Search

BackgroundPatients with interstitial lung disease (ILD) are at risk of developing nocturnal hypoxaemia due to ventilatory restriction and impaired gas exchange that worsen with supine posture and reduced ventilatory drive during sleep. This systematic review synthesised literature on the diagnostic evaluation, epidemiology, associations, management and prognosis of nocturnal hypoxaemia in ILD.MethodsOvid MEDLINE, Embase and CENTRAL databases were searched for eligible studies. Meta-analyses with subgroup analyses were conducted, where possible.ResultsFifty-three studies were included (total participant number=2590). The most common definition for clinically significant nocturnal hypoxaemia was ≥10% of total sleep time with oxyhaemoglobin saturation ConclusionNocturnal hypoxaemia is common, associated with DLCO impairment and markers suggestive of pulmonary hypertension, and a potential prognostic factor in patients in ILD. There is a need to establish a consensus definition of nocturnal hypoxaemia and evaluate long-term effects of nocturnal supplemental oxygen in ILD.

A 39-year-old woman presented with a 6-month history of breathlessness, productive cough and painful lumps on her lower legs. She had suffered with recurrent rhinosinusitis and frequent infections of the ears, throat and chest since childhood, as well as cutaneous herpes zoster in her 20s. There was no documented history of pneumonia, invasive or deep-seated infections. She had smoked lightly, was allergic to penicillin and worked as a commercial tea buyer. Examination showed a slim female with a normal breathing pattern. Chest expansion was reduced and fine inspiratory crackles were detected over the lower lung zones. Pulmonary function tests showed ventilatory restriction with decreased gas transfer. Forced expiratory volume in one second (FEV1) 2.10 L, 71% predicted; forced vital capacity (FVC) 2.22 L, 65% predicted; spirometric ratio 0.93; total lung capacity 3.04 L, 62% predicted; haemoglobin (Hb)-adjusted carbon monoxide transfer factor/TLco 45% predicted and its coefficient/Kco 81% predicted. Indices related to small airway function were normal, maximal expiratory flow (MEF)75/50/25 all above 80% predicted and air-trapping was absent. Bloods tests showed normal full blood count, C-reactive protein as well as kidney, bone and liver biochemistry. Serum ACE was elevated at 93 ACEU (ref: 12–68). Elispot assay and HIV serology were negative. A prereferral chest radiograph revealed widening of the superior mediastinum and ill-defined nodular opacities in the middle and lower zones. Despite the history of possible erythema nodosum and raised serum ACE, the account of recurrent infections suggested a differential diagnosis broader than typical sarcoidosis. Demonstration of ventilatory restriction and impaired gas transfer factor hinted towards an interstitial or diffuse lung pathology. The Kco, at nearly twice the TLco in %-predicted terms, indicated a low likelihood of major pulmonary vasculopathy and the absence of airflow limitation or small airway dysfunction steered the diagnosis away from primary bronchiolar disorders. CT with contiguous …

BackgroundNon-invasive biomarkers for the assessment of disease severity in idiopathic pulmonary fibrosis (IPF) are urgently needed. Calprotectin belongs to the S-100 proteins produced by neutrophils, which likely contribute to IPF pathogenesis. Calprotectin is a well-established biomarker in inflammatory bowel diseases. In this cross-sectional study, we aimed to establish the potential role of calprotectin as a biomarker in IPF. Specifically, we hypothesised that patients with IPF have higher serum calprotectin levels compared with healthy controls, and that calprotectin levels are associated with disease severity.MethodsBlood samples were obtained from healthy volunteers (n=26) and from two independent IPF cohorts (derivation cohort n=26, validation cohort n=66). Serum calprotectin levels were measured with a commercial kit adapted for that purpose and compared between healthy controls and patients with IPF. Clinical parameters, including forced vital capacity, diffusing capacity for carbon monoxide (DLCO) and the Composite Physiologic Index (CPI), were correlated with calprotectin serum levels.ResultsThe IPF derivation cohort showed increased serum calprotectin levels compared with healthy controls (2.47±1.67 vs 0.97±0.53 µg/mL, pConclusionSerum calprotectin levels are significantly increased in patients with IPF compared with healthy controls and correlate with DLCO and CPI. Calprotectin might be a potential new biomarker for disease severity in IPF.

ObjectiveTo assess survival and identify predictors of survival in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) who participated in the Scleroderma Lung Studies (SLS) I and II.MethodsSLS I randomised 158 patients with SSc-ILD to 1 year of oral cyclophosphamide (CYC) vs placebo. SLS II randomised 142 patients to 1 year of oral CYC followed by 1 year of placebo vs 2 years of mycophenolate mofetil. Counting process Cox proportional hazard modelling identified variables associated with long-term mortality in SLS I and II. Internal validation was performed using joint modelling.ResultsAfter a median follow-up of 8 years, 42% of SLS I patients died, and when known the cause of death was most often attributable to SSc. There was no significant difference in the time to death between treatment arms in SLS I or II. Higher baseline skin score, older age, and a decline in the forced vital capacity (FVC) and the diffusing capacity for carbon monoxide (DLCO) over 2 years were independently associated with an increased risk of mortality in SLS I. The Cox model identified the same mortality predictor variables using the SLS II data.ConclusionIn addition to identifying traditional mortality risk factors in SSc (skin score, age), this study demonstrated that a decline in FVC and DLCO over 2 years was a better predictor of mortality than baseline FVC and DLCO. These findings suggest that short-term changes in surrogate measures of SSc-ILD progression may have important effects on long-term outcomes.

Dr Andrew W Creamer (AWC), Respiratory Registrar : A 70-year-old retired teacher was referred to the respiratory clinic with a 12-month history of progressive exertional dyspnoea and dry cough. He denied haemoptysis, constitutional symptoms or diurnal variation. He took omeprazole, amlodipine and ezetimibe for a long-standing history of dyspepsia, hypertension and hypercholesterolaemia. He was an ex-smoker with a 30 pack-year history. He reported monophasic colour change in his fingers in the cold, but denied any other connective tissue disease (CTD) symptoms. He denied any significant environmental exposures such as organic dusts or moulds. His vital signs were normal. There was evidence of mechanic’s hands (a hyperkeratotic eruption with fissuring and cracking on the palmar and radial aspects of the fingers, strongly associated with idiopathic inflammatory myopathies) but no other features of CTD or clubbing. Bibasal fine inspiratory crepitations were audible on chest auscultation. Cardiovascular examination was normal. Initial investigations revealed pancytopenia (figure 1) with unremarkable liver and renal function, prompting referral to local haematology services for further assessment. Figure 1 Baseline blood tests at presentation. Abnormal values are highlighted in bold. Pancytopenia was evident, in the context of normal B12, folate and ferritin. Lung function testing revealed a restrictive pattern with significantly reduced gas transfer (figure 2), while 6 min walk test demonstrated baseline saturations of 95% on air dropping to 77% on exertion, achieving 260 m (48% of theoretical distance). Figure 2 Lung function tests at baseline and 4-month follow-up. Spirometry demonstrated a restrictive pattern with reduction in gas transfer factor. KCO, carbon monoxide transfer coefficient; TLCO, transfer factor for carbon monoxide. Chest X-ray showed prominent interstitial lung markings in the mid and lower zones (figure 3). High-resolution CT thorax (HRCT) demonstrated centrilobular emphysema throughout the lungs and a basally predominant interstitial process with features suggestive of non-specific interstitial pneumonia (NSIP) (figure …

