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Background The main clinical associations of anti-PM/Scl in Systemic Sclerosis (SSc) include calcinosis, joint and muscle involvement, interstitial lung disease (ILD), and, possibly, scleroderma renal crisis (1,2). A possible association of anti-PM/Scl with cancer was reported in single-centre SSc series (2,3), but was never analysed in large multicentre studies. Moreover, the characteristics of malignancies, in particular their temporal association with the onset of SSc, were not explored. Objectives To evaluate the association of anti-PM/Scl with malignancies in a large, international, multicentre cohort. Methods 16 EUSTAR centres provided data on anti-PM/Scl+ SSc patients in their cohorts (cases), and on anti-PM/Scl-negative controls, matched for sex, age at onset (±5 years), cutaneous subset, and disease duration (±24 months). Only SSc patients with age >16 years at disease onset were included in this analysis. Anti-RNA Polymerase3+ patients were not included in controls, given the known association with synchronous cancer. Malignancies diagnosed between 2 years before and after the onset of SSc were defined as “synchronous to the onset of SSc”. Results 123 anti-PM/Scl+ SSc patients and 160 matched anti-PM-Scl- controls (28% anti-Topoisomerase I, 40% anti-centromere, 32% others) were compared (Table 1): anti-Pm/Scl+ patients had a higher prevalence of myositis (p Conclusion: in this EUSTAR multicentre case control-study, the association of anti-Pm/Scl with malignancies in SSc patients could not be confirmed. Patients with older age at SSc onset seems to be at higher risk for synchronous malignancies, regardless the autoantibody status. References [1] Lazzaroni MG, et al. Ann Rheum Dis2018; 77:(Suppl 2),421-422. [2] Bruni C, et al. Rheumatology (Oxford). 2017;56:317-8. [3] Bernal-Bello D, et al. Autoimmun Rev2017;16:461-8. Acknowledgement Authors would like to thank GILS (Gruppo Italiano Lotta Sclerodermia) for the grant to support this project Disclosure of Interests Maria Grazia Lazzaroni: None declared, Stefania Zingarelli: None declared, Jeska de Vries-Bouwstra: None declared, Eric Hachulla Consultant for: Received consulting fees or other remuneration from Actelion, GSK, Pfizer, and Bayer, Elisabetta Zanatta: None declared, Simone Barsotti: None declared, Marie-Elise Truchetet: None declared, Giacomo De Luca Speakers bureau: Pfeizer, Sobi, Vanessa Smith: None declared, Ellen De Langhe: None declared, Roger Hesselstrand: None declared, Francesca Ingegnoli: None declared, Cristian Caimmi: None declared, Silvia Bellando Randone: None declared, Enrico Colombo: None declared, Angela Ceribelli: None declared, Franco Franceschini: None declared, Yannick Allanore Grant/research support from: Inventiva, F Hoffman La-Roche, Sanofi, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer, Roche, Sanofi, Paolo Airo: None declared

Background Some patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) develop progressive ILD, but the prevalence is unknown and no validated algorithms for early detection exist. Objectives To assess the frequency of, and parameters associated with, progressive SSc-ILD in the EUSTAR database. Methods Patients from the EUSTAR database registered after 2010, ≥18 yrs old, fulfilling SSc classification criteria, with serial lung function, HRCT assessments and disease duration recordings were eligible. Progressive ILD, assessed as absolute changes in%predicted, was defined as: significantly progressive (FVC decline >10% or FVC decline 5−10% and DLCO decline ≥15%); moderately progressive (FVC decline 5−10%); or stable ( Results 826 SSc-ILD patients were included; 219/826 (26.5%) showed moderate/significant ILD progression at 12±3 months’ follow-up. Baseline FVC, erythrocyte sedimentation rate, modified Rodnan skin score (mRSS), GERD and disease duration were significantly associated with significant progressive fibrosis in uni- and multivariable modelling (area under curve 0.67). Serial lung function data with median follow-up of 5 yrs were available in 411/826 (49.8%) patients. In 128/411 with initial progressive ILD at 12±3 months, 59/128 (46.1%) showed further progression, while 69/128 (53.9%) were stable. Baseline FVC, mRSS and disease duration were significantly associated with further ILD progression. The incident cumulative frequency of moderate and significant ILD progression was 22.9% (n=189/826) and 28.5% (n=235/826) during the median 5-yr follow-up and time to first progressive event (Figure). Conclusion This study provides novel insights into the frequency, severity and association of progressive fibrosis in patients with SSc-ILD in the EUSTAR database. Acknowledgement Funding: Boehringer Ingelheim (Schweiz) GmbH, Switzerland Disclosure of Interests Anna-Maria Hoffmann-Vold Grant/research support from: Received research funding or other remuneration from Boehringer Ingelheim, GSK, and Actelion, Consultant for: Received consulting fees or other remuneration from Boehringer Ingelheim, GSK, and Actelion, Speakers bureau: Actelion and Boehringer Ingelheim, Yannick Allanore Grant/research support from: Inventiva, F Hoffman La-Roche, Sanofi, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer, Roche, Sanofi, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Nicole Graf Grant/research support from: Received consulting fees or other remuneration from Astellas and Biotronik, Paolo Airo: None declared, Lidia P. Ananyeva: None declared, Laszlo Czirjak: None declared, Serena Guiducci: None declared, Eric Hachulla Consultant for: Received consulting fees or other remuneration from Actelion, GSK, Pfizer, and Bayer, Mengtao Li: None declared, Carina Mihai Consultant for: Received consulting fees or other remuneration from Actelion, Geneva, Roche, and Rofarm, Consultant for: F. Hoffmann-La Roche, Actelion, Geneva Romfarm, Gabriela Riemekasten Consultant for: Chugai, F. Hoffmann-La Roche, Speakers bureau: Chugai, F. Hoffmann-La Roche, Petros Sfikakis: None declared, Gabriele Valentini Grant/research support from: Received research funding and other remuneration from AbbVie, BMS, Lilly, Pfizer, and Sanofi, Consultant for: Received consulting fees and other remuneration from AbbVie, BMS, Lilly, Pfizer, and Sanofi, Otylia Kowal-Bielecka Consultant for: Received consulting fees or other remuneration from Bayer, Boehringer Ingelheim, Inventiva, Medac, Novartis, and Roche, Oliver Distler Grant/research support from: Prof. Distler received research funding from Actelion, Bayer, Boehringer Ingelheim and Mitsubishi Tanabe to investigate potential treatments of scleroderma and its complications, Consultant for: Prof. Distler has/had consultancy relationship within the last 3 years with Actelion, AnaMar, Bayer, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, iQvia, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Serodapharm and UCB in the area of potential treatments of scleroderma and its complications. In addition, he had/has consultancy relationship within the last 3 years with A. Menarini, Amgen, Abbvie, GSK, Mepha, MSD, Pfizer and UCB in the field of arthritides and related disorders

