables, while categorical variables are expressed as counts and percentages. Univariate comparisons were made with 2-sample t tests. we used the Spearman’s rank-order (Spearman’s p) correlations coefficients.ResultsA significant positive correlations were found between the SCTC-DI values and HAQ (r=0.31, p=0.003), SHAQ (r=0.28, p=0.0087), and values of EScSG activity index (r=0.31, p=0.0066) accordingly. The SCTC-DI values inversely correlated to values of 6MWT (r=-0.246, p=0.003). Moreover, the SCTC-DI values correlated inversely with forced vital capacity (r=-0.543, p0.05). Also we didn’t find any correlations the SCTC-DI values with ESR levels and hsCRP levels (r=0.18, p>0.05 and r=0.15, p>0.05).Conclusionthe SCTC-DI values correlate with dates of HAQ, SHAQ, EScSG activity index, values of 6MWT pulmonary function tests, supporting their use as measures of SSc severity.References[1]Ferdowsi N, Huq M, et al. Development and validation of the Scleroderma Clinical Trial Consortium Damage index (SCTC-DI): a novel instrument to quantify organ damage in systemic sclerosis. Ann Rheum Dis 2019;0:1–10. doi:10.1136/annrheumdis-2018-214764.Disclosure of InterestsNone declared

BackgroundNowadays, there is already published a lot of data on the treatment of systemic sclerosis (SSc) with rituximab (RTX). Recent studies reported about improvement of skin fibrosis and interstitial lung disease associated with SSc (ILD-SSc) on RTX treatment. However, there is not enough data on changes of pulmonary artery systolic pressure (PASP) in SSc patients (pts) on RTX therapy.ObjectivesTo evaluate changes of PASP in ILD-SSc pts on RTX therapy.Methods30 pts with initially elevated PASP (detected as ≥35mmHg by echocardiography) were retrospectively selected from a group of 103 SSc pts who received RTX as a therapy for ILD. The mean follow-up period was 25.3±2.4 months. The mean age was 52.6 years (30-65), female-26 pts (87%), the diffuse cutaneous subset of the disease had 13 pts (43%). The mean disease duration was 7.2±6.3 years. The cumulative mean dose of RTX was 2.3±1.1 grams. All pts received prednisolone at a dose of 11.3±3.7mg/day, immunosuppressants received 47% of them. All pts were positive for ANA. An assessment of basic parameters was obtained at baseline (Point 0), after 13.6±2.7 months (Point 1) and at the end of follow-up (25.3±2.4 months - Point 2). The results at baseline and at the end of the follow-up are presented in the form of mean values.ResultsThere was already an improvement of all main parameters at the point 1 and further - by the end of follow-up (Table 1). There was a significant decrease in PASP, which was accompanied by the improvement of lung function - increase in forced vital capacity % predicted (FVC), stabilization of diffusion capacity for carbon monoxide % predicted (DLCO). A moderate negative statistically significant correlation was found between the PASP and FVC (r=-0,522; p=0,003). There was a significant increase in 6-minute walk distance (6-mwd), ejection fraction of left ventricular (ER), activity index (EScSG-AI) and a decrease of Rodnan skin score.Table 1.Changes of the main parameters on RTX treatment.ParametersPoint 0 (baseline)Point 1 (13.6±2.7 month)Point 2 (25.6±2.4 month)P Point 0-1P Point 0-2FVC, %, M±σ75.6±20.182.5±19.288.2±22.50.010.002PASP, mmHg, M±σ48.2±13.844.4±12.339.5±11.80.0080.004DLCO, %, M±σ42.7±16.242.6±15.244.9±15.6NSNSER, %, M±σ61.6±5.563.5±6.265.8±5.70.020.01Rodnan skin score, M±σ11.1±12.47.2±8.16.1±7.60.0030.00016-mwd, m, M±σ419.6±103453.8±85458.8±78.40.020.02Activity index (EScSG-AI), M±σ3.3±1.51.5±1.31.4±1.10.0010.001Cumulative mean dose of RTX, g, M±σ-1.65±0.692.3±1.1--ConclusionIn our study, the PASP significantly decreased already in a year after initiation of RTX therapy and further there was an improvement of this parameter at the end of the observation. Decrease of PASP correlated with an increase of FVC and was accompanied by an increase of 6-minute walk distance, ejection fraction of left ventricular, improvement of Rodnan skin score and disease activity index. RTX could be considered as a potentially effective in combined treatment of ILD-SSc, complicated with pulmonary hypertension.Disclosure of InterestsNone declared

BackgroundSystemic Sclerosis-polymyositis/dermatomyositis overlap syndrome (SSc-PM/DM) occurs in 10 to 37% of cases and has great differential diagnostic difficulties. Muscle damage in SSc-PM/DM is represented by myositis with primary inflammatory and necrotic alterations in muscle fibers by type of PM/DM.ObjectivesTo evaluate joint and muscle damage in patients with SSc-PM/DM.Methods112 pts had idiopathic inflammatory myopathies, of which 73 pts with SSc-PM/DM (51 pts with lSSc and 22 pts with dSSc, male/female 24/49, mean age 44±14,5 years, average disease’s duration 7 (2;9) years) had the standard clinical examination, intramuscular electromyography (IM-EMG) and manual muscle testing (MMT-8).ResultsAll pts had polyarthralgia, 40% pts - arthritis. Damage to periarticular tissues with the formation of flexion contractures was observed in 70% pts, of which 16% - contractures of large joints (knee and elbow). X-ray changes in the hands and feet (distal osteoporosis, narrowing of the joint spaces, and smoothness of the phalangettes) were observed in all pts, 13% of pts had erosions associated with osteoarthritis. There was noticed significantly frequent development of flexion contractures in pts with dSSc (pConclusionMuscular syndrome in SSc-PM/DM has clear clinical symptoms, and the underlying symptom of involvement is sharp muscle weakness with movement disorders intrinsic to PM/DM. However, such disorders do not lead to complete immobility, as in PM/DM, and they are combined with other manifestations of SSc. Articular syndrome in pts with SSc-PM/DM is mainly represented by periarticular changes, in some pts with osteolysis and calcinosis common to SSc.Disclosure of InterestsNone declared

BackgroundInterstitial lung disease (ILD) is the most common internal organ manifestation of idiopathic inflammatory myopathies (IIM) that can severely affect the course of the disease.ObjectivesTo describe lung functions in IIM patients with ILD during ≥ 3 year of follow-up.MethodsOur prospective study included 44 pts with IIM fulfilling Bohan and Peter criteria and having ILD. The mean follow-up period was 46.2±11.2 months. The mean age was 52.3±11.7 years, 34 (77.3%) pts were female. The median disease duration was 1.125 [0.16-18] years, 24 (54%) of pts were positive for a-Jо-1 antibody. All pts had the standard examination including anti-Jo-1 antibodies (anti-Jo-1) assay; forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) evaluation as well as high-resolution computed tomography (HRCT) scanning of the chest were performed at baseline, and 36 and more months.Results61% with antisynthetase syndrome, 17% dermatomyositis (DM), 5% amyopathic DM, 15% with overlap myositis and 2 % with necrotizing myopathy were included. 70% patients had nonspecific interstitial pneumonia, 23% organizing pneumonia (OP) and 7% OP, transformed to diffuse alveolar damage.All pts received prednisolone at a dose of 11.8±4.1 mg/day, immunosupressants at inclusion received 75% pts: cyclophosphamide 54%, mycophenolate mofetil 16.9% and combination 4.54%; Rituximab was administered in case of intolerance or inadequate response to GC and other immunosuppressive drugs in 37 pts (84%)(1-8 courses). 7 patients died, ILD progression was the cause of death in 4 casesTable 1.Changes of the main parameters at the baseline and in 3 yearsparametersptsbaselinein ≥ 3 yearsрa-Jо-123177.2 ±41.790.5±76.70.000003FVC3783.3±21.796.7±210.0001DLCO %3752.4±14.960.8±17,30.001Prednison, mg/day3723.04±12.85.9±2.30,000000001ConclusionActive immunosuppressive therapy improves lung function in IIM patients. However, some forms of ILD have a fatal course.Disclosure of InterestsNone declared

BackgroundNowadays ILD is one of the most common manifestations of SSc and the leading cause of death of patients. 25% to 30% of patients develop progressive ILD.ObjectivesTo assess the course and outcomes of interstitial lung disease (ILD) in systemic sclerosis (SSc) based on lung function after three years of follow-up.MethodsThe study included 82 patients with SSc associated with ILD. There were 70 (85%) women and 12 (15%) men, whose average age was 49.86±12.30 years, 49 (60%) patients with limited SSc, 24 (29%) patients with diffuse SSD, 7 (9%) patients with overlap syndrome; median disease duration was 7 (4;11) years. The great majority of patients had a chronic course of the disease. The patients had systemic manifestations, vascular disorders and lesions of the musculoskeletal system. According to the results of CT scan of the thoracic organs, 28% of patients had more than 20% of pulmonary involvement. All patients took glucocorticoids (GCs); the average dose of prednisone was 8.6±4.6 mg. 50 (61%) patients took immunosuppressants (IS).The diagnosis was set according to ACR/EULAR criteria. The patients were examined twice in accordance with generally accepted approaches. To identify and assess the dynamics of ILD, there was used high-resolution computed tomography (HRCT) Their lung function was assessed by data obtained due to spirometry (in particular, forced vital capacity, FVC) and diffusing capacity of the lungs (DCL); Doppler echocardiography was also conducted.ResultsIn the group of patients with SSc, a significant improvement was noticed in some indicators demonstrating the peculiar manifestations of the disease. Therefore, skin induration (a decrease in skin score) decreased from the initial 5.8±5.2 to an average of 4.6±3.9 points after three years, p=0.0001. Functional capacities of the lungs and heart did not deteriorate. There was a trend towards an increase in FVC by 5.7% (from 91.8±19.1 to 96.15±18.26, respectively). However, these data were not clinically significant. Systolic pulmonary artery pressure (sPAP) also remained stable, mm Hg (31.83±8.10 and 33.57±9.03, respectively), indirectly indicating the absence of progression in pulmonary involvement. These positive alterations were the basis for reducing the daily dose of GCs in some patients. The reduction in dose of GCs was small but statistically significant (8.64±4.58 and 7.86±3.33, respectively, p=0.007).ConclusionTherefore, due to the study, stabilization of lung function and the absence of progression in the SSc-ILD group were noticed, which emphasizes the importance of continuous monitoring and follow-up of patients and continuation of therapy.Disclosure of InterestsNone declared