Background:Management of patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) is complicated by high inter-patient variability. To date, no validated predictors of treatment response are available for routine use. High resolution computed tomography (HRCT)-based radiomics, i.e. the high-dimensional, quantitative analysis of imaging metadata, have previously been shown to be successful in discriminating (SSc-)ILD phenotypes in preclinical and clinical studies1. Since HRCT is an integral part of the routine work-up in SSc, HRCT-based radiomic features may hold potential as non-invasive biomarkers.Objectives:To predict treatment response using two-dimensional (2D) HRCT-based radiomics in SSc-ILD patients from a prospectively followed cohort.Methods:Inclusion criteria were diagnosis of SSc-ILD in HRCT, availability of a suitable chest HRCT scan within 12 months prior to initiation of a new treatment, and availability of clinical baseline and follow-up information. Treatment response was defined as the absence of all of the following over a follow-up period of 12-24 months: relative decrease in forced vital capacity (FVC) ≥5%, increase of ILD in HRCT as assessed by a radiologist, change in treatment regimen due to insufficient response, ILD-related death or lung transplantation. Of each pre-treatment HRCT, 6 slices (15±5 mm apart, starting from the basal lung margin) were manually segmented and 1513 2D radiomic features were extracted using the in-house software Z-Rad (Python 2.7). Features were Z-score transformed and pre-filtered for inter- and intra-reader robustness (intraclass correlation coefficient >0.85) and inter-feature correlation (Spearman’s rho Results:A total of 64 pre-treatment HRCTs from 54 patients were analyzed. In 9 patients, >1 asynchronous treatments were assessed, while 45 patients had only 1 eligible treatment approach. The response rate within the assessed follow-up period was 45.3% (n=29). For score generation, 13 radiomic features were selected and an optimal cut-off value of -0.1589 was determined. Univariate linear regression showed significant association between our categorical radiomics-based score and treatment response (p=0.007, area under the curve = 0.65 (0.51-0.79), sensitivity=0.90, specificity=0.43), whereby a high score was predictive for treatment response.No differences between patients with high (n=46) or low (n=18) scores were detected for baseline age (mean±SD=55.5±12.0 and 55.5±13.6 years, p=0.84), duration of SSc (mean±SD=6.2±8.4 and 4.7±4.4 years, p=0.79), time since ILD diagnosis (2.7±2.9 and 2.4±3.1 years, p=0.59), FVC (77.6±20.6 and 80.1±17.9, p=0.41) or DLco (54.4±21.0 and 57.6±18.9, p=0.40). Distribution of anti-Scl-70 positivity (45.7% vs. 55.6%, p=0.58) and diffuse cutaneous disease (47.7% vs. 61.1%, p=0.41) was not significantly different between patients with high and low scores, respectively, although a trend towards higher percentages in the high score group was observed.Conclusion:Our results indicate that, following validation in external cohorts, radiomics may be a promising tool for future pre-treatment patient stratification. Moreover, our radiomics-based score seems not to be associated with commonly studied clinical predictors such as anti-Scl-70 positivity or lung function, underlining a possible additive value to ‘traditional’ clinical parameters.References:[1]Schniering, J., et al. Resolving phenotypic and prognostic differences in interstitial lung disease related to systemic sclerosis by computed tomography-based radiomics. medRxiv [Preprint] doi:10.1101/2020.06.09.20124800 (2020).Disclosure of Interests:Chantal Meier: None declared, Malgorzata Maciukiewicz: None declared, Matthias Brunner: None declared, Janine Schniering: None declared, Hubert Gabrys: None declared, Anja Kühnis: None declared, Oliver Distler Speakers bureau: Speaker fee on Scleroderma and related complications: Bayer, Boehringer Ingelheim, Medscape, Novartis, Roche. Speaker fee on rheumatology topic other than Scleroderma: MSD, iQone, Novartis, Pfizer, Roche, Consultant of: Consultancy fee for Scleroderma and its complications: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Bayer, Baecon Discovery, Boehringer, CSL Behring, ChemomAb, Corbus Pharmaceuticals, Horizon Pharmaceuticals, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, Kymera, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Roivant Sciences, Sanofi, UCB. Consultancy fee for rheumatology topic other than Scleroderma: Abbvie, Amgen, Lilly, Pfizer, Grant/research support from: Research Grants to investigate the pathophysiology and potential treatment of Scleroderma and its complications: Kymera Therapeutics, Mitsubishi Tanabe, Thomas Frauenfelder: None declared, Stephanie Tanadini-Lang: None declared, Britta Maurer Speakers bureau: Speaker fees from Boehringer-Ingelheim, Grant/research support from: Grant/research support from AbbVie, Protagen, Novartis Biomedical Research, congress support from Pfizer, Roche, Actelion, mepha, and MSD

Background:Interstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). However, there are few prospective studies for the natural course of lung physiology in most patients with RA-ILD.Objectives:To assess the natural course of lung physiology of RA-ILD and the relation between arthritis activity and pulmonary physiology in patients with RA-ILD.Methods:The KOrean Rheumatoid Arthritis ILd (KORAIL) cohort is the prospective observational cohort and aims to investigate the natural course of RAILD. Based on either 1987 or 2020 ACR criteria, patients diagnosed with RA and ILD based on CT scan were recruited from six tertiary medical hospitals in Korea since January 2015. RA disease activity was assessed using swollen and tender joint count by treating physician, inflammatory markers including CRP and ESR, and patient’s global assessment annually. Pulmonary function tests (PFT), including FVC, FEV1, DLCO, and chest CT scan, were conducted annually.Results:We analyzed 163 patients at baseline (V1), 141 at 1-year (V2), 122 at 2-year (V3), and 88 at 3-year follow-up (V4). The mean (±SD) duration since RA diagnosis and since ILD diagnosis was 7.6±8.0 and 2.7±3.1 years, respectively. The female to male ratio was about 2:1, and 58.9% of patients (n=96) were 65 years old or older. Only two patients were negative for RF and anti-CCP; 98.7% of patients (n=161/163) were positive for RF (n=143, 87.7%) or anti-CCP antibody (n=154, 94.5%). At enrollment, one-hundred-nine patients (66.9%) had FVC ≥80 % of predicted. Twenty-five patients (15.3%) showed FEV1/FVC≥0.7, of which seventeen patients, only ten percent of a total cohort (10.4%), had FVC ≥80% of predicted, which corresponds to the obstructive pattern. Proportion of patients showed a ≥10-point decline from the enrollment in FVC of the predicted value were around 10% at every year (Table 1). The proportion of patients with a relative decline of ≥10% from the enrollment in FVC predicted was increased every year because of cumulation. The proportion of patients with a relative decline of ≥10% from the previous visit in FVC predicted was also around 10-15% every year. Proportions of patients with 55% or more DLco % pred. has been decreased annually; 78.5% (n=128/158) at V1, 72.9% (n=105/139) at V2, 68.7% (n=90/117) at V3, and 56.6% (n=56/85) at V4. Patients with a relative decline of ≥10% from the enrollment in DLco predicted was 38 (27.5 %) at V2 and 37 (31.9%) at V3. Patients with a relative decline of ≥10% from the previous visit in DLco predicted was 29 (25.2%) at V3. Of note, thirty patients (21.7%) showed a relative 10% or more increase from enrollment in DLco predicted at V2, and so did 30 patients (25.9%) at V3.Table 1.The analysis of forced vital capacity (FVC) in KORIL cohortV1 (enrollment)V2 (1-year)V3 (2-year)V4 (3-year)FVC (mL), mean±SD2549.5 ± 743.32479.5±764.42435.8 ± 742.82405.7 ± 731.2FVC % of predicted, mean±SD84.70 ± 16.7484.7±18.184.3 ± 17.683.1 ± 19.1Rate of FVC decline, mL·year-1 (95% CI)--14 (-49, 21)-62 (-104, -21)-A 10-point decline from V1 in predicted FVC value, n (%)-10 (7.1)16 (13.3)8 (9.4)Relative decline of 10% from V1 in predicted FVC value, n (%)-17 (12.1)23 (18.9)17 (19.3)Relative decline of 10% from the previous visit in predicted FVC value, n (%)-17 (12.1)17 (14.2)13 (15.3)Conclusion:Annually, about 10-15% of patients experience a relative ≥10% decline from the previous visit in FVC predicted value in RA-ILD.Acknowledgements:This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant no.HI14C1277).Disclosure of Interests:None declared