Background We have little real-world data in France on the natural history and management of patients with GCA. Objectives The objective of this observational study, named ARTEMIS, was to describe the characteristics and management of patients with GCA in real-life settings in France. Methods This was a cross-sectional, non-interventional, multicentre, single-visit survey, conducted among hospital-based physicians specialized in internal medicine or rheumatology. Investigators enrolled consecutive patients ≥ 50 years old seen for GCA and currently under treatment. Information on medical practices, such as patient characteristics and diagnostic journey, diagnostic methods and specific GCA treatments, were collected on an eCRF. GCA activity was assessed on a 100-mm VAS completed by the patients (PtGA) and physicians (PGA). GCA was considered active for VAS scores ≥10 mm. Newly diagnosed GCA was defined as diagnosis (Dg)-to-visit interval 3 months). Descriptive statistics were used for quantitative and qualitative variables. Results Over the 3-month inclusion period (August–November 2018), 306 patients were recruited (females: 67.3%, age at Dg ≥70 years: 72.5%); 260 (85.0%) and 46 (15.0%) were followed by internists or rheumatologists, respectively. Overall, 39 (12.7%) had newly diagnosed GCA, 267 (87.3%) had a GCA duration ≥ 6 weeks (mean follow-up 24.0±27.0 months). Original referral of patients to specialized centres was from GPs (55.9%), ophthalmologists (10.1%), neurologists (6.9%), emergency physicians (5.6%), internists (4.2%) and rheumatologists (4.9%). Mean time to Dg was 3.3±6.9 months, with an “intermediate” Dg interval for 57.5% of patients. The most common prior medical histories were hypertension (45.8%), psychiatric disorders (10.1%), dyslipidemia (11.8%), diabetes (9.5%) and osteoporosis (5.9%); during follow-up psychiatric disorders, diabetes and osteoporosis were more often reported: 12.1%, 14.7% and 8.5% of patients respectively. Initial GCA presentations included cranial symptoms (89.5% of patients), constitutional symptoms (73.9%), polymyalgia rheumatica (48.4%), and other extra-cranial manifestations (34.0%). Initial mean ESR and CRP level were 73.0±30.7 mm/hr and 87.3±68.3 mg/l. Temporal artery biopsy, high-resolution temporal artery Doppler ultrasonography, 18FDG-PET and aortic angio-CT were performed for 84.7%, 31.2%, 26.4% and 29.7% of patients, respectively, and contributed to GCA Dg for 67.1%, 52.7%, 70.3% and 36.8%. At study visit, PtGA was 28.1±26.4 and PGA was 13.1±21.4. Ongoing medications included glucocorticoids (GC) for 273 (89.2%) patients (mean dose: 14.9±16.7 mg/d), methotrexate for 35 (11.4%) and tocilizumab for 44 (14.4%). In total, 122 (39.9%) patients had ≥1 relapse (mean number of relapses: 1.7±1.0) after a mean time to a first relapse of 13.3±12.8 months. Total cumulative oral GC dose was 5179±4987 mg. GCA-related complications occurred in 48 (15.7%) pts with eye disorders in 15 (5.2%). Conclusion This observational, cross-sectional study of a large number of patients provides insight into current medical practices for GCA in France. Despite extensive use of large-vessel imaging, the proportion of patients diagnosed with non-cranial GCA is small (10%). The substantial proportion of patients with relapsing disease results in high cumulative doses of glucocorticoids. The number of patients with tocilizumab treatment was slightly greater than that with methotrexate treatment. Disclosure of Interests Alfred Mahr Consultant for: Chugai Pharma France, Speakers bureau: Roche SAS Chugai Pharma France, Marc Paccalin Consultant for: Chugai, Eric Hachulla Consultant for: Received consulting fees or other remuneration from Actelion, GSK, Pfizer, and Bayer, Isabelle Idier Employee of: ChugaiPharma france, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche

Background: The European League Against Rheumatism Study Group on Microcirculation in Rheumatic Diseases is a non-profit international network of expert centres. Its main research focus is to investigate the morphology and function of the microcirculation with different non-invasive techniques such as nailfold videocapillaroscopy (NVC). NVC is of paramount importance for the differential diagnosis of primary and secondary Raynaud’s phenomenon [1], and is part of the 2013 ACR/EULAR classification criteria for systemic sclerosis. As there is a wide variety of non-scleroderma patterns, the categorisation of capillaroscopic images as non-scleroderma patterns may be a challenge to the capillaroscopist. Objectives: This study was designed to propose a simple fast track algorithm to differentiate scleroderma patterns from non-scleroderma patterns and to assess its interobserver reliability. Methods: During the 8th EULAR course on capillaroscopy held in Genoa, September 2018, a lecture on teaching the fast tract algorithm to categorise an image as non-scleroderma (category 1) or scleroderma pattern (category 2) (see figure) was given to all attendees (from 43 different countries): 6 experts, 68 novices, 53 moderately experienced ( 5 years of experience with capillaroscopy). Immediately after training, an examination was performed on 30 images. Classification of the images was defined by the presenter (VS) as the gold standard. Interobserver reliability was assessed by the calculation of kappa coefficients and proportion of agreement versus the gold standard. Results: The light kappa was 1 for the independent experts (n=6) and 0.92 for the attendees (n=135). When comparing with the gold standard, an equal mean kappa of 0.96 (95%CI 0.95 – 0.98) was found for both independent experts and attendees. Analyses according to the reported level of experience on capillaroscopy revealed a mean index of reliability of 0.98 (95%CI 0.96 – 0.99) for novices, 0.96 (95%CI 0.93 – 0.99) for moderately experienced raters and 0.93 (95%CI 0.85 – 1.01) for experienced raters. Conclusion: For the first time a fast track algorithm has been developed that was trainable within an hour to non-experienced capillaroscopists and has an excellent reliability to discern a non-scleroderma from a scleroderma pattern by medical doctors with varying levels of expertise in capillaroscopy. Reference [1] Koenig M, et al. Arthritis Rheum. 2008;58(12):3902-12. Disclosure of Interests: Vanessa Smith: None declared, Amber Vanhaecke: None declared, Miguel Guerra: None declared, Rossella De Angelis: None declared, Ellen Deschepper: None declared, Christopher Denton Grant/research support from: GlaxoSmithKline, Inventiva, CSF Behring, Consultant for: Roche-Genentech, Actelion, GlaxoSmithKline, Sanofi Aventis, Inventiva, CSL Behring, Boehringer Ingelheim, Bayer, Oliver Distler Grant/research support from: Prof. Distler received research funding from Actelion, Bayer, Boehringer Ingelheim and Mitsubishi Tanabe to investigate potential treatments of scleroderma and its complications, Consultant for: Prof. Distler has/had consultancy relationship within the last 3 years with Actelion, AnaMar, Bayer, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, iQvia, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Serodapharm and UCB in the area of potential treatments of scleroderma and its complications. In addition, he had/has consultancy relationship within the last 3 years with A. Menarini, Amgen, Abbvie, GSK, Mepha, MSD, Pfizer and UCB in the field of arthritides and related disorders, Ivan Foeldvari Consultant for: Chugai, Novartis, Eric Hachulla Consultant for: Received consulting fees or other remuneration from Actelion, GSK, Pfizer, and Bayer, Francesca Ingegnoli: None declared, Ulf Muller-Ladner Grant/research support from: Projekt supported by an unrestricted educational grant from Celgene GmbH., Yves Piette: None declared, Valeria Riccieri: None declared, Barbara Ruaro: None declared, Alberto Sulli: None declared, Jacob M. van Laar Grant/research support from: Genentech, Consultant for: F. Hoffmann-La Roche, Ariane Herrick: None declared, Maurizio Cutolo: None declared