BackgroundNailfold capillaroscopy is useful for the diagnosis and follow-up of autoimmune rheumatic diseases.Impaired microcirculation is one of the leading factors in local and general pathogenesis ofSSc. Nail-fold video-capillaroscopy (NFVC) stands as the most informative and atthe same time simple method used for evaluation of capillary circulation.ObjectivesTo identify characteristic and specific for SSc-RA capillaroscopic features.MethodsBoth hand II – V fingers of 32 pts with SSc-RA were subjected to widefield NFC, evaluated using a binocular 20x magnification Olympus microscope and analyzed in view of specific skin lesions discriminating diffuse and limited SSc forms.ResultsSSc-specific dilatations of capillary loops were the most common for SSc-RA and were found in all pts SSc-RA. 1/3 pts had signs of active scleroderma pattern, such as capillary loss or “avascular areas” (37,5%) and hemorrhages (28%). The morphological capillary abnormalities such as varying degrees of capillary loops tortuosity/vascular inhomogeneity were present in 69% of examined nailfolds, branching bushy behavior of capillary loops predominated. Architectural disorientation/disarrangement of capillary loops was seen in 37,5% of them. Mega-capillaries and formation of subcutaneous plexus were presented infrequently in 16%. Ramified/bushy capillaries (pConclusionThus, widefield NFVC revealed a “mixed” nature of capillaroscopic changes, combiningfeatures specific for SSc (capillary dilation, avascular areas, hemorrhages) and for RA (various changes in capillary loops).Disclosure of InterestsNone declared

Background:Although interstitial lung disease (ILD) occurs in the majority of patients with systemic sclerosis (SSc), treatment options for this manifestation is empirical and at present consists of Cyclophosphamide (CyP) or Mycophenolate Mofetil (MMF). However, the immunosuppressants (IS) use leads to rather limited improvement of ILD and is associated with many adverse reactions. The search for novel, more efficacious agents has been continued, such as attracting much attention RTM. However, the limited number of RTM-treated patients, considerably different dose regimens, cumulative doses, and observation periods does not allow univocal conclusions on RTM efficacy or definitive recommendations on RTM use in the patients with SSc.Objectives:To compare the impact of IS and RTM a single-agent therapy on SSc clinical manifestation and activity, and the safety of these agents in the open-label prospective non-randomized study.Methods:116 patients with the confirmed SSc diagnosis and ILD evidence based on MSCT findings were enrolled into the study. All patients received low and moderate-dose glucocorticoids regimens. Group A(n=35) received RTM as a single therapy agent for 13.3±2.3 months at total dose 1.35±0,5g (the patient’s average age was 45.0±15 years, with female proportion 80%; SSc duration 6.3±2.3 years; diffused/localized forms 1.3/1). Group B (n=36) received parenteral CyP for 12±6 months at total dose 10.6±5 g (the average age 47±12 years, females 92%, SSc duration 5.0±4.8 years, diffused/localized forms 1.6/1). Group C (n=45) received MMF for 12±6 months at a dose of 2 grams per day (the average age 49±13 years, females 91%, SSc duration 7.1±5 years, diffused/localized forms 1/1.3). The time courses of FVC, modified skin count (mRss, points), activity index (EScSG, points) were assessed into the study.Results:In Groups A, B and C the therapy was associated with significant decrease in mRss (р=0.02, 0.008, 0.007, respectively) and EScSG (р=0.00017, 0.000165, 0.01, respectively).Evaluation of FVC time course revealed significant FVC increase only in Groups A (р= 0.002) and B (p=0.034), with median increment about 5%.In Groups A and B 10% FVC increase was found in the third of the patients thus exceeding respective parameter twice in Group C (р=0.15 and 0.008, respectively). The patient percentage with FVC decrease by ≥10% did not differ significantly between groups.The therapy was better tolerated in RTM-treated group: during RTM therapy adverse reactions emerged in lower proportion of the patients (4/11%) compared with CyP (19/53%, p=0.0000) and MMF-treated group (12/27%, р=0,5).ParametersGroup АGroup ВGroup СActivity Index 1M ± SD2.8±1.4*3.2±1.9*1.9±1.5*Activity Index 2M ± SD1.4±1.2*1.4±1.2*1.2±0.9*Skin count 1M ± SD11.5±9.5 *11.2±7.9 *7.5±6.9 *Skin count 2M ± SD8.2±6.2 *7.9±6.8 *4.8±3.9 *FVC 1 M ± SD78.7±20.0 *80.5±20.1*90.3±20.8FVC 2 M ± SD84.2±20.0*85.8±20.4*92.2±21.0Δ FVC %5.3[0.8; 11.1]5.7[0; 11.2]1.9[-3.5; 6.0]FVC increment by ≥10%, n/%9/2614/316/13.3FVC decrement by ≥10% n/%2/5.72/4.44/8.9Notes:in Parameters column 1 = before treatment, 2 = after treatment; M ± SD = mean value and standard deviation; * = significant difference between the vales measured before and after the treatmentConclusion:All agents effectively alleviated skin induration and EScSG, but only RTM and CyP significantly improved FVC. The RTM single therapy was better tolerated compared to IS. The study findings substantiate potential use an RTM single therapy both as a first-line agent for ILD treatment in the patients with a progressive course of ILD damage SSc, and in the event of CyP inefficacy of poor tolerability. The MMF use is more preferable in patients with less pronounced ILD.Disclosure of Interests:None declared

Background:A sound experience has been accumulated up to date with the use of rituximab (RTХ) for treatment of systemic sclerosis (SSc). Some studies reported improvement of skin fibrosis following treatment with RTХ, but long-term follow-ups are really few.Objectives:to evaluate the effect of RTХ on the manifestations of skin fibrosis in patients (pts) with SSc in the long-term follow-up.Methods:This prospective study included 71 pts aged 46 years (17-66) on average, 59 (83%) pts were females, mean disease duration was 5,6±4,4 years, and mean follow-up - 42 months (12-72) (mo). Diffuse SSc was established in 42 (59%) pts. All pts received glucocorticoids in low doses. 45% of pts were receiving immunosuppressants at study entry. The following parameters were evaluated: Rodnan skin score (mRSS), interdigital space(IDS) (the distance between the tips of 1 and 5 fingers at maximum extension), oral aperture (OAp) and activity index (EScSG-AI) over the periods: 12-18 mo, 24-30 mo, 36-42 mo, 48-54 mo and 60-72 mo after initiation of RTX therapy. The results are presented as: mean values, delta (Δ), median, upper and lower quartiles.Results:RTX therapy resulted in significant decrease of disease activity index, which statistically significantly correlated with decrease of mRSS - the main indicator of the severity of skin fibrosis (r=0,39;p=0,001). Changes in parameters by follow-up periods are presented in the Table 1.Table 1.Changes in clinical and instrumental parameters at RTX treatment (delta; median; lower quartile; upper quartile).Parameters12-18 mo (n=71)24-30 mo (n=55)36-42 mo (n=36)48-54 mo (n=24)60-72 mo (n=17)ΔmRSS3,32 [3.3; 0; 8]5,4 [3; 0; 10]5,1 [3,5; 0; 9]5,3 [3; 0; 10]7,3 [5; 1; 14]p=0,001p=0,001p=0,001p=0,001p=0,001ΔOAp, cm0,24 [0,1; 0; 0,5]0,26 [0,1; 0; 0,6]0,39 [0,2; 0; 0,8]0,31 [0.3; 0; 0,7]0,36 [0,2; 0; 0,8]p=0,0009p=0,0006p=0,004p=0,006p=0,009ΔActivity index (EScSG-AI)1,49 [1,5; 0; 2,5]1,64 [1,5; 0; 2,5]1,11 [1; 0; 2]2 [2; 1; 3]2,17 [2; 1,5; 2]p=0,001p=0,001p=0,0001p=0,0001p=0,0001Cumulative dose of RTX, g1,43±0,62,97±0,83,45±1,33,96±1,15,15±1,7Decreasing of mRSS statistically significantly correlated with increasing cumulative dose of RTX (r=0,29;p=0,01). Decreasing disease activity index correlated with increasing cumulative dose of RTX (r=-0,37; p=0,01). IDS improvement was documented at all assessment time periods, although statistically insignificant.Conclusion:The results of this study confirm reported positive effect of RTX on the reduction of skin fibrosis in SSc. Long-term follow-up demonstrated steadily decreasing skin fibrosis and improvement of microstomia with increasing oral aperture in parallel with a decrease of the disease activity index and increasing cumulative dose of RTX.Disclosure of Interests:None declared

Background:Rituximab (RTX) is a new option in the treatment of systemic sclerosis (SSc) [1]. There is not enough data on changes in the level of autoantibodies and their clinical significance during RTM therapy. There are only a few reports on the higher efficiency of RTX in patients (pts) with SSc positive for anti-topoisomerase-1 antibodies (a-Topo-1), therefore the study of this issue might be interested.Objectives:To compare clinical parameters and B-lymphocytes (B-lymph) level in SSc pts depending on the presence or absence of a-Topo-1 during RTX therapy with prospective long-term follow-up.Methods:This study included 88 pts with SSc. The mean follow-up period was 26,3±10,7 months. The mean age was 47years (17-71), female-73 pts (83%), the diffuse cutaneous subset of the disease had 50 pts (57%). Symptoms of the interstitial lung disease (ILD) were observed in 70 pts (80%). The mean disease duration was 5,9±4,8 years. The cumulative mean dose of RTX was 2,9±1,1 grams. All patients received prednisone at a dose of 11,7±4,4 mg, immunosuppressants received 42% of them. There were 63 pts positive for a-Topo-1 and 25 pts - negative. The pts of the compared groups did not differ in the main demographic and clinical parameters, excepting lung involvement. In a-Topo-1 positive group 55 (87%) pts had ILD and only 15 (60%) – in a-Topo-1-negative group (p=0,02). The results at baseline and at the end of the follow up are presented in the form of mean values and changes in parameters (delta).Results:Considering the entire cohort, an improvement of almost all outcome parameters was found. When a-Topo-1 positive and a-Topo-1-negative pts were analyzed separately, we observed a significantly higher decrease in the activity score, depletion of B-lymph, an increase in forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) in a-Topo-1 positive group of pts (table 1).Table 1.Changes of the main outcome parameters depending on the presence of a-Topo-1 on RTX therapy.Parametersa-Topo-1positive ptsa-Topo-1negative ptsPDelta Activity score (EScSG-AI)1,790,90,001Delta Rodnan skin score (mRSS)4,95,2NSDelta B-lymphocytes (absolute count)0,2120,1930,001Delta FVC*, %8,646,460,001Delta DLCO**, %2,860,0320,001*FVC - forced vital capacity % predicted, **DLCO - diffusion capacity for carbon monoxide % predictedThe a-Тopo-1 level decreased from 174,2±50,1 to 148,1±66,1 units/ml (p=0,0009). In this group, a-Тopo-1 became negative in 5 pts (7,9%). The disappearance of a-Topo-1 positivity was accompanied by a more pronounced decrease in mRSS (delta mRSS=7,4) and a higher depletion of B-lymph. There was a higher cumulative dose of RTX (4±1,4grams) in this 5 pts compared with the pts who sustained a-Topo-1 positivity. There was a moderate negative statistically significant correlation between the a-Topo-1 and the total dose of RTX (r=-0,298, p=0,017). A moderate negative statistically significant correlation was found between the a-Topo-1 and FVC (r=-0,322, p=0,009).Conclusion:In our study, the a-Topo-1 level significantly decreased during RTX therapy in Russian pts. The decrease in a-Topo-1 titers correlated with the total dose of RTX and was accompanied by a decrease in mRSS, disease activity index and an increase in FVC and DLCO. A higher efficacy of RTX in the a-Topo-1 positive group with prevalence of ILD was revealed, therefore a-Topo-1 positivity could be considered as a predictor of a better response to RTX therapy.References:[1]Jordan S, et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis.2015;74:1188–94.Doi:10.1136/annrheumdis-2013-204522.[2]Ebata S, Yoshizaki A, et.al. Rituximab therapy is more effective than cyclophosphamide therapy for Japanese patients with anti-topoisomerase I-positive systemic sclerosis-associated interstitial lung disease. J Dermatol.2019.Nov;46(11):1006-1013.doi:10.1111/1346-8138.15079.Disclosure of Interests:None declared