Background:Interstitial lung disease (ILD) is a severe complication of Rheumatoid Arthritis (RA). Usual interstitial pneumonia (UIP) is considered to be more frequent and severe in RA than non-specific interstitial pneumonia (NSIP). Abatacept (ABA) and Rituximab have demonstrated efficacy in RA-ILD [1-3].Objectives:To compare the efficacy of ABA in RA-ILD patients according to radiological patterns of UIP or NSIP.Methods:From an observational multicenter study of 263 RA-ILD patients treated with ABA, we selected those with UIP or NSIP [2]. We analyzed in the 2 groups from baseline up to 24 months the following outcomes: a) Forced Vital Capacity (FVC), b) Carbon monoxide diffusing capacity (DLCO), c) Chest High Resolution Computed Tomography (HRCT), and d) dyspnea. Differences between final follow-up and basal visit were calculated as the average difference and 95% Confidence Interval (95% CI). Multivariable linear regression was used to assess the differences between the 2 groups.Results:We studied 190 patients with UIP (n=106) and NSIP (n=84). Patients with UIP were older, had more positivity for rheumatoid factor and had received more sulfasalazine (Table 1). ILD duration up to ABA initiation was relatively short in both groups, with a median [IQR] of 16 [4-50] and 11 [2-36] months in UIP and NSIP patterns, respectively. Mean baseline values of FVC and DLCO were > 80% and > 60%, respectively, in the 2 groups, with a lower FVC in UIP (82% vs 89% in NSIP, pConclusion:ABA seems to be equally effective in stabilizing of DLCO, FVC and HRCT in UIP and NSIP in RA-ILD. Our results suggest that an early administration of ABA in ILD, before significant structural lung damage development, may be preferable to prevent interstitial progression, regardless of the radiological pattern.References:[1]Fernández-Díaz C, et al. Semin Arthritis Rheum. 2018 Aug;48(1):22-27. doi: 10.1016/j.semarthrit.2017.12.012[2]Fernández-Díaz C, et al. Rheumatology (Oxford). 2020 Dec 1;59(12):3906-3916. doi: 10.1093/rheumatology/keaa621[3]Atienza-Mateo B, et al. J Clin Med. 2020 Sep 23;9(10):3070. doi: 10.3390/jcm9103070Table 1.Main general features at baseline.UIP (n=106)NSIP (n=84)p valueAge, years mean±SD66±1063±100.049Women, n (%)59 (56)49 (58)0.71Smoker ever, n (%)51 (48)45 (54)0.46ILD duration up toABA, months, median [IQR]16 [4-50]11 [2-36]0.57RF100 (94)71 (85)0.041ACPA, n (%)96 (91)75 (89)0.83FVC (% of the predicted), mean±SD82±2189 ±190.025DLCO (% of the predicted), mean±SD63 ±1965 ±160.46ABA monotherapy, n (%)45 (42)41 (49)0.38ABA combined+ MTX // + other cDMARD, n (%)15 (14) // 46 (43)16 (19) // 27 (32)0.17Prednisone at baseline, mg/day, median [IQR]7.5 [5-10]10 [5-10]0.20Previous immunosuppressive therapy, n (%)MTX81 (76)68 (81)0.45Leflunomide48 (45)31 (37)0.25Sulfasalazine16 (15)5 (6)0.046Hydroxychloroquine24 (23)16 (19)0.55Anti-TNF drugs37 (35)30 (36)0.80Rituximab19 (18)15 (18)0.99Tocilizumab12 (11)12 (14)0.54ABA, abatacept; ACPA, anti-citrullinated protein antibodies; DMARD, disease-modifying antirheumatic drug, ILD, Interstitial lung disease; MTX, methotrexate; NSIP, non-specific interstitial pneumonia; RA, rheumatoid arthritis; TNF, tumor necrosis factor; UIP, usual interstitial pneumonia.Figure 1.Evolution of pulmonary function tests in RA-ILD patients with UIP and NSIP patterns. FVC and DLCO are expressed as mean (95%CI) and compared between the 2 groups.Acknowledgements:the Spanish Collaborative Group of Abatacept in Interstitial Lung Disease Associated with Rheumatoid ArthritisDisclosure of Interests:Belén Atienza-Mateo: None declared, Carlos Fernández-Díaz Speakers bureau: Brystol Myers Squibb, Santos Castañeda: None declared, Rafael Melero: None declared, FRANCISCO ORTIZ SANJUAN: None declared, Ivette Casafont-Solé: None declared, Sebastián C Rodriguez-García: None declared, Iván Ferraz-Amaro: None declared, Miguel A González-Gay: None declared, Ricardo Blanco Speakers bureau: Brystol Myers Squibb

Background:In SSc, ILD is a major cause of morbidity and mortality. High resolution computed tomography (HRCT) is the gold standard for the diagnosis. Predictors of ILD onset are eagerly awaited to improve SSc-ILD management. Pulmonary function test (PFTs) are routinely performed to measure lung function changes.Objectives:Our aim was to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) in predicting the development of SSc-ILD.Methods:The longitudinal data of DLCO, FVC and ILD on HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0), after 12 (±4) (t1) and 24 (±4) (t2) months. Patients with negative HRCT for any sign of ILD both at t0 and t1 were included. Patients who presented or developed pulmonary hypertension during the study period were excluded. At baseline, demographic data, disease duration from Raynaud’s onset, disease subsets, autoantibodies and other laboratory and instrumental data were recorded.Results:474/17805 patients were eligible for the study (403 females, 71 males): 26.0% dcSSc, 58.3% lcSSc, 220 (48.0%) patients with positive anticentromere antibodies (ACA) and 117 (25.4%) with positive antitopoisomerase I antibodies (Topo-I abs). Among all enrolled patients, 46 (9.7%) developed HRCT signs of ILD at t2. Patients with Topo-I abs showed an association with ILD development at t2 (16.7% vs 7.8%, p=0.0031), contrarily ACA positive patients were negatively associated with ILD appearance after 2 years of follow-up (4.4% vs 14.4%, p=0.0001). Positive t2 HRCT patients had a significant lower value of DLCO and FVC at all three assessments when compared to patients with a negative HRCT at t2 (Table 1) and both t0 DLCO and FVC values negatively correlated with ILD development (Table 1). The mean t0 to t1 change (Δ) of DLCO in patients with negative t2 HRTC and positive t2 HRCT were -0.5 (±12.6) and -1.0 (±15.1), respectively. The mean t0 to t1 ΔFVC in patients with negative t2 HRTC and positive t2 HRCT were -0.2 (±10.6) and 0.1 (±11.5), respectively. None of them predicted the appearance of ILD at t2 (ΔDLCO: OR (IC) 0.997 (0.97-1.02), p=0.8024; ΔFVC OR (IC) 1.002 (0.97-1.03), p=0.8664). The data showed an association between t0 DLCO value0 FVC value0 DLCOConclusion:Our data suggest that an impaired baseline DLCO (Table 1.DLCO and FVC values at t0, t1 and t2 values in patients with positive or negative HRCT for ILD at t2 and their statistical differences.Patients without ILD at t2 (mean±SD)Patients with ILD at t2 (mean±SD)OR (95%CL)p-valueDLCO at t079.0 ± 16.669.9 ± 17.40.97 (0.95 - 0.99)0.0006DLCO at t178.4 ± 16.868.9 ± 18.60.97 (0.95 - 0.98)0.0005DLCO at t278.0 ± 17.065.1 ± 19.10.95 (0.93 - 0.97)FVC at t0102.2 ± 17.394.6 ± 16.20.97 (0.96 - 0.99)0.0052FVC at t1101.9 ± 17.994.7 ± 16.50.98 (0.96 - 0.99)0.0092FVC at t2101.6 ± 17.694.5 ± 20.00.98 (0.96 - 1)0.0126Disclosure of Interests:Gemma Lepri: None declared, Cosimo Bruni Speakers bureau: CB reports personal fees from Actelion, personal fees from Eli Lilly, Grant/research support from: CB reports personal fees from Actelion, personal fees from Eli Lilly, grants from European Scleroderma Trial and Research (EUSTAR) group, grants from New Horizon Fellowship, grants from Foundation for Research in Rheumatology (FOREUM), grants from Fondazione Italiana per la Ricerca sull’Artrite (FIRA), outside the submitted work, Lorenzo Tofani: None declared, Alberto Moggi Pignone: None declared, Martina Orlandi: None declared, Tomasetti Sara Speakers bureau: Speaker’s fees for Roche and Boehringer Ingelheim, Mike Hughes: None declared, Francesco Del Galdo: None declared, Rosaria Irace: None declared, Oliver Distler Grant/research support from: OD (last three years) 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)., Valeria Riccieri: None declared, Yannick Allanore Speakers bureau: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Grant/research support from: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Ana Maria Gheorghiu: None declared, Elise Siegert: None declared, Jeska de Vries-Bouwstra: None declared, Eric Hachulla: None declared, Mohammed Tikly: None declared, Nemanja Damjanov: None declared, Francois Spertini: None declared, Luc Mouthon: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Consultant of: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Grant/research support from: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Armando Gabrielli: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Speakers bureau: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Grant/research support from: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Daniel Furst: None declared, Silvia Bellando Randone: None declared