Background Early identification of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) at risk of progression could help tailor management and aid cohort enrichment in clinical trials to improve outcome. Objectives To assess the frequency of progressive SSc-ILD in the total ILD cohort and in subgroups enriched by risk factors in the EUSTAR database. Methods Patients from the EUSTAR database registered after 2010, ≥18 yrs old, fulfilling SSc classification criteria, with serial lung function and HRCT assessments were eligible. The following risk factors for progressive SSc-ILD available in the EUSTAR database were chosen as enrichment criteria: low forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), diffuse cutaneous SSc, anti-topoisomerase I antibody (ATA), short disease duration, older age, male sex, increased C-reactive protein, and presence of respiratory symptoms and reflux disease. Eligible patients with progressive ILD were assessed in the cohort and in subgroups enriched by the risk factors. Progressive SSc-ILD was assessed as absolute changes in%predicted and defined as: significant progressive (FVC decline >10%, or FVC decline 5−10% and DLCO decline ≥15%), moderate progressive (FVC decline 5−10%) or stable ( Results 6004 patients fulfilled the main entry criteria; of these, 1822 (30.3%) had ILD. At baseline, mean age was 57 yrs, 17.4% were male, 48.2% had diffuse SSc, 53.5% were ATA-positive, mean baseline FVC 86% and DLCO59%, mean disease duration 9.8 yrs, and follow-up was 2.5 yrs. In the total ILD cohort (30% eligible patients), 21% showed progressive ILD. Enriching with single risk factors reduced the number of eligible patients down to 6%, while the frequency of progressive ILD stayed stable (Figure). Combinations of risk factors did not result in increasing numbers of progressive ILD patients, but in further decreasing numbers of eligible patients. Conclusion There is still an unmet need to identify SSc-ILD patients at risk of progression with efficient risk factors. For clinical trials, it is a challenge to balance feasibility of recruitment and enrichment. Acknowledgement Funding: Boehringer Ingelheim (Schweiz) GmbH, Switzerland Disclosure of Interests Anna-Maria Hoffmann-Vold Grant/research support from: Received research funding or other remuneration from Boehringer Ingelheim, GSK, and Actelion, Consultant for: Received consulting fees or other remuneration from Boehringer Ingelheim, GSK, and Actelion, Speakers bureau: Actelion and Boehringer Ingelheim, Martina Gahlemann Employee of: Employee of Boehringer Ingelheim , Nicole Graf Grant/research support from: Received consulting fees or other remuneration from Astellas and Biotronik, Paolo Airo: None declared, Lidia P. Ananyeva: None declared, Laszlo Czirjak: None declared, Serena Guiducci: None declared, Eric Hachulla Consultant for: Received consulting fees or other remuneration from Actelion, GSK, Pfizer, and Bayer, Mengtao Li: None declared, Carina Mihai Consultant for: Received consulting fees or other remuneration from Actelion, Geneva, Roche, and Rofarm, Consultant for: F. Hoffmann-La Roche, Actelion, Geneva Romfarm, Gabriela Riemekasten Consultant for: Chugai, F. Hoffmann-La Roche, Speakers bureau: Chugai, F. Hoffmann-La Roche, Petros Sfikakis: None declared, Gabriele Valentini Grant/research support from: Received research funding and other remuneration from AbbVie, BMS, Lilly, Pfizer, and Sanofi, Consultant for: Received consulting fees and other remuneration from AbbVie, BMS, Lilly, Pfizer, and Sanofi, Otylia Kowal-Bielecka Consultant for: Received consulting fees or other remuneration from Bayer, Boehringer Ingelheim, Inventiva, Medac, Novartis, and Roche, Yannick Allanore Grant/research support from: Inventiva, F Hoffman La-Roche, Sanofi, BMS, Pfizer, Consultant for: Actelion, Bayer, BMS, Boehringer, Roche, Sanofi, Oliver Distler Grant/research support from: Prof. Distler received research funding from Actelion, Bayer, Boehringer Ingelheim and Mitsubishi Tanabe to investigate potential treatments of scleroderma and its complications, Consultant for: Prof. Distler has/had consultancy relationship within the last 3 years with Actelion, AnaMar, Bayer, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, iQvia, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Serodapharm and UCB in the area of potential treatments of scleroderma and its complications. In addition, he had/has consultancy relationship within the last 3 years with A. Menarini, Amgen, Abbvie, GSK, Mepha, MSD, Pfizer and UCB in the field of arthritides and related disorders