Background:Interstitial lung disease associated with systemic sclerosis (ILD-SSc) is a frequent manifestation of the disease, impairing the quality of life and the prognosis of the disease. The efficacy of rituximab (RTX) in patients (pts) with ILD-SSC have been shown [1]. The ‘‘biosimilar’’ versions of RTX might reduce the cost of therapy and increase pts accessibility to this treatment option. The RTX biosimilar Acellbia (ACB), “BIOCAD”, has received approval in Russian Federation in 2014 for all indications held by reference RTX.Objectives:to investigate the efficacy and safety of ACB in naive to biological therapy pts with ILD-SSc during at least 12 month of follow-up.Methods:Twenty pts were included in prospective observational study. The pts were aged 49,7 (s.d.14) years, 14 (70%) were females, mean disease duration was 3,5±2,7years, with diffuse subset in 11 (55%), 13 (65%) were anti-topoisomerase positive, all pts has NSIP-pattern by HRCT. All pts were naive to ACB, received glucocorticoids in low doses, 10 (50%) pts were previously treated with immunosuppressants and 4(20%) of them continued to take mycophenolate mofetil as a concomitant therapy. Pts received two courses of ABC with the same scheme: 1 g repeated 1 week apart (4 g ACB in total). An assessment of basic measurements was obtained at baseline (Point 0), before the second course (after 7,2±1,7 mo, Point 1) and at the end of follow-up (13,4±1,6 mo, Point 2). The results are presented in the form of mean values and standard deviations.Results:We observed a gradual improvement in the main parameters from Point 0 to Point 2 (table). Importantly, that at Point 1 there were no differences in most parameters, except for Rodnan skin score (mRSS) and the absolute number of B-lymphocytes (B-lymph), but at Point 2 there were significant differences between most basic outcome measures.Table 1.Follow-up data of ACB treatment in ILD-SSC ptsParametersPoint 0(n=20)Point 1(n=20)Point 2(n=18)#P 1-2P 1-3mRSS12,75±11,18,25±7,726,16±5,650,0020,002FVC*, % pred89,1±18,292,31±19,2198,26±16,13NS0,0002DLCO**, % pred56,67±15,758,11±17,7161,86±17,16NS0,019SHAQ1,13±0,6280,98±0,6780,61±0,495NS0,00001IgG, g/l12,61±2,34811,5±1,6110,19±2,18NS0,002a-Topo-1, unit/ml109,68±86,9296,46±81,7272,46±69,46NS0,004B-lymph, absolute count0,329±0,340,0016±0,0030,00189±0,0030,00040,001Glucocorticoids, mg/day11,0±2,710,75±2,09,4±2,3NS0,03*FVC - forced vital capacity % predicted, **DLCO - diffusion capacity for carbon monoxide % predicted.# Of the 20 patients who received the second course, 2 (10%) dropped out the follow-up due to pregnancy (1) and lung cancer (1).The frequency and spectrum of adverse events (AE) corresponds to the known in the treatment of RTX, most AEs were classified as mild ones.There were 11 (55%) of AE in 9 (45 %) pts. Infections were observed in 7 (35%) pts: 4 cases of acute respiratory tract infections, 2 cases of positivity in interferon-gamma release assayand one case each of otitis, cystitis, cholecystitis (9 AE in total). One pts developed low limb vein thrombosis and one - lung cancer. There were no infusion-related reactions.Conclusion:The data from this prospective pilot study showed the effectiveness of the АСB in ILD-SSc. The clinical effect of АСB arises gradually and the baseline outcome measures reliably improve by the end of the first year. Our study have demonstrated a well-tolerated safety profile. We believe that ACB can be prescribed at SSc-ILD as a first-line drug and/or in the form of monotherapy.References:[1]Erre G.L., et.al. Efficacy, Safety, and Tolerability of Treatments for Systemic Sclerosis-Related Interstitial Lung Disease: A Systematic Review and Network Meta-Analysis. J.Clin.Med.2020,9,2560;doi:10.3390/jcm90825-60.Disclosure of Interests:None declared

Background:The classification criteria of SSC (EULAR/ACR 2013) compared to the criteria of 1980 showed high sensitivity and allow to detect the full spectrum of systemic sclerosis (SSc). The use of the new criteria led to the fact that some of the patients who were diagnosed with MCTD began to meet the criteria of SSс. Since these patients have hyperproduction of antibodies to RNP, but no other SSc-specific autoantibodies, we believe that they represent a special clinical and immunological phenotype of SSc. Lung involvement in SSc impairеs the quality of life and the prognosis, so the study of interstitial lung disease(ILD)in different phenotypes is relevant.Objectives:To compare the main manifestations of ILD in two groups of patients who meet the classification criteria of SSc 2013 - positive for a-Topo-1 and for a-RNP.Methods:The study included 100 patients. The first group - 50 patients positive for a-Topo-1 (45 women and 5 men, mean age 55±10 years, duration of the disease 10.2±8 years, subset of the disease: diffuse 52%, limited 48%) and the second group - 50 patients positive for a-RNP (43 women and 7 men, mean age 44.5±14 years, duration of the disease 11.7±8 years; form of the disease: diffuse 14%, limited 86). The diagnosis of ILD was established by HRCT.Results:In patients of group I ILD was detected in 94% of cases, in group II - 68% (pTable 1.Data of laboratory and instrumental parametersParametersa-Topo-1- positiven (%)a-RNP-positiven (%)pDecrease of DLCO < 80%49 (98)43 (86)рDLCO 33 (66)16 (32)рDecrease of FVC< 80 %19 (38)10 (20)рFVC13 (26)7 (14)NSGround glass opacity25 (50)26 (52)NSHoneycombing 17 (34)8 (16)рSPAP >40mm.Hg,6 (12)10 (20)NSincluding PAH**2 (4)3 (4,6)NSANA> 1:64037 (74)45 (90)р* ANA – antinuclear antibodies, PAH – pulmonary arterial hypertension, SPAP - systolic pulmonary artery pressure ** confirmed by the data of catheterization of the right heartTypical changes according to HRCT were detected in both groups, but fibrotic changes dominates in group I. There were no significant differences in the frequency of occurrence of PAH. Patients of group II had high level of ANA more often.Conclusion:In both groups, a high frequency and similar manifestations of ILD were noted. In patients with SSc positive for anti-U1RNP, despite the predominance of limited skin lesions (in 86% of patients), a high incidence of ILD was detected, while the frequency of PAH was comparable to SSc in general. Compared with a-Topo-1 positive patients, ILD was significantly less frequent in anti-U1RNP positive patients and was accompanied with a smaller reduction of DLCO and/or FVC and a lower frequency of severe lung fibrosis. These data confirm the similarity of lung involvement in compared phenotypes of SSc and indicate the importance for screening for ILD in patients with hyperproduction of a-RNP, especially at an early stage of the disease.References:[1]Van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2013;72:1747-55.Disclosure of Interests:None declared.

Background:Systemic sclerosis (SSc) is a multisystem autoimmune disease. Pulmonary alterations are the major cause of mortality in SSc. SSc-ILD has heterogeneous disease progression: many patients will have a chronic, indolent course while others may develop progressive, life-threatening disease.Objectives:To assess prognosis intervals for pts with SSc-ILD.Methods:It was a longitudinal study involving 140 pts with SSc-ILD. The mean age was 46.7±13.9years, females 82%, SSc duration 6.2±5.8 years, diffuse subset - 54%. The mean duration of follow up was 73,2±27,8 months. Clinical, laboratory, and immunologic data were collected on all patients.Based on analysis of discrimination function the equation of prognosis was developed. The equation is 3.14GGO (ground glass opacities) + 0,7 index EScSG – 1,326 FVC - 0,1 the maximum daily dose of glucocorticoids + 0,136 Gamma globulins + 1.066 CYP – 1.075 DLCO ≤ 5,8. Value of equation of prognosis to 5.8 corresponds to stabilization or good prognosis and value after 5.8 corresponds to poor prognosis. The equation of prognosis had 86% sensitivity and 56% specificity. The cut-off point 4.7 was represented 65% sensitivity and 67% specificity. The prognosis intervals were following: value of equation to 4.7 corresponds to good prognosis; value from 4.8 to 5.8 corresponds to stabilization and value after 5.8 corresponds to poor prognosis.Results:Pts were distributed into groups depending on results of discrimination function: 14 pts (10%) - zone of good prognosis; 8 pts (6%) - zone of stabilization and 118 (84%) - zone of poor prognosis. We have decided to join pts from zone good prognosis and zone stabilization into united group (U-group) - 22 pts (16 %).Table 1.Comparative characteristics of the groupsParametersGroup 1 (n=14)Group 2(n=8)U-Group(n=22)Group 3(n=118)Age years45,4±16,450,2±15,847,2±1647,5±13P>0,05GenderMale3(21%)1(12,5%)4(18%)21(18%)Female11(79%)7(87,5%)18(82%)97(82%)P>0,05Limited form8(57%)2(35%)10(46%)54(46%)Diffuse form6(43%)6(75%)12(54%)64(54%)P>0,05Duration of disease years6,8±7,65±4,26,2±6,46,5±5,7p>0,05CRP mg/ml10±108,5±10,69,4±10,412,6±23,9p>0,05ESR mm/h16,7±13,117,4±21,917±16,323,5±16,7p>0,05ANA-hep-2525±322*420±190487±281*774±430*p: Gr1 vs Gr3 =0,038; Gr2 vs Gr3=0,02; Gr1,2 vs Gr3 =0,032a-Scl-70 u/ml59,9±82,7*67±94,5116±93**62,5±85* **p: Gr1 vs Gr3 =0,03; Gr1,2 vs Gr3 =0,013Ejection fraction(EF)(%)67,3±5,3*65,5±6,166,7±5,5**63±6,8* **p: Gr1 vs Gr3 =0,02; Gr1,2 vs Gr3 =0,017PAP mm hg31,6±5,832,4±9,331,9±736,4±14p>0,056MWT m(6 Minute walk test)490±110477±104485±104430±100p>0,05The age, SSc duration, gender proportion and SSc forms, were similar in the all groups (p>0,05). In the study mean dates of ANF-hep-2, a-Scl-70 were significantly lower and EF was significantly higher in groups 1 and U-group than in group 3. In groups 1,2 and U-group the mean levels of ESR, CRP, PAP were lower and value of 6MWT were higher than mean levels in group 3 accordingly. So separately group 2 didn’t have significant differences with group 1 and 3.Conclusion:In the study we didn’t find any correlation between meanings of group 2 and groups 1,3 but the meanings of group 1 and U-group have had the same correlation. It would be rational to highlight only one zone of prognosis before and after 5,8.Disclosure of Interests:None declared.