Background:Interstitial lung disease (ILD) is a severe complication of RA. Abatacept (ABA) have demonstrated efficacy in RA-ILD [1,2], although combined treatment with MTX or others DMARDs remain controversial.Objectives:To assess the efficacy and safety of ABA in monotherapy (ABAMONO) versus combined-ABA, ABA plus MTX(ABAMTX) or ABA plus other non-MTX DMARDs (ABANON-MTX), in RA-ILD.Methods:Observational multicenter study of RA-ILD caucasian patients treated with ABA. We analyzed in three groups (ABAMONO, ABAMTX, ABANON-MTX) the following outcomes: a) Dyspnea, b) FVC and DLCO, c) HRCT, d) DAS28-ESR, e) corticosteroid-sparing effect. Differences between basal and final follow-up were evaluated. Multivariable linear regression was used between the three groups.Results:We studied 263 RA-ILD patients (mean age 64.6±10 years) [ABAMONO (n=111), ABAMTX (n=46) and ABANON-MTX (n=106)]. At baseline, ABAMONO patients were older (67±10 years) and took higher prednisone dose (10 [IQR 5-15] mg/day). There was no statistically significant differences in sex, seropositivity, ILD patterns, FVC, DLCO or disease duration. In all groups, most patients experienced stabilization or improvement in FVC, DLCO, dyspnea, HRCT as well as improvement in DAS28-ESR. A statistically significant difference between basal and final follow-up was only found in corticosteroid-sparing effect in ABAMTX or ABANON-MTX(Figure 1). However, in the multivariable analysis, there were no differences in any outcome between the three groups(Table 1).Table 1.Effect in FVC, DLCO, dyspnea (mMRC) and HRCT pulmonary scan after abatacept.ABAMONON=111ABAMTXN=46ABANON-MTXN=106ABAMTXvs ABAMONOABANON-MTXvs ABAMONOpppp*UnadjustedAdjusted**UnadjustedAdjusted**Follow-up, median [IQR] months12 [6-36]12 [6-36]18[12-36]0.400.670.17Differences between basal and final follow-upFVC, %-0.5 (-2.5, 1.5)0.641.2(-0.6, 3.1)0.17-1.2 (-2.9, 0.5)0.170.330.300.390.590.90DLCO, %1.8 (-0.7, 4.34)0.160.5 (-3.8, 4.8)0.82-1.5 (-4.1, 1.1)0.260.200.580.800.070.32mMRC, n (%)Worsening5 (5)3 (8)5 (5)0.830.470.99Stable or improving93 (95)36 (92)87 (95)HRCT pulmonary scan, n (%)Worsening13 (28)2 (11)15 (25)0.240.100.78Stable or improving34 (72)19 (89)44 (75)DAS28-ESR-1.5 (-1.9, -1.0)0.000-1.2 (-1.8, -0.6)0.000-1.5 (-1.8, -1.2)0.0000.740.580.92Prednisone, mg/day-3.8 (-8.3, 0.8)0.10-2.7 (-4.6, -0.8)0.006-4.8 (-6.3, -3.4)0.0000.690.670.65Differences in DAS28-ESR, prednisone, FVC and DLCO are expressed as mean difference (95%CI) comparing final follow-up minus basal values.*Differences between the 3 groups.**Differences between ABAMTX vs. ABAMONO, and between ABANON-MTX vs ABAMONO are adjusted for age, disease duration until abatacept treatment, and DAS28 and prednisone dose at baseline.Abbreviations(DAS28-ESR: Disease activity score-erythrocyte sedimentation rate; DLCO: Carbon Monoxide Diffusing Capacity; HRCT: High resolution computed tomography; FVC: Forced vital capacity, mMRC: modified Medical Research Council scaleFigure 1.Conclusion:In caucasian individuals with RA-ILD, ABAMONO or ABAMTX or ABANON-MTX seems to be equally effective and safe. However, a corticosteroid-sparing effect is only observed in combined-ABA.References:[1]Fernández-Díaz C, et al. Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients. Semin Arthritis Rheum. 2018 Aug;48(1):22-27. doi: 10.1016/j.semarthrit.2017.12.012.[2]Fernández-Díaz C, et al. Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients. Rheumatology (Oxford). 2020 Dec 1;59(12):3906-3916. doi: 10.1093/rheumatology/keaa621.Acknowledgements:Spanish Collaborative Group of Interstitial Lung Disease Associated to Rheumatoid ArthritisDisclosure of Interests:Carlos Fernández-Díaz Speakers bureau: Roche, bristol myers squibb, Belén Atienza-Mateo: None declared, Santos Castañeda: None declared, Rafael Melero: None declared, Francisco Ortiz-Sanjuán: None declared, Ivette Casafont-Solé: None declared, J. Loricera: None declared, Sebastián C Rodriguez-García: None declared, Iván Ferraz-Amaro: None declared, Miguel A González-Gay: None declared, Ricardo Blanco Speakers bureau: bristol myers squibb

ObjectivePulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc). In this longitudinal study, we aimed to identify factors associated with an unfavourable outcome in patients with SSc with early PAH (SSc-PAH) from the DETECT cohort.MethodsPatients with SSc-PAH enrolled in DETECT were observed for up to 3 years. Associations between cross-sectional variables and disease progression (defined as the occurrence of any of the following events: WHO Functional Class worsening, combination therapy for PAH, hospitalisation or death) were analysed by univariable logistic regression.ResultsOf 57 patients with PAH (median observation time 12.6 months), 25 (43.9%) had disease progression. The following factors (OR (95% CI)) were associated with disease progression: male gender (4.1 (1.2 to 14.1)), high forced vital capacity % predicted/carbon monoxide lung diffusion capacity (DLCO)% predicted ratio (3.6 (1.2 to 10.7)), high Borg Dyspnoea Index (1.7 (1.1 to 2.6)) and low DLCO% predicted (non-linear relationship).ConclusionMore than 40% of early-diagnosed patients with SSc-PAH had disease progression during a short follow-up time, with male gender, functional capacity and pulmonary function tests at PAH diagnosis being associated with progression. This suggests that even mild PAH should be considered a high-risk complication of SSc.

Background:Interstitial pneumonia with autoimmune features (IPAF)1describes a group of patients with interstitial lung disease and autoimmune features who do not meet the classification criteria for a specific connective tissue disease. Limited data regarding IPAF are available so far.Objectives:To identify the epidemiological and clinical characteristics of patients with IPAF and to observe disease progression, response to treatment and frequency of infections in 1-year follow-up period.Methods:Thirty-nine patients from ‘Attikon’ University Hospital of Athens fulfilling the IPAF criteria were enrolled. Clinical and laboratory findings, comorbidities, medications, pulmonary outcomes assessed with repeated pulmonary function tests (PFTs) and chest HRCT and complications in a 1-year follow-up period were documented for each patient. Univariate models were performed in order to identify determinants of infection and clinically significant difference in PFTs (defined as change of ≥ 10% in FVC and/or ≥ 15% in DLCO).Results:The mean age at the time of IPAF diagnosis was 63.2 (±11) years and 62% of the patients were female. The most common clinical features included in the IPAF criteria were arthritis (82%) and Raynaud’s phenomenon (26%). A morbilliform and/or polymorphic rash of the face, neck and extremities (not included in the IPAF criteria) was noted in 54% of patients. ANA (59%) and anti–Ro (21%) were the most common auto-antibodies. Non-specific Interstitial Pneumonia (NSIP) was the most prevalent radiological pattern (61.5%) as shown in table 1. Treatment comprised corticosteroids and immunosuppressants including hydroxychloroquine, methotrexate, azathioprine, mycophenolate and cyclophosphamide. PFTs following treatment at 6 and 12 months from baseline showed a trend of improvement (Table 2, p> 0.05). At 1 year from baseline, 20.5% of patients showed a clinically significant deterioration while 25% had a clinically significant improvement. Infections were observed in 23.1% of patients during the first semester and in 12.8% during the second semester of the follow-up period. All were respiratory tract infections and two patients (5.1%) required hospitalization. All infections occurred in patients with non-UIP pattern (p=0.02) which might be attributed to higher doses of corticosteroids used in these patients (mean initial prednisolone dose = 27 (±18) mg/d in patients with non-UIP pattern versus 17 (±16) mg/d in patients with UIP pattern, p=0.4).Table 1.Prevalence of HRCT patterns in 39 patients.Radiological patternNo (%)NSIP24 (61,5%)OP2 (5,1%)NSIP with OP overlap2 (5,1%)LIP1 (2,6%)UIP7 (18%)NSIP and UIP3 (7,7%)NSIP: Non-specific Interstitial Pneumonia, OP: Organizing Pneumonia, LIP: Lymphocytic Interstitial Pneumonia, UIP: Usual Interstitial Pneumonia.Table 2.PFTs at baseline, 6 and 12 months.PFTs (% of predicted value ± SD)Baseline6 months12 monthsP valueFVC79% (±19%)82% (±18%)84% (±17%)nsDLCO49% (±16%)52% (±17%)53% (±17%)nsConclusion:Rash is a common feature in IPAF and may be considered for inclusion into IPAF criteria. A trend of improvement in PFTs and a significant risk of respiratory tract infections mainly in the first semester of treatment and in patients with non-UIP radiological pattern were observed. Larger prospective studies are warranted in order to elucidate IPAF’s prognosis and to identify effective management approaches.References:[1]Fischer A, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J 2015; 46: 976-987.Disclosure of Interests:Maria Karampeli: None declared, Konstantinos Thomas: None declared, Dimitrios Tseronis: None declared, Michail Aggelakos: None declared, Dimitra Kassara: None declared, Katerina Havatza: None declared, Sofia Flouda: None declared, Dionysis Nikolopoulos: None declared, Antigoni Pieta: None declared, Vasiliki Tzavara: None declared, Pelagia Katsimbri: None declared, Dimitrios Boumpas Grant/research support from: Unrestricted grant support from various pharmaceutical companies, Theofanis Karageorgas: None declared