Background: The ERN ReCONNET (European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases) is the ERN aimed at improving the management of Rare Connective Tissue and Musculoskeletal Diseases across the European Union (EU). The ERN ReCONNET involves 26 health care providers (HCPs), from eight different EU countries: Belgium, France, Germany, Italy, the Netherlands, Portugal, Romania, Slovenia and 7 european Patient Advocacy Group (ePAGs). An intense collaboration has been established between HCPs and ePAGs. Patient Education (PE) was defined in 1998 by the World Health Organization as a continuous process including organized awareness information, self-care learning and psychological support regarding the disease, treatment, care and health care setting. It is designed to help patients to maintain or improve their quality of life with specific PE programmes designed to help them acquiring new skills. Objectives: To evaluate PE practice in the ERN ReCONNET based on a survey send to the HCPs members and to the patients of the corresponding countries. Methods: A questionnaire designed on a google form was send to the HCPs members asking about their practices in PE in their department and an other one was send to ePAGs who translated the patients’ survey in the different languages. Various versions of the same questionnaire was then send to patients’ associations in the different countries. Results: 33 HCPs members or representatives answered the survey. 52.9% (18) had no specific staff members dedicated to PE. In the department with staff trained in patient education, 33% (4) had no specific PE programmes. In the HCPs with dedicated staff for PE, 83.3% (10) estimated care providers are insufficient to meet the patients’ needs. 1608 patients answered the patient survey (France, n=246; Germany, n=23; Italy, n=500; Portugal, n=339; Slovenia, n=240; Belgium, n=190; the Netherlands, n=42), mostly women (84,5%, n=1359), around 48,5 years old (SD=13,6). Patients suffered mostly from Connective Tissue Diseases and Ehler-Danlos disease. 68%% (1093) of the patients had never heard about PE and were for 74% (804) interested in taking part in a PE programme. In the remaining patients who had heard about PE, 66% (342) never took part in a programme. For patients who had already taken part in a PE programme, they expressed satisfaction in several domains listed in the following bar chart: For all respondents, patients expressed needs for a better knowledge in disease and symptoms, treatments, well-being, nutrition, exchanging experiences with other patients, and daily life with the disease. Conclusion: Based on the EULAR recommendations for PE (Zangi HA et al.), PE should be apply in all EU countries. E-learning on PE for staff members and ePE for patients will be developed by the ERN ReCONNET. Reference [1] Zangi HA, Ndosi M, Adams J, Andersen L, Bode C, Bostrom C, Van Eijk-Hustings Y, Gossec L, Korandova J, Mendes G, Niedermann K, Primdahl J, Stoffer M, Voshaar M, van Tubergen A; European League Against Rheumatism (EULAR). EULAR recommendations for patient education for people with inflammatory arthritis. Ann Rheum Dis. 2015 Jun;74(6):954-62. doi: 10.1136 Disclosure of Interests: Meryem-Maud Farhat: None declared, Alain Cornet Grant/research support from: No direct financial grants from Pharmaceutical companies, but some grants accrued LUPUS EUROPE does, in the form of Grants or payment for attending advisory boards or providing patient views, Speakers bureau: I have been involved in GSK panels to provide patient perspective. However, the minor service fee obtained accrued to LUPUS EUROPE ratyher than the company, charissa frank: None declared, Ilaria Galetti: None declared, Juergen Grunert: None declared, vera guimaraes: None declared, lisa matthews: None declared, Ana Vieira: None declared, Eric Hachulla Consultant for: Received consulting fees or other remuneration from Actelion, GSK, Pfizer, and Bayer

Background Systemic sclerosis (SSc) is an autoimmune disease characterised by an extensive multi-organs fibrosis. Immunosuppressants are effective in some extent but their incomplete efficacy is hampered by a higher infection risk. Intravenous immunoglobulins (IVIG) have a good safety profile, exhibit immunomodulatory and antifibrotic properties and hence could be a relevant treatment for SSc. Objectives The purpose of this study was to investigate the effects of IVIG in an experimental model of SSc. Methods SSc was induced in 6 weeks old Balb/c mice by subcutaneous injections of HOCl five days a week during six weeks (n=20), whereas control mice received subcutaneous injections of PBS (n=20). Human IVIG was administrated intravenously by single retro-orbital injection at a dose of 2 g/kg the first day of HOCl administration (n=20). A control group received an injection of 2% Maltose (n=20). Skin thickness was assessed during the protocol until the sacrifice (day 42). Skin tissues were collected in 4% PFA and processed for histological analysis. Dermal thickness was measured by performing a May-Grunwald–Giemsa staining of 4 µm skin sections; collagen deposition was assessed by performing a Picrosirius red-staining and quantified by using a colour deconvolution method. In addition, immunostaining of skin sections was performed in order to evaluate the α-smooth muscle actin (α-SMA) expression. Frozen skin tissues were analysed to also assess the mRNA expression of main inflammatory and pro-fibrotic genes (by quantitative reverse transcription polymerase chain reaction). Collagen deposition was also evaluated by measuring the content of hydroxyproline in 10 mg of frozen tissue. Results Mice exposed to HOCl developed a diffuse cutaneous SSc with higher dermal thickness compared to the PBS group. IVIG significantly reduced dermal thickness and collagen deposition in HOCl-receiving mice. The amount of α-SMA positive cells evaluated by immunofluorescence was reduced in the HOCl treated mice receiving IVIG. mRNA expression profile of various markers of fibrosis (fibronectin, TGFβ) or inflammation (TNFα, IL-1β, IL-6) were also significantly decreased in the skin of HOCl mice treated with IVIG compared to HOCl-treated mice receiving 2% maltose. Conclusions These results demonstrate the efficacy of IVIG in preventing experimental fibrosis in a HOCl murine model of SSc. Disclosure of Interest None declared

Background Digital ulcers (DUs) affect about half of systemic sclerosis (SSc) patients during disease course. In some patients, peripheral vasculopathy can promote critical ischemia and gangrene, severe complications with potential life threatening consequences. Recently the DUO registry suggested a 18% prevalence of gangrene in DU-SSc patients, with smoking and a high number of DUs being predictive factors. However, little is known about gangrene in unselected SSc patients. Objectives To investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort. Methods We included patients from the EUSTAR database satisfying the ACR 1980 or the ACR/EULAR 2013 classification criteria for SSc, with at least one visit recording data on gangrene. We extracted from this database data regarding the reporting of DUs, DUs history and digital gangrene. Centres were asked for supplementary data on traditional cardiovascular (CV) risk factors. We analysed by uni- and multivariable logistic regression the cross-sectional relationship between gangrene and its potential risk factors such as history of DUs, cutaneous subset, disease duration, autoantibodies, traditional CV risk factors. Furthermore, longitudinal data were analysed by Cox proportional hazards regression. Results 1757 patients matched the inclusion criteria (age at inclusion 55.9±14.5 years, disease duration since first non-Raynaud’s symptom 7.9±10.3 years and from onset of Raynaud’s phenomenon (RP) 11.1±11.0 years, male sex 16.7%, 24.6% diffuse cutaneous subset (DcSSc)). At inclusion, 8.9% of patients had either current or previous digital gangrene, 15.7% had current DUs and a further 25.8% had previously had DUs. Among the potential risk factors, older age, a history of DUs and the DcSSc subset were statistically significant risk factors in the cross-sectional multivariable model. For the longitudinal part, during the entire follow-up (median [Q1,Q3] 13.1 [9.6, 19.3] months), 16/771 patients had incident gangrene (2.1%), accounting for an incidence of 1.73/100 patient-years. All 16 patients who developed incident gangrene had previously had DUs and gangrene. Further risk factors for incident gangrene were the DcSSc subset and longer disease duration: hazard ratio [95% confidence interval]: 8.97 [2.90–27.71] and 1.08 [1.04–1.13] respectively, both p Conclusions In unselected SSc patients, gangrene still occurs in about 9% of SSc patients. Of the most importance, a history of DUs and, to a lesser extent, the DcSSc subset are strongly and independently associated with gangrene, while traditional CV risk factors were not identified as risk factors. Our results confirm that gangrene is still a concern in SSc. They emphasise the importance of microvascular SSc-associated disease in the pathogenesis of gangrene and suggest that the DcSSc subset should be prioritised for risk-stratification of the patients. Acknowledgements The authors thank all the contributing EUSTAR investigators and patients. Disclosure of Interest C. Mihai Grant/research support from: Actelion Pharmaceuticals Ltd, Abbvie, Speakers bureau: Roche, Geneva Romfarm, O. Distler Grant/research support from: Actelion, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe Pharma, Roche, Consultant for: Actelion, Bayer, BiogenIdec, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Sinoxa, A. M. Gheorghiu Grant/research support from: Geneva Romfarm, Abbvie, P. Constantin: None declared, R. Dobrota Grant/research support from: Actelion Pharmaceuticals Ltd, Pfizer, S. Jordan: None declared, V. Smith Grant/research support from: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH, Bayer AG, Roche NV/SA, Fund for Scientific Research Flanders, E. Hachulla: None declared, J. Henes: None declared, E. Siegert: None declared, S. Vettori: None declared, U. Muller-Ladner: None declared, M. Matucci-Cerinic: None declared, Y. Allanore Grant/research support from: BMS, Genentech-Roche, Inventiva, Pfizer, Sanofi, Consultant for: Actelion, Bayer, Biogen, Genentech-Roche, Galapagos, Medac, Pfizer, Sanofi, Servier, UCB