Background:Systemic Sclerosis (SSc) overlap syndromes (SSc with polymyositis / dermatomyositis (PM/DM), rheumatoid arthritis (RA), etc.) still remain a group of very heterogenous and not very well studied clinical variants of SSc that are characterized by certain clinical and immunological features.Objectives:Identify clinical and immunological features of the SSc-overlap syndromesMethods:80 pts with SSc-PM/DM and 35 pts with SSc-RA undergoing standard clinical examination and laboratory immunological evaluation.Results:ANA Hep2 was positive in 98% of SSc-PM/DM pts; a-Scl-70 was in 34%, a - PM-Scl and RF were in 20%. ACA (6%), a-RNP (9%), and a - Jo-1 (5%) were significantly less common. Correlation analysis showed significant prevalence of conduction abnormalities in pts with a-Scl-70- (pANA Hep2 was positive in 96% of SSc-RA pts; a-Scl-70 – in 28%, and a-RNP - in 30%. RF-positivity was in 72% of pts, and Anti-CCP - in 27%. Simultaneous Anti-CCP and a-Scl-70 was found in one case, and Anti-CCP - anti-RNP – in another, both were associated with low RF titers. All pts had early joint involvement which became prevailing in subsequent years, and onset of the disease between 30 and 36 years. There was a correlation between laboratory signs of inflammatory activity and immunological disorders: ESR and a-Scl-70 (pConclusion:SSc-PM/DM and SSc-RA appear to be an active disease from the immunological point of view, confirming therefore an important role of immune alterations in disease progression. Laboratory findings display specific pathogenetic features of SSc-overlap syndromes; laboratory abnormalities can be used to measure the activity and specify characteristics of the pathological process.Disclosure of Interests:None declared

Background:Rituximab (RTM) is considered as a promising therapeutic agent for treatment of With Interstitial Lung Disease (ILD) in the patients with systemic sclerosis (SSc). However, the limited number of RTM-treated patients, considerably varying dose regimens, cumulative doses and observation periods, lack of data on potential predictors of RTM therapy response do not allow univocal conclusions on RTM efficacy or definitive recommendations on RTM use in the patients with SSc.Objectives:The study of potential efficacy predictors of anti-B-cell therapy in the patients with SSc associated with ILD.Methods:90 patients with SSc-ILD verified by multispiral computed tomography were enrolled to the study and received RTM therapy for 12-42 months at cumulative dose 2.9±1.1 grams (disease duration 5.9±4.8 years, diffused/limited SSc 1.3/1, average age 47 ± 13.6 years, females 83%). All patients received low or moderate dose glucocorticoids. 45 patients received RTM in addition to immunosuppressive therapy (cyclophosphamide and mycophenolate mofetil) because of inadequate efficacy of immunosuppressants. After evaluation of FVC trends in the patients receiving RTM the overall study population was divided into two patient groups for the analysis: group A (n=35) comprised the patients with ≥10% FVC increase (disease duration 6.1±5.8 years, diffused/limited SSc 1,3/1, average age 50±12 years, females 86%, cumulative RTM dose 3.2±1.24 grams), and group B (n=11) comprised the patients with ≥5% FVC decrease (disease duration 5.2±4, diffused/limited SSc 0.8/1, average age 43±16, females 72%, cumulative RTM dose 2.5±0.99 grams). Subsequently correlation analysis was made to clarify the association between delta FVC and a number of clinical (age, gender, duration and form of SSc, modified skin count, presence of gastroesophageal reflux, mPAP, SSc activity (EScSG, points), cumulative RTM dose, immunosuppressive therapy) and laboratory parameters (ESR, ANA-НЕР-2, a-Scl-70, CRP, B cell count).Results:In the overall patient population RTM therapy was associated with significant FVC increase from 77.0±19.9 % to 84.7±20.9% (р=0.000000), with median FVC increment 6.6% [0;14.1].In group A FVC increased from 75.3±19.9 to 94.3±20.4) (р=0.000000), with median FVC increment 16.3 [12.6; 24.7].In group B FVC decreased from 82.5 ±23.2 to 72,3±19.4 (р=0,000176), with median FVC decrement 10.4% [-13.4; -6].Correlation analysis in groups A and B showed significant association of between delta FVC and the patient age (R=0.36), cumulative RTM dose (R=0.34) and EScSG during the last examination (1.2±.,0 and 3.1±1.4 in groups A and B, respectively; R=-0.42).No significant correlation between delta FVC and any other tested parameters was found.Conclusion:Therefore, older patients who received the cumulative rituximab dose more than 3 grams with suppressed SSc activity achieved greater FVC increase at the background of therapy. These data allow to consider the above parameters as potential predictors of response to anti-B-cell therapy in the patients with SSc-ILD.Disclosure of Interests:None declared

Background:Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction, immunological disorders, and excessive synthesis of collagen and its deposition in various tissues and organs. The juvenile onset SSc before the age of 16 is very rare, with annual incidence of 0.27-0.5 cases per million children according to English and Finnish authors [1,2].Objectives:To present a clinical case of juvenile onset SSc, manifesting from the childhood predominantly with fibrous contractures.Methods:Patient K., 30 yo. Clinical presentation on admission to the Institute of Rheumatology in September 2020: thickening of the trunk and limbs skin (mRSS 10 scores), pronounced induration of subcutaneous tissues and muscles; contractures of the elbow, shoulder, hip and knee joints, short stature (height 142 cm) with proportional shortening of the limbs. ANA (HEp-2) 1/320, a-Scl-70, a-RNP-70 and ACA tests were negative. Ultrasonography revealed left-sided coxitis, esophagogastroduodenoscopy - Barrett’s esophagus. Chest CT, echocardiography, electrocardiography and capillaroscopy yielded no specific findings.The patient has been ill since the age of 3, when SSc manifested with skin thickening, “dry” arthritis and rapid development of contractures of the large joints. Thorough diagnostic elaboration ruled out such potential causes as phenylketonuria, glycogenosis, mucopolysaccharidoses, primary amyloidosis, and porphyria. Histological findings (2007) of a biopsied skin specimen containing subcutaneous fat and muscle tissue included focal vacuolization of keratinocytes, poor perivascular lymphocytic and histiocytic infiltration, fibrosis and hyalinosis of collagen fibers of varying intensity in the in mid- and deep dermis, infiltration of collagen fibers by fibroblasts, skin appendages atrophy – all of them representing a pattern of morphological changes characteristic of SSc. Therapeutic regimens including prednisone at 5-15 mg/day and D-penicillamine were ineffective.Results:In this case, in view of fibrotic arthropathy, a differential diagnosis was made with deep morphea and stiff skin syndrome. Visceral involvement, immunological disorders and biopsy findings substantiated a diagnosis of juvenile onset SSc. Oral MTX was initiated at 15 mg to target skin lesion and osteoarticular symptoms.Conclusion:Predominance of fibrotic arthropathy in presented case caused difficulties in establishing SSc diagnosis, as this patient did not have such inherent features as the Raynaud’s phenomenon, interstitial lung disease or pulmonary hypertension. Juvenile onset SSc manifesting before the age of 16 has its own clinical features, usually persisting through the adulthood, and therefore, such one-of-a-kind appearances of juvenile onset SSc should not be missed or misinterpreted.References:[1]Herrick AL, Ennis H, Bhushan M et al. Incidence of childhood linear scleroderma and systemic sclerosis in the UK and Ireland. Arthritis Care Res. 2010 Feb;62(2):213-8. doi: 10.1002/acr.20070.[2]Pelkonen PM, Jalanko HJ, Lantto RK et al. Incidence of systemic connective tissue diseases in children: a nationwide prospective study in Finland. J Rheumatol. 1994 Nov;21(11):2143-6Disclosure of Interests:None declared

Background:Interstitial lung disease (ILD) frequently complicates SSc and can be a debilitating disorder with a poor prognosis. Several risk factors for progressive SSc-ILD have been identified and prognostic scoring systems have identified predictors of mortality. It’s important to develop treatment recommendation.Objectives:To use the discrimination function for pts with SSc-ILD and highlight pts with different prognosis.Methods:It was a longitudinal study involving 140pts with SSc-ILD. The mean age was 46.7±13.9ys, females 82%, SSc duration 6.2±5.8ys, diff subset-54%. The mean duration of follow up was 73,2±27,8months. All pts received low- and moderate-dose glucocorticoids (Gc), RTM (the mean dose 3,14±2,38g) and 77 pts had received parenteral CyP(mean dose 15,9±15,6g).We have got the discrimination function that included: ground glass opacities (GGO)(1–the absents of GGO; 2–the presents of GGO); index EScSG(the digital value); FVC(FVC≥75=0, FVCThe equation of prognosis is 3.14GGO+0,70index EScSG–1,326 FVC-0,1 the maximum daily dose of glucocorticoids+0,136 Gamma globulins+1.066 CYP–1.075DLCO≤5,8.Value of equation of prognosis to 5.8 corresponds to stabilization or good prognosis and value after 5.8 corresponds to poor prognosis.Results:Оn results of discrimination function pts were distributed in the following order: 22 pts(16%) were into zone of stabilization(Group 1) and 118(84%) - in zone of poor prognosis, among which 13pts died during the study. That`s why pts in zone of poor prognosis were divided into group 2 - survived pts (n=105(75%)) and group 3– died pts(n=13 (9%)).So we have got 3groups; the age, SSc duration, gender proportion and SSc forms, were similar in the all groups(p>0,05).Table 1.Baseline characteristics of the groupsParametersGroup 1 (n=22)M±SDGroup 2 (n=105)M±SDGroup 3 (n=13)M±SDCRP mg/ml9,4±10,411,5±23,421,5±27,1ME [25‰/75‰] 7,5 [1,9;11,2]5 [1,6;10,4]9,9 [5;32,8]ESR mm/h17±16,3523,6±1722,9±14,3a-Scl-70 u/ml62,5±85*118,6±93,09*102,1±96Skin score9,63±7,711,5±9,99±9,23Index EScSG1,9±1,7**3,4±1,9**2,9±1,1Mean PAP mm hg31,9 ±7β ββ35±11,9 β47,5±23,3ββCumulative dose of CyP g1,5±3γ γγ11,4±14,4γ18,9±23,3γγME [25‰/75‰]0 [0;2]4,9 [0;17]4 [0;46,5]Сumulative dose of RTM, g3,15±1,62,63±1,362,2±1,5* - p=0,01; **p=0,0008; β - p=0,006; ββ - p=0,03; γ- p=0,002; γγ - p=0,0018Mean level a-Scl-70, Index EScSG were significantly lower in group 1 vs group 2. Mean value of PAP and dose of CyP were significantly increased in group 3. It should be noted that pts with good prognosis have had low level of all parameters and high dose of RTM.Conclusion:The discrimination function is a proposed screening algorithm for pts with SSc-ILD who could develop progression disease. Usage of discrimination function revealed that 84% pts with ILD-SSc have got poor prognosis and 9% of them have got fatal outcome. Usage the equation of prognosis is very useful to choice of treatment and observation pts SSc-ILD.Disclosure of Interests:None declared.

