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Background:Tocilizumab (TCZ) showed trends for improving skin fibrosis and prevented progression of lung fibrosis in patients with systemic sclerosis (SSc) in placebo-controlled randomised clinical trials (RCTs). However, safety and effectiveness of TCZ beyond these selected and enriched clinical trial populations in SSc is still unknown.Objectives:To assess safety and effectiveness of TCZ treatment compared to standard of care in SSc patients from the large, multicentre, observational, real-life EUSTAR network/database using propensity score matching.Methods:SSc patients from the EUSTAR network/database, who fulfilled the ACR/EULAR 2013 classification criteria, with a baseline and a follow-up visit at 12±3 months, receiving TCZ or standard of care (controls), were selected. The following variables were used for the propensity score matching (1:1): age at diagnosis, gender, disease subtype, baseline modified Rodnan skin score (mRSS), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO), co-therapy with immunosuppressives, disease duration, and year of treatment. Primary endpoints were mRSS and FVC at 12±3 months follow-up compared between the groups, using paired t-tests. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months follow-up according to standard definitions (1,2). Sensitivity analyses assessed pre-processing decisions (selection of most recent vs. random observation for control patients with multiple suitable time intervals), as well as the matching method (optimal vs. exact matching). Missing values were addressed with 100-fold multiple imputation using chained equations. Safety data were analysed in all patients. The study including the statistical analysis plan was pre-registered at www.drks.de (DRKS-ID: DRKS00015537).Results:We identified 93 SSc patients treated with TCZ and 2370 SSc patients with standard of care who fulfilled the inclusion criteria. Forty nine (57.7%) of the TCZ treated patients were diffuse, eight patients were not classified, disease duration was (mean±SD) 6.35±5.40 years, their baseline mRSS was 15.05±10.85, and 76 (81.7%) received immunosuppressive therapy in addition to TCZ.Through multiple imputation and propensity score matching, 100 imputed sets of 93 pairs of TCZ/controls were generated. Comparison between groups showed consistent effects of TCZ across all pre-defined primary and secondary endpoints: mRSS was lower in the TCZ group (mean difference (95% confidence interval (CI)) -1.8 (-4.79 to 1.19), p=0.24, Figure 1A). Similarly, FVC % predicted was higher in the TCZ group mean difference (2.25, 95% CI -4.57 to 9.06), p=0.51, Figure 1B). Considering secondary endpoints, the percentage of skin progressors as well as lung progressors at follow up was lower in the TCZ group (odds ratio OR 0.67 (95% CI 0.07 to 6.41), p=0.74 and OR 0.53 (95% CI 0.16 to 1.7); p=0.2, respectively. Consistently, the percentage of regressors for skin (OR 1.6 (95% CI 0.56 to 4.54), p=0.38) and for lung (OR 1.74 (95% CI 0.66 to 4.58), p=0.26) was higher in TCZ. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles.Conclusion:In this large, observational, controlled, real-life EUSTAR study, effectiveness of TCZ did not reach statistical significance compared to standard of care treatment but showed consistent positive effects of TCZ on skin and lung fibrosis across all pre-defined primary and secondary endpoints confirming data from recent RCTs.References:[1]Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis. Ann Rheum Dis 2016:1743-8.[2]Progressive interstitial lung disease in patients with systemic sclerosis-associated interstitial lung disease in the EUSTAR database. Ann Rheum Dis 2021:219-227.Disclosure of Interests:Simon Kuster: None declared, Suzana Jordan: None declared, Muriel Daniele Elhai: None declared, Ulrike Held: None declared, Klaus Steigmiller: None declared, Cosimo Bruni: None declared, Florenzo Iannone: None declared, Serena Vettori: None declared, Elise Siegert: None declared, Simona Rednic: None declared, Veronica Codullo: None declared, Paolo Airò Consultant of: Dr. Airo’ reports personal fees (consultancies) from Bristol Myers Squibb, Bohringer Ingelheim, non-financial support from CSL Behring, SOBI, Janssen, Roche, Sanofi, Pfizer, Yolanda Braun-Moscovici: None declared, Nicolas Hunzelmann: None declared, Maria Joao Salvador: None declared, Valeria Riccieri: None declared, Ana Maria Gheorghiu: None declared, Juan Jose Alegre Sancho: None declared, Katarzyna Romanowska-Prochnicka: None declared, Ivan Castellví: None declared, Ina Koetter: None declared, Marie-Elise Truchetet Consultant of: Marie-Elise Truchetet has had consultancy relationships and/or has received research funding from Boehringer Ingelheim, Genentech/Roche, and Sanofi in the area of potential treatments of scleroderma and its complications., Grant/research support from: Marie-Elise Truchetet has had consultancy relationships and/or has received research funding from Boehringer Ingelheim, Genentech/Roche, and Sanofi in the area of potential treatments of scleroderma and its complications., Francisco J López-Longo: None declared, Pavel Novikov: None declared, Alessandro Giollo: None declared, Yuichiro Shirai: None declared, Laura Belloli: None declared, Elisabetta Zanatta: None declared, Eric Hachulla: None declared, Vanessa Smith: None declared, Christopher Denton: None declared, Ruxandra Ionescu: None declared, Tim Schmeiser: None declared, Jörg H.W. Distler: None declared, Armando Gabrielli: None declared, Anna-Maria Hoffmann-Vold Consultant of: AMHV has received research funding and/or consulting fees and/or other remuneration from Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX, Lilly and Medscape, Grant/research support from: AMHV has received research funding and/or consulting fees and/or other remuneration from Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX, Lilly and Medscape. Masataka Kuwana: None declared, Yannick Allanore: None declared, Oliver Distler Speakers bureau: Oliver Distler has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: Oliver Distler has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: The study was partially supported by a grant from Roche. Roche was not involved in analysis or interpretation of the results.

Background:Systemic lupus erythematosus (SLE) is a severe, lifelong autoimmune disease known for its multisystem organ involvement. SLE patients are known to be at risk for premature atherosclerosis at a relatively young age (1). Endothelial dysregulation is one of the pathophysiologic mechanisms that can lead to the higher risk for cardiovascular disease in SLE (2). Multiple endothelial markers with dysregulation in SLE have been described so far, of which some are associated with disease activity.Objectives:To report a systematic literature review regarding endothelial markers that are dysregulated in SLE and search for associations with disease activity.Methods:The search was performed according to the Preferred Reporting Items for Systematic review and Meta-analysis Protocols (PRISMA-P) 2015 (3). In July 2020, the search terms were used in Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) published studies after the year 2000 that reported measurements of endothelial cell markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles and 3) disease activity measurement (i.e. SLEDAI, BILAG, SLAM, ECLAM or PGA). Exclusion criteria were 1) case reports or editorials, 2) studies performed in animals and 3) studies with microRNA/cytokine biomarkers. There was no minimum count for study population. The screening process is shown in figure 1.Results:From 1892 hits, we identified 110 eligible articles. Table 1 shows an overview of the most frequently studied endothelial markers. These identified endothelial markers are involved in endothelial cell (EC) activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. In most studies, dysregulation of the endothelial marker was associated with disease activity. The majority of the studies had a cross-sectional design, longitudinal data on endothelial markers in SLE are scarce.Conclusion:We identified multiple endothelial markers that are dysregulated in SLE and this dysregulation was often associated with disease activity in cross-sectional studies. Our future plan is to test the identified endothelial markers in (longitudinally collected) samples of (childhood onset) SLE patients, disease- and healthy controls. This will be a next step in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE-patients in young adulthood.Figure 1.References:[1]Vavlukis M, Pop-Gjorceva D, Poposka L, Sandevska E, Kedev S. Myocardial Infarction in Systemic Lupus Erythematosus - the Sex Specific Risk Profile. Curr Pharm Des. 2020 Dec 9.[2]Westerweel PE, Luyten RK, Koomans HA, Derksen RH, Verhaar MC. Premature atherosclerotic cardiovascular disease in systemic lupus erythematosus. Arthritis Rheum. 2007 May;56(5):1384-96.[3]Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015 Jan 2;350:g7647.Table 1.Endothelial markerArticles(no. of studies)Significant correlation with SLEDAI(no. of studies)Studies with control groups(no. of studies)Longitudinal data(no. of studies)YesNoUnknownHealthy controlsDiseased controlsVCAM-12620152338VEGF2213542022ICAM-11811521734Thrombomodulin1710521322E-Selectin136521021MCP-18620712P-Selectin6321611IP-106510501Pentraxin-35500512vWF5410502Neopterin3210202Fas3021201Angiopoeietin-2330021-Endothelin-1312030-PAI-1311120-Adrenomedullin320120-TWEAK311112-PECAM-1311130-Disclosure of Interests:None declared

Background:Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of around 3 in 1, 000,000 children. It is known that in pediatric jSSc cohorts, there are a significant number of patients with overlap features, such as arthritis and myositis. However, the disease burden between those with and without overlap features in jSSc has not been defined.Objectives:Compare the clinical phenotype between children with and without overlap features in the juvenile systemic scleroderma inception cohort (jSScC).Methods:A cross-sectional study was performed using baseline visit data. Demographic, organ system evaluation, autoantibody profile, treatment, and patient and physician reported outcome variables were extracted from jSScC. Comparison between patients with and without overlap features was performed using chi-square test and Mann Whitney U-test.Results:At the time of data extraction, 175 jSSc patients were enrolled in the cohort, 81% were Caucasian and 81% female. Mean disease duration was 3.1 year (±2.7). Mean age at Raynaud´s onset was 10 years (±3.8) and mean age of first non-Raynaud´s was 10.2 years (±3.8). Overlap features occurred 17% (n=30) of the cohort, 12.5% in the diffuse cutaneous (dc) jSSc and in 30% in the limited cutaneous (lc) jSSc. Significant differences in clinical characteristics were found between those patients with compared to without overlap characteristics. Patients with overlap features presented more frequently with Gottron papules (p=0.007), swollen joints (p=0.019), muscle weakness (p=0.003), and lung involvement documented by decreased DLCO < 80% (p=0.06) and/or abnormal high resolution computed tomography (p=0.049). Anti-PM/Scl autoantibodies were also more common in this group (p=0.001). Significantly more patients without overlap features had Raynaud´s (p=0.006). Physician Global Assessment of disease activity was significantly higher in patients with overlap features (41 vs 34; p=0.041). (Table 1.)Table 1.Demographic and clinical characteristics of jSSc patients with and without overlap features.Whole CohortN=175Patients without overlapN=145Patients with overlapN=30P valueFemale to Male Ratio 4.3:1(142/33)4:1(116/29)6.5:1(26/4)0.395Cutaneous subtypeDiffuse subtype (N)73% (128)11216Limited subtype (N)27% (47)3317Mean disease duration (years)3.1 (± 2.7)3.2 (± 2.8)3.1 (± 2.2)0.291Mean age of onset of Raynaud´s (years)10.0 (± 3.8)17 non-Raynaud10.0 (± 3.8)10 non-Raynaud10.0 (± 3.7)7 non-Raynaud0.931Mean age of onset of non-Raynaud´s (years)10.2 (± 3.8)10.2 (± 3.9)9.8 (± 3.7)Disease modifying drugs (N)88% (154) 89% (129)83% (25)0.388Raynaud´s phenomenon90% (158)93% (135)77% (23)0.006Anti-PMScl18% (12/68)9% (5/53)47% (7/15)0.001Gottron Papules (N)27% (46/171)23% (33/144)48% (13/27)0.007DLCO 44% (39/88)39% (28/71)65% (11/17)0.06Abnormal findings in HRCT (N)44% (59/133)40% (43/107)62% (16/26)0.049Proportion of patients with swollen joints 18% (32) 14% (21) 37% (11)0.019Muscle Weakness (N) 21% (31/149)16% (20/123) 42% (11/26)0.003Physician global disease activity(0-100) min -max35 (0-90) n=14134 (0-90) n=11441 (0-80) n=270.041Conclusion:Results from this large international cohort of jSSc patients demonstrate significant differences between patients with and without overlap features. Patients with overlap have significantly more interstitial lung disease and more physician rated disease activity and should not be considered to have more “mild disease”.Supported by the “Joachim Herz Stiftung”Disclosure of Interests:None declared

Background:Non-specific abnormalities could be detected by nailfold videocapillaroscopy (NVC) in subject with primary Raynaud’s Phenomenon (RP) several years before the clinical onset of connective tissue diseases (CTD)s [1]. Previous findings from our group proved that ≤30 μm capillary dilations in RP patients have a negative predictive value for developing the ‘scleroderma pattern’ during follow-up [2].Objectives:To investigate the role of NVC >30 μm capillary dilations as positive predictive factors of the ‘scleroderma pattern’ in RP patients later developing systemic sclerosis (SSc)-related RP.Methods:A 10-year retrospective NVC-based investigation evaluated the dataset of sequential NVCs of 18 RP patients later developing SSc (cases) and 19 sex- and age-matched RP patients later developing other CTDs (controls). Both cases and controls had ≥1 NVC performed before the ‘scleroderma pattern’/CTD diagnosis (basal NVC) showing >30 μm dilated capillaries. Each NVC was qualitatively and semi-quantitatively assessed, recording number of total capillaries, number and average/site-specific diameters (arterial, apical, venous) of >30 μm dilated capillaries [3]. Statistical analysis was performed to stratify the risk of developing the ‘scleroderma pattern’.Results:Significant differences of capillary diameters were observed between cases and controls both at basal NVC and during follow-up (p30 μm dilated capillaries in basal NVC was the strongest predictor of ‘scleroderma pattern’ in a median 3-year time, with a 27% cut-off (PPV 0.79, 95%CI 0.54,0.94; p40 μm (p25 µm (pConclusion:This is the first study to show that NVC-detected homogeneous and progressive capillary loop dilations in RP patients significantly contribute to predict the ‘scleroderma pattern’ evolution within a median 3-year time, possibly providing a “very early” window of opportunity in SSc pre-clinical stages.References:[1]Cutolo M et al. Expert Rev Clin Immunol. 2019;15(7):753–64. [2] Trombetta AC et al. J Rheumatol 2016;43:599–606. [3] Smith et al. Autoimmun Rev 2020; 19(3):102458.Disclosure of Interests:None declared

Background:Some patients with SSc-ILD develop dyspnoea secondary to parenchymal lung disease, while others do not report dyspnoea even when their lung function is impaired. It is unclear whether the presence of dyspnoea is associated with a worse course of SSc-ILD or with response to therapy.Objectives:To investigate the rate of decline in FVC in patients with SSc-ILD in the SENSCIS trial in subgroups by patient-reported dyspnoea at baseline.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom within ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients were randomised to receive nintedanib or placebo until the last patient reached week 52. In post-hoc analyses, we analysed the rate of decline in FVC (mL/year) over 52 weeks in patients with and without dyspnoea at baseline based on the question about dyspnoea in the St. George’s Respiratory Questionnaire (SGRQ). Patients who reported having shortness of breath “most days a week”, “several days a week” or “a few days a month” (rather than “only with chest infection” or “not at all”) over the last month were considered to have dyspnoea at baseline. A random slope and intercept model was used to assess the rate of decline in FVC (mL/year) and an interaction test was applied to assess potential heterogeneity in the treatment effect of nintedanib between the subgroups.Results:Of 576 patients, 69.8% had dyspnoea at baseline. At baseline, in patients with and without dyspnoea, respectively, mean (SD) extent of fibrotic ILD on HRCT was 37.7 (21.7)% and 31.6 (19.4)%; mean (SD) FVC was 71.0 (16.3) and 76.5 (16.8) % predicted; 50.7% and 44.8% were taking mycophenolate; 53.5% and 41.9% were taking corticosteroids. In the placebo group, the rate of decline in FVC (mL/year) was similar in patients with and without dyspnoea at baseline (Figure). The effect of nintedanib versus placebo on reducing the rate of decline in FVC (mL/year) was numerically more pronounced in patients without dyspnoea (difference: 79.8 [95% CI: 9.8, 149.7]) than with dyspnoea (difference: 25.7 [-19.9, 71.3]), but the exploratory interaction p-value did not indicate heterogeneity in the treatment effect between subgroups (p=0.20).Conclusion:In the SENSCIS trial, patients with SSc-ILD who had dyspnoea at baseline had a numerically greater extent of fibrotic ILD on HRCT and numerically lower FVC % predicted at baseline. The rate of decline in FVC in the placebo group was similar in patients with and without dyspnoea. Nintedanib had a numerically greater treatment effect in patients without dyspnoea. These data suggest that the presence of dyspnoea should not be used as a criterion for starting nintedanib in patients with SSc-ILD.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by Fleishman Hillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Michael Kreuter Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Grant/research support from: Boehringer Ingelheim and Roche, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Lilly, Merck Sharp & Dohme and Roche, Consultant of: Actelion, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche, Grant/research support from: Boehringer Ingelheim, Marlies Wijsenbeek Speakers bureau: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Consultant of: Boehringer Ingelheim (fees paid to institution), Bristol-Myers Squibb (fees paid to institution), Galapagos NV (fees paid to institution), Hoffmann-La Roche (fees paid to institution), NeRRe Therapeutics (fees paid to institution), OncoArendi Therapeutics (fees paid to institution), Respivant Sciences (fees paid to institution) and Savara (fees paid to institution), Grant/research support from: Boehringer Ingelheim (fees paid to institution) and Hoffmann-La Roche (fees paid to institution), Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen-Cilag NV, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Janssen-Cilag NV and Research Foundation - Flanders (FWO), Dinesh Khanna Shareholder of: Eicos Sciences, Inc. (less than 5%), Consultant of: Acceleron Pharma, Actelion, AbbVie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead Sciences, Galapagos NV, Genentech/Roche, GlaxoSmithKline, Horizon Therapeutics, Merck Sharp & Dohme, Mitsubishi Tanabe Pharma, Sanofi-Aventis and United Therapeutics, Grant/research support from: Bayer, Bristol-Myers Squibb, Horizon Therapeutics, Immune Tolerance Network, National Institutes of Health and Pfizer, Employee of: Chief Medical Officer- CiviBioPharma/Eicos Sciences, Inc., Christopher Denton Speakers bureau: Boehringer Ingelheim, Corbus, Janssen, and Mallinckrodt Pharmaceuticals, Consultant of: Acceleron Pharma, Arxx Therapeutics, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, Galapagos NV, GlaxoSmithKline, Horizon Therapeutics, Janssen, Mallinckrodt Pharmaceuticals, Roche, Sanofi and UCB, Grant/research support from: Arxx Therapeutics, GlaxoSmithKline and Servier, Wim Wuyts: None declared, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Steven Sambevski Employee of: Currently an employee of Boehringer Ingelheim, Yannick Allanore Consultant of: Boehringer Ingelheim, Medsenic, Menarini and Sanofi, Grant/research support from: Alpine Pharmaceuticals