Background Interstitial lung disease (ILD) is a leading cause of morbidity and mortality in systemic sclerosis (SSc). While factors associated with the presence of ILD in SSc (SSc-ILD) are identified, those associated with ILD outcome are still debated and studies assessing the evolution of SSc-ILD on HRCT are scarce. Yet, it is important to identify patients at risk of SSc-ILD worsening because those patients are thought to benefit the most from immunosuppressants. Objectives Thus, the aims of our study were: to describe the evolution of HRCT extension and patterns of SSc-ILD, to identify baseline prognosis factors of ILD outcome on serial HRCT and to investigate whether the evolution of pulmonary function tests (PFTs) parameters correlated with the evolution on HRCT. Methods We included 58 SSc patients with HRCT proven ILD, with at least two available HRCT, and collected clinical, biological data and PFT at baseline. We collected all HRCT and PFTs available during follow-up. We modelized PFTs and HRCT evolution using linear mixed model with random coefficients. Results Mean ILD extension at baseline was 32.3%±28.7%. During a mean follow-up of 5.3±4.9 years, we found a significant mean progression of ILD extension of 0.92%±0.36% per year (p=0.018). Male sex, anti-topoisomerase 1 antibodies, diffuse cutaneous SSc were associated with faster progression of ILD extension. Limited ILD according to Goh et al. staging system, and a coarseness score at zero (meaning 100% of ground glass opacification) were associated with a faster progression of ILD extension. We also found a significant decline of DLCO, FVC and TLC during follow-up. There was a significant correlation between the progression of ILD extension on HRCT and the decline of DLCO, but not with the evolution of FVC. Conclusions Male patients, patients with diffuse SSc/antitopoisomerase 1, patients with less severe and less extensive ILD at baseline were more likely to experiment a faster progression of ILD extension on serial HRCT. To our knowledge, this is the first study that clearly highlighted the diffuse form of SSc/presence of antitopoisomerase 1 as a worsening factor of SSc-ILD on HRCT. FVC might not be the best mirror of ILD progression while DLCO significantly correlated with change in ILD extension. Our study helps to define the profile of patients who are going to experience a progression of ILD on HRCT during follow up. Disclosure of Interest None declared

Background Several studies have consistently showed that the extent of skin involvement has a major impact on disease prognosis in the diffuse cutaneous subtype of systemic sclerosis. The large majority of the ongoing clinical trials aim at identifying efficient drug in this subset. By contrast, little is known about the limited cutaneous subset (LcSSc) and the translation of the data coming for DcSSc to LcSSc is uncertain. Objectives Therefore, our aim was to investigate skin and lung involvement trajectories of LcSSc patients using the large EUSTAR registry. Methods We analysed the longitudinal data extracted from the EUSTAR cohort collected before February 2017. Worsening of skin fibrosis was defined by an increase in modified Rodnan skin score (mRSS) >3.5 points from baseline to 2nd visit. Interstitial lung disease (ILD) was defined by any fibrosis on imaging (X-ray/computed tomography). Worsening of ILD was defined by a decrease of FVC >10% from baseline to 2nd visit. For predicting models, predictors with p Results 8013 LcSSc were included with a mean follow-up of about 3.3±3.7 years. At baseline, mean ±SD mRSS was 6±5 and ILD was present in 28.4% of all patients. Worsening of skin fibrosis was observed in 6.4% (19/298), 7.8% (97/1248) and 9.8% (289/2957) of LcSSc patients at 6, 12 and 24 months follow-up respectively. In multivariate analysis, variables predicting skin fibrosis progression were elevated European Scleroderma Study Group activity index (EScSG-AI) (OR [95 IC]: 1.22 [1.05–1.4], p=0.007) for 12 months progression and EScSG-AI (1.24 [1.13–1.38], p Worsening of ILD was observed in 11.7% (23/196) and 19.9% (65/326) of LcSSc patients with ILD at baseline, at 12 and 24 months follow-up respectively. In multivariate analysis, variables predicting ILD progression at 24 months were EScSG-AI >3 (OR [95 IC]: 3.8 [1.51–9.56], p=0.005), FVC (1.03 [1.01–1.04], p Conclusions It appears that only few LcSSc patients progress for skin fibrosis ; this limits the use of mRSS in this subset and the potential of anti-fibrotic drugs of skin disease. However, a substantial rate of ILD progression was identified as well as relevant predictors. These results support the inclusion of LcSSc patients in SSc-ILD trials evaluating anti-fibrotic drugs. Our predictive models will be helpful to define enriched population in future clinical trials. Acknowledgements: This work was supported by an unrestricted grant from INVENTIVA Disclosure of Interest None declared