Background:Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) virus infection or COVID-19 is a serious problem for patients with systemic autoimmune diseases Given the serious complications, including acute lung injury, patients with systemic sclerosis (SSc), especially SSs associated with interstitial lung disease (ILD), may represent a high risk group for infection and the development of severe COVID-19.Objectives:We present an analysis of the COVID-19 course and outcomes in 110 SSc pts.Methods:The study included 147 patients with SSc. The information was clarified by means of telephone survey after 10 months of the pandemic (December 2020). Covid-19 was diagnosed when confirmed by positive oral /nasopharyngeal swab, in the presence of positive antibodies and/or characteristic symptoms, and data from chest computed tomography (CT). 110 pts (77%) out of 147 patients in the SSc registry, gave the necessary information. COVID-19 was diagnosed in 59 pts (53 %). 42 pts (71%) had SSc-ILD. Pts mean age was 54.96 (s.d.11, min 31, max 79), 83% women (49 women and 10 men). 38 pts (65%) had a limited form of SSc, 15 (26%) pts had diffuse form SSc, 6% had overlap (SSc-polymyositis (PM) and SSc had rheumatoid arthritis (RA) and 3% had visceral form of SSc). All patients received low-dose prednisone, and more than half of the pts received immunosuppressive therapy. Rituximab therapy was performed in 24 pts (41%).Results:Almost all patients had positive swab from the oral cavity/nasopharynx. And only in 4 (7%) pts nasopharyngeal swabs were negative, in these patients specific antibodies and characteristic CT changes were detected. Chest CT was performed in 51 (86%) pts. Novel coronavirus pneumonia developed in the vast majority of pts - in 46 (78 %) pts. CT1 (up to 25% of lung lesions) had 10 (17%) pts, CT2 (25-50%) – 21(36%) pts, CT 3 (50-75%) – 15(25%) pts. In 5 (8.5%) pts no changes were detected on CT. The course of COVID-19 was mild and moderate (20 (34%) pts and 18 (31%) pts respectively), severe course was observed in 21 (35%) pts, including fatal in 12 (20%) pts. Among the deceased pts, only 1 patient with SSc-PM had not had ILD, but 7 patients had been treated with rituximab.Conclusion:SSc SARS-CoV-2-infected patients may be at risk of severe disease and mortality due to the frequent presence of ILD and the frequent use of immunosuppressive, including biological, therapy.Disclosure of Interests:None declared

Background:Inflammatory disorders of the skeletal muscle include polymyositis (PM), dermatomyositis (DM), amyopathic dermatomyositis ADM, (immune mediated) necrotizing myopathy (NM), overlap syndrome with myositis (overlap myositis, OM) and including anti-synthetase syndrome (ASS).The detection of myositis-specific antibodies, the clinical effect of which remains to be determined, may be of great importance for diagnosis.Objectives:To study clinical-immunological characteristics of patients with inflammatory myopathies.Methods:57 pts were enrolled in this study: 28 (47%) pts were diagnosed with DM, 14 (23%) pts – OM, 5(8%) pts – PM, 5 (8%) pts-NM, 4 (7%) pts-ADM, 1 (2%)- ACC. Duration of disease in average 11,29 (2-48) month. Standard clinical examination and laboratory immunological evaluation including myositis-specific autoantibodies were performed.Results:There were 3 age groups: 18-39 years old – 16 (28%) pts, 40-49 yo – 28 (49%) pts and > 60 yo – 13 (33%) pts. Symptoms of myositis were muscle weakness 57 (100%) pts, dysphagia 29 (51%) pts, arthritis -12 (21%) pts, Raynaud’s phenomenon 21 (37%) pts, skin lesions- 37 (65%) pts (Gottron signs- 7 (12%) pts, digital ulcers -11 (19) pts, panniculitis – 6(11%) pts, hand of mechanic 16(28%) pts). MMT 8 was 55,57 (SD 18,49) (20-80) score. Clinical features of myositis were myocarditis 8 (14%) pts and arrhythmia 9 (16%) pts, interstitial lung disease 20 (35%) pts, esophageal involvement 29 (51%) pts of them 5 (9%) pts needed enteral feeding. 2 (4%) pts had oncopathology. СК was increased in 49 (86%) pts: < 10 N -15 (26%) pts, >10 N – 28 (49%) pts, > 50 N – 6 (11%). ANA positive - in 39 (70%) pts. Antibodies identified in 25(44%) pts: Pm-Scl 7 (12%) pts, PL-7 1 (2%), Mi-2 10 (17,5%), Ku 2 (3,5%) pts, AMA-M2 2 (2%)pts, a-SRP 4 (7%) and SS-A/Ro-52 13 (23%), SS-A/Ro-60 2 (3%) pts.Conclusion:The group of inflammatory myopathies is characterized by clinical and immunological heterogeneity. Finding antibodies specific for myositis can help diagnose the disease.Disclosure of Interests:None declared.

Background:Impaired microcirculation is one of the leading factors in local and general pathogenesis of SSc. Widefield nail-fold video-capillaroscopy (NFVC) stands as the most informative and at the same time simple method used for evaluation of capillary circulation.Objectives:To identify characteristic and specific for SSc– PM/DM capillaroscopic features.Methods:Both hand II – V fingers of 68 pts with SSc-PM/DM were subjected to widefield NFC, evaluated using a binocular 20x magnification Olympus microscope and analyzed in view of specific skin lesions discriminating diffuse and limited SSc forms.Results:SSc-specific dilatations of capillary loops were the most common for SSc-PM/DM and were found in all pts; 50% of them had signs of active scleroderma pattern, such as capillary loss or “avascular areas” (50%) and hemorrhages (51.5%), associated with generalized microvascular spasm in early disease and capillary sclerosis in advanced disease. The morphological capillary abnormalities such as varying degrees of capillary loops tortuosity/vascular inhomogeneity were present in 63% of examined nailfolds, branching bushy behavior of capillary loops and mega-capillaries predominated; architectural disorientation/disarrangement of capillary loops with formation of subcutaneous plexus was seen in more than 50% of them. Capillaroscopic changes consistent with active scleroderma pattern were present in 54 % and were associated with lab signs of inflammatory muscle syndrome and immunological disorders: giant capillaries (pConclusion:Thus, widefield NFVC revealed a “mixed” nature of capillaroscopic changes, combining features specific for SSc (capillary dilation, avascular areas, hemorrhages) and for PM/DM (bushy and giant capillaries, disorientation of capillary loops of the nailfold with formation of subcutaneous plexuses.)Disclosure of Interests:None declared

Background:Rituximab (RTX) has been used for the treatment of systemic sclerosis (SSc) for a long time, but data on tolerance and long-term adverse events (AE) are insufficient.Objectives:To assess the tolerability and safety of RTX in the patients (pts) with SSc in long-term prospective follow-up.Methods:Data on the safety and tolerability of RTX were evaluated in 149 SSc pts who received at least one RTX infusion in a long-term open-label prospective observational study. The mean age was 48±13,5 years (17-74), women - 122 (82%), diffuse cutaneous subset of the disease had 52%, limited-37% and overlap-11%. The mean disease duration was 6,4±5,8 years (0,5-30). The observation period was 12 years. All pts received prednisolone at a dose of 11,7±4,8mg/day, and 73 patients (49%) received immunosuppressants at inclusion. The indications for the appointment of RTX were ineffectiveness or impossibility of standard therapy and a severe course of the disease with high activity and unfavorable prognosis factors. AE were assessed and recorded by a physician at a hospital immediately after the infusion of RTX, then by patient reported outcome during the observation period. Severe AE were defined as those that required hospitalization for more than 24 hours, exacerbation of the disease requiring therapy, malignancies, life-threatening situations. All causes of death were considered, regardless of treatment.Results:The mean follow-up period after the first infusion of RTX was 5,6±2,6 years [834,4 patient-years (PY)]. Pts received a mean of 3,4 courses of RTX (1–10). The cumulative mean dose of RTX was 3,2±2,4 gr (0,5-11). AE were reported in 77 patients (52%), the overall frequency of AE was 9,3/100 PY (95% Confidence Interval (CI) 8-11). The highest frequency of all AE was observed in the first 2-6 months after the first infusion of RTX, however these were mainly mild AE (71%). There was a decrease of AE in the follow-up period (3,4/100 PY, 95% CI 2,4-4,9 – at the period from 3 to 10 course of RTX). The overall incidence of serious AE was 2,22/100 PY (95% CI 1,4–3,5). The specter of serious AE included: pneumonia in 7 pts, infusion reactions in 5, as well as in one case: cerebral ischemia, acute pancreatitis, allergic pneumonitis, lymphoma of pharynx, purulent arthritis, lower limb vein thrombosis, pulmonary embolism of small arteries. The most frequent AE were infections (n=53), with no serious opportunistic infections reported. The overall incidence of all infections was 6,4/100 PY (95% CI 4,9-8,3), serious infections – 1,32/100 PY (95% CI 0,7-2,4). The level of immunoglobulin G during follow-up period decreased from 12,9±4,9 to 10,1±3,4g/l (p=0,0001), but remained within normal limits. Infusion reactions occurred in 15 pts (1,8/100 PY, 95% CI 1-3). Other AE were observed in 9 pts (6%) (1,1/100 PY, 95% CI 0,53-2,12). Sixteen deaths were recorded – 10,7% or 1,91/100 PY, 95% CI 1,2-3,1. In most cases, pts died from the progression of the major organ failure. The causes of death were: progression of the interstitial lung disease (ILD) in 4 pts, heart failure associated with SSc cardiomyopathy (2), renal crisis (4), pulmonary arterial hypertension and ILD (2), pneumonia (2), sepsis after tooth extraction (1), acute pulmonary embolism (1).Conclusion:In our study, we considered the overall safety profile of RTX in SSc as favorable. It was similar to the AE profile in other autoimmune diseases treated with RTX. With an increase of the cumulative dose of RTX, there was no increase in AE. RTX could be considered as a relatively safe drug for the complex therapy of SSc when standard therapy is ineffective or impossible.Disclosure of Interests:None declared