Background:Our previous study demonstrated that Hsp90 is overexpressed in the skin of patients with systemic sclerosis (SSc), in cultured SSc fibroblasts and preclinical models of SSc in a TGF-β dependent manner. We showed that Hsp90 is a new regulator of canonical TGF-β signaling and its inhibition prevents the stimulatory effects of TGF-β on collagen synthesis and dermal fibrosis1.Objectives:The aim of this study was to evaluate plasma Hsp90 of SSc patients and characterize its potential association with skin changes and SSc-related features.Methods:A total of 92 patients (79 females; mean age 52.7; disease duration 6.0 years; diffuse cutaneous (dc)SSc / limited cutaneous (lc)SSc = 38/54) and 92 age- and sex- matched healthy individuals were included. Plasma Hsp90 levels were measured by ELISA (eBioscience, Vienna, Austria). Data are presented as median (IQR).Results:Plasma Hsp90 levels were increased in SSc patients compared to healthy controls [12.5 (9.6–17.9) vs. 9.8 (7.7–12.4) ng/mL, p=0.0001]. Hsp90 levels in all patients positively correlated with CRP (r=0.271, p=0.015). Furthermore, Hsp90 concentrations were negatively associated with functional parameters of ILD: FVC (r=-0.291, p=0.013), FEV1 (r=-0.248, p=0.036), DLCO (r=-0.290, p=0.012) and SpO2(r=-0.317, p=0.038). When adjusted for CRP, these correlations still remained significant in multivariate analysis. Higher Hsp90 concentrations were associated with presence of synovitis [17.6 (15.4 – 24.0) vs. 12.2 (9.3 – 17.3), p=0.039]. In addition, only in patients with dcSSc, Hsp90 levels positively correlated with the mRSS (r=0.437, p=0.006). In a prospective analysis of patients with progressive SSc-ILD treated with 6 (n=21 patients) or 12 (n=14 patients) monthly i.v. pulses of cyclophosphamide (CPA, 10 mg/kg) we did not observe any significant differences between the baseline sample (month 0) and blood drawn after 1, 6 and 12 months. However, baseline Hsp90 was able to predict long-term response after one year of CPA treatment (DLCOm12-m0; r=-0.494, p=0.037). Moreover, change in Hsp90 after one month of CPA treatment (Hsp90m1-m0) was able to predict the short-term inflammatory response (CRPm3-m0, r=-0.495, p=0.019; ESRm3-m0, r=-0.496, p=0.031). Concentrations of extracellular Hsp90 were not significantly affected by other main clinical parameters of SSc.Conclusion:We demonstrated higher plasma levels of Hsp90 in SSc patients compared to healthy controls. Concentrations of extracellular Hsp90 increase with higher inflammatory activity, with deteriorated lung functions in ILD and also with the extent and severity of the skin involvement in patients with diffuse cutaneous SSc. These data further highlight the role of Hsp90 as a significant regulator of fibroblast activation and tissue fibrosis in SSc. In addition, Hsp90 could become a predictor of treatment response.References:[1]Tomcik M et al., Ann Rheum Dis.2014;73(6):1215-22.Acknowledgments:Supported by AZV-16-33542A, MHCR 023728 and SVV – 260373.Disclosure of Interests:Hana Štorkánová: None declared, Sabina Oreska: None declared, Maja Špiritović: None declared, Barbora Heřmánková: None declared, Kristyna Bubova: None declared, Martin Komarc: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiří Vencovský: None declared, Jörg Distler Grant/research support from: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Paid instructor for: Boehringer Ingelheim, Speakers bureau: Boehringer Ingelheim, Ladislav Šenolt: None declared, Radim Bečvář Consultant of: Actelion, Roche, Michal Tomcik: None declared

Background:Systemic sclerosis (SSc) is known as the most severe connective tissue disorder, and to be associated with a high mortality risk. Moreover, there is a great variability of mortality rate in the literature.Objectives:To determine the mortality rate and its predictors in systemic sclerosis in a long-term follow- up of a bi-centric cohort of SSc patientsMethods:We have carried out a retrospective observational study by systematically analysing the medical records of patients diagnosed with SSc in Toulouse University Hospital and Ducuing Hospital. We included patients over 18 years old, whose diagnosis was made after 01/01/2000 and who met the classification criteria for the American College of Rheumatology (ACR) /EULAR 2013, and with at least one follow-up visit after the inclusion visit. Patients were followed until 30/05/2018. We quantified mortality as Standardized Mortality Ratio (SMR) and percentage mortality at 1, 3, 5, 10 and 15 years of disease. For comparison, we used the mortality rate for the population in the French Region of Occitanie in 2016, using data from the French National Statistical Agency. We determined a single primary cause of death (SSc or non-SSc related) and evaluated predictors of mortality using multivariable Cox regression.Results:We included 375 patients (292 females), 63 (15.2%) patients with diffuse cutaneous SSc, 279 (76.7%) with limited cutaneous SSc and 33 (8.1%) with sine scleroderma SSc. During the study period 6 patients were lost to follow-up and 69 died (18.4%). The SMR ratio was 1.85 (95% CI 1.45-2.34). The overall survival rates were 97.5% at 1 year, 93.4% at 3 years, 87.1% at 5 years, 77.9% at 10 years and 61.3% at 15 years. Among the 69 deaths recorded 46.4% were SSc related deaths, 53.6% were non-related. Among the SSc related deaths, three main causes were identified: interstitial lung disease (ILD) (34.4%), pulmonary hypertension (31.2%) and digestive tract involvement (18.8%). Among the causes of SSc non-related deaths, cardiovascular disorders (37.8%) and various infections (35.1%) largely distanced those from cancer (13.5%). Four significant independent predictive factors were identified using multivariable Cox regression: carbon monoxide diffusingcapacity(DLCO) < 70% (HR=3.01; p=0.0053),C-reactive protein(CRP) >5 mg/l (HR=2.13; p=0.0174), cardiac involvement (HR=2.86; p=0.0012) and the fact of being male (HR=3.25; p=0.0004) (Table 1). The same four factors were identified as predictive of mortality at 5 and 10 years in multivariable Cox regression (Table 2).Table 1.Multivariate analyses of mortality prognosis factorsHRIC95pSex: Male3.251.69-6.220.0004DLCO 3.11.40-6.880.0053Cardiac involvement2.861.52-5.410.0012CRP >5 mg/l2.131.14-5.410.0174Table 2.Multivariate analyses of mortality prognosis factors at 5 and 10 yearsAt 5 yearsAt 10 yearsHR95% CIpHR95% CIpSex: Male2.1310.99-4.580.05263.421.75-6.670.0003DLCO 5.4891.61-18.600.00634.541.74-1.850.002Cardiac involvement2.8931.30-6.410.00893.181.62-6.240.0008CRP >5 mg/l3.2831.42-7.530.0052.371.23-6.460.01Conclusion:Our results confirm that SSc is a devastating condition as reflected by a pooled SMR of 1.85. The two principal causes of SSc-related death remain PH and ILD. However, SSc non-related death are represented mainly by cardiovascular diseases. This work identified sex (male), DLCO 5mg/l as independent predictors of mortality. With the emergence of new therapies, these important observations should help refine the monitoring and management to prolong these patients’ survival.Disclosure of Interests:None declared