Background Few small-sized observational studies have suggested that rituximab might be a promising treatment in systemic sclerosis (SSc) Objectives To evaluate the outcomes of SSc-patients receiving in routine care Rituximab Methods Retrospective longitudinal multicenter observational study which included SSc-patients treated with rituximab upon the decision of their physician within the framework of EUSTAR. We interrogated the participating centres and EUSTAR database to determine epidemiological and clinical characteristics, the indication for initiating the treatment, and the following parameters at baseline and at the last visit under treatment: modified Rodnan Skin Score (mRSS), joint, lung and gastrointestinal involvements, treatment, laboratory tests and safety events. Results 248 patients were included: 70 (28%) men, mean age: 51±13 years, mean disease duration: 7±7 years; 150 (65%) had diffuse cutaneous-SSc, 54% were positive for anti-topoisomerase and 71% had lung fibrosis. Overlap disease was noticed in 62 patients (26%) including 23 with rheumatoid arthritis. The indication for the treatment was lung involvement (56%) followed by articular (42%) and skin involvements (30%). At baseline, 175 patients were treated with steroids and 132 with DMARDs. Mean follow-up was 2.4 (±1.9) years. In the whole sample, mRSS decreased from 15±11 to 10±8 (p For SSc-patients treated for lung with baseline FVC In the whole population, 45 patients could stop steroids and mean dose decreased from 10 mg to 7 mg in the other. During the follow-up, 78 (31%) patients had side effects including 35 (14%) with severe side effects leading to discontinuation of the treatment in 10%. Six deaths were recorded (1 heart failure, 1 sepsis, 2 respiratory insufficiencies, 2 sudden deaths). 76 patients had infection, requiring hospitalisation in 20 patients. Conclusions In this study, skin, lung and joint involvement appeared to improve under rituximab. Infections and other severe adverse events were frequently reported. A comparative study including control patients from EUSTAR centres is ongoing. Disclosure of Interest M. Elhai: None declared, O. Distler Grant/research support from: Actelion, Bayer, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Sanofi, Sinoxa and UCB in the area of potential treatments of scleroderma and its complications, V. Smith : None declared, M. Matucci-Cerinic: None declared, J. J. Alegre-Sancho : None declared, M.-E. Truchetet: None declared, Y. Braun-Moscovici: None declared, F. Iannone: None declared, F. Chotchaeva: None declared, A. Lescoat : None declared, E. Siegert : None declared, I. Castellvi: None declared, P. Airo : None declared, S. Vettori: None declared, E. Hachulla: None declared, A. Erler : None declared, L. Ananieva : None declared, M. Krusche: None declared, F. Lopez-Longo : None declared, J. Distler : None declared, N. Hunzelmann : None declared, A.-M. Hoffmann-Vold : None declared, V. Riccieri: None declared, V. Hsu: None declared, M. Pozzi: None declared, C. Ancuta : None declared, E. Rosato : None declared, C. Mihai: None declared, M. Kuwana: None declared, Y. Allanore Grant/research support from: Actelion, Bayer, Boehringer Ingelheim, ChemomAb, Genentech/Roche, Inventiva, Pfizer, Sanofi, Servier, in the area of potential treatments of scleroderma and its complications.

Background Antiphospholipid antibodies (aPL) can be detected in systemic sclerosis (SSc) patients. While their clinical signification is well known in the primary antiphospholipid syndrome (APS), their frequency and clinical association remain debated matter of issue. In a previous study, we reported the prevalence and their clinical association of a single aPL testing a French cohort of SSc patients. Yet, the persistence of aPL during follow-up of patients has never been assessed. Objectives This study aimed to assess i. the persistence of aPL at least 12 weeks after the first dosage and ii. the clinical associations. Methods At least 12 weeks apart after the first test, 213 SSc patients were consecutively tested for lupus anticoagulant (LA), anticardiolipin (aCL) and anti-s2glycoproteine 1 (anti-s2Gp1) antibodies. aCL and anti-β2GpI were measured using commercial ELISA assays (Orgentec, Trappes, France), positivity was defined as ≥10 UGPL/mL (aCL) or ≥10 UA/mL (anti-β2GpI). Clinical associations were studied using binomial logistic regressions. Results The mean time between two tests was 13.2±6.3 months. One or more type of aPL was persistent in 7 patients (3%). Patients with persistent aPL developed more frequently venous thrombosis (VT) [4/7 (57%) versus 23/205 (11%), p=0.006]. Arterial or/and venous thrombosis were more common in patients with persistent aPL than other patients [4/7 (57%) versus 33/205 (16%), p Conclusions The prevalence of persistent aPL in our cohort was 3%. VT and miscarriages were associated with persistent aPL. References [1] Parodi A, Drosera M, Barbieri L, Rebora A. Antiphospholipid antibody system in systemic sclerosis. Rheumatology (Oxford)2001;40:111–12. [2] Sanna G, Bertolaccini ML, Mamali A, et al. Antiphospholipid anti- bodies in patients with scleroderma: prevalence and clinical signifi- cance. Ann Rheum Dis2005. [3] Marie I, et al. Anticardiolipin, ab2GPI antibodies and lupus-like anticoagulant in SSc. [4] Miryakis S, Lockshin MD, Atsumi T, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost2006;4:295. Disclosure of Interest None declared

Background Fibroblasts (Fb) are key effectors cells in systemic sclerosis (SSc).1 Fb stimulation with TGF-β1 is usually considered as the positive control in studies assessing the fibrogenesis in SSc.2 Yet, the lack of standardisation of TGF-β1 stimulation might be responsible for discrepancies in experiments performed in different conditions. Proteomic approach allows the analysis of differential expression of the whole proteins (proteome) in Fb, and appears an interesting approach to compare different culture conditions. Objectives We designed this study to compare the whole protein expression in Fb stimulated by TGF-β1 in different conditions. Methods At fifth passage, primary culture of human Fb from healthy subjects (ATCC; PCS-201–012) were stimulated or not with different concentrations of recombinant human active TGF-β1 (0.04, 1, and 5 ng/mL) (R and D Systems; 240-B-002) during 24, 48 and 72 hours. Proteins were extracted and analysed using an eFASP LC-MS/MS approach on an Orbitrap mass spectrometer (Thermo Scientific; Q Exactive +). Proteins quantitation was performed by Maxquant and statistical analysis by Perseus using ANOVA and principal component analysis (PCA). Results A total of 3267 proteins were identified, of which 1957 showed differential expression using ANOVA analysis. PCA revealed several clusters of differential proteins expression (figure 1). There were clear clusters of protein expression related to (i) unstimulated and stimulated conditions, (ii) between the three different times of stimulation and (iii) to TGF-β1 concentrations used. Although the expression of proteins in Fb exposed to 0.04 and 1 ng/mL of TGF-β1 during 72 hour were rather close, there was a unique proteins profile related to the condition with 5 ng/mL of TGF-β1 during 72 hour. Figure 1: PCA representation of differential proteins expression in different conditions. [TGF-β1]=0.04 ng/mL: square; [TGF-β1]=1 ng/mL: circle; [TGF-β1]=5 ng/mL: diamond. The more the points appear distanced, the more different is the protein expression. Conclusions This study highlights a variation of proteins expression depending on both stimulation time and TGF-β1 concentrations in Fb culture. The identification of protein differentially expressed will provide insights in the impact of TGF-β1 on Fb physiology under stimulation conditions. These data underline the need of standardisation of culture conditions to allow inter-data comparisons using in sensitive “omic” approaches. References [1] Garret SM, Frost DB, Feghali-Bostwick C. The mighty fibroblast and its utility in scleroderma research. J Scleroderma Relat Disord2017;2(2):69–134. [2] Verrecchia F, Mauviel A. Transforming growth factor-beta signaling through the Smad pathway: role in extracellular matrix gene expression and regulation. J Invest Dermatol2002Feb;118(2):211–5. Disclosure of Interest None declared