Background:Vitamin D regulates the innate and adaptive immune system responses and low vitamin D levels have been associated with the increased risk of respiratory tract infections (1). Vitamin D deficiency has been recently reported to interfere with the prognosis of COVID-19 (2,3).Objectives:The aim of this study was to correlate the 25OH-vitamin D serum levels with lung involvement and disease severity, in a cohort of elderly patients hospitalized for SARS-CoV-2 infection.Methods:Sixty-five COVID-19 patients (mean age 76±13 years) and sixty-five sex- and age-matched control subjects (CNT) were included in the study. Respiratory parameters (PaO2, SO2, PaCO2, PaO2/FiO2), clinical and laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein) and type of radiological pulmonary involvement were collected at hospital admission. Statistical analysis was performed by non-parametric tests.Results:Vitamin D sufficiency (>30 ng/ml), insufficiency (between 20 and 30 ng/ml), deficiency (between 10 and 20 ng/ml) and severe deficiency (2 (p=0.05), PaO2 (p=0.03), PaO2/FiO2 (p=0.02). A statistically significant negative correlation was found between vitamin D serum levels and severity of radiologic pulmonary involvement: vitamin D was significantly lower in COVID-19 patients with either diffuse/severe interstitial lung involvement (p=0.05) or multiple lung consolidations (p=0.0001) than in those with mild radiological lung involvement. Significantly lower vitamin D serum levels were found in COVID-19 patients who died during hospitalization, compared to those who survived (median 3 vs 8 ng/ml, p=0.05). Finally, a statistically significant negative correlation was found between vitamin D serum levels and D-dimer (p=0.04), C-reactive protein (p=0.04) and disease duration (p=0.05).Conclusion:This study confirms that severe vitamin D deficiency is associated with more severe lung involvement, longer disease duration and risk of death in elderly COVID-19 patients.References:[1]Cutolo M, et al. RMD Open. 2020; 6(3):e001454.[2]Bilezikian JP, et al. Eur J Endocrinol. 2020; 183(5):R133-R147.[3]Weir EK, et al. Clin Med (Lond). 2020; 20:e107-e108.Disclosure of Interests:None declared

Background:COVID-19 is a multifaceted condition with a wide range of clinical manifestations, including microvascular/endothelial dysfunction, that starts in the early phase of the disease and may become dramatically harmful in the late stage, causing a massive pro-thrombotic state. Nailfold videocapillaroscopy (NVC) is the most used tool to identify microvascular status in a large spectrum of diseases [1]. Recently, non-specific NVC abnormalities have been described in a cohort of COVID-19 patients (no controls used) [2].Objectives:To assess microvascular damage in recovered COVID-19 patients (range of 40-270 days from recovery) by considering the previous severity of the disease, and, as mandatory, the comparison with matched individuals suffering from primary Raynaud’s phenomenon (PRP) and healthy volunteers (HV).Methods:NVC investigations were performed during standard clinical assessments in forty-four recovered COVID-19 patients (mean age 58±14 years, mean days from disease onset 129±54, mean days from disease recovery 106±52), twenty-two patients with PRP (mean age 60±15 years, mean years from disease onset 11±10) and twenty-two HV (mean age 60±14 years). COVID-19 patients were divided into two subgroups, according to the need of oxygen supplementation: twenty-two patients with severe lung involvement (need of Continuous Positive Airways Pressure and/or mechanical ventilation, mean age 57±12 years) vs twenty-two patients with mild-moderate lung involvement (need of Venturi mask or no need of oxygen supplementation, mean age 59±15 years). Clinical and demographic data of all the enrolled subjects were collected, during NVC examination. The following capillaroscopic parameters were evaluated: capillary number, dilated capillaries, giant capillaries, microhemorrhages, angiogenesis, disorganization of the microvascular array. A validated semiquantitative scoring (0-3) was adopted for NVC abnormalities [3-5]. Statistical analysis was carried out by non-parametric tests.Results:After COVID-19 recovery, no statistically significant difference was observed between COVID-19 patients and control groups of subjects concerning the score for the following NVC parameters: dilated capillaries, giant capillaries, disorganization of the microvascular array, angiogenesis. However, the capillary number per linear millimeter was significantly lower in COVID-19 patients (8.3±0.9) than in PRP (8.8±0.7, p=0.05) and HV (9.3±0.6, pConclusion:COVID-19 doesn’t seem to significantly induce, in short-term, specific alterations in peripheral microvascular array as evaluated by NVC, despite the severity of the disease, except for a significant reduction of the absolute number of nailfold capillaries. The topic needs longer time of evaluation and larger number of COVID-19 recovered cases to also assess the role of concomitant therapies.References:[1]Ingegnoli F et al. Curr Rheumatol Rev. 2018;14:5-11.[2]Natalello G et al. Microvasc Res. 2021;133:104071.[3]Smith V et al. Autoimmun Rev 2020;19:102458.[4]Cutolo M et al. Clin Rheumatol. 2019;38:2293-2297.[5]Sulli A et al. Ann Rheum Dis. 2008;67:885-7.Disclosure of Interests:None declared

Background:Rheumatoid arthritis (RA) is a long-term, progressive, and disabling autoimmune disease1. The disease activity can be quantified by the Disease Activity Score 28-joint count – C reactive protein (DAS28crp)2; the evaluation of disability function (DF) is actually mainly performed only by subjective Patient Reported Outcomes (PROs) like Health Assessment Questionnaire (HAQ)3; to investigate the functional aspects of RA hands it is usually used the grip strength (GS)4. However, in the scientific literature no tool, which objectively evaluates movement speed, has been reported. The Hand Test System (HTS, ETT) is an engineered glove (RAGLOVE), nowadays applied for neuroscience studies to evaluate hand motility5Objectives:To objectively evaluate the RA hand’s speed of the fine movements, through the HTS and to compared with a group of age and sex matched healthy controls. To verify the correspondence with the HAQ, DAS28, GS.Methods:55 consecutives RA patients (pts) (6 males, age 61 ± 16 years, mean duration of disease 12 ± 8 years), classified according to 2010 ACR/EULAR criteria6, and 50 matched healthy controls (HCs) were enrolled. After consent, all participants undergone HTS test that recognizes the touches between the finger tips during the opposition movements of the hands in standard sequences of movements, after dressed the glove. A multiple finger evaluation (MFE) and a single finger evaluation (SFE) were performed using a dedicated software that provided the physician the following quantitative parameters: Touch Duration (TD), Inter Tapping Interval (ITI) and Movement Rate (MR). Average time for hand 2 minutes. RA pts compiled the HAQ, performed the GS and a DAS28cpr was performed.The student’s t-test was used to compare the glove’s parameters between the groups whereas the analysis of variance (ANOVA) was utilized to verify potential differences between the populations. In order to evaluate the single correlations, the r and p values of Pearson were employed.Results:For MFE, glove parameters TD and ITI were significantly higher in RA pts than HCs, whereas; MR was significantly lower in RA pts compared to HCs (all p For SFE non-affected fingers (not swollen and not tender) of RA pts performed better than a clinically affected fingers, but in any case significantly worse than average HCs fingers (p < 0.001).There is a statistically significant correlation between the GS and MR (r= 0.39 p=0.003) and TD (r=-0.33 p=0.015).TD, ITI e MR of RA pts showed a significant correlation with the total score of the HAQ (r = 0.56, r = 0.39, r = -0.56, all p < 0.001;). DAS28, considered as a continuous variable, proved to be significantly correlated with the TD (r = 0.36, p = 0.009). When the RA patients were grouped according to the disease activity by DAS28cpr7, there was an increase of one third of the TD’s logarithm for each increase in the activity class (linear regression with ordinal predictors, beta = 0.33; 95%CI 0.03, 0.63,p < 0.0297). Finally, even RA pts in remission showed a TD significantly higher compared with HCs (p= 0.034).Conclusion:The RAGLOVE is shown as a new safe and fast tool to evaluate a new objective parameter in the hand’s functionality: the speed of finger movements. In RA pts, an inversely proportional correlation emerges between the speed of movement and disease activity.The significant correlation found with HAQ, highlights the loss of motility of the hands as one of the main determinant of disability. The RAGLOVE is now tested in RA patients undergoing treatment.References:[1]Hakkinen et al Ann Rheum Dis. 2005;[2]Van Der Heijde et al J of Rheum. 1993;[3]Fries et al Arthritis Rheum. 1980;[4]Mathiowetz et al J Hand Surg Am. 1984;[5]Carmisciano et al Eur J Neurol. 2020;[6]Aletaha et al. Ann Rheum Dis. 2010;[7]Aletaha et al Arthritis Rheum 2005.Disclosure of Interests:None declared

Background:Gastrointestinal (GI) involvement is common in patients with SSc and may lead to weight loss and malnutrition. In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks, with mainly GI adverse events. The Malnutrition Universal Screening Tool (MUST) was developed to identify adults who are at risk of malnutrition and has been used in studies of patients with SSc.Objectives:To evaluate nutritional status over 52 weeks in the SENSCIS trial based on a modified MUST score.Methods:The SENSCIS trial enrolled patients with SSc-ILD with first non-Raynaud symptom ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT and FVC ≥40% predicted. Patients who had taken a stable dose of mycophenolate for ≥6 months were eligible to participate. Patients were randomised to receive nintedanib 150 mg bid or placebo. Dose reductions to 100 mg bid and treatment interruptions were allowed to manage adverse events and specific recommendations were provided for the management of diarrhoea. We calculated a modified MUST score at baseline and weeks 12, 24, 36 and 52 based on (A) BMI, (B) weight loss (week 12 vs baseline; week 24 vs week 12; week 36 vs week 24; week 52 vs week 36), and (C) a surrogate for acute disease effect (if the patient had any serious adverse event that led to hospitalisation between weight assessments and received ≥1 medication from the WHO classification code for “solutions for parenteral nutrition” for ≥5 days). MUST score at baseline was based solely on BMI. With scores ranging from 0 to 6, the risk of malnutrition is defined as low (score = 0), medium (score = 1) or high (score ≥2).Results:Among 576 patients who received nintedanib (n=288) or placebo (n=288), mean (SD) age at baseline was 54.0 (12.2) years, weight was 69.7 (15.9) kg and BMI was 25.9 (5.0) kg/m2; median time since onset of first non-Raynaud symptom was 3.4 years; and 75.2% of patients were female. In the nintedanib and placebo groups, respectively, MUST scores suggested that 74.0% and 78.1% of patients were at low risk of malnutrition at baseline and remained at low risk at their last measurement (Table 1). At weeks 12 and 52, respectively, mean (SD) MUST scores were 0.3 (0.6) and 0.4 (0.7) in the nintedanib group and 0.2 (0.5) and 0.2 (0.6) in the placebo group. At weeks 12, 24, 36 and 52, respectively, the proportions of patients at low risk of malnutrition were 81.8%, 80.9%, 72.9% and 76.5% in the nintedanib group and 86.6%, 86.4%, 88.3% and 80.8% in the placebo group; the proportions at medium risk were 12.1%, 13.1%, 18.0% and 13.5% in the nintedanib group and 8.5%, 8.6%, 5.8% and 13.1% in the placebo group; and the proportions of patients at high risk were 6.1%, 5.6%, 8.3% and 9.6% in the nintedanib group and 4.9%, 4.3%, 4.7% and 5.4% in the placebo group.Table 1.Risk of malnutrition at baseline and at last assessment over 52 weeks in the SENSCIS trial.Last assessment of riskNintedanib (n=288)Placebo (n=288)Baseline riskBaseline riskLowMediumHighTotalLowMediumHighTotalLow213 (74.0)1 (0.3)0214 (74.3)225 (78.1)7 (2.4)0232 (80.6)Medium31 (10.8)8 (2.8)039 (13.5)20 (6.9)14 (4.9)4 (1.4)38 (13.2)High13 (4.5)8 (2.8)7 (2.4)28 (9.7)3 (1.0)2 (0.7)10 (3.5)15 (5.2)Missing7 (2.4)007 (2.4)3 (1.0)003 (1.0)Total264 (91.7)17 (5.9)7 (2.4)288 (100)251 (87.2)23 (8.0)14 (4.9)288 (100)MUST score ranges from 0 to 6. Score of 0 = low risk: score of 1 = medium risk; score of ≥2 = high risk. Baseline MUST score was based solely on BMI.Conclusion:In the SENSCIS trial, scores based on a modified MUST indicated that most patients treated with nintedanib were at low risk of malnutrition at baseline and remained at low risk over 52 weeks. The proportions of patients at high risk of malnutrition were low but were numerically greater in patients who received nintedanib than placebo. Management of disease manifestations and gastrointestinal adverse events that may be associated with weight loss is important to reduce the risk of malnutrition in patients with SSc-ILD treated with nintedanib.Acknowledgements:The SENSCIS trial was funded by Boehringer Ingelheim. Medical writing support was provided by FleishmanHillard Fishburn, London, UK. The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE).Disclosure of Interests:Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus and Forbius, Zsuzsanna McMahan: None declared, Sindhu Johnson Consultant of: Boehringer Ingelheim, CSL Behring and Ikaria, Grant/research support from: Bayer, Boehringer Ingelheim, Corbus, GlaxoSmithKline, Merck and Roche, Vanessa Smith Speakers bureau: Boehringer Ingelheim and Janssen, Consultant of: Boehringer Ingelheim, Grant/research support from: Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim, Research Foundation - Flanders (FWO) and Janssen, Stéphane Jouneau Speakers bureau: Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GlaxoSmithKline, LVL Mediphar, Mundipharma, Novartis, Pfizer, Roche and Sanofi, Consultant of: AIRB, Boehringer Ingelheim, Novartis and Roche, Grant/research support from: AIRB, Boehringer Ingelheim, LVL Mediphar, Novartis and Roche, Corinna Miede Employee of: Currently an employee of mainanalytics GmbH, contracted by Boehringer Ingelheim, Margarida Alves Employee of: Currently an employee of Boehringer Ingelheim, Ariane Herrick Speakers bureau: Janssen, Consultant of: Boehringer Ingelheim, Camurus, CSL Behring and Gesynta Pharma, Grant/research support from: Actelion and Gesynta Pharma

Background:Digital ulcers (DUs) affect half of the patients with systemic sclerosis (SSc) and can be complicated by gangrene and amputation. The direct involvement of platelets in the development of DUs has been suggested by in vitro studies, which encouraged physicians to consider platelet inhibitors as a therapeutic option in the management of DUs. However, until now, there is no clinical study to assess the efficacy of platelet inhibitors for DUs in SSc patients.Objectives:To demonstrate a possible relationship between treatment with platelet inhibitors and the occurrence of DUs at the next follow-up visit in patients with SSc.Methods:This study used prospectively collected data from the European Scleroderma Trials and Research group (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR SSc classification criteria with complete longitudinal data on the presence of DUs and platelet inhibitors were included in the analysis. Multiple imputation using a random forest algorithm was implemented to handle missing values.The dataset was split into a derivation and validation cohort. To investigate the response for the binary dependent variable of DUs, a generalized linear mixed model (GLMM) was developed in the derivation cohort and validated using ROC analysis and Brier scores to address discrimination and calibration, respectively.Results:Of 3,463 patients (2,961 in the derivation cohort, 722 in the validation cohort), 453 had current DUs at the baseline and 245 were exposed to platelet inhibitors (table 1).Our GLMM revealed that the exposure to platelet inhibitors is associated with a reduced risk of DUs at the next follow up visit (OR = 0.33, 95% CI = [0.13 to 0.82]). Further factors associated with absence or presence of DUs at the next follow-up visit are shown in figure 1. This confirmed the previously identified risk factors for the presence of DUs, supporting the overall robustness and the validity of our model.The performance was evaluated by ROC curve analysis and showed an AUC = 97.97% (95% CI = [96.93% to 97.67%]) for the derivation cohort and AUC = 77.3% (95% CI = [74.01% to 81.39%]) for the validation cohort, respectively, showing an acceptable discrimination. The Brier score was 0.05 in the derivation cohort and 0.07 in the validation cohort, suggesting a good calibration of the model.Conclusion:Our model, with acceptable discrimination and good calibration, suggests a positive treatment effect of platelet inhibitors on DUs in clinical practice.Table 1.Baseline characteristics of patients before imputationCharacteristicsOverallDerivation setValidation setn3,4632,691772Age (median [IQR])56.00 [47.00, 66.00]56.00 [47.00, 65.00] 57.00 [48.00, 67.00]Disease duration (median [IQR]) 9.00 [4.00, 16.00] 9.00 [4.00, 16.00] 8.00 [4.00, 15.00]Disease subset = Limited cutaneous SSc (%) 1562 (65.2) 1164 (64.6) 398 (66.9)DUs (%): Current 453 (13.1) 378 (14.0) 75 (9.7)DUs (%): Never 1783 (51.5) 1326 (49.3) 457 (59.2)DUs (%): Previously 1227 (35.4) 987 (36.7) 240 (31.1)mRSS (median [IQR]) 5.00 [2.00, 11.00] 6.00 [2.00, 12.00] 4.00 [1.00, 11.00]Joint Contractures = Yes (%) 881 (26.8) 770 (29.4) 111 (16.5)LVEF (median [IQR])62.00 [60.00, 65.00]60.00 [60.00, 65.00] 65.00 [60.00, 67.00]Dyspnea NYHA III and IV (%)300 (9.5)214 (8.6)86 (12.7)Pulmonary hypertension = Yes (%) 244 (10.7) 200 (11.3) 44 (8.4)Lung fibrosis on HRCT = Yes (%) 685 (46.6) 600 (47.7) 85 (39.7)FVC % predicted (median [IQR])97.00 [82.00, 111.00]95.00 [81.00, 110.00]101.00 [85.00, 115.00]Serum creatinine mg/dl (median [IQR]) 0.70 [0.60, 0.90] 0.70 [0.60, 0.90] 0.70 [0.70, 0.90]Anti-Scl-70 positive = Yes (%) 1147 (33.1) 958 (35.6) 189 (24.5)CRP elevation = Yes (%) 639 (21.1) 490 (20.8) 149 (22.1)Platelet inhibitors therapy = Yes (%) 245 (7.1) 206 (7.7) 39 (5.1)Oral anti-coagulants therapy = Yes (%) 53 (1.5) 50 (1.9) 3 (0.4)Disclosure of Interests:None declared