Background:Systemic sclerosis (SSc) is a progressive, multi-organ disease with limited treatment options. Interleukin-4 (IL-4) and IL-13 have been implicated in the fibrotic pathway and pathogenesis of SSc and are promising targets. Romilkimab (RKB) is an engineered humanized bispecific Ig-G4 antibody that binds and neutralizes both IL-4/IL-13. We report a Phase IIa randomized, double-blind, placebo-controlled trial (NCT02921971, Sanofi funded) employing RKB in SSc.Objectives:To evaluate the efficacy and safety of RKB in dcSSc.Methods:Patients with dcSSc duration ≤36 months, mRSS 10-35, with or without immunosuppressive background therapy were randomized (1:1) to subcutaneous RKB 200mg or placebo (PBO) for 24 weeks and stratified on history of SSc-ILD. Primary endpoint was mean change in mRSS at Week 24 and FVC/DLco and HAQ-DI were secondary endpoints. All analyses used a 1-sided p-value Results:Ninety-seven patients with similar baseline characteristics between arms, including use of background therapy (RKB 59.2% vs. PBO 52.1%) were randomized. Six (12.2%) and 4 (8.3%) patients discontinued study treatment early in the PBO and RKB arms, respectively. Primary endpoint showed an absolute change in mRSS of -2.45 (0.85) and -4.76 (0.86) for PBO and RKB groups, respectively with a difference of -2.31 (1.21) favoring RKB (p=0.029). Subgroup analysis based on background therapy showed a similar treatment effect with a PBO subtracted difference in mRSS of -2.69 (1.83) and -2.38 (1.59), suggesting an additive effect between background therapy and RKB. Secondary endpoints did not show a statistically significant difference between RKB vs. PBO arms, although there was numerically less decline in FVC with RKB with a PBO subtracted difference of 70ml (p=0.06). Exploratory endpoints suggested possible effect of RKB on overall pain, Raynaud’s, digital ulcers, and EQ-5D-5L. Post-hoc analysis was undertaken to determine time to progression (first event defined as death, ≥10% relative decline in % predicted FVC, ≥15% relative decline in % predicted DLCO, ≥20% increase or +5 in mRSS, or other events: cardiac, SRC, PAH development) and showed a benefit for RKB (HR: 0.47 p=0.04). Adverse events were balanced between the two groups (RKB 83.3% vs. PBO 83.7%). There were 5 and 4 SAEs in the PBO and RKB arms, respectively. One death occurred in each arm (SRC – RKB, cardiomyopathy – PBO).Conclusion:Patients with dcSSc who were treated with RKB showed a statistically significant reduction in mRSS compared to those receiving PBO. Secondary outcomes were not met, although RKB was associated with a smaller decline in FVC than PBO. Post-hoc analysis showed a possible reduction on time to progression with RKB. RKB was well tolerated with no major safety concerns.References:None.Disclosure of Interests:Yannick Allanore Grant/research support from: Yannick Allanore has received grants from Inventiva, Roche and Sanofi, Consultant of: Yannick Allanore has received fees from Actelion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Curzion, Inventiva, Roche, Sanofi, Peter Wung Shareholder of: I own Sanofi stock, Employee of: I work for Sanofi, Christina Soubrane Employee of: I work for Sanofi., Corinne Esperet Employee of: I work for Sanofi., MARRACHE Frederic Employee of: I work for Sanofi, Raphael Bejuit Employee of: I work for Sanofi., Amel Lahmar Employee of: I work for Sanofi., 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, 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:Interstitial lung disease (ILD) is one of the main contributor to morbidity and mortality in patients with primary Sjogren syndrome (pSS), and whether immunosuppressive treatments are effective for pSS-ILD is uncertain. Cyclophosphamide (CYC) and rituximab (RTX) are effective in stabilizing pulmonary function in patients with ILD caused by systemic sclerosis, inflammatory myositis, and rheumatoid arthritis1,2. Reports regarding the treatment response for cyclophosphamide or rituximab in pSS-ILD patients are lacking.Objectives:To investigate whether add-on CYC or RTX in addition to steroid and oral DMARDs leads to greater improvement in pulmonary function test than conventional treatment in patients with pSS-ILD with impaired baseline pulmonary function.Methods:pSS-ILD patients with ILD confirmed by a chest computed tomography were screened. Those with imparied baseline pulmonary function test (FVCResults:This study enrolled 22 patients. The median age of these patients was 65. Among them, 68% were female and 18% were smokers. The median baseline FVC was 63.5% and the median DLCO was 54.4%. The predominant CT pattern was NSIP (54%), followed by UIP (22%), LIP (13.6%) and OP (9%) (table 1).Five patients received steroid and oral DMARDs alone (hydroxychloroquine +/- azathioprine), while 17 patients received add-on CYC and/or RTX (8 patients received CYC, 3 received RTX, and 6 received CYC and RTX). There was no significant difference in baseline characteristic between these two groups (table 1).With a median follow-up period of 9.8 months (interquartile range 7.6 - 13.4 months) after treatment, the FVC improved significantly from 61.3% to 65.5% (p=0.013) in CYC/RTX group, while the FVC improvement was not significant in steroid/oDMARD group (figure 1A). In CYC/RTX group, patients with non-UIP pattern (NSIP, LIP and OP) on chest CT had significant FVC improvement (p=0.021), contrasting to the patients with UIP pattern on chest CT (figure 1B).Conclusion:In pSS patients with ILD and impairment of pulmonary function at baseline (FVCReferences:[1]Wells AU, Denton CP. Interstitial lung disease in connective tissue disease--mechanisms and management. Nat Rev Rheumatol. 2014 Dec;10(12):728-39.[2]Gao Y, Moua T. Treatment of the Connective Tissue Disease-Related Interstitial Lung Diseases: A Narrative Review. Mayo Clin Proc. 2020 Mar;95(3):554-573.Table 1.Baseline characteristics of patients with Sjögren’s syndrome and interstitial lung diseaseTotal(n = 22)Steroid/oDMARDs (n = 5)Add-on CYC/RTX(n = 17)Comparison between two groups (p-value)Age, year, median (IQR)65.1 (61.7 - 69.1)64 (64.6 - 67.4)65.6 (61.6 - 69.2)0.88Female sex, n (%)15 (68%)4 (80%)12 (70%)1.00Smoking, n (%)4 (22%)0 (0%)4 (21%)0.54Baseline FVC, % of predicted value, median (IQR)63.6% (53.8 - 68.2)63.9% (63.7 - 67.5)61.3% (50.2 - 68.2)0.43Baseline DLCO, % of predicted value, median (IQR)54.4% (39.4 - 66.4)69.1% (57.8 - 75.5)52.1% (38.5 - 58.1)0.12CT pattern, n (%)NSIP - 12 (54%)NSIP 1 (20%)NSIP - 11 (65%)-UIP - 5 (22%)UIP 1 (20%)UIP - 4 (24%)LIP - 3 (13.6%)LIP 2 (40%)LIP -1 (6%)OP - 2 (9%)OP 1 (20%)OP -1 (6)UIP pattern, n (%)5 (22%)1 (20%)4 (24%)1.00CYC, cyclophosphamide; oDMARDs, oral DMARDs; RTX, rituximabFigure 1.FVC change before and after the immunosuppressive treatmentDisclosure of Interests:None declared