Background Genetic and environmental factors play a significant role in systemic sclerosis (SSc). African Americans are known for a higher SSc incidence, an earlier age of onset, and a greater frequency of interstitial lung disease and pulmonary hypertension (PH) compared to white patients. Data on blacks mostly stem from African Americans and studies on SSc in Asians are mostly from outside Asia and lack direct comparison with other racial groups. Objectives We aimed to evaluate differences of SSc presentations between white, Asian and black patients. Methods Characteristics of self-reported white, Asians or black SSc patients from the EUSTAR cohort were compared across racial groups; survival and multiple logistic regression analyses were used to adjust for age, sex, disease duration and antibody status. Results 9162 white, 341 Asian and 181 black patients were included. Of the Asian patients 208 stem from within Asia and 133 from 34 centres outside Asia; of the black patients 65 stem from within Africa and 116 from 35 centres outside Africa. Asian and black patients were on average 10 years younger than white patients (p Among ANA specificities, ACA predominated in white patients (whites: 40%, Asians: 16%, blacks: 10%; p The prevalence of PH (defined as PAPsys >40 mmHg as estimated by echocardiography) was similar in the three groups (whites: 13%, Asians: 17%, blacks: 14%; p=0.10); however multivariably, Asians were more likely to have PH (OR[Asians] 2.0, p Patients who experienced their first non-RP feature of the disease before the onset of RP were included with a simultaneous onset. Conclusions Several clinical and serological differences were evident between the three racial groups. Asians had high prevalences of Scl-70, PH and of a reduced FVC. Black patients in contrast had fast disease onset and a high prevalence of diffuse skin involvement. Disclosure of Interest None declared

Background Antibodies to the PM/Scl complex are found in patients with Systemic Sclerosis (SSc), but also with Polymyositis, Dermatomyositis and overlap syndromes. Historically, the main clinical association of anti-PM/Scl antibodies in SSc, which include calcinosis, articular and muscle involvement, and interstitial lung diseases, were described by some large single-centre studies, or by multicenter studies which recruited a relatively small number of positive patients. Therefore, some unresolved issue deserves further research. In particular, scleroderma renal crisis was recently identified in a sizeable number of anti-PM/Scl+SSc patients in a large monocentric British cohort (4 out of 70; 5.7%), a somewhat unexpected finding since this antibody type is generally considered not to be associated with renal crisis. 1 Objectives To evaluate clinical associations of anti-PM/Scl in patients with SSc in the large multicenter EUSTAR database, with specific focus on scleroderma renal crisis. Methods Patients from the EUSTAR database were included when the item anti-PM/Scl was fulfilled in at least one visit; clinical data were collected from the last visit available. Results Anti-PM/Scl status was available in 8,287 SSc patients from EUSTAR database: 295 were anti-PM/Scl +. After exclusion of 145 patients with multiple autoantibody positivity, 150 anti-PM/Scl+patients were compared with 7992 anti-PM/Scl -negative patients. Among these, 2530 were positive for anticentromere, 1933 for anti-topoisomerase I, 186 for anti-RNA polymerase III, and 220 for anti-U1Rnp antibodies. Renal crisis was identified in 8 of 150 anti-PM/Scl+SSc patients (5.3%), and was significantly more frequent than in anti-PM/Scl-negative SSc patients (1.6%; p=0.0015). Positivity for anti-PM/Scl was also associated with male sex, diffuse cutaneous subsets, joint and muscle involvement, lung fibrosis at chest X-rays, heart conduction blocks, stomach and intestinal symptoms (table 1). However, in multivariate analysis, adjusted for age at disease onset, sex, and disease duration, the association of anti-PM/Scl with renal crisis was not significant, whereas the associations with joint and muscle involvement, lung fibrosis, and intestinal symptoms were confirmed (table 1). Table 1 Results of the univariable and multivariable analysis adjusted on sex, age at disease onset and disease duration (n=8142 patients). Results are presented as number/number available data (%) unless stated otherwise. Conclusions In the largest series of anti-PM-Scl positive patients so far reported, well-known clinical associations were confirmed. Moreover, scleroderma renal crisis was more frequent than in the antibody-negative patient controls (which included a majority of anticentromere-positive patients, and a relatively small number of anti-RNA polymerase III-positive patients). However, this association was probably explained by covariates, such as joint and muscle involvement, or lung fibrosis. A possible role of corticosteroid therapy might therefore be suspected. Reference [1] Bruni C, et al. Rheumatology (Oxford). 2017;56:317–8. Acknowledgements Authors would like to thank the non-profit organisation ‘Gruppo Italiano Lotta alla Sclerodermia’ (GILS) for its substantial grant for this research project. Disclosure of Interest None declared