Background Systemic sclerosis (SSc) is a severe connective tissue disorder causing vascular, immune, and fibrotic changes in the skin and internal organs. Patients with SSc may have an increased risk of osteoporosis (OP) and fractures due to a chronic inflammatory state, latent malabsorption or malnutrition, immobilization, and use of corticosteroid therapy. Objectives: to determine the frequency of low mineral density, falls, low energy fractures and 10-year probability of new fracture in patients with SSc. Methods 191 patients with SSc were enrolled in the study: 160 women (mean age 51±13 yrs), among them 107 postmenopausal, and 31 men (mean age 53±14 yrs). Bone mineral density (BMD) was measured at lumbar spine (LS), femoral neck (FN) and total hip (TH) by dual energy X-ray absorptiometry (DXA, Hologic 4500A). BMD decreasing grade was determined in accordance to WHO criteria. All patients were interviewed on a special questionnaire and assessment of 10-year probability of new fracture by FRAX® was performed. Vitamin D level was measured in 104 patients. Results Low BMD was found in 68% women and 55% men: osteopenia in 30% and 32% and OP in 38% (21% in reproductive age and 50% in postmenopausal) and 23%, respectively. BMD in LS, FN and TH associated with body mass index (r=0,3, p=0,030; r=0,41, p=0,0027; r=0,49, p=0,0002, respectively) and duration of postmenopausal period in women (r=-0,56, p=0,023; r=-0,66, p=0,006; r=-0,63, p=0,009, respectively). BMD of LS and FN correlated with age (r=-0,22, p=0,045; r=-0,23, p=0,016, respectively), duration of SSc (r=-0,32, p=0,037; r=-0,31, p=0,046, respectively), glucocorticoid cumulative dose for LS only (r=-0,31, p=0,024). Mean 25(OH)D level was 19,83±11,06 ng/ml. Normal vitamin D level had 9% of SSc patients. No correlation between BMD and 25(OH)D level was found. 46 (24%) patients reported falls in the year prior to the interview, among them in 2 patients the fall led to fracture. A total of 48 (25%) patients had low energy fractures in the past, among them 8 (4%) of women had two or more fractures. Frequency of low energy fractures was 35%, 8% and 25% among postmenopausal women, women of reproductive age and men, respectively. The mean age at which the fracture occurred was 55±11 yrs. in postmenopausal women, 30±12 yrs. in young women and 60±12 yrs. in men. The most frequent were the fractures of distal forearm and vertebrae: 13 (7%) and 26 (14%) patients, respectively. Five patients each (3%) had ankle and humerus neck fractures and 7 – other localizations. Nobody reported the fracture of the proximal femur. Patients with abnormal BMD (OP or osteopenia) had a risk of falls and low energy fractures more than 2 times higher than patients with normal BMD (OR 2.93 [95% CI 1.11; 8.01], p=0,016 and OR 2.58 [95% CI 1.04; 6.6], p=0,025, respectively). 10-year probability of any major osteoporotic fracture was 18.4 ± 9.6% in women and 9.7 ± 8.6% in men and of hip fracture - 3.5 ± 3.7% and 1.5 ± 3.9%, respectively. Among all patients, 55% of women and 4% of men had a high risk of subsequent fractures using the FRAX® algorithm. Conclusion Low BMD was diagnosed in 68% of women and 55% of men with SSc. The correlations between BMD and age, body mass index, the duration of postmenopause were revealed. Additionally, we found associations with risk factors related to the disease itself: disease duration and glucocorticoid cumulative dose. Reduced BMD was associated with an increased risk of falls and fractures. 55% of women and 4% of men had a high risk of further fractures. Disclosure of Interests Olga Dobrovolskaya: None declared, Nikolay Demin: None declared, Oxana Desinova: None declared, Natalia Toroptsova Speakers bureau: Amgen, Lilly

Background Cyclophosphamide (CyP) is considered as a drug of choice for the treatment of interstitial lung disease (ILD) in the patients with systemic sclerosis (SSc). However, according to the literature, the use of CyP leads to rather limited and transient improvement of the pulmonary fibrosis. In this context the search for novel, more efficacious agents has been continued, such as attracting much attention retuximab (RTM). Objectives To compare the impact of CyP and RTM on SSc clinical manifestation and activity, and the safety of these agents in the open-label prospective non-randomized study. Methods 107 patients with the confirmed SSc diagnosis and ILD evidence based on HRCT findings were enrolled into the study. All patients received low-dose and moderate-dose prednisolone regimens. 36 patients (Group A) received parenteral CyP for 12±6 months at total dose 10.6±5 g (the average age 47±12 years, females 92%, SSc duration 5.0±4.8 years, diffused/localized forms 1.6/1). 71 patients (Group B) received RTM at total dose 1.43±0.66 g over the follow-up period 13.2±2 months (the average age 46±13 years, females 83%, SSc duration 5.6±4.4 years, diffused/localized forms 1.4/1); to 32 (45%) of them RTM was added to immunosupressants due to inadequate efficacy of the latter. The time courses FVC(%), modified skin count (mRss, points), activity index (EScSG, points), left ventricle ejection fraction (LVEF,%), mean pulmonary arterial pressure (EchoCG), and cardiac rhythm and conductivity disorders (ECG) were evaluated. Results In Groups A and B the therapy was associated with significant decrease in mRss (p=0.009 and 0,001, respectively) and EScSG (p=0.000165 and 0.001, respectively). Increase in LVEF (61.8±7.3 и 63.6±7.3. p=0.02) was observed only in RTM-treated patients. Evaluation of FVC time course in Groups A and B revealed significant FVC increase (p= 0.034 and 0.000045, respectively), with median increment about 5%. In Group A FVC 10% FVC increase was found in the third of the patients thus exceeding respective parameter in Group B (p=0.2). The patient percentage with FVC decrease by ≥10% was similar in both groups. During the follow-up period no change of the other studied parameters was observed. The therapy was better tolerated in RTM-treated group: during RTM therapy adverse reactions emerged in significantly lower proportion of the patients (11/14%) compared with CyP-treated group (19/53%), p=0,0000. Conclusion Both agents effectively alleviated skin induration and EScSG, and significantly improved FVC. However, CyP use for a year slightly more frequently resulted in clinically significant FVC increase, probably due to low RTM cumulative dose. RTM was better tolerated compared to CyP. The study findings substantiate potential use of anti-B-cell therapy both as a first-line agent for ILD treatment in the patients with SSc, and in the event of CyP inefficacy of poor tolerability, especially in the patients with cardiopathy. Disclosure of Interests None declared

Background Systemic sclerosis (SSc) is a rare connective tissue disease with a heterogeneous clinical course. Interstitial lung disease (ILD) is a common manifestation of SSc and a leading cause of death. Patients with early active SSc are at great risk for progressive ILD. Objectives To assess the EScSG-AI in patients with systemic sclerosis (SSc) and interstitial lung disease over a five year period. Methods It was a longitudinal study involving 77 pts with SSc-ILD (mean age was 46,2±13,4; 69% have limited subset of the disease; 93% were female). The mean duration of follow up was 58,9±11,4 months. Pts. were investigated with HRCT twice (at first visit and at the end of the study) and according the CT-changes were divided into 3 groups: the 1st group (16 pts) with improvement; 2nd group (39 pts) without any changes and 3rd group (22 pts) with worsening of fibrosis. Disease activity was assessed by the 2001 European Scleroderma Study Group Activity Index (EScSG- AI). Results There were no significant differences between groups related to sex, frequency of diffuse form and duration disease. Mean dates of EScSG-AI score of all pts and in the each groups in first visit and the end of follow up are present in table 1. After 5 years of follow up mean values of EScSG-AI score increased significantly in group 3 and was more than 3, this actually means the activity of the disease. The mean values of EScSG-AI score in group 3 was significantly higher than in groups 1,2 (p Conclusion Mean values of EScSG-AI score associated with and were accompanied by progression pulmonary alterations in pts SSc so EScSG-AI score can be used as valuable tool for long-term follow-up studies. Disclosure of Interests None declared

Background: There is a large clinical experience about the efficiency of rituximab (RTX) for the treatment of systemic sclerosis (SSc). There are several studies showing the decrease in skin induration and interstitial fibrosis in the lungs as the effect of therapy. However, there are not many long-term observations. Objectives: To describe the efficacy of RTX on lung function and skin score in patients with systemic sclerosis-associated interstitial lung disease, in long-term follow-up. Methods: This study included 71 patients (pts) with SSc. Data were collected prospectively. The mean follow-up period was 42 mo (12-72). Mean age was 46 years (17-66), female-59 (83%), diffuse cutaneous subset of the disease had 42 (59%), Scl-70 positivity-73% of pts. Duration of the disease was 5,6±4,4 yrs. All pts received concomitant treatment with low dose prednisolone and 45% - with immunosupressants. The following indicators were evaluated: forced vital capacity,% predicted (FVC), diffusing capacity for carbon monoxide,% predicted (DLCO) and Rodnan skin score (mRss) over a periods of 12-18 months (point 1), 24-30 months (point 2), 36-42 months (point 3), 48-54 months (point 4) and 60-72 months (point 5) after the start of therapy. The results are presented in the form of mean values, delta, median, upper and lower quartile. Results: In point 1 (n=71) the cumulative mean dose of RTX was 1,43±0,6 gr. The mRss decreased from 11,3±9,6 to 8±6,6 (p = 0,000007). FVC increased from 77,4±19,9 to 82,6±20,7% (p=0.0001). DLCO remained stable (from 47,0±18,5 to 47,23±16,7%). In point 2 (n=55) the cumulative mean dose of RTX was 2,97±0,8 gr. ΔmRss – 5,4 (median 3; 25th% 0; 75th% 10). ΔFVC – 7,5% (median 8,2; 25th% -1,1; 75th% 14,4). ΔDLCO – 0,21% (median -0,2; 25th% -6,2; 75th% 6,6). In point 3 (n=36) the cumulative mean dose of RTX was 3,45±1,3 gr. ΔmRss – 5,1 (median 3,5; 25th% 0; 75th% 9). ΔFVC – 9,3% (median 7,7; 25th% 1,45; 75th% 15,3). ΔDLCO – 3,4% (median 3,6; 25th% 2,45; 75th% 7,76), p=0,02. In point 4 (n=24) the cumulative mean dose of RTX was 3,96±1,1 gr. ΔmRss – 5,3 (median 3; 25th% 0; 75th% 10). ΔFVC – 12,2% (median 7,9; 25th% 1,1; 75th% 24,2). ΔDLCO – 3,9% (median 0,45; 25th% -0,95; 75th% 6,8). In point 5 (n=17) the cumulative mean dose of RTX was 5,15±1,7 gr. It should be noted that this group included patients with initially the lowest DLCO (below 40%). ΔmRss – 7,3 (median 5; 25th% 1; 75th% 14). ΔFVC – 13,2% (median 11; 25th% 8,7; 75th% 23,4). ΔDLCO – 5,9% (median 1,6; 25th% -4,8; 75th% 13,8). Conclusion: The results of this study confirm the data on the positive effect of RTX in patients with SSc (decrease of skin induration, increase of FVC, stabilization of DLCO). The decrease of skin score is accompanied by the improvement of lung function indicators. In our study, there was a significant increase of DLCO associated with long-term treatment (over 36 mo) and a cumulative dose of RTX over 3,45±1,3 gr. Patients with initially lower DLCO can achieve a significant improvement by the 60th month of RTX therapy. Our work shows that patients with SSc-associated interstitial lung disease are required long-term treatment with RTX (at least 3-5 years) to achieve an obvious improvement of the lung function. Reference [1] Jordan S, Distler JH, Maurer B, Huscher D, van Laar JM, Allanore Y. et al; EUSTAR Rituximab study group. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis 2015;74(6):1188–94. Disclosure of Interests: None declared