Background:Interstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). However, the effect of RA treatment on the course of ILD is not yet known.Objectives:To assess the effect of RA treatment on the course of lung physiology of RA-focusing on biologic DMARDs treatment.Methods:The Korean Rheumatoid Arthritis ILd (KORAIL) cohort is the prospective observational cohort and aims to investigate the natural course of RAILD. Based on either 1987 or 2020 ACR criteria, patients diagnosed with RA and ILD based on CT scan were recruited from six tertiary medical hospitals in Korea since January 2015. RA disease activity was assessed using disease activity (DAS)28-ESR and CRP, annually. Pulmonary function tests (PFT), including FVC and DLCO were conducted annually. In the current study, we analyzed patients who completed a 2-years follow-up or had died during those terms till October 2020. They classified patients into three groups: patients treated with abatacept ≥24 weeks ever (Group 1), those with other bDAMRDs ≥24 weeks ever (Group 2), and those without any bDMARDs or with bDMARDs Results:Of a total of 125 patients who completed 2-year follow-up, 21 patients were classified as Group 1, 26 for Group 2, and 78 for Group 3. The mean age or the number of patients with ≥ 65-year-old was comparable between groups(Table 1). The mean duration since RA diagnosis was shorter in Group 3, but that since ILD diagnosis was comparable. DAS28-ESR score was comparable between Group 1 and 2 at enrollment, so was in 1-year-follow-up (p=0.75) and 2-year-follow-up (p=1.00). FVC and % of the predicted value in FVC, FEV1, and DLco were also comparable among the three groups at enrollment. The numbers of patients with ≥10-point decline in % of FVC predicted was 2 (10.0%) for Group 1, 1 (3.8%) for Group 2, 3 (3.9%) for Group3 during the first 1-year follow-up, and 3 (15.8%), 3 (11.5%), 10 (14.1%) during the last 1-year follow up. The percent of FVC predicted was 81.6 ± 17.5 %, 87.4 ± 17.9 %, 85.2 ± 17.7 % for Group 1,2 and 3, respectively, at 1-year-follow-up, and 79.5 ± 18.8 %, 89.0 ± 16.8 %, 83.5 ± 17.3 % at 2-year-follow-up. (Figure 1A). The percent of DLco predicted was 75.5 ± 23.4 %, 66.7 ± 18.1 %, 67.5 ± 16.7 % for Group 1,2 and 3, respectively, at 1-year-follow-up, and 74.0 ± 23.7 %, 69.1 ± 18.9 %, 67.0 ± 18.5 % at 1-year-follow-up (Figure 1B).Conclusion:Treatment of bDMARDs did not exacerbate FVC than without bDMARDs treatment and mitigated the decline of DLCO compared to without bDMARDs treatment during 2-year-follow-up.Table 1.Clinical characteristics at enrollment (V1)TotalGroup 1.Group 2.Group 3.PN125212678Age at enrollment65.9±8.266.0±8.863.9±8.066.6±8.10.3465, n (%)72 (57.6)13 (61.9)11 (42.3)48 (61.5)0.21Female, n (%)89 (71.2)16 (76.2)17 (65.4)56 (71.8)0.71RA duration, years8.0±8.49.6±6.69.2±9.07.2±8.60.05ILD duration, years3.0±3.33.8±3.73.8±3.52.5±3.10.10BMI, kg/m224.1±3.123.8±3.724.8±2.923.9±3.00.39Ever-smoker1855180.57RF positive, n (%)111 (88.8)19 (90.5)22 (84.6)70 (89.7)0.72Anti-CCP positive, n (%)119 (95.2)20 (95.2)25 (96.2)74 (94.9)1.00Arthritis activityDAS28-ESR4.0 ± 1.44.1 ± 1.14.3 ± 1.83.8 ± 1.40.60*DAS28-CRP3.1 ± 1.43.2 ± 1.23.4 ± 1.63.0 ± 1.40.76*HAQ-DI0.70 ± 0.760.64 ± 0.490.82 ± 0.820.67 ± 0.800.28*Pulmonary function testFVC, ml2522.5 ± 765.42406.2 ± 772.62617.3 ± 965.22522.2 ± 692.30.65FVC, % of pred.84.6 ± 16.980.9 ± 17.786.12 ± 17.8285.08 ± 16.50.53FEV1, % of pred.92.4 ± 21.492.0 ± 24.890.6 ± 22.193.0 ± 20.40.88DLco, % of pred.71.5 ± 19.772.3 ± 26.769.1 ± 16.472.0 ± 18.70.80Figure 1.Acknowledgements:This research was supported by Bristol Myers Squibb Inc.Disclosure of Interests:Sung Hae Chang: None declared, Ji Sung Lee: None declared, Jeong Seok Lee: None declared, Chan Ho Park: None declared, Min Uk Kim: None declared, You-Jung Ha: None declared, Eun Ha Kang: None declared, Yeon Ah Lee: None declared, Yongbeom Park: None declared, Jung-Yoon Choe: None declared, Eun Young Lee Grant/research support from: Bristol Myers Squibb Inc.

Background:Patient Reported Outcomes (PROs) are used to capture disease impact on patients’ Health Related Quality of Life (HRQoL) and they have been increasingly used as endpoints in clinical trials for Systemic Sclerosis (SSc). The DeSScipher project within the EUSTAR group highlighted dyspnea as one of the factors more strongly related with the highest SHAQ scores (1). Nevertheless, the SENSCIS trial in SSc-ILD (2) showed the efficacy of Nintedanib in reducing the annual rate of FVC loss, as compared to placebo, without significant changes in the PROs used as secondary endpoints (St. George’s Respiratory Questionnaire and the FACIT-Dyspnoea questionnaire). Since patient’s perspective is a crucial determinant to define the overall relevance of an intervention, the performance of PROs in reflecting different lung functional stages is a relevant issue in SSc.Objectives:To analyse in a prospective SSc cohort the inference of reduced lung function as measured by FVC on median PRO scores and the correlation among distinct commonly used PROs.Methods:A cross-sectional study was performed on data exported from the STRIKE database regarding SSc patients followed in Leeds Scleroderma Programme for SSc. Data included records of periodical visits with scores of different PROs commonly used in SSc (Scleroderma-Health Assessment Questionnaire (SHAQ), Cochin Hand Function Scale (CHFS) and Borg dyspnoea scale) and FVC%-predicted (%pFVC) and DLCO%-predicted (%pDLCO). SHAQ score was calculated as the mean value of HAQ (0-3) with the average of the 7-VAS scores divided by 3.33. The 7-VAS (score 1-10) were 1: pain, 2: general function, 3: arthritis, 4: gastro-intestinal, 5: dyspnoea, 6: Raynaud Phenomena; 7: digital ulcers. The correlation of FVC with distinct PROs, and the inter-PRO correlation, were analysed through the non-parametric Spearman test.Results:Complete data were available from 182 visits of 87 SSc patients (41 with diffuse and 46 with limited cutaneous involvement). Mean %pFVC was 95.16 ±24.93 (median 95) and mean %pDLCO was 59.31±16.51 (median 59). Overall, FVC and DLCO showed a moderate correlation with SHAQ (r=-0.36, pInter PROs analysis showed that CHFS score had a stronger correlation with SHAQ than Borg dyspnoea score in the overall population (r:0.86 vs. r:0.57, both pConclusion:The analysis of a single centre prospective cohort of SSc patients, suggests a small inference of lung function in the overall SHAQ. The stronger correlation of SHAQ with CHFS, than with Borg score, suggests a higher weight of hand function on SHAQ in this population with relatively conserved lung function. In patients with %pFVC 70%, suggesting that mild reductions in FVC might not be perceived by the patients, or at least they might not modify HrQoL as measured by SHAQ.References:[1]Jaeger VK, et al. Rheumatology 2017;57(3):441-50.[2]Distler O, et al. N Engl J Med 2019; 380:2518-2528.Disclosure of Interests:Maria Grazia Lazzaroni Grant/research support from: Boehringer-Ingelheim, Giuseppina Abignano: None declared, Michelle Wilson: None declared, Vishal Kakkar: None declared, Francesco Del Galdo Consultant of: Astra-Zeneca, Boehringer-Ingelheim, Mitsubishi-Tanabe, Capella Biosciences, Kymab, Actelion, Grant/research support from: Astra-Zeneca, Boehringer-Ingelheim, Mitsubishi-Tanabe, Capella Biosciences, Kymab, Actelion