Background:Juvenile systemic sclerosis (jSSc) is a rare disease with a prevalence of around 3 in 1,000,000 children. To better capture the clinical manifestations of jSSc the juvenile systemic sclerosis inception cohort (jSScC) has been prospectively enrolling patients with predetermined clinical variables over the past 12 years. One of the goals is to study the demographic, clinical features, and physician and patient reported outcome differences between those with juvenile limited cutaneous (lc) compared to diffuse cutaneous (dc) disease subtypes, to determine if characteristics are similar or different between dc and lc jSSc.Objectives:Evaluation of the baseline clinical characteristics of jSSc patients in the jSScC. Compare clinical phenotype between diffuse (dcjSSc) and limited cutaneous (lcjSSc) subtypes.Methods:Demographic, physical examination, organ system evaluation, autoantibody profile, treatment, and patient and physician reported outcome variables were evaluated from the jSSc Inception cohort and summary statistics applied using chi-square test and Mann Whitney U-test comparing lcjSSc and dcjSSc subtypes.Results:At the time of data extraction, 175 jSSc patients were enrolled in the cohort, 81% were Caucasian and 81% female. Diffuse cutaneous jSSc subtype predominated (73%). Mean disease duration was 3.1 year (±2.7). Mean age at Raynaud´s was 10 years (+3.8) and mean age of first non-Raynaud´s was 10.2 years (±3.8). Significant differences were found between dcjSSc versus lcjSSc, regarding several clinical characteristics. Patients with diffuse cutaneous subtype had significantly higher modified Rodnan skin score (p=0.001), presence of sclerodactyly (p=0.02), presence of Gottron’s papules (p=0.003), presence of telangiectasia (p=0.001), history of digital tip ulceration (p=0.01), and frequency of elevated CK value (p=0.04). Cardiac involvement was significantly higher in limited cutaneous jSSc subtype (p=0.02). Diffuse cutaneous jSSc patients had significantly worse scores for Physician Global Assessment of disease activity (38 vs 25; p=0.002) and disease damage (34 vs 19; p=0.008).Table 1.Comparison of demographic data and significant differences between dcjSSc and lcjSSc at time of inclusionWhole CohortN=175Diffuse SubtypeN=128Limited SubtypeN=47P valueFemale to Male Ratio4.3:1 (142/33)4.1:1 (103/25)4.8:1 (39/8)0.829Cutaneous subtypeDiffuse subtype73% (128)1280Limited subtype27% (47)047Mean Disease duration (years)3.1 (± 2.7)3.3 (± 2.9)2.6 (± 2.2)0.135Mean age of onset of Raynaud´s (years)10.0 (± 3.8)17 non-Raynaud9.8 (± 3.6)10 non-Raynaud10.6 (± 4.3)7 non-Raynaud0.219Mean age of onset of non-Raynaud´s (years)10.2 (± 3.9)10.0 (± 3.7)10.9 (± 4.3)0.173Disease modifying drugs88% (154)89% (114)85% (40)0.446CutaneousMean modified Rodnan skin score14.3 (0-51)17.4 (0-51)6.1 (0-24)0.001Gottron Papules27% (46/171)33% (41/124)11% (5)0.003Sclerodactyly78% (126/162)82% (98/119)65% (28/43)0.020Laboratory valuesElevated CK25% (30/122)30% (26/88)12% (4/34)0.041VascularTelangiectasia36% (56/154)44% (49/111)16% (7/43)0.001History of ulceration53% (91/173)61% (77/127)30% (14/46)0.001CardiacCardiac Involvement6% (10)2% (3)15% (7)0.002Patient Related OutcomesPhysician global disease activity(0-100) min -max35(0-90) n=14138(0-90) n=10825(0-80) n=330.002Physician global disease damage(0-100) min -max31(0-85) n=14034(0-85) n=10819(0-60) n=320.008Conclusion:Results from this large international cohort of jSSc patients demonstrate significant differences between dcjSSc and lcjSSc patients. According to the general organ involvement and physician global scores, the dcjSSc patients had significantly more severe disease. These observations strengthen our previous findings of the unique organ pattern of pediatric patients.Supported by the “Joachim Herz Stiftung”Disclosure of Interests:None declared.

Background:Antiphospholipid syndrome (APS) is an autoimmune condition characterized by arterial and/or venous thrombosis and/or obstetric morbidity, associated with the presence in the serum of antiphospholipid antibodies (aPL) [1]. Subjects with confirmed positivity of aPL in absence of thrombotic/obstetric manifestations are identified as aPL carriers [2] The microangiopathy detected by nailfold videocapillaroscopy (NVC) in APS and in aPL-carrier patients is poorly investigated, as well as the possible interference of anticoagulant drugs [3].Objectives:To compare microvascular damage in APS, aPL carriers and a group of patients (CTR) without aPL positivity and on regular warfarin therapy for cardiovascular indicationsMethods:NVC investigations were performed as part of standard procedures in APS patients (18, mean age 50.0±12.8 years), aPL carriers (24, mean age 46.4±16.4 years) and CTR without aPL (18, mean age 74±12.5 years) in therapy with oral anticoagulant (warfarin) for non-immunological vascular complications (atrial fibrillation, mechanical heart valve, deep venous thrombosis). Only patients affected by primary APS form were selected from data files (2006 Sapporo classification criteria). The following NVC parameters were availble: dilated capillaries, giant capillaries, microhemorrhages (with particular attention to linear and thin hemosiderin deposits, arranged perpendicularly and parallel to the nailfold bed, “comb-like”), abnormal shape (i.e. brunched “bushy” capillaries) and capillary number reduction. Those parameters were scored according to a semi-quantitative scale [4,5]. Statistical analysis was performed by non-parametric tests. Any p values equal or lower than 0.05 was considered statistically significant.Results:APS patients showed a higher score for dilated capillaries (p=0.001), more frequent microhemorrhages (p=0.03), in particular “comb-like” microhemorrhages (p=0.007) than simply aPL carriers. Of note, there wasn’t a statistically significant difference in the number of microhemorrhages between APS and CTR group (p=0.23), but again the number of “comb-like” hemorrhages, was almost absent in the CTR group (p=0.03). No significant correlation was found between the different aPL subtypes and the NVC parameters.Conclusion:APS patients showed significantly higher number of non-specific NVC abnormalities than aPL carriers. Anticoagulant treatment could represent a further risk factor for the appearance of microhemorrhages in all the patients, being the NVC “comb-like“ pattern mainly associated with the APS. Further investigations with larger cohorts of patients are needed for the definition of a possible APS specific NVC-pattern.References:[1]Ruiz-Irastorza G et al. Lancet. 2010;376(9751):1498-509. 2. Pengo V et al. Semin Thromb Hemost. 2012;38:322-7. 3. Sulli A et al. J Rheumatol. 2000;27:1574-6. 4. Smith V et al. 2020. Autoimmun Rev. 19:102458. 5. Sulli A et al. Ann Rheum Dis. 2008;67:885-7.Disclosure of Interests:None declared

Background:It has been suggested that a capillary scleroderma pattern in patients with systemic lupus erythematosus (SLE)-patients predisposes for clinical signs of systemic sclerosis (SSc) or overlap disease (1). However, this was previously shown not to be the case in a cross-sectional study in childhood-onset SLE (cSLE) (2).Objectives:To assess if nailfold capillary patterns in cSLE change over time and if a capillary scleroderma pattern is associated with prospective development of clinical SSc-features, higher SLE disease activity or –damage.Methods:Prospective clinical and capillaroscopy data were used from a longitudinal cohort of cSLE patients. Patients with a disease onset before the age of 18 years and diagnosis according to SLICC 2012 criteria were included. Disease activity was defined by SLEDAI score and disease damage by the SLICC damage index. Nailfold images from eight fingers (excluding thumbs) were obtained by videocapillaroscopy. A scleroderma pattern was defined according to the ‘fast track algorithm’ (3). An abnormal capillary pattern that did not match the criteria for a scleroderma pattern was defined as ‘microangiopathy’.Results:Our longitudinal study cohort consisted of n=53 cSLE patients with a median disease onset of 14 years (IQR 12.5-15.5 years) and a median SLEDAI score at diagnosis of 11 (IQR 8-15.5). Clinical follow-up data were available from 0.5-16 years after disease onset. Median disease duration at first capillaroscopy was 17 months (IQR 5.5-51.5 months) and 17/53 (32.1%) of patients had Raynaud’s phenomenon. In total, n=9 (17%) showed a scleroderma pattern (at some point in time), n=37 (70%) had microangiopathy and n=7 (13%) showed a normal capillary pattern. N=27 patients had follow up with capillaroscopy (1-7 times over 1-5 years). In most patients (23/27) we did not observe any change in capillary pattern during follow-up. Two patients showed changes from microangiopathy to a scleroderma pattern, one patient from a scleroderma pattern to microangiopathy and one patient from microangiopathy to a normal pattern. Raynaud’s phenomenon was equally distributed among patients with different capillaroscopy patterns (p=0.487), as was median SLEDAI score at diagnosis (p=0.285). Follow-up patients with a capillary scleroderma pattern did not show any clinical features for SSc over time (follow-up over 1-5 years, Table 1 below. Patients with a capillary scleroderma pattern showed significantly more disease damage (Chi-square, p=0.008), also indicated by a survival analysis for disease damage (Figure 1, p=0.042).Conclusion:Our study indicates that a capillary scleroderma pattern in cSLE correlates with disease damage but not with clinical SSc features during follow-up period.References:[1]S. Pavlov-Dolijanovic et al. Is there a difference in systemic lupus erythematosus with and without Raynaud’s phenomenon? Rheum Int 2013;33: 859–865[2]D. Schonenberg-Meinema et al. Nailfold capillary abnormalities in childhood-onset systemic lupus erythematosus. Revised manuscript after review re-submitted to Lupus in January 2021[3]V. Smith et al. Fast track algorithm. Autoimm Rev 2019 Nov;18(11): 102394Table 1.Clinical characteristics of cSLE-patients (n=9/53) with a nailfold capillary scleroderma patternButterfly rashPhotosensitive rashLupus nephritisAutoimmune cytopeniaPositive CoombsLow C3/C4SerositisDamageType of auto-antibodiesFollow-up in years1++-+++-+ANA, Anti-ds-DNA, anti-Sm, anti-RNP, anti-Ro52, anti-SS-A52++-+++-+ANA, Anti-ds-DNA, anti-Sm, anti-RNP, anti-SS-A53-+++++++ANA, Anti-ds-DNA, anti-Sm, anti-RNP, anti-SS-A104-++-++++ANA, Anti-ds-DNA, anti-Sm, anti-RNP, anti-Ro52, anti-SS-A95-+--+-+-ANA1 (lost)6-++++++-ANA, Anti-ds-DNA, anti-c1q37---+----ANA, Anti-ds-DNA, anti-Sm, anti-RNP18++-+----ANA99-+++++++ANA, Anti-ds-DNA, anti-RNP, anti-SS-A8Figure 1.Occurrence of disease damage (with survival as ‘no damage’) in cSLE patients with microangiopathy (blue) and a capillary scleroderma pattern (red)Disclosure of Interests:None declared

Background:Among the cells involved in the inflammatory process of rheumatoid arthritis (RA) [1], macrophages play a key role through their capacity to polarize into “classically” or “alternatively” activated phenotypes (M1 or M2) and making macrophages important players for the inflammatory cascade or for the anti-inflammatory reaction, respectively [2]. CTLA4-Ig fusion protein (abatacept) has been shown to contribute to macrophage shift from M1 to M2 [3].Objectives:We aimed to investigate the effects of abatacept to induce the polarization from the pro-inflammatory M1 phenotype into the anti-inflammatory M2 phenotype in cultured human macrophages obtained from RA patients’ and healthy subjects’(HS) circulating monocytes.Methods:Cultured monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of three early RA patients and ten HS, after signing informed consent and Ethics Committee approval. Cells were treated with phorbol myristate acetate (PMA) [5ng/ml] for 24 hours (hrs) to induce their differentiation into monocyte-derived macrophages (MDMs). Therefore, cultured HS MDMs were stimulated with lipopolysaccharides [LPS, 1mg/mL] for 4hrs [4] in order to induce their polarization into a pro-inflammatory M1 phenotype and then treated or not with abatacept at the concentrations of 100mg/mL and 500mg/mL for 3, 12, 24 and 48hrs. Cultured RA MDMs, were directly treated with abatacept as previous described. Cultured HS and RA MDMs without any pro-inflammatory stimuli and abatacept treatment were used as respective control.The transition of MDMs from M1 to M2 phenotype was evaluated through gene expression and protein synthesis of M2 macrophage markers, namely scavenger receptors (CD163 and CD204), and mannose receptor-1 (CD206) by quantitative real-time polymerase chain reaction (PCR) and by Western blotting. The statistical analysis evaluation was carried out by GraphPad Prism 8 analysis software using the Wilcoxon non-parametric t-test. Any p-value lower than 0.05 was considered as statistically significant. Results were indicated as median±standard deviation (SD).Results:In cultured RA MDMs (three cases), abatacept upregulated the gene expression of all investigated M2 markers, specifically after 12hrs of treatment with the concentration of 100mg/mL. In these cells, abatacept upregulated only the CD204 protein synthesis with more evidence at 24hrs of treatment and with the 500mg/mL concentration. In cultured HS MDMs (ten cases), abatacept upregulated the gene expression of M2 markers, significantly for that of CD206 [at 3hrs with 100mg/mL concentration, p= 0.0312] and CD163 [at 12hrs with 500mg/mL concentration, p= 0.0312]. Moreover, in these cells, abatacept significantly upregulated the protein synthesis of CD206 [at 48hrs with 500mg/mL concentration, p= 0.0195] and CD204 [at 24hrs with 100mg/mL concentration, p= 0.0156; both at 24 and 48hrs with 500mg/mL concentration, p= 0.0234].Conclusion:Preliminary data seem to indicate that abatacept can promote the in vitro shift from the M1 into the M2 macrophage phenotype, by upregulating specific markers (CD163, CD204, CD206) in cultured M1-MDMs from RA patients and in M1 macrophages induced from HS.References:[1]McInnes IB, et al. N Engl J Med 2011;365:2205–19.[2]Fujii M, et al. Biochem Biophys Res Commun. 2013;438(1):103-9.[3]Cutolo M, et al. Arthritis Res Ther. 2009;11:R176.[4]Pelegrin P., Surprenant, A. EMBO J. 2009 Jul 22; 28(14): 2114–2127.Disclosure of Interests:Samuele Tardito: None declared, Stefano Soldano: None declared, Emanuele Gotelli: None declared, Paola Montagna: None declared, Sabrina Paolino: None declared, Vanessa Smith: None declared, Maurizio Cutolo Grant/research support from: I received grant/research support from Bristol-Myers Squibb, Boehringer, Celgene.

Background:Fibroblast-to-myofibroblast transition is one of the fundamental steps involved in the fibrotic process that characterise systemic sclerosis (SSc) [1]. Myofibroblasts are α-smooth muscle actin (αSMA) positive cells that contribute to fibrosis through the excessive synthesis and deposition of extracellular matrix (ECM) proteins, primarily fibronectin (FN) and type I collagen (COL1) [2].Among the cells involved in the fibrotic process of SSc, circulating fibrocytes seem to have an emerging role as an important source of fibroblasts and myofibroblasts [3].Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis that interferes with the signalling pathways involved in the pathogenesis of fibrosis (4). Nintedanib was recently demonstrated to have a beneficial effect in patients with interstitial lung disease (ILD) associated with SSc (5).Objectives:To investigate nintedanib effect in inhibiting the in vitro transition of circulating SSc fibrocytes into myofibroblasts and their pro-fibrotic activity.Methods:Circulating fibrocytes were obtained from 14 SSc patients (mean age 64±14 years), who fulfilled the 2013 ACR/EULAR criteria for SSc and that underwent complete disease staging in a day-hospital setting at the Rheumatology Division of Genoa University. Five age-matched healthy subjects (HSs) were also analysed. All SSc patients and HSs signed the informed consent and the local EC approved the study. Peripheral blood mononuclear cells were isolated by density gradient centrifugation and plated on FN-coated dishes. After overnight culture, non-adherent cells were removed, and adherent cells were maintained in growth medium for 8 days (T8) to obtain fibrocytes [6]. T8-cultured SSc fibrocytes were maintained in growth medium (untreated cells) or treated with nintedanib 0.1μM and 1μM for 3 and 24 hours. Fibroblast specific protein-1 (S100A4) and αSMA, as markers of fibroblast/myofibroblast phenotype, together with COL1 and FN, were investigated by qRT-PCR and Western blotting. Non-parametric Mann-Whitney and Wilcoxon tests were used for the statistical analysis.Results:Significantly elevated gene and protein expressions of αSMA, S100A4, COL1 and FN were observed in SSc fibrocytes compared to HS fibrocytes (gene: αSMA p+ILD+) or Scl70 negative patients without ILD (Scl70-ILD-). Significant αSMA, S100A4, COL1 and FN gene expressions were found in fibrocytes from Scl70+ILD+ compared to HS fibrocytes (αSMA p+ILD+patients showed a more significant gene expression of fibroblasts/myofibroblasts markers compared to Scl70-ILD-patients (pNintedanib reduced the gene and protein expression of αSMA, COL1 and FN in SSc fibrocytes compared to untreated ones with different statistical significance.Noteworthy, nintedanib significantly downregulated αSMA, S100A4, COL1 and FN gene expression (all p+ILD+fibrocytes, whereas only that of S100A4 and FN was significantly downregulated (p-ILD- fibrocytes compared to untreated cells.Conclusion:Nintedanib seems to downregulate in vitro the transition of fibrocytes into myofibroblasts and their pro-fibrotic activity, particularly in cells isolated from Scl70+ILD+SSc patients.References:[1]Cutolo M et al. Exp Rev Clin Immunol. 2019;15:753-64.[2]Van Caam A et al. Front. Immunol. 2018;9:2452.doi:10.3389/fimmu.2018.02452.[3]Distler JH et al. Arthritis Rheumatol. 2017;69:257-67.[4]Distler O et al. New Eng J Med. 2019; 380:2518-28.[5]Maher TB et al. Arthritis Rheumatol.2020.doi:10.1002/art.41576.[6]Cutolo M et al. Arthritis Res Ther. 2018;20:157.doi:10.1186/s13075-018-1652-6.Acknowledgements:We thank Stefano-Lutz Willing for the scientific support through the study.Disclosure of Interests:Stefano Soldano: None declared, Paola Montagna: None declared, Emanuele Gotelli: None declared, Samuele Tardito: None declared, Sabrina Paolino: None declared, Claudio Corallo: None declared, Carmen Pizzorni: None declared, Alberto Sulli: None declared, Carlotta Schenone: None declared, Greta Pacini: None declared, Vanessa Smith: None declared, Maurizio Cutolo Grant/research support from: I received grant/research support from Bristol-Myers Squibb, Boehringer, Celgene