Background Macrovascular damages of systemic sclerosis (SSc) were poorly investigated, and the link between macrovasculopathy and microvasculopathy of SSc, cardiovascular disease, and mortality remain unclear. Objectives To evaluate if macrovascular damage in SSc predicts the occurrence of new digital ulcers (DU), cardiovascular events and mortality, and to further assess the relationship between micro and macrovascular damages in SSc. Methods All consecutive SSc patients followed in our SSc National Reference Centre, who underwent an arterial doppler ultrasonography (aDUS) of the upper limbs, were included and prospectively followed up until October 2017. Inclusion criteria were: 1) adults; 2) a diagnosis of SSc according to 2013 ACR/EULAR criteria; 3) aDUS performed in our vascular exploration department. Results Ninety-nine SSc patients were included. Median follow-up duration was 35 (IQR, 21 to 39) months. Macrovascular damages mainly affected ulnar arteries, with ulnar artery occlusion (UAO) in 28 (28.3%) patients (bilateral 60.7%). New DU occurred in 26 (27.1%) patients, new cardiovascular event in 10 (10.4%) patients, and 11 patients died during the study period. Interestingly, UAO was not associated with traditional cardiovascular risk factors (except dyslipidemia) nor with history of cardiovascular diseases, and was not predictive of new cardiovascular events. Conversely, UAO was associated with makers of microvascular damages, such as late nailfold capillaroscopy pattern (33.3% vs 6.8%; OR=6.88, 95% CI=1.76 to 26.82; p=0.03) and was predictive of new ischaemic DU (44.5% vs 24.8%; HR=2.23, 95%CI=1.02 to 4.86; p=0.037), pleading for a SSc specific vasculopathy. Conclusions Our study confirms that macrovascular damages are frequent in SSc patients and mainly affect ulnar arteries. Interestingly, UAO was associated with severe microvasculopathy, but not with markers of cardiovascular diseases. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis and composed of two subtypes, limited and diffuse cutaneous forms. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Objectives To expand the list of susceptibility genes and deepen biological insights for SSc. Methods We performed trans-ethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4,436 cases and 14,751 controls. Associations between significant single nuclear polymorphisms (SNPs) and neighboring genes were evaluated. Enrichment analysis of H3K4Me3, a representative histone mark for active promoter was conducted with an expanded list of SSc susceptibility genes. Results We identified two significant SNP in two loci, GSDMA and PRDM1 , both of which are related with immune functions and associated with other autoimmune diseases (p=1.4x10 -10 and 6.6x10 -10 , respectively). GSDMA also showed a significant association with limited cutaneous SSc. We also replicated the associations of previously reported loci including a non-GWAS locus, TNFAIP3 . PRDM1 encodes BLIMP1, a transcription factor regulating T cell proliferation and plasma cell differentiation. The top SNP in GSDMA was a missense variant and correlated with gene expression of neighboring genes, and this could explain the association in this locus. We found different HLA association patterns between the two populations or two subtypes. Enrichment analysis suggested the importance of CD4 naive primary T cell. Conclusions GSDMA and PRDM1 are associated with SSc. These findings provide enhanced insight into the genetic and biological basis of SSc. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is a rare, multisystem autoimmune disorder. It is characterised by generalized microangiopathy, in which hypoxia and oxidative stress have been implicated in its pathogenesis. Tobacco inhalation increases free radicals and strongly promotes vascular damage. So far, data available with regards to a role of tobacco exposure with SSc severity and progression are scarce. Objectives We aimed to assess the effects of smoking on the speed of worsening of organ manifestations, namely lung involvement (forced vital capacity, FVC; forced expiratory volume, FEV1/FVC ratio; diffusing capacity for carbon monoxide corrected for alveolar volume, DLCO/VA), skin involvement (modified Rodnan skin score; mRSS), and digital ulcers (DU) in the European scleroderma trials and research (EUSTAR) database. Methods Adult SSc patients from the EUSTAR cohort with a follow-up visit 12±4 months after their baseline visit and available data on their smoking habits were included. The associations of smoking behaviour (never smokers vs ex-smokers vs current smokers) with the disease manifestations at follow up were assessed after adjusting for potentially confounding covariates using multivariable linear or logistic regression analyses. Missing data were imputed using multiple imputations. Results Of the 3,023 patients included (mean age 57 years, SD 13; 85% female), 66% stated that they never smoked, 23% were ex-smokers and 11% were current smokers. On average, ex-smokers had smoked for 19.5 years (SD 12) while current smokers smoked for 29.1 years (SD 13). Ex-smokers had smoked on average 17.3 pack-years (SD 20) and current smokers 29.3 pack-years (SD 36). The mean time since smoking cessation in ex-smokers was 15.8 years (SD13). The FEV1/FVC ratio changed from 96.3 (SD 14) at baseline to 96.2 (SD 13) at follow up. Taking into account the effect of age, sex, autoantibody status, disease duration and SSc subset as well as the baseline values of the outcome, the FEV1/FVC ratio decreased faster in currently smoking SSc patients than in never smokers (β=-2.8, p=0.001). Similarly, the DLCO/VA diminished faster in current smokers (β=-3.7, p=0.006) while on average the DLCO/VA decreased from 78.1 (SD 18) to 76.5 (SD 17). Changes in FVC were however not associated with smoking behaviour (p=0.13). The mRSS changed between baseline and follow-up from an average of 7.6 (SD 7) to 7.3 (SD 7); on average, in smokers the mRSS improved faster than in never smokers (β=-0.65, p=0.015). The presence of DUs at follow-up was not associated with current smoking (p=0.9). Having previously smoked was not significantly associated with the progression of any of the assessed outcomes. Conclusions Although the adverse effects of smoking on bronchial airways that is known in the general population could be replicated in the SSc population, the lack of a measurable adverse effect of smoking on SSc organ manifestations argues against a major role of tobacco associated free radicals and vasoconstriction in the pathogenesis of SSc vasculopathy and fibrosis. Disclosure of Interest V. Jaeger: None declared, G. Valentini: None declared, E. Hachulla: None declared, L. Czirjak: None declared, E. Siegert: None declared, O. Distler Grant/research support from: 4 D Science, AbbVie, Actelion, Active Biotec, Bayer, BiogenIdec, BMS, Boehringer Ingelheim, ChemomAb, EpiPharm, espeRare foundation, Genentech/Roche, GSK, Inventiva, iQone Healthcare, Lilly, medac, Mepha, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Pfizer, Sanofi, Serodapharm and Sinoxa, Consultant for: 4 D Science, AbbVie, Actelion, Active Biotec, Bayer, BiogenIdec, BMS, Boehringer Ingelheim, ChemomAb, EpiPharm, espeRare foundation, Genentech/Roche, GSK, Inventiva, iQone Healthcare, Lilly, medac, Mepha, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Pfizer, Sanofi, Serodapharm and Sinoxa, L. M. Bambara: None declared, E. Rosato: None declared, Y. Allanore: None declared, M. Matucci-Cerinic: None declared, P. Airό: None declared, U. Walker: None declared

Background Autologous bone marrow transplant is a new treatment for autoimmune diseases (AD). Objectives To determine the feasibility, tolerance and efficacy of autologous HSC transplantation with CD34+ selection in severe scleroderma (Sc) and myositis (M). Methods We designed a national, non randomised, open, phase I-II trial.1Mobilisation of HSC used cyclophosphamide (CYCLO) (4 g/m2)+ G-CSF (5 microg/kg day) or G-CSF alone (10 microg/kg day) if left ventricular ejection fraction (LVEF) was Results 12 Sc + 3 M, age 36 yrs, were included in 2 years, meanwhile 10 candidates died from their disease. HSC mobilisation was successful in 14 patients, but in 2 cases did not yield enough HSC to allow CD34+ selection. After 2 (1–4) aphereses, the total number of CD34+ collected for each patient was 10.9 × 106/kg (3.9?34.3). Purity was 99.2% (92–99.8). CD34+ cells yield was 60.7% (46.4–80). Intensive immunosuppression was performed in 13 patients with low toxicity. Number of reinfused cells was 5.8 × 106 CD34+/kg (3.3–10.2). Duration of aplasia was 2.9 weeks (2.5–3) with low toxicity. No mortality was associated with the procedure. Early clinical evolution (18 mths) showed improved functional status (PS, SHAQ) and fall in skin score in 8/12 Sc and no clinical benefit in M. Conclusion Autologous HSC transplantation is feasible in Sc and M, with a lower risk compared to spontaneous evolution of AD and early clinical benefit in Sc. These results call for phase III studies to compare cyclophosphamide alone versus autologous transplantation in Sc and for more myositis in phase I–II studies. Reference Farge D, Gluckman E, Tyndall A. Treatment of severe autoimmune diseases by immunoablative chemotherapy and autologous bone marrow transplantation. EJIM 1999;10:88–96