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by skin and multi- organ involvements induced by overproduction of autoantibodiies by B cells. Objectives: To assess the influence of Rituximab (RTX) therapy on the dynamics of the basic parameters and activity of SSc during long-term follow-up. Methods: There were 90 SSc patients (pts) in the prospective study. 75% were women. 57% pts had diffuse SSc. SSc was confirmed aCR/EULAR criteria. The average duration of the disease was 5,8 years and of the study was 27 months. For the purpose of the analysis, a group of pts was selected that had no less than two evaluation points from 12 to 42 months and having received 2,9±1.1 g RТХ in average during such period. The examination included both routine clinical laboratory parameters and special research. We evaluated the modified Rodnan skin score (mRSS), forced vital capacity (FVC), diffusing capacity of carbon monoxide (DLCO), the Valentini Disease activity index, estimated glomerular filtration rate (eGFR) before and after completed RTX. All pts included in the study received treatment with vascular, anti-inflammatory and/or immunosuppressive medicines. The average dose of prednisolone was 11,8±4,4 mg/day. Results: In general, more than 90% pts demonstrated different kinds of improvements. A reliable improvement was documented based on a number of indicators, which reflect typical features of the disease. Thus, skin induration was reduced (skin score decreased), lung functional capacity increased (increase of FVC of more than 5%). The skin score was reliably decreased from 11,2±9,3 to 6,2 ±4,9 (р Conclusion: Thus, RTX has a positive influence on the basic parameters of SSc, mainly on skin damage and lung functionality, reduces the general disease activity. The influence of the RTX on kidney function requires further long-term study. Disclosure of interests: None declared

Background: Rituximab (RTM) is considered as a promising therapeutic agent for treatment of insterstitial lung disease (ILD) in the patients with systemic sclerosis (SSc). However, the limited number of RTM-treated patients, heterogeneity of the studies in relation to main parameters, considerably different dose regimens, cumulative doses, and observation periods does not allow univocal conclusions on RTM efficacy or definitive recommendations on RTM use in the patients with SSc. The question whether to combine RTM with immunosupressants (IS) or it is possible to use it as a single-agent therapy in the patients with SSc associated with ILD is still relevant. Objectives: To compare the time courses of pulmonary function parameters and dermal fibrosis parameters during the use of RTM in combination with IS and as a single-agent therapy in the patients with SSc associated with ILD in the open-label prospective non-randomized study. Methods: 90 patients with the confirmed SSc diagnosis and ILD evidence based on HRCT findings were enrolled into the study. All patients received low-dose and moderate-dose prednisolone regimens. Group A (n=45) received a total RTM dose 3.1±1.2 g in combination with IS (27/60% mycophenolate mofetyl, 16/35.6% cyclophosphamide, 2/4.4% methotrexate; the patient’s average age was 47.4±11.6 years, with female proportion 82%; SSc duration 4.6±3.5 years; diffused/localized forms 1.3/1). Group B (n=45) received RTM as a single therapy agent in a total dose 2.7±1 g (average age 45.0±15 years, female proportion 82%, SSc duration 6.7±5.6 years, diffused/localized forms 1.5/1). The age, gender proportion, SSc form, FVC and DLCO, and RTM cumulative doses were similar in the both groups. The follow-up period was 42 months. The time courses of FVC, DLCO, modified skin count (mRss, points), activity index (EScSG, points) were assessed in the study. Results: In Groups A and B during the therapy significant decrease in mRss (p=0.00034 and 0.000002 respectively) and EScSG (p=0.00011 and 0.000000 respectively), FVC increase (p;=0.00017 and 0.00001, respectively), and stabilization of the DLCO were observed. The treatment groups did not differ significantly in the median FVC increment, clinically meaningful FVC and DLCO increments of decrements, and EScSG and mRss time courses. Notes:in Parameters column 1 = before treatment, 2 = after treatment; M ± SD = mean value and standard deviation; * = significant difference between the vales measured before and after the treatment Conclusion: RTM administration both in combination with IS and as a single agent therapy in the patients with SSc associated with ILD effectively alleviated skin induration and EScSG, improved or stabilized the pulmonary function parameters. The absence of statistically significant difference in the time course of evaluated parameters between the groups substantiate potential RTM use as a single-agent therapy that, this is most important for the patients with poor tolerability or contraindications to IS administration. Disclosure of Interests: None declared

Background:Raynaud’s phenomenon (RP) secondary to rheumatic diseases (RD) can progress to irreversible tissue damage with digital ulceration, scarring and, rarely, gangrene requiring amputation1. Current medical treatments for RP are far from ideal: they are often either ineffective and/or poorly tolerated, thus a significant proportion of patients discontinue drug therapy2.Objectives:To determine RP expression levels and to evaluate the long-term efficacy of iloprost and alprostadil in RP patients with RD.Methods:Indicated therapy with intravenous iloprost (n=10), alprostadil (n=17) or their combinations (n=13) was carried out for three years in patients with secondary RP in RD. Frequency of Raynaud’s attacks, digital ulcers (DU) formation and pain intensity on visual analogue scale (VAS) were evaluated. A control group included 30 patients with RP in RD who did not receive prostanoid therapy. By factor analysis method a generalized index of RP expression was identified, on the basis of which levels of RP expression were determined.Results:“RP expression” scale, revealed as an indicator of RP generalized manifestation, was an average value of two subscales: (1) consisted of 4 indices “DU”, “digital pitting scars”, “phalange amputation” and “frequency of Raynaud’s attack”, (2) included 3 indicators: “intensity of pain”, “duration of illness”, “whitening of fingers”. Correlation of subscales showed their reliability (r=0.294, p=0.053). RP final expression (severity) was 1.51±0.86. A low level of RP expression had values below 0.65, a high level – over 2.37. At baseline, the high level of RP severity was defined in 16 (22.9%) patients, medium – in 43 (61.4%), low – in 11 (15.7%).RP treatment with iloprost was effective in the healing of DU in 100% of patients and led to decrease of RP expression generalized index from 2.25 [1; 3] to 1.75 [1; 2] (p=0.012). Alprostadil therapy reduced pain intensity on VAS (pConclusion:Based on RP clinical manifestations in RD patients, a generalized index of RP expression was identified and levels of RP severity were determined. Treatment with iloprost or alprostadil has significant effects on reducing the clinical manifestations of RP with a corresponding decrease in its severity. Iloprost is indicated in patients with medium and high levels of RP expression index, alprostadil – with medium and low index and non-effectiveness of calcium channel blockers.References:[1]Hughes M, Herrick AL. Digital ulcers in systemic sclerosis.Rheumatology (Oxford) 2017;56 (1):14–25.[2]Kowal-Bielecka O, Fransen J, Avouac J et al. Update of EULAR recommendation for the treatment of systemic sclerosis.Ann Rheum Dis2017;76(8):1327–39.Acknowledgments:Professor LP. Anan’evaDisclosure of Interests:Ilshat Gaisin Speakers bureau: Boehringer Ingelheim, KRKA, Berlin-Chemie Menarini, Sanofi, Zukhra Bagautdinova: None declared, Marianna Glavatskikh: None declared, Nikolay Maximov Speakers bureau: Pfizer, KRKA, Rosa Valeeva: None declared, Oxana Desinova: None declared, Rushana Shayakhmetova: None declared

Background:Although ILD occurs in the majority of patients with SSc, treatment options for this manifestation is empirical and at present consists of cyclophosphamide or MMF. However, the immunosuppressants(IS) use leads to rather limited improvement of ILD and is associated with many adverse reactions. The search for novel, more efficacious agents has been continued, such as attracting much attention RTM.Objectives:To compare the impact of MMF and RTM a single-agent therapy on SSc clinical manifestation and activity, and the safety of these agents in the open-label prospective non-randomized study.Methods:80 patients with the confirmed SSc diagnosis and ILD evidence based on MSCT findings were enrolled into the study. All patients received low and moderate-dose glucocorticoids regimens. Group A(n=35) received RTM as a single therapy agent for 13.3±2.3 months at total dose 1.35±0,5g(the patient’s average age was 45.0±15 years, with female proportion 80%; SSc duration 6.3±2.3 years; diffused/localized forms 1.3/1). Group B(n=36) received MMF for 12±6 months at total dose 10.6±5 g(the average age 49±13 years, females 91%, SSc duration 7.1±5 years, diffused/localized forms 1/1.3). The time courses of FVC, DLCO, modified skin count(mRss, points), activity index (EScSG, points), and cardiac rhythm and conductivity disorders(ECG) were assessed into the study.Results:In Groups A and B the therapy was associated with significant decrease in mRss(р=0.02 and 0.009, respectively) and EScSG(р=0.00017 and 0.000165, respectively). Reducing the number of patients with cardiac conductivity disorders was observed only in MMF-treated patients(p=0.03).Evaluation of FVC time course revealed significant FVC increase only in Group A(р= 0.002), with median increment about 5%.In Group A 10% FVC increase was found in the third of the patients thus exceeding respective parameter in Group B(р=0.2). The patient percentage with FVC decrease by ≥10% did not differ significantly between groups.During the follow-up period no change of the other studied parameters was observed.The therapy was better tolerated in RTM-treated group: during RTM therapy adverse reactions emerged in lower proportion of the patients(4/11%) compared with MMF-treated group(12/27%), р=0,5.ParametersGroup АGroup ВActivity Index1M ± SD2.8±1.4*1.9±1.5*Activity Index2M ± SD1.4±1.2*1.2±0.9*Skin count1M ± SD11.5±9.5 *7.5±6.9 *Skin count2M ± SD8.2±6.2 *4.8±3.9 *FVC1M ± SD78.7±20.0 *90.3±20.8FVC2M ± SD84.2±20.0*92.2±21.0ΔFVC %5.3[0.8; 11.1]1.9[-3.5; 6.0]FVC increment by≥10%, n/%9/266/13.3FVC decrement by≥10% n/%2/5.74/8.9DLCO1M ± SD51.8±19.952.2±17.4DLCO2M ± SD49.5±16.051.9±17.0ΔDLCO %0.5[-4.5; 8.8]-1.15[-6.6; 3,65]DLCO increment by≥10%, n/%3/8.64 /8.9DLCO decrement by≥10% n/%3/8,66/13.3number of patients with cardiac conductivity disorders1, n/%13/3713/29*number of patients with cardiac conductivity disorders2, n/%14/405/11*Notes:in Parameters column 1 = before treatment, 2 = after treatment; M ± SD = mean value and standard deviation; * = significant difference between the vales measured before and after the treatmentConclusion:Both agents effectively alleviated skin induration and EScSG, and significantly improved FVC. However, only RTM use revealed significant FVC increase including clinically significant FVC increase. RTM was slightly better tolerated compared to ММF. The study findings substantiate potential use of RTM both as a first-line agent for ILD treatment in the patients with SSc, and in the event of IS inefficacy of poor tolerability. The MMF use is more preferable in patients with less pronounced ILD and cardiopathy.Disclosure of Interests:None declared