Background:Microvascular damage is a frequent feature in connective tissue diseases (CTDs) and can be easily detected trough nailfold videocapillaroscopy (NVC) (1,2). Mixed and Undifferentiated connective tissue diseases (MCTD and UCTD) do not show a specific and unique NVC pattern (3). However, a variety of microvascular abnormalities can occur in these two CTDs, both non-specific or specific for the scleroderma like-pattern (3-5).Objectives:To retrospectively assess and compare nailfold microangiopathy observed by NVC in MCTD and stable UCTD versus primary Raynaud’s phenomenon (PRP) (6). In addition, the aim was to correlate NVC findings with serum levels of autoantibodies (Abs) against extractable nuclear antigen (ENA) detected in UCTD.Methods:Files of fourty-six MCTD patients (Kasukawa’s criteria) (mean age 42.8±16 SD years), fourty-seven UCTD patients (mean age 47.7±16.1 SD years), fifty-one PRP (mean age 45.9±17.3 SD years) were retrospectively evaluated in the study. Among UCTD and MCTD patients 95% of both showed Raynaud’s phenomenon. Main NVC parameters (i.e. dilated capillaries, giant capillaries, microhemorrhages, abnormal shapes and number of capillaries) and related semiquantitative scale (score 0–3 for every parameter), were analyzed and compared between the two distinct CTD groups and PRP. Furthermore, ENA Abs (in particular, Ro/SSA, La/SSB, Scl70 and Jo1) were evaluated. The CTD patients were receiving different immunosuppressive treatments. Statistical analysis was performed by non-parametric tests.Results:Among UCTD group, 36% of patients showed a normal NVC pattern, 53% had non-specific NVC abnormalities and 11% had a scleroderma like-pattern. The latter was significantly more frequent in MCTD than in UCTD (pConclusion:NVC features in UCTD patients seem very close to the pattern observed in PRP (mostly non-specific capillary abnormalities), conversely in MCTD the scleroderma-like pattern was found significantly prevalent together with a significant capillary number reduction. The transition from the scleroderma-like to the scleroderma pattern (mean systemic sclerosis) is matter of actual investigation.References:[1]Cutolo M. et al. Best Pract Res Clin Rheumatol 2008; 22:1093-108.[2]Sulli A, Ann Rheum Dis. 2008;67:885-7.[3]Smith V. et al. Autoimmunity Reviews 2020; 19:102458.[4]De Holanda Mafaldo DA, et al. Lupus. 2007; 16:254–8.[5]Smith V, et al. Ann Rheum Dis 2010; 69: 1092-96.[6]Antunes M, et al. RMD Open. 2019, 26;4.Disclosure of Interests:None declared

Background:Juvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence of 3 per 1 000 000 children. There are limited data regarding the clinical presentation of jSSc. The Juvenile Systemic Scleroderma Inception Cohort (JSSIC) is the largest multinational registry that prospectively collects information about jSSc patients.Objectives:Evaluation of the jSSc patients at the time of inclusion in the JSSIC.Methods:Patients were included in the JSSIC if they fulfilled the adult ACR/EULAR classification criteria for systemic scleroderma, if they presented the first non-Raynaud symptom before 16 years of age and if they were younger than 18 years of age at time of inclusion. Patients’ characteristics at time of inclusion were evaluated.Results:Until 15thof December 2019 hundred fifty patients were included, 83% of them being Caucasian and 80% female. The majority had the diffuse subtype (72%) and 17% of all jSSc had overlap features. The mean age of first presentation of Raynaud´s phenomenon was 9.8 years in the diffuse subtype (djSSc) and 10.7 years in the limited subtype (ljSSc) (p=.197). The mean age at first non-Raynaud’s symptoms was 10.0 years in the djSSc and 11.2 years in the ljSSc (p=0.247). Mean disease duration at time of inclusion was 3.4 years in the djSSc and 2.4 years in the ljSSc group.Significant differences were found between the groups regarding mean modified Rodnan skin score, 18.2 in the djSSc vs 6.2 in the ljSSc (p=0.02); presence of Gottron´s papulae (djSSc 30% vs ljSSc 13%, p=0.43);presence of teleangiectasia (djSSc 42% vs 18% ljSS, p=0.01); history of ulceration (djSSc 42% vs 18% ljSSc,p=0.008); 6 Minute walk test below the 10thpercentile (djSSc 85% vs ljSSc 54%, p=0.044), total pulmonary involvement (djSSc 49% vs ljSSc 31%, p=0.045), cardiac involvement (ljSSc 17% vs djSSc 3%, p=0.002). djSSc patients had significantly worse scores for Physician Global Assessment of disease activity compared to ljSSc patients (VAS 0-100) (40 vs 15) (p=0.001) and for Physician Global Assessment of disease damage (VAS 0-100) (36 vs 17) (p=0.001).There were no statistically significant differences in the other presentations. Pulmonary hypertension occurred in approximately 6% in both groups. No systemic hypertension or renal crisis was reported. ANA positivity was 90% in both groups. Anti-Scl70 was positive in 35% in djSSc and 36% in the ljSSc group. Anticentromere positivity occurred in 3% in the djSSc and 7% in the ljSSc group.Conclusion:In this unique large cohort of jSSc patients there were significant differences between djSSc and ljSSc patients at time of inclusion into the cohort regarding skin, vascular, pulmonary and cardiac involvement. According to the physician global scores the djSSc patients had a significantly more severe disease. Interestingly the antibody profile was similar in both scleroderma phenotypes.Supported by the “Joachim Herz Stiftung”Disclosure of Interests: :Ivan Foeldvari Consultant of: Novartis, Jens Klotsche: None declared, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Kathryn Torok: None declared, Maria T. Terreri: None declared, Ana Paula Sakamoto: None declared, Valda Stanevicha: None declared, Flávio R. Sztajnbok: None declared, Jordi Anton Grant/research support from: grants from Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Grant/research support from: Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Consultant of: Novartis, Sobi, Pfizer, abbvie, Consultant of: Novartis, Sobi, Pfizer, abbvie, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Brian Feldman Consultant of: DSMB for Pfizer, OPTUM and AB2-Bio, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Maria Katsikas: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, edoardo marrani: None declared, Mikhail Kostik: None declared, Natalia Vasquez-Canizares: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: None declared, Anjali Patwardhan: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Sujata Sawhney: None declared, Dieneke Schonenberg: None declared, Cristina Battagliotti: None declared, Lillemor Berntson Consultant of: paid by Abbvie as a consultant, Speakers bureau: paid by Abbvie for giving speaches about JIA, Blanca Bica: None declared, Juergen Brunner Grant/research support from: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Abbvie, Roche, BMS, Speakers bureau: Pfizer, Novartis, Abbvie, Roche, BMS, Patricia Costa Reis: None declared, Despina Eleftheriou: None declared, Liora Harel: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Daniela Kaiser: None declared, Dragana Lazarevic: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Yosef Uziel: None declared, Nicola Helmus: None declared

Background:RISE-SSc (NCT02283762) was a multicenter, double-blind, Phase IIb study of riociguat in early dcSSc. Primary endpoint was change in mRSS from baseline to Wk 52.Objectives:Exploratory, descriptive analyses of riociguat target engagement and effects on disease biomarkers in RISE-SSc and their relationship with effects on the primary endpoint. All biomarker p-values are for information only.Methods:Pts with dcSSc (duration ≤18 mo; modified Rodnan skin score [mRSS] 10–22 units) were randomized to riociguat 0.5−2.5 mg tid (n=60) or placebo (n=61). Biomarkers of target engagement (cGMP), inflammation and/or vascular/endothelial function (e.g. high-sensitivity C-reactive protein [hsCRP], soluble platelet endothelial cell adhesion molecule 1 [sPECAM-1], soluble E-selectin, chemokine ligand 4 [CXCL-4]), and fibrosis (e.g. alpha-smooth muscle cell actin [alphaSMA], pro-collagen mRNA expression) were measured in plasma, serum, and skin biopsies at baseline and Wk 14.Results:Mean±SD change from baseline in mRSS was –2.09±5.66 (n=57) with riociguat and –0.77±8.24 (n=52) with placebo (p=0.08). From baseline to Wk 14, plasma cGMP rose by mean (SD) 94% (78%) (n=52) with riociguat and 10% (39%) (n=52) with placebo (nominal pConclusion:Primary study endpoint (change in mRSS) was not met. Plasma cGMP rose with riociguat, confirming engagement with the NO-sGC-cGMP pathway. Serum sPECAM-1 (marker of endothelial activation) and CXCL-4 (marker of progressive SSc) fell with riociguat; hsCRP and E-selectin did not. Some serum and skin biomarkers of higher disease activity at baseline were associated with a greater effect of riociguat on skin fibrosis.Acknowledgments:RISE-SSc was jointly funded by Bayer AG and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Disclosure of Interests:Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Frank Kramer Employee of: Bayer AG, Josef Höfler Employee of: Josef Höfler is an employee of Staburo GmbH, Munich, Germany, contracted by Bayer AG to perform the biomarker analyses, Mercedeh Ghadessi Employee of: Bayer AG, Peter Sandner Employee of: Bayer AG, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Tatsuya Atsumi Grant/research support from: Eli Lily Japan K.K., Alexion Pharmaceuticals, Inc., Bristol-Myers Squibb Co., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Consultant of: Gilead Sciences, Inc., Eli Lilly Japan K.K., UCB Japan Co. Ltd., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Speakers bureau: Eli Lilly Japan K.K., UCB Japan Co. Ltd., Bristol-Myers Squibb Co., AbbVie Inc., Eisai Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Radim Bečvář Consultant of: Actelion, Roche, László Czirják Consultant of: Actelion, BI, Roche-Genentech, Lilly, Medac, Novartis, Pfizer, Bayer AG, Ellen De Langhe Consultant of: member of advisory board for Boehringer, Eric Hachlla: None declared, Tomonori Ishii: None declared, Osamu Ishikawa: None declared, Sindhu Johnson Grant/research support from: Boehringer Ingelheim, Corbus Pharmaceuticals, GlaxoSmithKline, Roche, Merck, Bayer, Consultant of: Boehringer Ingelheim, Ikaria, Kaisa Laapas Employee of: Partly in-sourced to Bayer, Valeria Riccieri: None declared, Elena Schiopu: None declared, Richard Silver: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Chiara Stagnaro: None declared, Viginia Steen Grant/research support from: The associated affiliation has received grants/research from Boehringer Ingelheim, Corbus Pharmaceuticals, CSL Behring, Eicos, Galapagos, Immune Tolerance Network, Reata, Consultant of: Virginia Steen has acted as a consultant for Boehringer Ingelheim, Corbus, CSL Behring, Eicos, Forbius, Wendy Stevens: None declared, Gabriella Szücs: None declared, Marie-Elise Truchetet: None declared, Melanie Wosnitza Employee of: Bayer AG, Dinesh Khanna Shareholder of: Eicos Sciences, Inc./Civi Biopharma, Inc., Grant/research support from: Dr Khanna was supported by NIH/NIAMS K24AR063120, Consultant of: Acceleron, Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Corbus Pharmaceuticals, Horizon Therapeutic, Galapagos, Roche/Genentech, GlaxoSmithKline, Mitsubishi Tanabe, Sanofi-Aventis/Genzyme, UCB

BackgroundThe European Scleroderma Trials and Research Group (EUSTAR) recently developed a preliminarily revised activity index (AI) that performed better than the European Scleroderma Study Group Activity Index (EScSG-AI) in systemic sclerosis (SSc).ObjectiveTo assess the predictive value for short-term disease severity accrual of the EUSTAR-AI, as compared with those of the EScSG-AI and of known adverse prognostic factors.MethodsPatients with SSc from the EUSTAR database with a disease duration from the onset of the first non-Raynaud sign/symptom ≤5 years and a baseline visit between 2003 and 2014 were first extracted. To capture the disease activity variations over time, EUSTAR-AI and EScSG-AI adjusted means were calculated. The primary outcome was disease progression defined as a Δ≥1 in the Medsger’s severity score and in distinct items at the 2-year follow-up visit. Logistic regression analysis was carried out to identify predictive factors.Results549 patients were enrolled. At multivariate analysis, the EUSTAR-AI adjusted mean was the only predictor of any severity accrual and of that of lung and heart, skin and peripheral vascular disease over 2 years.ConclusionThe adjusted mean EUSTAR-AI has the best predictive value for disease progression and development of severe organ involvement over time in SSc.

Background:Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the main cause of death in SSc and accounts for up to 30-35% of SSc-mortality (1-2). All SSc cases, irrespective of the extent of the skin disease, should be evaluated for ILD (3). The epidemiology of SSc-ILD in Belgium is unknown. In literature, the prevalence of ILD in SSc varies between 19% and 52%. However, different criteria were used to diagnose ILD (4). In 2008, Goh et al. proposed a flow diagram to diagnose SSc-ILD based on chest high-resolution CT-scan (HRCT) and pulmonary function tests (PFTs). Their categorization into limited or extensive ILD has prognostic value (5).Objectives:To determine the prevalence and incidence rate of SSc-ILD in Flanders.Methods:Up to 12-year follow-up data of consecutive SSc patients were obtained by 2 Flemish expert centres (University Hospitals Ghent and Leuven). Patients fulfilling the LeRoy and/or ACR-EULAR classification criteria were included consecutively in the prospective cohort (6). Patients received HRCT at baseline and on indication thereafter, as well as yearly PFT. All HRCTs were centrally analyzed (Ghent) and patients were categorized according to the Goh criteria as without ILD, with limited ILD (limILD) or with extensive ILD (extILD) (5).Results:Between 2006 and 2018, 797 SSc patients (557 Ghent/240 Leuven; 22% limited SSc (LSSc)/59% limited cutaneous SSc (LcSSc)/19% diffuse cutaneous SSc (DcSSc)) had baseline HRCT and PFT. The baseline characteristics are depicted in the table. The mean age (SD) was 53 +/-15 years and the majority of patients was female (76%).272 SSc patients had ILD at baseline, implicating a baseline prevalence of 34% (272/797). The baseline prevalences were 35% and 55% for the LcSSc and DcSSc subgroups respectively. During a median follow-up of 39 months (IQR: 11-79 months), 44 patients were diagnosed with incidental SSc-ILD, resulting in an incidence rate of 21,0/1000 person-years (PY), 95% CI:15,2-28,1. The incidence rates were 21,7/1000 PY, 95%CI: 14,3-31,6 and 43.9/1000PY, 95%CI: 22.7-76.8 for the LcSSc and DcSSc subgroups respectively.Table.Baseline characteristicsSSc (n=797)LcSSc (n=470)DcSSc (n=149)age (years) °53+/-1554+/-1554+/-14♂/♀ *193(24%)/604(76%)109(23%)/361(77%)58(39%)/91(61%)Disease Duration (months) #for 718: 22 (5-72)for 443: 25 (5-80)for 145: 16 (7-52)LSSc/LcSSc/DcSSc *178(22%)/470(59%)/149(19%)follow-up (months) #39 (11-79)38.5 (9.75-81)44 (17.5-78)Anti-centromere antibodies§252/538 (47%)163/317 (51%)19/108 (18%)Anti-topoisomeraseI antibodies§119/519 (23%)66/297 (22%)45/112 (40%)ILD at baseline, *272 (34%)163 (35%)82 (55%)LimILD, *230 (29%)139 (30%)67 (45%)ExtILD, *42 (5%)24 (5%)15 (10%)New ILD during follow-up, §44/52527/30712/67°: mean +/- standard deviation, *: number of patients (percent), #: median (interquartile range), §= number of patients/total number of patients with available data (%)Conclusion:In an unselected cohort of SSc patients, a third of the patients has ILD at baseline which is in line with previous prevalence reports. Importantly, this is the first study reporting incidence rates of SSc-ILD.References:[1]Steen VD and Medsger TA, Ann Rheum Dis 2007;66:940-4[2]Elhai M et al. Ann Rheum Dis 2017;76:1897-1905[3]Smith V et al. RMD Open 2019;4:e000782. doi:10.1136/rmdopen-2018-000782[4]Bergamasco A et al. Clinical Epidemiology 2019;11:257-73[5]Goh N et al. Am J Respir Crit Care Med 2008;177:1248-54[6]van den Hoogen et al. Arthritis Rheumatol 2013;65:2737-47Disclosure of Interests:Els Vandecasteele Grant/research support from: my institution has received a research grant from the Research Foundation Flanders FWO), Speakers bureau: my institution has received speaker fees from Actelion, Karin Melsens: None declared, Daniel Blockmans Consultant of: yes, Speakers bureau: yes, Charlotte Carton: None declared, Filip De Keyser: None declared, Ellen De Langhe Consultant of: member of advisory board for Boehringer, Bernard Lauwerys: None declared, Yves Piette: None declared, Amber Vanhaecke: None declared, Koen Verbeke: None declared, Wim Wuyts Grant/research support from: my institution has received a grant from Boehringer Ingelheim and Roche, Consultant of: my institution has received payments for consultancy from Boehringer Ingelheim and Roche, Speakers bureau: my institution has received speaker fees from Boehringer Ingelheim and Roche, Guy Brusselle: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl

Background:Vasculopathy is a hallmark of systemic sclerosis (SSc). Laser speckle contrast analysis (LASCA) is a research tool to assess peripheral blood perfusion (PBP) (1). At this moment, its reliability has been attested in SSc patients, but its predictive value for future ischemic digital trophic lesions (DTL) is unknown (1).Objectives:To investigate in an unselected, prospective SSc cohort if baseline LASCA PBP measurements can discriminate between patients who will develop ischemic DTL (iDTL) and those who will not.Methods:Patients (fulfilling 2013 ACR/EULAR criteria and/or 2001 LeRoy and Medsger criteria) were recruited during the period of December 2017 to September 2018. LASCA was performed at baseline, in standardized conditions (1). Regions of interest (ROIs) (diameter 1 cm) were outlined at the 2nd-5thfingertip both volar and dorsal. The ‘average PBP’ of these ROIs was calculated (expressed in arbitrary perfusion units [PU]). A monthly telephone survey was conducted for 1 year to investigate DTL occurrence. DTL were considered ‘ischemic’ if not related to calcinosis. Logistic regression and ROC analysis were used to assess if average PBP is predictive of future iDTL.Results:Of the 106 patients with complete follow-up (92 women [86,8%]; 18 limited SSc [17,0%], 82 limited cutaneous SSc [77,4%], 6 diffuse cutaneous SSc [5,7%]), 29 patients (27,4%) had a DTL history. Forty-nine patients (46,2%) were on vasodilator therapy. Only 7 patients developed at least 1 iDTL during follow-up (6,6%) (Figure 1a). Performing univariate logistic regression (ULR), average PBP was not predictive for future iDTL (Table 1). Of note, analyzing only the patients not taking vasodilators, average PBP in the ‘iDTL group’ (n = 3) was median 46,8 PU (min. 45,6 - max. 68,8) vs. median 141,4 PU (min. 24,4 - max. 269,5) in the ‘no iDTL group’ (n = 54) (Figure 1b). In this subgroup, all 3 patients who developed iDTL (100%) had an average PBP ≤ 70 PU whereas only 9 of the 54 patients without iDTL development (16,7%) had such PBP values.Table 1.Results of ULRSummary statisticsULRVariableiDTL cases(n = 7)Non-iDTL cases(n = 99)ParameterOR(95% CI)pROC AUC(95% CI)Average PBP (PU) mean (+/- SD)123,0 (74,6)142,9 (61,9)Average PBP (linear)0,995(0,982-1,007)0,4180,597(0,352-0,843)Conclusion:In this pilot study with an unselected day-to-day SSc population, where patients were allowed to continue vasodilators, there was an unexpected low iDTL incidence, undermining the power of our study. Even though, the observations in the subgroup of patients not taking vasodilators deserve future investigation to assess whether low PBP values, as measured by LASCA, are associated with a higher iDTL incidence.References:[1]Cutolo M, Vanhaecke A, et al. Autoimmun Rev. 2018;17(8):775-80.Figure 1.Distribution of ‘average PBP’ as measured by LASCA for ‘no iDTL group’ and ‘iDTL group’Disclosure of Interests:Claire Debusschere: None declared, Amber Vanhaecke: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Ellen Deschepper: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl

Background:RISE-SSc (NCT02283762) was a multicenter Phase IIb trial of riociguat in pts with early (duration ≤18 months) dcSSc and modified Rodnan skin score (mRSS) 10−22 units. Pts were randomized double-blind to placebo or riociguat 0.5–2.5 mg t.i.d. for 52 weeks. The primary endpoint, mRSS change from baseline to Week (Wk) 52, did not reach statistical significance (p=0.08, riociguat vs placebo), but there were favorable trends in some other outcomes.Objectives:To present open-label long-term extension (LTE) results of RISE-SSc.Methods:Pts who completed Wk 52 of double-blind therapy could enter LTE on riociguat. Endpoints included mRSS, adverse events (AEs), and serious AEs (SAEs).Results:Of 60 pts randomized to riociguat and 61 to placebo, 42 (riociguat−riociguat group) and 45 (former placebo group), respectively, entered LTE. At LTE start, mean±SD mRSS was 16.4±3.2 and 16.3±4.2 units, and mean disease duration was 8.9±7.8 and 8.9±5.8 months, in the riociguat−riociguat and former placebo groups, respectively. Other demographics/disease characteristics were also comparable. Median duration of riociguat treatment was 1092 d in riociguat−riociguat pts and 649 d in former placebo pts. Throughout the study, mRSS decreased in both groups (Figure 1). From Wk 52 to last visit, mRSS fell by −3.02±5.51 in riociguat−riociguat patients and −3.96±5.43 in former placebo pts. Rates of mRSS regression (decrease by >5 units and ≥25% from Wk 52 to last visit) and of % declines in mRSS were similar in the two groups (Figure 2). mRSS progression (increase by >5 units and ≥25% from Wk 52 to last visit) occurred in 1 pt (2%) in each group. During the entire study, rescue therapy agents were used in 15 (36%) riociguat−riociguat pts and 17 (38%) former placebo pts. AEs were reported from Wk 52 to last visit in 82 pts (94%): 40 (95%) riociguat−riociguat and 42 (93%) former placebo. Most common AEs overall: nasopharyngitis (24%), gastroesophageal reflux disease (17%), diarrhea (15%), and hypotension (14%). AEs of special interest (dizziness, postural dizziness, or hypotension) occurred in 5 riociguat−riociguat pts (12%) and 4 former placebo pts (9%). SAEs were reported in 21 (24%) pts: 10 (24%) riociguat−riociguat pts and 11 (24%) former placebo pts, with no SAE reported in >1 patient, no SAEs of special interest, and no deaths.Conclusion:During LTE riociguat treatment, mRSS decreased in both groups from Wk 52 onwards and mRSS progression was uncommon. Riociguat had acceptable safety, similar to the main study, with no new safety signal.Acknowledgments:RISE-SSc was jointly funded by Bayer AG and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Disclosure of Interests:Dinesh Khanna Shareholder of: Eicos, Grant/research support from: NIH NIAID, NIH NIAMS, Consultant of: Acceleron, Actelion, Bayer, BMS, Boehringer-Ingelheim, Corbus, Galapagos, Genentech/Roche, GSK, Mitsubishi Tanabi, Sanofi-Aventis/Genzyme, UCB Pharma, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Masataka Kuwana Grant/research support from: Acetelion, Consultant of: Acetelion, Bayer, Chugai, Corbus Pharmaceuticals, CSL Behring and Reata Pharmaceuticals. He was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Melanie Wosnitza Employee of: Bayer AG, Marie-Elise Truchetet: None declared, Gabriella Szücs: None declared, Wendy Stevens: None declared, Viginia Steen Grant/research support from: The associated affiliation has received grants/research from Boehringer Ingelheim, Corbus Pharmaceuticals, CSL Behring, Eicos, Galapagos, Immune Tolerance Network, Reata, Consultant of: Virginia Steen has acted as a consultant for Boehringer Ingelheim, Corbus, CSL Behring, Eicos, Forbius, Chiara Stagnaro: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Richard Silver: None declared, Elena Schiopu: None declared, Valeria Riccieri: None declared, Frank Kramer Employee of: Bayer AG, Sindhu Johnson Grant/research support from: Boehringer Ingelheim, Corbus Pharmaceuticals, GlaxoSmithKline, Roche, Merck, Bayer, Consultant of: Boehringer Ingelheim, Ikaria, Osamu Ishikawa: None declared, Tomonori Ishii: None declared, Eric Hachlla: None declared, Ellen De Langhe Consultant of: member of advisory board for Boehringer, László Czirják Consultant of: Actelion, BI, Roche-Genentech, Lilly, Medac, Novartis, Pfizer, Bayer AG, Radim Bečvář Consultant of: Actelion, Roche, Tatsuya Atsumi Grant/research support from: Eli Lily Japan K.K., Alexion Pharmaceuticals, Inc., Bristol-Myers Squibb Co., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Astellas Pharma Inc., Consultant of: Gilead Sciences, Inc., Eli Lilly Japan K.K., UCB Japan Co. Ltd., AbbVie Inc., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Speakers bureau: Eli Lilly Japan K.K., UCB Japan Co. Ltd., Bristol-Myers Squibb Co., AbbVie Inc., Eisai Co. Ltd., Otsuka Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Pfizer Inc., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., Astellas Pharma Inc., Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

Background:Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence in around 3 in a million children. Pulmonary involvement in jSSc occurs in approximately 40 % in the inception cohort. Traditionally in jSSc, pulmonary function testing (PFT) with FVC and DLCO are used for screening and computed tomography (HRCT) was more reserved for those with abnormal PFTs. More recently, it has become apparent that PFTs might not be sensitive enough for detecting ILD in children.Objectives:Utilizing a prospective international juvenile systemic scleroderma cohort (JSScC) [2], to determine if pulmonary screening with FVC and DLCO is sufficient enough to assess the presence of interstitial lung disease in comparison to CT evaluation.Methods:The international juvenile systemic scleroderma cohort database was queried for available patients with recorded PFT parameters and HRCT performed to determine sensitivity of PFTs detecting disease process.Results:Of 129 patients in the jSScC, 67 patients had both CT imaging and an FVC reading from PFTs for direct comparison. DLCO readings were also captured but not in as many patients with tandem HRCT (n =55 DCLO and HRCT scan). Therefore, initial analyses focused on the sensitivity, specificity and accuracy of the FVC value from the PFTs to capture the diagnosis of interstitial lung disease as determined by HRCT.Overall, 49% of the patients had ILD determined by HRCT, with 60% of patients having normal FVC (>80%) with positive HRCT findings, and 24% of patients having normal DLCO (> 80%) with positive HRCT findings. Fourteen percent (n = 3/21) of patients with both FVC and DLCO values within the normal range had a positive HRCT finding.Conclusion:The sensitivity of the FVC in the JSScC cohort in detecting ILD was only 39%. Relying on PFTs alone for screening for ILD in juvenile systemic sclerosis would have missed the detection of ILD in almost 2/3 of the sample cohort, supporting the use of HRCT for detection of ILD in children with SSc. In addition, the cut off utilized, of less than 80% of predicted FVC or DLCO could be too low for pediatric patients to exclude beginning ILD. This pilot data needs confirmation in a larger patient population.Supported by the “Joachim Herz Stiftung”Disclosure of Interests:Ivan Foeldvari Consultant of: Novartis, Bernd Hinrichs: None declared, Kathryn Torok: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Valda Stanevicha: None declared, Flávio R. Sztajnbok: None declared, Maria T. Terreri: None declared, Ana Paula Sakamoto: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Jordi Anton Grant/research support from: grants from Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Grant/research support from: Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Consultant of: Novartis, Sobi, Pfizer, abbvie, Consultant of: Novartis, Sobi, Pfizer, abbvie, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Maria Katsikas: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Rolando Cimaz: None declared, Mikhail Kostik: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: None declared, Dieneke Schonenberg: None declared, Cristina Battagliotti: None declared, Lillemor Berntson Consultant of: paid by Abbvie as a consultant, Speakers bureau: paid by Abbvie for giving speaches about JIA, Blanca Bica: None declared, Juergen Brunner Grant/research support from: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Abbvie, Roche, BMS, Speakers bureau: Pfizer, Novartis, Abbvie, Roche, BMS, Patricia Costa Reis: None declared, Despina Eleftheriou: None declared, Liora Harel: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Dragana Lazarevic: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Anjali Patwardhan: None declared, Yosef Uziel: None declared, Nicola Helmus: None declared

Background:Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by specific vascular and obstetric manifestations and by antiphospholipid antibodies (aPL) positivity [1].To date, little is known regarding nailfold videocapillaroscopy (NVC) alterations in APS patients and in asymptomatic aPL-carriers, non-specific abnormalities being the most frequently reported [2,3,4].Objectives:To retrospectively analyze NVC alterations in APS patients and in asymptomatic aPL-carriers and to correlate NCV alterations with both clinical manifestations and serum aPL profile.Methods:Thirty-five aPL positive patients having received at least one NCV investigation (mean age 47 years, range 16-81, 31 female and 4 male) were retrospectively included in the study. For each patient complete medical history was collected with a particular attention to past vascular thrombosis and pregnancy morbidity. Patients were classified as affected by APS according to the updated Sapporo classification criteria [5]. Lupus anticoagulant (LAC), IgM and IgG anti-cardiolipin antibodies (ACL) and IgM and IgG anti-Beta2 Glycoprotein 1 (anti-B2GP1) were assessed in each patient according to the recommended procedures [5]. NCV parameters were analyzed in each patient, with a particular interest to hemorrhages or nailfold bed-parallel hemosiderin deposits (“comb-like”hemorrhages) presence [2,6]. Statistical analysis was performed by parametric and non-parametric tests.Results:Seventeen patients (mean age 49 years, range 16-81 years) were asymptomatic aPL-carriers and 18 (mean age 46 years, range 26-71 years) were affected by APS. Within APS patients, 16 had a history of vascular thrombosis and 2 had pregnancy morbidity; in 6 patients APS was secondary to other autoimmune rheumatologic conditions (3 to Systemic Lupus Erythematosus, 2 to vasculitides and 1 to Mixed Connective Tissue Disease).Among the total number of aPL-carriers and APS patients six patients showed a normal NVC pattern, 24 patients had non-specific NVC abmormalities and 5 patients had a “scleroderma-like” pattern. Interestingly, NCV microhemorrhages were significantly more frequent in APS patients than in asymptomatic aPL-carriers, both in score and in absolute (p=0.05 andp=0.04, respectively). Particularly, in APS patients “comb-like”hemorrhages had a statistically significant higher prevalence than isolated hemorrhages (p=0.03). Dilated capillaries score was significantly higher in APS patients than in asymptomatic aPL-carriers (p=0.01).Not any statistically significant difference was observed regarding other capillary parameters (score of giant capillaries, loss of capillaries, or anormal shpaes, i.e. angiogenesis). Not any statistical correlation was observed between NVC parameters and different aPL profile.Conclusion:The study shows that the total number of microhemorrhages and in particular the“comb-like”subtype, are significantly the most frequent specific abnormalities in APL patients when compared to asymptomatic aPL carriers. The presence of the “scleroderma like” NVC pattern may suggest a concomitant overlap syndrome. Not any correlation was found between aPL profile and other NVC parameters. Further studies need to develop a more specific APS NVC pattern for APS patients.References:[1]Tektonidou MG, et al RMD Open 2019; 5(1);[2]Cutolo M, Elsevier 2010, pp141-143;[3]Candela M, et al.1998:444-9;[4]Aslanidis S, et al. Clin Exp Rheumatol 2011, 29:307-9;[5]Miyakis S, et al. J Thromb Haemost 2006, 4:295–306;[6]Cutolo M, et al Best Pract Res Clin Rheumatol 2008, 22:1093-108Disclosure of Interests: :Giorgia Ferrari: None declared, Sabrina Paolino: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Carmen Pizzorni: None declared, Greta Pacini: None declared, Emanuele Gotelli: None declared, Adriano Lercara: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in FVC over 52 weeks vs placebo, with no difference between groups in change in mRSS.Objectives:Analyse correlation between progression of skin fibrosis and progression of SSc-ILD in the SENSCIS trial.Methods:Patients with SSc-ILD were randomised to receive nintedanib or placebo until the last patient reached week 52 but for ≤100 weeks. We calculated Spearman correlation coefficients between FVC (mL) at baseline and change from baseline in mRSS, mRSS at baseline and change from baseline in FVC (mL), and changes from baseline in mRSS and FVC at weeks 52 and 100 in all patients. We analysed the rate of decline in FVC (mL/year) in patients who did and did not have progression of skin fibrosis (relative change from baseline in mRSS >25% and absolute change from baseline >5 points) at week 52.Results:In the nintedanib (n=288) and placebo (n=288) groups, respectively, mean (SD) baseline FVC (mL) was 2459 (736) and 2541 (816) and mRSS was 11.3 (9.2) and 10.9 (8.8); 53.1% and 50.7% had dcSSc;18.4% and 16.0% had progression of mRSS at week 52. No meaningful correlations were observed in analyses between mRSS and FVC (Table). The mean (SE) annual rate of decline in FVC in the placebo group was similar in patients who did and did not have progression of mRSS (-95.2 [27.1] and -91.4 [15.7] mL/year, respectively). The effect of nintedanib vs placebo on reducing the rate of decline in FVC was numerically more pronounced in patients who did not have progression of mRSS vs those who did (difference [95% CI] 44.3 mL/year [0.6, 88.1] vs 24.6 [-53.7, 102.9]), but the interaction p-value (0.66) did not indicate heterogeneity in treatment effect between subgroups.Conclusion:In the SENSCIS trial, the proportion of patients who had progression of skin fibrosis over 52 weeks was low, without significant differences between placebo and nintedanib. No meaningful correlations were observed between skin fibrosis at baseline or progression of skin fibrosis and progression of SSc-ILD. The rate of decline in FVC was similar between patients who did and did not have progression of mRSS. These findings suggest that in the overall patient population in the SENSCIS trial, progression of skin fibrosis and progression of ILD were distinct manifestations of disease progression.Table:FVC at baseline and change from baseline in mRSSmRSS at baseline and change from baseline in FVCChanges from baseline in mRSS and FVCNCorrelation*NCorrelation*NCorrelation*Week 52Nintedanib2470.11 (-0.01, 0.23)241-0.08 (-0.20, 0.05)238-0.07 (-0.19, 0.06)Placebo2540.12 (-0.00, 0.24)257-0.15 (-0.27, -0.03)2520.03 (-0.09, 0.15)Week 100Nintedanib730.21 (-0.02, 0.42)73-0.06 (-0.29, 0.17)700.06 (-0.17, 0.30)Placebo660.28 (0.04, 0.49)730.04 (-0.19, 0.27)66-0.14 (-0.37, 0.10)*Spearman correlation coefficient (95% CI)Disclosure of Interests:Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Kristin Highland Grant/research support from: Boehringer Ingelheim - PI for SENSCIS and SENSCIS-ON trials (paid to my institution), Consultant of: Kristin Highland has acted as a consultant to Boehringer Ingelheim. She was a member of the SENSCIS trial Steering Committee (Boehringer Ingelheim), Speakers bureau: Kristin Highland reports speaker fees from Boehringer Ingelheim, Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Otylia Kowal-Bielecka Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Inventiva, MSD, Novartis, Speakers bureau: Boehringer Ingelheim, Medac, Novartis, Roche, Sandoz, Ulrich Walker Grant/research support from: Ulrich Walker has received an unrestricted research grant from Abbvie, Consultant of: Ulrich Walker has act as a consultant for Abbvie, Actelion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Phadia, Roche, Sandoz, Sanofi, and ThermoFisher, Paid instructor for: Abbvie, Novartis, and Roche, Speakers bureau: Abbvie, Actelion, Bristol-Myers Squibb, Celgene, MSD, Novartis, Pfizer, Phadia, Roche, Sandoz, and ThermoFisher, Francesco Del Galdo: None declared, Madelon Vonk Grant/research support from: Janssen and Ferrer, Consultant of: Boehringer Ingelheim, Janssen and GSK, Speakers bureau: Boehringer Ingelheim, BMS and Roche, Laura Hummers Grant/research support from: Boehringer Ingleheim, Corbus pharmaceuticals, CSL Behring, Cumberland Pharmaceuticals, and GlaxoSmithKline, Consultant of: Boehringer Ingleheim, Corbus pharmaceuticals, and CSL Behring, Elvira Erhardt Employee of: Employee of Boehringer Ingelheim, Manuel Quaresma Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl

Background:Presence of anti-centromere antibodies (ACA) generally associates with a better prognosis than many other systemic sclerosis (SSc) associated autoantibodies. However, presentation of the disease can be very heterogeneous and prediction of the disease course is challenging. Some older studies suggest a possible association between clinical characteristics and isotypes of ACA in patients with SSc. It is unknown whether ACA can serve as biomarker for future SSc development.Objectives:To evaluate the clinical course of very early SSc and to assess whether ACA isotype levels can identify subjects that will progress to definite SSc.Methods:ACA IgG+ patients with very early SSc (defined as presence of ACA IgG AND Raynaud and/or puffy fingers and/or abnormal nailfold capillaroscopy but not fulfilling ACR 2013 criteria) from five prospective SSc cohorts (Leiden, Zurich, Oslo, Bordeaux, Ghent) were included. Presence and levels of ACA IgG, IgM and IgA were determined at first clinical assessment and clinical course was evaluated annually. Disease progression to definite SSc, which was defined as fulfillment of the ACR 2013 criteria for SSc, and included any development of: digital ulcers (DU), interstitial lung disease (ILD) assessed by high resolution chest tomography, pulmonary arterial hypertension assessed by right heart catheterization, gastro-intestinal involvement, renal crisis or myocardial involvement was determined. ACA response characteristics were compared between very early SSc patients that progressed to definite SSc and those who did not. Logistic regression was performed to determine whether ACA response characteristics can predict progression to definite SSc, with adjustment for age and follow-up duration.Results:In total 92 subjects were included with median follow-up (FU) of 3 years (table 1); 39% progressed to definite SSc, mostly based on the development of skin involvement (77%). Twenty-three percent of patients developed lung involvement, 11% DU, 17% gastro-intestinal involvement and 4% myocardial involvement. Progression on more than one organ system was present in 31% of the very early SSc patients. In the multivariable logistic regression, with adjustment for age and follow-up duration, ACA IgG levels at baseline were significantly associated with progression to definite SSc (OR 3.0 (1.1-8.8)). Likewise, a trend was observed for higher ACA IgM levels (OR 1.8 (0.9-3.5)) in the very early SSc patients progressing to definite SSc (figure 1).Table 1.Baseline characteristics and ACA isotype levels in patients with very early SSc, and between progressors and non-progressors. * p value < 0.05.Progressors(n=35)Non-progressors(n=57)Female, n(%)32 (91)50 (91)Age, mean (SD)56 (14)53 (13)Disease duration since non Raynaud phenomenon, median(IQR) in years3 (0.8-10)2 (0.6-7)Follow-up duration in years, median (IQR)4 (2-6)2 (1-3)*Abnormal Nailfold videocapillaroscopy, n(%)17 (65)27 (60)IgA level [aU/mL], median (IQR)63 (34-120)75 (35-144)IgM level [aU/mL], median (IQR)131 (32-585)79 (18-391)IgG level [U/mL], median (IQR)342 (162-720)195 (93-488)*Conclusion:In this study we illustrate that 39% of the ACA positive very early SSc subjects progress to definite SSc within median 4 years. We identified higher ACA IgG level as a predictive biomarker for progression to definite SSc indicating that it might be a useful biomarker for risk stratification in clinical practice.Disclosure of Interests:Nina van Leeuwen: None declared, Jaap Bakker: None declared, Annette Grummels: None declared, Corrie Wortel: None declared, Suzana Jordan: None declared, Sophie Liem: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Anna-Maria Hoffmann-Vold Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Actelion, Bayer, GlaxoSmithKline, Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Karin Melsens: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Marie-Elise Truchetet: None declared, Hans Ulrich Scherer Grant/research support from: Bristol Myers Squibb, Sanofi, Pfizer, Speakers bureau: Pfizer, Lilly, Roche, Abbvie, Rene Toes: None declared, Thomas Huizinga Grant/research support from: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Consultant of: Ablynx, Bristol-Myers Squibb, Roche, Sanofi, Jeska de Vries-Bouwstra: None declared

Background:muscle actin (aSMA)+cells involved in the overproduction of extracellular matrix proteins, primarily fibronectin (FN) and type I collagen (COL1) at the level of damaged tissues (1). These cells may originate from different cell types including fibroblasts, endothelial and epithelial cells, and fibrocytes (1). Circulating fibrocytes are bone marrow progenitor cells expressing specific markers of hematopoietic (CD34, CD45, and MHC class II) and stromal cells (COL1 and COL3), chemokine receptors (CCR2, CCR7), and CXCR4 (2). CXCR4 regulates fibrocyte migration into injured tissues allowing their differentiation into fibroblasts/myofibroblasts (2).In vitro, fibrocytes differentiate from circulating CD14+monocytes showing an antigen-presenting capability through the expression of HLA-DR and costimulatory molecule CD86 (2). CTLA4-Ig fusion protein (abatacept) interacts with CD86 on cell surface of antigen presenting cells (APCs), such as macrophages and endothelial cells (3,4).Objectives:To investigate the possible effect of CTLA4-Ig treatment on cultured human fibrocytes and skin fibroblasts isolated from the same systemic sclerosis patients (SSc pts).Methods:Fibrocytes isolated from the peripheral blood mononuclear cells of SSc pts and healthy subjects (HSs) were cultured on fibronectin-coated plates in DMEM at 20% of FBS; for further 8 days (T8) to allow their complete differentiation. Differentiated fibrocytes were maintained in growth medium or treated with CTLA4-Ig at different concentrations (10, 50, 100, and 500μg/ml) for 3 hours. Fibroblasts were isolated from the skin biopsies of the same patients and HSs, cultured until the 3rdpassage in RPMI at 10% FBS and then treated with CTLA4-Ig for 24 and 48 hours. Fibrocytes were characterized as CD45+CXCR4+COL1+cells and the expression of CD86 and HLA-DR was also evaluated. The gene expression of aSMA, COL1, CXCR4, TGFb1 and CD86 was investigated by quantitative real-time polymerase chain reaction in cultured fibrocytes and skin fibroblasts. In cultured skin fibroblasts, COL1 and fibronectin synthesis was evaluated by Western blotting.Results:Treatment with CTLA4-Ig for 3 hours significantly downregulated aSMA and COL1 gene expression in cultured SSc fibrocytes at T8 (pConclusion:Due to their high expression of CD86, circulating fibrocytes seem to be more responsive to CTLA4-Ig treatment than the skin fibroblasts isolated from the same SSc patient.References:[1]Cutolo M et al. Expert Rev Clin Immunol. 2019;15:753-64.[2]Bucala R. Mol Med.2015;2:S3-5.[3]Cutolo M et al. Clin Exp Rheumatol. 2015;33:250-4.[4]Brizzolara R et al. J Rheumatol. 2013;40:738-40.Disclosure of Interests:Stefano Soldano: None declared, Paola Montagna: None declared, Sabrina Paolino: None declared, Elisa Alessandri: None declared, Carmen Pizzorni: None declared, Greta Pacini: None declared, Federica Goegan: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Carlotta Schenone: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Alternatively activated (M2) macrophages seem to play a role in the fibrotic process of systemic sclerosis (SSc) as potential inducers of tissue fibrosis through their secretion of specific cytokines and chemokines, such as interleukin-10 (IL-10), macrophage derived chemokine (CCL-22) and pro-fibrotic metalloproteases (i.e. MMP9) (1-3).Objectives:To investigate the presence of circulating cells belonging to the monocyte lineage showing an M2 phenotype in SSc patients (pts) and possible correlation with the clinical parameters of the disease. Moreover, to investigate if the treatment of cultured monocytes isolated from healthy subjects with serum derived from early SSc pts may induce theirin vitropolarization into M2 macrophages.Methods:Fifty female SSc pts (mean age 64±13 yrs), fulfilling the EULAR/ACR criteria, and 27 gender-matched healthy subjects (HSs, mean age 57±7 yrs) were considered at the Rheumatology Division of Genoa University after written informed consent. Nailfold videocapillaroscopy (NVC), serum SSc-related antibodies and skin involvement were investigated. Circulating cells belonging to the monocyte populations (CD45+and CD14+cells) were characterised by flow cytometry using specific surface markers of M2 phenotypes (CD204, CD206, CD163). Each SSc pt had been under stable treatment regimen for at least six months. Cultured monocytes, isolated by negative selection from peripheral blood mononuclear cells (PBMCs) of 8 HSs, stimulated for 48 hrs with 10% of serum of lcSSc pts with “Early” NVC pattern, as well as serum of dcSSc pts with “Active” and “Late” NVC patterns. Cultured monocyte human cell line (THP1) was differentiated into macrophages (5ng/ml of phorbol myristate acetate) and then stimulated with SSc sera. The expression of CD204, CD206 (M2 markers) and CD68 was investigated by immunocytochemistry, whereas MMP9 secretion was investigated by zymography. Statistical analysis was performed using Mann-Whitney and Kruskal-Wallis tests, and correlations were explored by bivariate Pearson’s analysis.Results:In SSc pts the percentage of circulating M2 cells (CD14+CD204+CD163+CD206+cells) was significantly increased compared to both HSs and SSc pts not under immunosuppressive treatment (pConclusion:The study confirmed that SSc pts are characterized by a significant increase of circulating M2 cells, suggesting their possible involvement in the pathogenesis of the disease. Interestingly, results insinuate that sera from SSc patients already in an “Early” NVC condition (sera known to contains specific profibrotic molecules such as cytokines, growth factors like TGFb1 or endothelin-1) seem able to inducein vitroa profibrotic M2 macrophage phenotype.References:[1]Cutolo M et al. ExpRevClin Immunol. 2019;15:753-64.[2]Stifano G et al. Curr Rheumatol Rep. 2016; 18:2. doi: 10.1007/s11926-015-0554-8.[3]Medeiros NI et al. Parasite Immunol. 2017;39: doi: 10.1111/pim.12446.Disclosure of Interests:Stefano Soldano: None declared, Samuele Tardito: None declared, Sabrina Paolino: None declared, Massimo Patanè: None declared, Emanuele Gotelli: None declared, Claudio Corallo: None declared, Carmen Pizzorni: None declared, Greta Pacini: None declared, Federica Goegan: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Carlotta Schenone: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease, characterized by autoimmune inflammatory microvascular damage with progressive loss of capillaries, fibrosis and ischemia of skin and internal organs. (1) Nailfold videocapillaroscopy (NVC) is a safe toll for early diagnosis of SSc, it identify morphological changes of vessel that are predictive for clinical disease progression and organ involvement.(2) About clinical complication the loss of bone mass and body composition abnormalities, particularly muscle mass and strength loss (sarcopenia), are recognized in advanced disease.(3)Objectives:To evaluated in SSc patients, the body composition and the bone status according to the microvascular condition, assessed and scored by nailfold videocapillaroscopy (NVC, “Early”,”Active”,”Late” patterns).Methods:Body composition and bone mineral density (BMD) were assessed by DEXA in 35 female SSc patients classified according to the 2013 EULAR/ACR criteria and 32 sex-matched healthy subjects. Clinical, laboratory, body composition and bone parameters were analysed according to the different NVC patterns. Means were compared by the Student’s t test or one way analysis of variance; medians were compared by the Kruskall Wallis test; and frequencies by the chi square test.Results:Higher prevalence of vertebral (26.4%vs 9.3%) and femoral (32.3% vs 9.3%) osteoporosis (OP) was found in SSc. Particularly SSc patients with “Late” NVC pattern showed a significantly higher prevalence of vertebral (p=0.018) and femoral OP (p=0.016). Regional assessment of bone mass (BM) in 7 different body areas showed a significant lower BMD only at the total spine (P=0.008) and femoral neck (p=0.027) in advanced microvascular damage. Patients with “Late” NVC pattern showed lower whole body lean mass (LM) compared to “Early” and “Active” NVC patterns, particularly at upper limbs. To note, in all body sites, BMD correlate with LM and BMC according to NVC pattern severity.Conclusion:SSc patients with most severe microvascular damage show a significantly altered body composition and bone status suggesting a strong link between microvascular failure and associated muscle/bone sufference.References:[1]Cutolo M et al. Expert Rev Clin Immunol 2019; 15(7):753-64[2]Cutolo M et al. Clin Rheumatol 2019; 38(9):2293-7[3]Corallo C et al. Rheumatol Int 2019;39(10):1767-75.Disclosure of Interests:Sabrina Paolino: None declared, Emanuele Gotelli: None declared, Andrea Casabella: None declared, Francesco Cattelan: None declared, Carlotta Schenone: None declared, Massimo Patanè: None declared, Greta Pacini: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Nailfold videocapillaroscopy (NVC) abnormalities in subjects with isolated Raynaud’s phenomenon (RP) may be present before transition to secondary RP(SRP) and development of a NVC “scleroderma pattern” and are known to predict for evolution to a connective tissue disease (CTD) within few years [1]. In a previous study, we have demonstrated that the very early increase of capillary diameter over 30 μm is an independent predictor for development of Systemic Sclerosis (SSc) associated SRP [2].Objectives:Present pilot retrospective study aimed to investigate in a cohort of patients affected by CTD–related RP the presence of very early capillaroscopic morphological and quantitative abnormalities in the acquired pictures of NVC performed before the development of the NVC scleroderma-pattern. In particular, the study was addressed to identify a “very early”scleroderma pattern, in order to intercept patients with RP at high risk of evolution in a CTD, specifically SSc.Methods:We selected the NVCs of 273 SSc patients presenting one of the validated NVC “scleroderma patterns”. We enrolled 26 SSc patients having a NVC analysis performed before the development ofthe “very early”NVC pattern. As controls, we evaluated 26 patients affected by other CTDs with stable non-scleroderma pattern over time. The 16 images per patient obtained by NVC examination were analyzed for total number of capillaries, number and the limbs diameters of capillaries with a diameter >30 μm, and microhemorrhages. Statistical analysis was performed using non-parametric tests.Results:All 26 SSc patients showed dilated capillaries with a diameter >30 μm in their previous NVC. Patients later developing scleroderma pattern had statically higher number and percentage of capillaries with a diameter >30 μm (p=0.0004 and p=0.0005), as well as a larger apical dilatation >40 μm (p=0.002). A progressive and significant increase in all capillary diameters were only detected in patients later diagnosed for SSc (apical p=0.006, venous p=0.02, arterial p=0.03). A significant homogeneous and progressive dilation was observed from the apical region and then involving both venous and arterial branches, only in SSc patients (p=0.002).Conclusion:Present pilot study demonstrates, for the first time that, before to develop a validated NVC scleroderma-pattern, all potential SSc patients present significant very early morphological and quantitative NVC changes. In particular, the progressive and homogeneous capillary loop dilation over 40 μm in over 40% of total number capillaries significantly could contribute to identify RP patients who will develop a SSc pattern after 4-5 years.References:[1]Cutolo M, Sulli A, Pizzorni C, Accardo S. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol. 2000;27:155-60.[2]Trombetta AC, et al. J Rheumatol 2016;43:599-606.Disclosure of Interests:Monica Pendolino: None declared, Carmen Pizzorni: None declared, Sabrina Paolino: None declared, Federica Goegan: None declared, Emanuele Gotelli: None declared, Carlotta Schenone: None declared, Francesco Cattelan: None declared, Massimo Patanè: None declared, Elisa Alessandri: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:In the SENSCIS trial, nintedanib reduced the progression of SSc-ILD vs placebo, as shown by a lower rate of decline in forced vital capacity (FVC). The adverse event (AE) profile of nintedanib was characterised mainly by gastrointestinal (GI) events, including weight loss.Objectives:Assess FVC decline and AEs in subgroups by weight loss ≤5% vs >5% over 52 weeks in the SENSCIS trial.Methods:Patients with SSc-ILD with first non-Raynaud symptom 5%) over 52 weeks.Results:In the nintedanib (n=288) and placebo (n=288) groups, respectively, 112 (38.9%) and 43 (14.9%) patients had weight loss >5% over 52 weeks. At baseline, patients with weight loss >5% over 52 weeks had a higher mean age (57.0 vs 52.9 years), greater proportion of females (81.3% vs 72.9%), and similar mean BMI (26.5 vs 25.7 kg/m2, respectively) and FVC % predicted (71.0% vs 73.1%, respectively) vs patients with weight loss ≤5%. In the placebo group, the mean (SE) annual rate of decline in FVC was similar between patients who had weight loss ≤5% and >5% over 52 weeks (-92.7 [14.7] mL/year and -96.4 [34.9] mL/year, respectively). The estimated annual rate of decline in FVC was lower in patients treated with nintedanib than placebo, with between-group differences in patients who had weight loss ≤5% and >5% of 49.9 mL/year [95% CI 4.2, 95.6]) and 30.2 mL/year [95% CI -50.5, 110.9]), respectively, with no evidence of heterogeneity between subgroups by weight loss (p=0.68 for interaction). Standardised differences in baseline values of potential confounders were 5%, respectively), nausea (30.1% and 33.9%, respectively) and vomiting (19.3% and 33.3%, respectively). In the nintedanib and placebo groups, respectively, AEs leading to discontinuation of study drug occurred in 17.0% and 8.6% of patients with weight loss ≤5%, and 14.3% and 9.3% of patients with weight loss >5% over 52 weeks.Conclusion:In the SENSCIS trial in patients with SSc-ILD, a greater proportion of patients treated with nintedanib than placebo had weight loss >5% over 52 weeks. The rate of decline in FVC was numerically lower in the nintedanib group than in the placebo group both in patients with weight loss ≤5% and >5% over 52 weeks. AEs leading to discontinuation of nintedanib were not more frequent in patients with weight loss >5% vs ≤5%.References:Disclosure of Interests: :Alain LESCOAT: None declared, Stéphane Jouneau Grant/research support from: AIRB, Boehringer Ingelheim, LVL Medical, Novartis, Roche, Bellorophon Therapeutics, Biogen, Fibrogen, Galecto Biotech, Gilead Sciences, Pharm-Olam, Pliant Therapeutics, Savara Pharmaceuticals/Serendex Pharmaceuticals, Consultant of: Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GlazoSmithKline, LVL Medical, Mundipharma, Novartis, Pfizer, Roche, Sanofi, Bruno Crestani Grant/research support from: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Novartis, Roche, Sanofi, Consultant of: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Roche, Sanofi, Speakers bureau: AstraZeneca, Boehringer Ingelheim, Roche, Sanofi, Gabriela Riemekasten Consultant of: Cell Trend GmbH, Janssen, Actelion, Boehringer Ingelheim, Speakers bureau: Actelion, Novartis, Janssen, Roche, GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Yasuhiro Kondoh Consultant of: Boehringer Ingelheim, Asahi Kasei Pharma, Janssen, Shionogi, Speakers bureau: Boehringer Ingelheim, Asahi Kasei Pharma, Janssen, Eisai, KYORIN, Mitsubishi Tanabe Pharma, Novartis, Shionogi, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Nina Patel Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Speakers bureau: Genentech, John Huggins Consultant of: I was a site PI for the SENSCIS trial for Boehringer Ingelheim, Christian Stock Employee of: Employee of Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Christopher Denton Grant/research support from: GlaxoSmithKline, CSL Behring, and Inventiva, Consultant of: Medscape, Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Corbus Pharmaceuticals, Acceleron, Curzion and Bayer

Background:Nailfold capillaroscopy (NVC), a non-invasive technique to assess microcirculation, is increasingly being incorporated into rheumatology routine clinical practice. Currently, the degree of description of NVC methods varies amongst research studies, making interpretation and comparison between studies challenging. In this field, an unmet need is the standardization of items to be reported in research studies using NVC.Objectives:To perform a Delphi consensus on minimum reporting standards in methodology for clinical research, based on the items derived from a systematic review focused on this topic.Methods:The systematic review of the literature on NVC methodology relating to rheumatic diseases was performed according to PRISMA guidelines (PROSPERO CRD42018104660) to July 22nd2018 using MEDLINE, Embase, Scopus. Then, a three-step web-based Delphi consensus was performed in between members of the EULAR study group on microcirculation in rheumatic diseases and the Scleroderma Clinical Trials Consortium. Participants were asked to rate each item from 1 (not appropriate) to 9 (completely appropriate).Results:In total, 3491 references were retrieved in the initial search strategy, 2862 were excluded as duplicates or after title/abstract screening. 632 articles were retrieved for full paper review of which 319 fulfilled the inclusion criteria. Regarding patient preparation before the exam, data were scarce: 38% reported acclimatization, 5% to avoid caffeine and smoking, 3% to wash hands and 2% to avoid manicure. Concerning the device description: 90% reported type of instrument, 77% brand/model, 72% magnification, 46% oil use, 40% room temperature and 35% software for image analysis. As regards to examination details: 76% which fingers examined, 75% number of fingers examined, 15% operator experience, 13% reason for finger exclusion, 9% number of images, 8% quality check of the images and 3% time spent for the exam. Then, a three-round Delphi consensus on the selected items was completed by 80 participants internationally, from 31 countries located in Australia, Asia, Europe, North and South America. Some items reached the agreement at the second round (85 participants), and other items were suggested as important to consider in a future research agenda (e.g. temperature for acclimatization, the impact of smoking, allergies at the application of the oil to the nailbed, significance of pericapillary edema, methods of reporting hemorrhages, ramified and giant capillaries). The final agreement results are reported below:Conclusion:On the basis of the available literature the description of NVC methods was highly heterogeneous and individual published studies differed markedly. These practical suggestions developed using a Delphi process among international participants provide a guidance to improve and to standardize the NVC methodology in future clinical research studies.Disclosure of Interests:Francesca Ingegnoli: None declared, Tommaso Schioppo: None declared, Ariane Herrick: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Francesca Bartoli: None declared, Nicola Ughi: None declared, John Pauling: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl

Background:Systemic sclerosis (SSc) is a chronic connective disease characterized by microvascular alterations, dysregulated immune response and fibrosis [1,2]. Myofibroblasts are alpha-smooth muscle actin (alphaSMA)+cells and play a crucial role in fibrosis, through the excessive synthesis and deposition of extracellular matrix (ECM) proteins, in particular fibronectin (FN) and type I collagen (COL1) [3]. Despite myofibroblasts primarily derive from resident fibroblasts transition and differentiation, another important source is represented by circulating fibrocytes [4]. Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis that interferes with the signalling pathways involved in the pathogenesis of fibrosis [5].Objectives:To investigate the possible effects of nintedanib in contrasting the ability of cultured mature fibrocytes from SSc patients to differentiate into profibrotic myofibroblasts.Methods:Circulating fibrocytes were obtained from peripheral blood mononuclear cells isolated from 5 limited cutaneous SSc patients (mean age 68 +/- 10 years) and then plated on FN-coated tissue culture dishes in growth medium (DMEM at 20% of fetal bovine serum, 1% of penicillin-streptomycin and 1% L-glutamine), to allow the adhesion of fibrocyte precursors. Adherent cells were maintained in growth medium for 8 days in order to allow their differentiation into fibrocytes. Differentiated fibrocytes were treated with nintedanib at the concentrations of 100nM and 1000nM for 3 and 24 hours (hrs) or maintained in growth medium without any treatment. The differentiation of fibrocytes into myofibroblasts was determined evaluating the gene expression of alphaSMA, fibroblast specific protein-1 (S100A4) COL1, FN and CXCR4 by quantitative real-time polymerase chain reaction, and the protein synthesis of alphaSMA, COL1 and FN by western blotting.Results:Nintedanib inhibited alphaSMA and S100A4 gene expression already at the concentration of 100nM in cultured fibrocytes and after 3 hrs of treatment, when compared with untreated cells. Furthermore, both concentrations of nintedanib (100nM and 1000nM) reduced the gene expression of COL1 and FN, whereas only 100nM downregulated the CXCR4 gene expression. At protein level, nintedanib 100nM and 1000nM reduced the synthesis of alphaSMA and COL1 after 24 hrs of treatment, whereas FN synthesis was reduced only by the nintedanib concentration of 1000nM.Conclusion:The preliminary results show that nintedanib may inhibit thein vitrotransition of SSc fibrocytes into myofibroblasts and their profibrotic activity, through the reduction of specific myofibroblast phenotype markers and ECM protein production. The results seem to suggest fibrocytes as further possible target of the antifibrotic action of nintedanib in SSc.References:[1]Cutolo M et al. Expert Rev Clin Immunol. 2019;15:753-64 2. Barsotti S et al. Clin Exp Rheumatol. 2016;34(Suppl.100):S3-S13 3. Wynn TA et al. Nat Med. 2012;18:1028-40. 4.Distler JHW et al. Arthritis Rheumatol. 2017;69:257-67 5.Hilberg F et al. Cancer Res. 2008;68:4774-82.Disclosure of Interests:Stefano Soldano: None declared, Giulia Martinelli: None declared, Samuele Tardito: None declared, Sabrina Paolino: None declared, Massimo Patanè: None declared, Emanuele Gotelli: None declared, Claudio Corallo: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Carlotta Schenone: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Sjögren Syndrome (SS) is a rheumatic connective tissue disease in which vascular involvement (e.g. Raynaud’s phenomenon) may occur. No systematic review exists elucidating on the role of nailfold capillaroscopy in SS.Objectives:To give a standardised overview of capillaroscopic changes and clinical associations in SS.Methods:The literature was searched through in three databases by two reviewers. All published original studies which assess patients with SS by capillaroscopy were revised. A quality assessment was applied, based on sample size, population description, presence of a control group, presence of instrumental specifications and/or standardly applied capillaroscopic methodology, presence of clear descriptions of capillaroscopic parameters and based on the used statistical analysis. The capillaroscopic findings were described in a EULAR consented standardised way (1). Significant associations of capillaroscopic parameters in SS-patients with clinical and laboratory variables were also reported.Results:The literature search resulted in 826 hits. Based on title and abstract screening 519 original studies were retained and of these, 12 full texts described an assessment by nailfold capillaroscopy in SS. Six studies (four case-control studies and two case-series) were retained after performing a critical quality assessment (fig 1). EULAR standardised description (table 1) attested conclusive results for capillary ‘morphology’, suggesting a not higher prevalence of abnormal shapes in SS than in healthy (2,3). Concerning clinical associations, capillary density was associated with Raynaud in two studies and with interstitial lung disease in one study (2-4). No association between serologic features (anti-nuclear antibodies, anti-SSA, anti-SSB and anti-RF) and capillaroscopic parameters were found (2,5).Table 1.Standardised description of capillaroscopic characteristics in Sjögren’s Syndrome vs Healthy Legend. Only studies mentioning p-values were considered in this table. *Tektonidou et al. did not report differences between healthy controls and the SS group as a whole, but rather reported differences between healthy controls and subgroups of patients with/without Raynaud’s and with/without centromere antibodies.AssessmentParameterSignificantNot significantConclusionQuantitativeDensity1 study [2]1 study [3]Not conclusiveDimensionDilationGiant0 studies0 studies0 studies1 study [2]Not conclusiveNormal morphologyHairpin shapedTortuosityCrossing0 studies0 studies0 studies0 studies1 study [3]1 study [3]Not conclusiveAbnormal morphology0 studies2 studies [2,3]Equal absence of abnormal morphology in SS vs healthy controlsHaemorrhages0 studies2 studies [2,3]Not conclusive*Semi quantitative0 studies0 studiesNo dataQualitativeNormalNon specific abnormalitiesScleroderma pattern0 studies0 studies0 studies1 study [3]1 study [3]0 studiesNot conclusive*Not conclusive*No dataConclusion:A small number of studies have investigated the role of nailfold capillaroscopy in SS. Prospective follow up studies with standard evaluation and capillaroscopy in SS are warranted.References:[1]Smith et al Autoimmun Rev 2020, DOI: 10.1016/j.autrev.2020.102458[2]Capobianco et al Clin Exp Rheumatol 2005;23(6):789-94[3]Tektonidou et al Rheumatology (Oxford, England) 1999;38(9):826-30[4]Cakmakci et al Tuberk Torakx 2015;63:22-30[5]Corominas et al Rheumatol Int 2016;36(3):365-9Disclosure of Interests:Karin Melsens: None declared, Maria C. Leone: None declared, Sabrina Paolino: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Dirk Elewaut: None declared, Roberto Gerli: None declared, Isabelle Peene: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl

Background:Lower urinary tract symptoms (LUTS) are an underdiagnosed but frequent manifestation in systemic sclerosis (SSc) [1]. LUTS pathogenesis in SSc is undetermined, mainly involving dysautonomia, fibrosis and a possible antibody-mediated damage [2]. Divergently from general population, female sex and advanced age are not reported to significantly impact LUTS in SSc [2].Objectives:To evaluate the potential influence of gender and hormone-related factors in LUTS prevalence and severity among SSc patients (Pts).Methods:A population of 42 SSc Pts and 50 age- and sex-matched healthy subjects (HSs) was evaluated. SSc diagnosis was based on 2013 ACR/EULAR criteria. Demographic data, medications interfering with pelvic floor dynamics and general comorbidities commonly associated with LUTS – diabetes mellitus, chronic heart failure, chronic obstructive pulmonary disease, peripheral neuropathy, pelvic organ prolapse, fecal incontinence – were recorded. Validated self-reported questionnaires derived from the International Conference on Incontinence were used to assess prevalence and severity of LUTS, namely of urinary incontinence (UI) and overactive bladder (OAB) [3]. Data were analysed using non-parametric tests. Apvalue Results:There were no significant differences in main demographic data between SSc Pts and HSs. Specifically, median age was 61 years (IQR 21-85)vs57 years (IQR 28-93) and female prevalence 83%vs84% in SSc PtsvsHSs, respectively. Amongst the female population, 83% of SSc Ptsvs84% of HSs was in post-menopausal state, with a median of 1 (IQR 0-3)vs1 (IQR 0-4) pregnancy by natural route, respectively. No woman of the study had received hormone replacement therapy or local hormonal therapies prior to the study. Similarly, there were not any significant differences in analysed comorbidities, while ongoing treatment was significantly different between the two populations, SSc patients more frequently receiving calcium channel blockers and glucocorticoids than healthy subjects (p< 0.001). In SSc Pts, statistically significant correlation was observed between stress UI and sex, with an increased female-to-male ratio (p< 0.005), but any significant difference was observed in US distribution depending on parity and menopausal state, nor on other analysed variables. Interestingly, female dominance has not resulted as a significant predictive factor for LUTS prevalence or severity in SSc Pts. In fact, in the regression analysis, SSc disease was the only significant predictor for LUTS (OR 3.45, 95% CI 1.41-7.95; p< 0.01), independently of other analysed variables, particularly of gender and hormone-related factors.Conclusion:This study confirms the absence of pathogenic female-gender participation in LUTS prevalence among SSc Pts. However, consistently with findings on general population, a significant increased prevalence of urinary symptoms, particularly of stress UI, in SSc female Pts has emerged [4]. It is therefore conceivable that hormonal factors may act as a catalytic circumstance rather than pathogenic players in LUTS progression during SSc disease.References:[1]John G et al. Arthritis Care Res (Hoboken) 2018;70(8):1218–27.[2]John G. Clin Rheumatol. 2020;39(1):5–8[3]Abrams P et al, J Urol. 2006;175:1063–6[4]Abelson B et al. Biol Sex Differ. 2018;9(1):45Disclosure of Interests:Greta Pacini: None declared, Sabrina Paolino: None declared, Federica Goegan: None declared, Pietro Francesco Bica: None declared, Elisa Alessandri: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Emanuele Gotelli: None declared, Francesco Cattelan: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Systemic lupus erythematosus (SLE) patients shown an increased risk of low bone mass as a result of multifactorial events: physical inactivity, persistent inflammation, low vitamin D levels (photosensitivity) and glucocorticoid treatment. Trabecular Bone Score (TBS), is an index extracted from the dual-energy X-ray absorptiometry (DXA) that provides an indirect measurement of bone axial microarchitecture and allows to get information about bone quality in several rheumatic diseases (1-4).Objectives:The aims of this study were to examine the prevalence and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in female patients affected by SLE and to compare with matched healthy subjects (CNT).Methods:70 female patients (mean age 41±20 years) affected by SLE and 65 age- matched CNT (mean age 46±7 years) were enrolled. Bone Mineral Density (BMD, g/cm2) of the lumbar spine (L1-L4) was analyzed using a DXA scan (GE, Lunar Prodigy). Lumbar spine TBS was derived for each spine DXA examination using the TBS index (TBS iNsight Medimaps).Results:The mean BMD±SD was 0.47±0.57 g/cm2 at the lumbar spine and 0.78 ± 0.22 g/cm2 at the hip in SLE patients. The prevalence of osteopenia was 40.0% and was 19.4% of osteoporosis in SLE patients. Most of SLE patients (75%) presented a bone loss that was significantly higher when compared with control group (pConclusion:The study shows that the further TBS analysis, independently from the concomitant BMD value, is significatively lower then expected in SLE patients. The detection of the TBS, together with the BMD, may offer a more reliable indication of the real whole bone condition in chronic and systemic inflammatory rheumatic diseases, such as SLE.References:[1]Cutolo M et al. Ann Rheum Dis. 2009;68 446-7; 2 Dey M et al. Lupus. 018;271547-1551; 3 Ruaro B, Casabella A, et al. Rheumatology (Oxford). 2018;57:1548-1554. 4 Ruaro B, Casabella A, et al. Clin Rheumatol. 2018 Nov;37(11):3057-3062.Disclosure of Interests:Andrea Casabella: None declared, Sabrina Paolino: None declared, Elisa Alessandri: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Barbara Ruaro: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

OBJECTIVES: In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes. METHOD: We performed a prospective observational study using the latest 2013 data extract from the EULAR scleroderma trials and research (EUSTAR) cohort. We looked at (i) sex influence on disease characteristics at baseline and (ii) then focused on patients with at least 2 years of follow-up to estimate the effects of sex on disease progression and survival. RESULTS: 9182 patients with SSc were available (1321 men) for the baseline analyses. In multivariate analysis, male sex was independently associated with a higher risk of diffuse cutaneous subtype (OR: 1.68, (1.45 to 1.94); p

In systemic sclerosis (SSc), microvasculopathy is an important feature, resulting in digital ulcers in 30% of patients with SSc each year.1 ,2 Assessment of microvasculopathy in SSc is of clinical interest mostly for diagnostic and therapeutic purposes. Nailfold videocapillaroscopy has in recent years earned its place in SSc as it makes early diagnosis of SSc possible in a Raynaud's population by evaluating morphological capillary abnormalities.3–5 Within an SSc population however, there is need for a technique that can evaluate blood perfusion in a dynamic way, to evaluate evolution of disease and more importantly response to therapy. For the latter, there is no validated technique available so far. Laser speckle contrast analysis (LASCA) is a relatively new technique that measures peripheral blood perfusion (PBP) in real time over a large area, in a non-contact manner, and is less time-consuming; it is thus convenient to implement in daily practice. …

Background Nailfold videocapillaroscopy (NVC) has been proposed as an outcome measure for systemic sclerosis [SSc] related microvascular disease. Objectives To assess the reliability of both measure availability and measured value of 4 parameters extracted from NVC images: capillary density, capillary (apex) width, overall image grade (normal, early, active, late), and the presence of giant capillaries. Methods 173 subjects were recruited in the study (101 with SSc, 22 with primary Raynaud9s phenomenon and 50 controls). Panoramic NVC imaging was performed on all 10 digits using a 300x magnification microscope with green LED illumination for best capillary contrast. Ten capillaroscopy experts (“raters”) from 7 centres assessed images using custom software. Raters were asked to: (1) assess overall image grade (“Normal”, “Early”, “Active”, “Late”, “Non-specific”, or “Ungradeable”), (2) mark the location of capillary apices (capillary density calculated from distal vessel locations), (3) categorically grade the distal vessels in terms of size and shape, and (4) measure the apical width of distal vessels using a click-and-drag tool. Results The 10 raters analysed a median (range) of 129 (98–1641) images, returning 3401 evaluations of 1650 images, including a sub-sample analysed twice by the same rater to measure intra-rater reliability. Of these, 2731 evaluations (80%) satisfied the criteria to allow vessel density to be measured (at least 2 distal vessels identified). The reliability (intra- and inter-rater) of both measure availability and measured value for the 4 parameters are shown in the table. Overall image grade was available in only around 45% of observations due to the exclusion of “non-specific” gradings from the analysis. Conclusions Capillary density and (especially) apical width, parameters likely to be helpful in quantifying temporal change, were reliable measures in evaluable nailbeds. The reliability of measured values is generally high, but is conditional on measure availability. This must be accounted for when considering the applicability of outcome measures to clinical trial situations. With standardised training (and potentially increased automation of analysis), high magnification NVC has strong potential as an outcome measure of SSc-related microangiopathy. Acknowledgement Work funded by the Raynaud9s & Scleroderma Association. Disclosure of Interest None declared