Background:Systemic sclerosis (SSc) is a connective tissue disease (CTD) most frequently associated with Raynaud’s phenomenon – RP (96%), followed by mixed CTD (MCTD) (86%), systemic lupus erythematosus – SLE (31%), undifferentiated CTD (30%), rheumatoid arthritis – RA (22%) and Sjogren’s disease – SD (13%)1. RP can manifest as a classical triple-colour change with pallor (ischaemic phase) followed by cyanosis (deoxygenation) and erythema (reperfusion)2,1. However, this triple-colour change only occurs in 19% of cases2,3. Majority of patients report an episodic double-colour change, consisting of pallor and cyanosis, pallor and erythema or cyanosis and erythema2. In a 4.8-year follow-up, 37.2% of RP patients developed rheumatic diseases (RD), 8.1% had other causes, in 54,7% RP remained primary4.Objectives:To study the incidence and manifestations of secondary RP in RD.Methods:A questionnaire survey conducted in 230 patients with RD.Results:RP was detected in 45.6% of RD patients (n=105), 54.4% of patients with RD had no RP (n=125). RP was 4 times more frequent in females than in males (F:M 4:1). In RP group, 87 patients (82%) had autoimmune RD: SSc (55.2%), SLE (17.1%), RA (6%),dermatomyositis (3.8%), cross syndrome (3.8%), MCTD (1.9%), SD (0.9%).Only 84% of RP patients had positive answers to all three questions that characterizeRP (1. Is there an unusual sensitivity of fingers to cold? 2. Do fingers change colorwhen exposed to cold? 3. Do they turn white and/or bluish?). Biphasic color changes (whitening-blueness; whitening-redness; blue-redness) were observed in 33 (31.4%) patients with RP, three-phase changes – in 32 patients (30.5%). Blueness of fingers to cold was more frequent in SLE than in SSc (p=0.027).Redness of fingers to cold occurred more often in cross syndrome, MCTD, SD, RA, vasculitis than in SSc (pThe frequency of RP attacks was detected more than once a day in 44 (42%) patients. In 73% of cases, RP did not show signs of deep digital ischemia. Digital ulcers (active) were observed in 13 (12.3%) patients, fractures in a finger area – 23 (21.9%), digital scars – 15 (14.2%), phalange amputations – 7 (6.6%).Conclusion:Patients with RD and secondary RP most often have SSC (55%), less often – SLE (17%), RA (6%), DM (3%). In SSc and SLE patients, Raynaud’s reddening of fingers to cold is less common than in other RD. In SSc, two-/three-phase changes of fingers color in the cold are more frequent than single-phase changes. In SLE, fingers turn blue in the cold more often than in SSc.References:[1]Prete M, Fatone MC, Favoino E, Perosa F. Raynaud’s phenomenon: from molecular pathogenesis to therapy.Autoimmun Rev2014;13:655–67.[2]Linnemann B, Erbe M. Raynaud’s phenomenon – assessment and differential diagnoses.Vasa2015;44:166–77.[3]Heidrich H, Helmis J, Fahrig C, Hovelmann R, Martini N. Clinical characteristics of primary, secondary and suspected secondary Raynaud’s syndrome and diagnostic transition in the long-term follow-up. A retrospective study in 900 patients.Vasa2008;37 (Suppl. 73):3–25.[4]Pavlov–Dolijanovic S, Damjanov NS, VujasinovicStupar NZ, Radunovic GL, Stojanovic RM, Babic D. Late appearance and exacerbation of primary Raynaud’s phenomenon attacks can predict future development of connective tissue disease: a retrospective chart review of 3035 patients.RheumatolInt2013;33:921–6.Acknowledgments:Professor LP. Anan’eva, Professor RT. AlekperovDisclosure of Interests:Ilshat Gaisin Speakers bureau: Boehringer Ingelheim, KRKA, Berlin-Chemie Menarini, Sanofi, Zukhra Bagautdinova: None declared, Rosa Valeeva: None declared, Nikolay Maximov Speakers bureau: Pfizer, KRKA, Oxana Desinova: None declared, Rushana Shayakhmetova: None declared, Irina Sabelnikova: None declared, Anna Tukmacheva: None declared, Larisa Gibadullina: None declared, Natalya Burlaeva: None declared, Elena Agareva: None declared, Yulia Ochkurova: None declared, Tatyana Bragina: None declared, Ksenia Alexandrova: None declared, Elvira Reutova: None declared

Background:Patients with systemic sclerosis positive for anti-U1RNP have special clinical picture and disease progression. The autoimmune profile in this group is poorly understood.Objectives:The purpose of our work was to study the level of major autoantibodies in patients with systemic sclerosis positive for anti-U1RNP.Methods:The study included 80 patients (71 women and 9 men, mean age 44,5±14 years) positive for antibodies to RNP and meeting the criteria of the systemic sclerosis (ACR/EULAR 2013). Patients were examined for autoantibodies: RF, ACCP, ACA, anti-Scl70, anti-RNAP-III, anti-Ro, anti-La, anti-dsDNA, anti-Sm, ACL, anti-Jo1. 44 patients were examined in dynamics in 24 months.Results:In the study group the clinical picture was dominated by inflammatory musculoskeletal lesions (synovitis and myopathy), skin manifestations were poorly expressed. Interstitial lung disease was detected in 68% of cases. Overlaps (34%) with other rheumatic diseases (rheumatoid arthritis, systemic lupus erythematosus) and combination with Sjogren’s syndrome (32.5%) were frequently noted. Other antibodies were often detected: commonly - RF (31%), anti-Ro (38%), anti-dsDNA (42%), rarely - anti-Sm (11%), ACCP (8%), anti-La (8%), ACA (6%), anti-Scl70 (6%), AKL (2%). Anti-Jo1 and anti-RNAP-III were not detected at all. In patients with systemic sclerosis highly-positive for anti-U1RNP (more than 2 upper normal limits) RF, anti-Ro, anti-dsDNA were significantly more common in comparison with low-positive(p=0.00). In dynamics 80% of patients maintained anti-U1RNP, while other autoantibodies were detected with the same frequency. In patients with initially low titer of anti-U1RNP, their disappearance was noted.Conclusion:Patients with systemic sclerosis positive for anti-U1RNP differ in the predominance of inflammatory musculoskeletal manifestations and frequent combination with Sjogren’s syndrome and overlaps. Highly positivity for anti-U1RNP is accompanied by a persistent increase in RF, anti-Ro, anti-dsDNADisclosure of Interests:None declared

Background:The Systemic Sclerosis-overlap syndromes are a typical representative of the well-known group of overlap syndromes in rheumatology, causing great difficulties in diagnostic and therapeutic aspects.Objectives:To identify specific features of vascular disorders in patients with Systemic Sclerosis-overlap syndromes.Methods:100 patients (pts) were followed, including 68 pts with Systemic Sclerosis-polymyositis/dermatomyositis (SSc-PM/DM) (f:m 52: 16), aged 17 to 74 years (mean 43±13.9) and mean disease duration 5 [2-7] years, and 32 pts with Systemic sclerosis-Rheumatoid arthritis (SSc-RA) (f:m 31:1), aged 17 to 74 years (mean age 48±14.8) and average disease duration 11.5 [5-18,5] years. The comparison group consisted of 100 pts with Systemic sclerosis (SSc) (f:m 90:10), aged 51 to 75 years (mean 51±12.9) and mean disease duration 10.6 [5-13,5] years.Results:In 1/3 of pts with SSc-PM/DM, the Raynaud’s phenomenon (RP) preceded the emergence of skin lesions and was the first symptom of the disease (33%), developing in the first year in the majority (68%) of cases, being a unique sign of the disease in only 6 (9 %) pts, while in all other cases it was associated with articular involvement, skin lesions and muscle disease. In the first year of the disease 7 pts (10%) already had signs of digital ischemia (scars, ulcers), and by the end of 3 years such signs were present in 1/3 of SSc-PM/DM pts (32%). 29 pts (43%) developed recurrent digital trophic disorders, such as digital scars in 12 (18%), digital ulcers in 16 (23.5%) and digital necrosis of the distal phalanx in 1 pts (1.5%).In 25 (78%) SSc-RA pts there was a gradual, monosymptomatic – with isolated RP - onset of the disease, similar to chronic cutaneous cSSc. In 29 SSc-RA (91%) pts, RP developed in the first year, and in 23 (72%) it was the first sign of the disease, and in 12 (37.5%) it preceded the development of skin and joint symptoms. Vascular disorders progressed with increasing duration and activity of the process. 7 patients (22%) developed recurrent digital trophic disorders - predominantly finger scars, while 3 (9%) pts had digital ulcers, developing in 11.66±7.62 years on average from the onset of the disease. Correlation analysis revealed a link between patients’ age of and presence of telangiectasias (ppComparing of SSc-overlap syndromes and SSc pts showed, that although RP was present in all of them, nevertheless digital vascular-trophic disorders such as scars, ulcers (ppp=0.04) distinguishing SSc-overlap syndromes from limited SSc (Table). Although, SSc-overlap syndromes pts had more severely affected muscles and joints as compared to SSc.Table 1.Comparative characteristics of vascular disorders in SSc and SSc patientsAnalyzed featuresSScn=100 (%)SSc- overlap syndromesn=100 (%)SSc-PM/DMn= 68 (%)SSc-RAn=32 (%)Raynaud phenomenon100 (100)100 (100)68 (100)32 (100)Digital trophic disorders: scars19 (19)19 (19)12 (18)7 (22) ulcers34 (34)**19 (19)**16 (23,5)3 (9)* necrosis16 (16)***1 (1)***1 (1,5)***0 (0)***Telangiectasia60 (60)*46 (46)*34 (50)12 (37,5)*Osteolysis37 (37)*24 (24)*16 (23,5)8 (25)* рConclusion:Digital trophic disorders (ulcers, necrosis), as well as telangiectasia and osteolysis are significantly less likely to develop in SSc-overlap syndromes than in SSc, which should be taken into account when panning therapeutic strategies in this category of patients.Disclosure of Interests:None declared