Background Data on pregnancy in Systemic Sclerosis (SSc) are limited;we recently published IMPRESS,a retrospective multicenter study that compared 109 pregnancies from 99 SSc women with a general obstetric population (GOP).In SSc women preterm deliveries (PD, Methods This is a fully prospective,multicenter case-control study of 3 groups of people: 1) 100 pregnant SSc patients, 2) 200 not-pregnant SSc women (matched for age, auto-antibody pattern, limited/diffuse/sine scleroderma – L/D/S – form and obstetric history), 3) 200 healthy pregnant women (matched for age and obstetric history).We will prospectively investigate disease activity during pregnancy and further year,pregnancy outcome and children health status at birth and at 1 year Results 39 pregnancies are currently ongoing,22 patients have already delivered:8 ACA+ (6 L,1 D,1 S),13 Scl70+ (7 L,4 D, 2 S),1 RNA-P3+ D, 2 L form without SSc-specific autoantibodies.We observed 4 miscarriages (1 ACA+, 2 Scl70+,1 RNA-P3+), 1 therapeutic abortion at W22 (ACA+ D in treatment with prednisone 15mg/d and cyclophosphamide),1 early voluntary termination,2 SPD in Scl70+ L (1 cesarean section at W30, due to IUGR and fetal heart rate alteration;1 spontaneous in twin pregnancy: one twin with VLBW and both of them with respiratory distress at birth), 2 PD (both of them in SCl70+ L disease at W 36), 1 pre-eclampsia at W 37 in Scl70+ limited disease, with pulmonary embolism during post-partum. Till now,16 mothers and 28 SSc controls had completed one year surveillance after delivery.We observed disease progression in two cases: the ACA+D patient treated with prednisone and cyclophosphamide who underwent therapeutic abortion showed a kidney function worsening till hemodyalisis;the Scl70+L patient who underwent twin pregnancy showed significant worsening in pulmonary function testing,without specific findings at chest CT. One child,born at W36 from Scl70+L mother, died at 3 months due to cardiac malformation and aesopaghus atresia;all other children showed a regular growth at 12 months pediatric evaluation Conclusions IMPRESS 2 is still going on,and we hope to answer to important questions: 1) are complications of SSc more frequent during pregnancy? 2) Are some autoantibodies protective for prematurity? 3) Which is the impact of prematurity on children development? Disclosure of Interest None declared

The difference between a normal capillaroscopy and an “abnormal” capillaroscopy is important in the differential diagnosis between a primary Raynaud9s phenomenon (=not linked to any condition) from a secondary RP. A normal capillaroscopic pattern, by qualitative assessment, is characterized by a homogeneous distribution of hairpin shaped capillaries as a “comb-like structure”, with a density of between 9–14 capillaries per mm. Yet, there exists a wide intra- and inter-individual variety in a normal population (non-specific variations) which will be discussed during the workshop. An abnormal capillaroscopic image due to systemic sclerosis (SSc) is characterized by (a combination) of specific changes (giants, capillary loss, hemorrhages and abnormal shapes (ramifications)). Depending on their relative prevalence three SSc-patterns are described by Cutolo et al. with a 200 magnification videocapillaroscope: the “early”, “active” and “late” scleroderma pattern. The combination of the presence of a scleroderma pattern on capillaroscopy with the presence of an SSc-specific antibody in a patient with Raynaud9s phenomenon allows the “early” diagnosis of SSc. When the patient also has “puffy” fingers he/she meets the VEDOSS criteria for very early diagnosis of SSc. In patients with connective tissue diseases “other than” SSc and diseases of the scleroderma spectrum there are no “unique” capillary patterns. A variety of capillary abnormalities (change in morphology, dimension, presence of hemorrhages) have been observed. These abnormalities by themselves are not predictive of any defined condition and may be referred to as non-specific abnormalities. Disclosure of Interest None declared

Background Iloprost (ILO) and bosentan (BOSE) integrated therapy was demonstrated to improve microvascular structure in systemic sclerosis (SSc) patients, in two long-term follow up studies [1]. Objectives Since the alterations in capillary number seem to predict the incidence of clinical SSc complications [2], present study aimed to quantify, by nailfold videocapillaroscopy (NVC), long-term effects of BOSE treatment on nailfold capillary absolute number and their possible correlation with clinical parameters of the disease. Methods Thirty SSc patients entered the study, with a follow up of for 4 years. Fifteen patients were treated with ILO mono-therapy (80 μg/day, for 5 continuous days, every 3 months), while other 15 patients, because of the onset of systolic pulmonary hypertension (sPAP) or digital ulcers (DUs) were treated with BOSE (125 mg twice/day) and ILO integrated therapy (ILO+BOSE). Nailfold capillaries absolute number, DU incidence, diffusing capacity of the lung for carbon monoxide (DLCO), sPAP and renal artery resistive index (RI) were evaluated yearly. Friedman test, Cochran9s q test, Marginal homogeneity and mixed modelling were used to study variables with repeated measures. A p value lower then 0.05 was considered significant. Results In the ILO+BOSE group, capillary absolute number was found to have a significant increase (p=0.01) from T0: 6.8±1.3 to T4: 7.8±1.5 (14.7%), whereas in the ILO group, a non-significant decrease in capillary number from T0: 7.18±0.5 to T4: 6.5±1.1 (9.4%) was found. According to multivariate analysis, the most significant associations, other then BOSE treatment, were observed between capillary number increase and baseline capillaroscopic “Early” pattern (p Conclusions Capillary absolute number count seems a reliable parameter to evaluate long-term effects of BOSE on microvasculature in SSc. A significant reduction in the annual incidence of new DUs and stabilization of lung function was observed and appeared to be associated to the increased number of capillaries during a four-years integrated treatment with BOSE and ILO. References Cutolo M et al. 2013;40:40–5. Smith V et al. 2011;70:180–3. Disclosure of Interest None declared

Background Patients with anti-RNA polymerase III antibodies (anti-RNAP) have an increased risk of malignancies synchronous to the onset of Systemic Sclerosis (SSc). In a multicentre EUSTAR case-control study, however, only moderate odd ratio was observed (OR 3.85, 95%CI 1.3–10.9), except than for breast cancer (OR 20.2, 95%CI 1.4–355) (1). Defining clinical and demographic features characteristic of anti-RNAP+ SSc patients who suffer from simultaneous malignancy would be useful to individuate risk factors who can guide the clinicians in every-day practice to screen anti-RNAP+ SSc patients for cancer. Objectives To individuate risk factors for malignancies synchronous to the onset of SSc in anti-RNAP+ patients. Methods EUSTAR centers were asked to participate to this study, providing data on malignancy history of their anti-RNAP+ patients in a dedicated form. Results Among 158 anti-RNAP+ SSc patients collected from 13 EUSTAR centers, 14 cases of malignancies synchronous to the onset of SSc were identified. When compared with the other 144 anti-RNAP+ patients, patients with synchronous malignancies had an older mean age at SSc onset (65.3 yrs (SD 10.0) vs 49.3 (SD13.3); p Conclusions Anti-RNAP+ SSc patients of older age, and with diffuse cutaneous subset, are particularly at risk for malignancies synchronous to the onset of SSc. The risk of malignancies other than breast cancers is greatly increased in male patients. These risk factors may help in the screening for cancer in these patients. References M.G. Lazzaroni et al. Anti-RNA Polymerase III Antibodies in Patients with Systemic Sclerosis: A Eustar Multicenter Collaborative Study. Ann Rheum Dis 2015;74:Suppl 2 88 doi:10.1136/annrheumdis-2015-eular.1728 Disclosure of Interest None declared

Background Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading causes of death in Systemic Sclerosis (SSc). Although the six-minute walk test (6MWT) is used for evaluating ILD and PAH in clinical practice, no data are available on six-minute walk distance (6MWD) in SSc without ILD and PAH. Objectives This study wants to evaluate the 6MWT at baseline and 6-month follow-up in a cohort of unselected SSc patients without ILD and PAH. Methods Prospectively collected data of the 6MWTs at baseline and 6-month follow-up of 300 consecutive SSc patients, included in the Ghent University Hospital Systemic Sclerosis Cohort between May 2006 and April 2015 were analysed. Results 98% (286/292) of the SSc patients performed a 6MWT at baseline or 6-month visit, after exclusion of 8 of the 300 SSc patients due to logistic problems. Two patients were unable to perform a 6MWT due to leg amputation and 4 due to immobility. 76% of the patients were female with a mean age of 51±14 years. Six patients had PAH, five had ILD and four were not evaluated with HRCT. Eventually 271 SSc patients without ILD and PAH performed a 6MWT at baseline or 6-month visit and 193 at both moments. The mean 6MWD of those 271 SSc patients was 460±108m. Patients in the diffuse cutaneous (DcSSc) subgroup (422±118m) walked less than in the limited (LSSc) subgroup (476±109m, p=0.02) and tended to walk less than in the limited cutaneous (LcSSc) subgroup (463±101m, p=0.06). In 193 SSc patients without ILD and PAH who walked at both moments, there was no significant difference between the 6MWDs (mean difference 2.11m 95%CI [-6.75m; 10.98m], p=0.64). Conclusions In SSc, execution of the 6MWT is feasible, as 98% of the SSc patients were able to perform a test. The baseline mean 6MWD of 271 SSc patients without ILD and PAH is 460±108m and is clinically stable over a 6 months period. The DcSSc subgroup walks less than the LSSc subgroup and the LcSSc subgroup. Disclosure of Interest None declared

Clinical rheumatologists frequently get patients with Raynaud9s phenomenon (discoloration of extremities upon exposure to cold or stress) referred. The challenge is to distinguish patients with a primary Raynaud9s phenomenon (not connected to any connective tissue disease) from patients with a secondary Raynaud9s phenomenon (due to a connective tissue disease). A large 20-year follow-up study (Koenig Arthritis Rheum 2008) of patients presenting at baseline with merely the Raynaud9s phenomenon and no sign of a connective tissue disease has taught the scientific community that if a CTD is to develop in such a population then it is systemic sclerosis. Subsequently it makes sense to screen for SSc in a Raynaud9s phenomenon population. In 1992 LeRoy and Medsger proposed criteria to distinguish primary from secondary Raynaud9s phenomenon. Retrospective validation of these criteria allow correct classification of a patient in one clinical consultation in 89%. Amongst other criteria, a “normal” capillaroscopy is obligatory to be able to speak of a “primary” Raynaud9s phenomenon. Conversely patients with a secondary RP due to SSc have the combination of a SSc-specific antibody and a scleroderma pattern on capillaroscopy. These criteria have prospectively been validated. The triade of RP, SSc-specific antibody and scleroderma pattern on capillaroscopy has a high positive predictive value for the development of SSc, whilst the absence of SSc-specific antibodies and a scleroderma pattern has a high negative predictive value for the non-occurrence of SSc. Disclosure of Interest None declared

Background Peripheral blood perfusion is reduced in patients with both primary (PRP) or secondary Raynaud9s phenomenon (SRP) (1–2). Objectives To investigate blood perfusion (BP) in different skin areas of hands in patients with PRP, SRP to systemic sclerosis (SSc), and healthy subjects (CNT). Methods 70 SSc patients (ACR/EULAR criteria) (3) (mean age 63±12 years, mean disease duration 6±5 years), 31 PRP patients (LeRoy criteria) (4) (mean age 48±18 years, mean Raynaud duration 3±2 years) and 68 CNT (mean age 59±19 years) were enrolled during winter time, after informed consent. BP was assessed by Laser speckle contrast analysis (LASCA) at the level of fingertips, periungual areas, dorsal and palmar aspect of 3rd finger bilaterally, dorsum and palm of both hands, and the average BP calculated as perfusion units (PU) (1). Nailfold videocapillaroscopy (NVC) was also performed to distinguish between PRP and SRP, and to detect the proper pattern of nailfold microangiopathy (“early”, “active” or “late”) in SSc patients (5). Patients were not taking vasodilator drug since at least two weeks. Results Both PRP and SSc patients showed a statistically significant lower BP than CNT at the level of fingertips (median 86, 88, 186 PU, respectively, p Conclusions By considering a small cohort of patients, BP of hand was found lower in PRP than in SSc patients with the “early” NVC pattern of microangiopathy. Also the gradients of perfusion between distal and proximal areas of hand were significantly lower in PRP than in SSc patients. The clinical value of this new early finding is matter of further analysis. References Ruaro B, et al. Ann Rheum Dis 2014;73:1181–5. Rosato E, et al. Rheumatology 2009;36:2257–63. van den Hoogen F, et al. Ann Rheum Dis 2013;72:1747–55. LeRoy EC, et al. Clin Exp Rheumatol.1992;10:485–8. Sulli A, et al. Arthritis Rheum. 2012;64:821–5. Disclosure of Interest None declared

Background Microcirculatory impairment in patients with Raynaud9s phenomenon (RP) may be assessed by different techniques, but real-life data concerning their roles and current usage are not available. Objectives To obtain an overview of the specific techniques which may be used for the assessment of adult patients with RP in clinical and research settings: nailfold videocapillaroscopy (NVC), dermoscopy, stereomicroscopy, and digital USB microscopy, laser Doppler flowmetry, imaging, and anemometry/velocimetry, laser Speckle Contrast Analysis (LASCA), thermographic imaging, upper limb arterial Doppler ultrasound. Methods This survey was conducted online between October and December 2015 on behalf of EULAR study group on Microcirculation in Rheumatic Diseases (SG_MC/RD). Emails with a link to the survey were sent to physicians from the European Scleroderma Trials and Research group (EUSTAR) and SG_MC/RD mailing lists. Of those e-mailed, 418 were physicians looking after adult patients, and this group was considered in the following descriptive analysis. Results Of the 418 eligible physicians, 107 completed the survey, giving an overall response rate of 25.6%. Among the respondents 89 (83.2%) were rheumatologists, 74 (69.2%) European; 87 (81.3%) were practising for more than 10 years and 50% looked after between 31 and 60 patients per year with primary and/or secondary RP. The most routinely performed technique was NVC (63/107, 58.9%) both by rheumatologists and non-rheumatologists (54/89, 60.7% and 9/18, 50.0%). NVC was reported as the most available technique (93/107, 86.9%), and available in the place of work in 78/107 (72.9%) among both rheumatologists and non-rheumatologists. Nailfold capillaroscopy was the most frequently performed by the physician him/herself by using different types of equipment relating to availability: NVC 64/94 (68.0%), dermoscopy 38/63 (60.3%), stereomicroscopy 31/42 (73.8%), and digital USB microscopy 34/39 (87.1%). Most rheumatologists reported high levels of “appropriateness” for NVC in both clinical and research settings for global assessment (86/88, 97.7% clinical setting, 87/88, 98.9% research setting), and differential diagnosis of primary and secondary RP (clinical and research setting both 84/87 96.5%). In clinical setting NVC showed the highest percentage of appropriateness for monitoring primary RP (84/88, 95.4%), RP secondary to connective tissue diseases other than systemic sclerosis (82/87, 94.2%) and to systemic sclerosis (87/87, 100%). All techniques other than capillaroscopy reached a consensus lower than 2/3 of respondents based on their knowledge/experience. In research setting, all techniques were judged as potentially useful with a consensus more than 2/3 of respondents. Conclusions Of all the different techniques upon which opinion was sought, nailfold capillaroscopy was the one most used by physicians looking after adult patients in both clinical and research settings, the majority of whom use NVC in their everyday practice. The low proportion of clinicians using other techniques suggests that these are currently confined to specialist centres. Disclosure of Interest None declared

Objective Assessment of associations of nailfold videocapillaroscopy (NVC) scleroderma patterns (‘early’, ‘active’ and ‘late’) with future severe clinical involvement in a systemic sclerosis (SSc) population. Methods Sixty-six consecutive patients with SSc according to the LeRoy and Medsger criteria underwent NVC assessment at baseline. Videocapillaroscopic images were classified into ‘normal’, ‘early’, ‘active’ or ‘late’ NVC pattern. Clinical evaluation was performed for nine organ systems (general, peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart and kidney) according to the disease severity scale of Medsger (DSS) at 18–24 months of follow-up. Severe clinical involvement was defined as category 2–4 per organ of the DSS. Results NVC patterns were significantly associated with future severe, peripheral vascular/lung involvement at 18–24 months. The OR rose steadily throughout the patterns. The OR for future severe peripheral disease based on simple/multiple (correcting for disease duration, subset and medication) logistic regression was 2.49/2.52 (95% CI 1.33 to 5.43, p=0.003/1.11 to 7.07, p=0.026) for early, 6.18/6.37 for active and 15.35/16.07 for late NVC scleroderma patterns versus the normal NVC pattern. The OR for future severe lung involvement based on simple/multiple regression was 2.54/2.33 (95% CI 1.40 to 5.22, p=0.001/1.13 to 5.52, p=0.021) for early, 6.43/5.44 for active and 16.30/12.68 for late NVC patterns. Conclusions This pilot study is the first demonstrating an association between baseline NVC patterns and future severe, peripheral vascular and lung involvement with stronger odds according to worsening scleroderma patterns. This may indicate a putative role of capillaroscopy as a biomarker.

ObjectiveTo identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc).MethodsA list of items provided by European League Against Rheumatism (EULAR) Scleroderma Trial and Research(EUSTAR) centres were subjected to a Delphi exercise among 110 experts in the field of SSc. In round 1, experts were asked to choose the items they considered as the most important for the very early diagnosis of SSc. In round 2, experts were asked to reconsider the items accepted after the first stage. In round 3, the clinical relevance of selected items and their importance as measures that would lead to an early referral process were rated using appropriateness scores.ResultsPhysicians from 85 EUSTAR centres participated in the study and provided an initial list of 121 items. After three Delphi rounds, the steering committee, with input from external experts, collapsed the 121 items into three domains containing seven items, developed as follows: skin domain (puffy fingers/puffy swollen digits turning into sclerodactily); vascular domain (Raynaud's phenomenon, abnormal capillaroscopy with scleroderma pattern) and laboratory domain (antinuclear, anticentromere and antitopoisomerase-I antibodies). Finally, the whole assembly of EUSTAR centres ratified with a majority vote the results in a final face-to-face meeting.ConclusionThe three Delphi rounds allowed us to identify the items considered by experts as necessary for the very early diagnosis of SSc. The validation of these items to establish diagnostic criteria is currently ongoing in a prospective observational cohort.