Background:Juvenile systemic scleroderma (jSSС) is a rare multisystem disease with a poor prognosis. The current therapy is imperfect. Biologics, as a modern efficient option for treatment of rheumatic diseases don`t have official indication for jSSС, but it seems to be useful in severe cases, especially lung and heart damage.Objectives:To analyze the existing experience of Biologics therapy in children with jSSС in single center in order to improve the understanding of the indications for use and the results of using these drugs.Methods:The retrospective study include 9 patients with jSSC with severe course of disease, 7 of them were girls.Results:Among this group of patients the age at disease onset was 9.1 years (min-max 1.1-15.1). Clinical manifestations: Raynaud’s syndrome (n = 9), ulcers (n = 3), skin changes (n = 9), joints (n = 8), muscles (n = 4), interstitial lungs disease (n = 6), heart (n = 3), esophagus (n = 5), calcification (n = 3). The main therapy prior to the use of biological agents: glucocorticoids (GC) (n = 9), cyclophosphamide (CF) (n = 2), hydroxychloroquine (HC) (n = 5), therapy for the microcirculation improvement. Biologics were prescribed in the case of insufficient effectiveness of previously conducted therapy, primarily in relation to lung damage (interstitial disease) and heart (with reduced contractility, arrhythmia), as well as changes in the skin and musculoskeletal system. In addition, the possibility to reduce the dose of GC (n=6), withdrawal of CF (n=2) was taken into account. Our experience consist of follows: rituximab (RTM) (n=7) at a dose of 375 mg/m2 interval 3-6 months, abatacept i.v.(ABT) (n=2) 10 mg/kg every 4 weeks, tocilizumab i.v.(TCZ) (n=2) 8 mg/kg. In all cases Biologics was prescribed not earlier than 1.5 year after disease onset (4.6 years in average). By present most patients continued to use biological therapy; of them - RTM was used for 2.2 (0.5-6.0) years, in 1 patient – was canceled after 6 years due to the loss of efficasy; ABT is used in 2 children for 0.5 and 3.6 years, TCZ - in 2 children for 0.3 (withdrawal) and 2.0 years (continues to use)., TCZ was prescribed in 1 patient after 6 years of RTM use. In 1 patient TCZ was withdrawal due to an infusion reaction, and ABT was prescribed. As a result of the therapy, it has been found to improve habitus, quality of life and well-being, reduce skin tightening, improve joint function; no progression of changes in the lungs according to CT and functional tests (FVC, DLCO), improvement in cardiac lesions. It seems that disease improvement became notable at least 3-6 months after the Biologics start. In most patients there were no serious adverse events (AE). No significant infections have been reported. But we met an unexpected case of substantial increasing of neutrophil’s count just after each TCZ infusions up to 21,000 and reversed by following infusions for a one year of treatment from 2 years of total duration of using.Conclusion:Our data shown that Biologics could be efficient and well-tolerated option for severe and resistant to «traditional» therapy course of jSSC. Because this kind of condition is extremely rare further multicenter study is needed.Disclosure of Interests:None declared

Background:Interstitial lung disease (ILD) is a severe extra-articular manifestation of rheumatoid arthritis (RA). However, the effect of RA disease activity on the course of ILD is not yet known.Objectives:To assess the natural course of lung physiology of RA-ILD and the relation between arthritis activity and pulmonary physiology in patients with RA-ILD.Methods:The Korean Rheumatoid Arthritis ILd (KORAIL) cohort is the prospective observational cohort and aims to investigate the natural course of RAILD. Based on either 1987 or 2020 ACR criteria, patients diagnosed with RA and ILD based on CT scan were recruited from six tertiary medical hospitals in Korea since January 2015. RA disease activity was assessed using disease activity (DAS)28-ESR and CRP, annually. Pulmonary function tests (PFT), including FVC and DLCO were conducted annually. According to the transition of DAS28-ESR status, we classified patients into four groups: Group A. persistent remission or low disease activity, Group B. improvement, Group C. worsening, Group D. persistent moderate to high disease activity.Results:We analyzed 143 patients who completed a 2-year follow-up (visit 2) or had died with available PFT results at least twice. Mean duration since RA diagnosis and since ILD diagnosis was 7.6±8.0 and 2.7±3.1 years, respectively. Twenty-four patients were Group A, 33 Group B, 10 Group C and 30 Group D. The mean of FVC (mL) and % of the predicted value in FVC was significantly lower in Group D than in other groups (Table 1). The annual rate of decline in FVC was -42 (95% CI -93~10) mL·year-1 in Group B while -113 (95% CI -206~-21) mL·year-1 in Group C (Figure 1A). The annual decline rate in Group C was further exaggerated in patients with ≥ 80% of FVC predicted (-141, 95% CI -251~-32 mL·year-1). During two years of follow-up, patients ever experienced a relative decline of ≥10% from the enrollment in FVC predicted was 27.3%(n-9/33) in Group B whereas 30.0% (3/10) in Group C. The annual rate of decline in % of DLco predicted value was also the largest in Group C (-4.6 %·year-1, 95%CI -8.5~-0.7), which further exaggerated in patients with ≥ 80% of FVC predicted (-4.9%·year-1, 95 %CI -8.3~-1.5, Figure 1B). Of note, about half of patients with maintained not only low disease activity (Group A) but also moderate to severe disease activity (Group D) improved in DLco at least 10% or more from the enrollment of DLco predicted value (Group A: 54.2%, n=13/24, Group D: 46.7%, n=14/30).Conclusion:RA disease activity is associated with the change of lung physiology in patients with RA-ILD; worsening disease activity associated with a further decrease of annual change in FVC and maintaining low disease activity associated with a further increase of annual change in % of DLco predicted value.Table 1.The analysis of forced vital capacity (FVC) according to disease activity transition group.Group AGroup BGroup CGroup DFVC (mL), mean±SD2810.0±771.12528.8±735.32801.0±952.72048.3±575.7FVC % of predicted, mean±SD87.5±14.586.5±16.693.0±15.677.2±17.3Rate of FVC decline, mL·year-1 (95% CI)-52 (-112,7)-42 (-93,10)-113 (-206, -21)1 (-52, 54)A 10-point decline from V1 in predicted FVC value, n (%)29 (20.3)6 (25.0)6 (18.2)3 (30.0)Relative decline of 10% from the enrollment in predicted FVC value, n (%)35 (24.5)5 (20.8)9 (27.3)3 (30.0)Figure 1.The annual change of pulmonary physiology according to disease activity transition group.Acknowledgements:This work was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant no.HI14C1277).Disclosure of Interests:None declared

Background:Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is the most common type of lung involvement in rheumatoid arthritis (RA). The existence of RA-ILD is associated with worse survival. There is no mainstay treatment for RA-ILD. However, in recent studies, rituximab (RTX) seems to be effective in RA-ILD.Objectives:To determine the effects of RTX in patients with RA-ILD from a single-centre.Methods:In our biological treatment outpatient clinic, a retrospective study was conducted in patients with RA who were treated with RTX. Among them, patients with RA-ILD were analysed. For lung response to RTX, progression was defined as a decline of 10% ≥ in forced vital capacity (FVC) and/or a decline of 15% ≥ in diffusion capacity of carbon monoxide (DLCO). Computed tomography of the chest (chest-CT) were integrated to lung response so as to constitute missing data of pulmonary function tests (PFTs).Results:A total of 165 patients who are followed-up in our biological treatment outpatient clinic have been using RTX for their RA diagnosis. Among 165 patients, 26 (15.8%) patients with RA-ILD were initiated RTX. Five patients were diagnosed with RA-ILD while using RTX (incidence rate 3%). Patients‘ characteristics were demonstrated in table 1. Of 26 patients, the most commonly used concomitant disease-modifying antirheumatic drugs was leflunomide (46.2%) followed by mycophenolate mofetil (11.5), methotrexate (11.5%) and azathioprine (3.8%). Twenty-four (92.3%) patients used steroids. For the evaluation of lung response, 20 patients who had follow-up PFTs and/or chest-CT were compared. Median DLCO values for pre- and post RTX were 71.0% (60.0-77.0) and 63.0% (47.0-74.0), respectively (p= 0.061). Median pre and post-RTX FVC were 74.0% (61.0-99.0) and 84.0% (63.0-100.0), respectively (p= 0.28). After a median of 2.7 years, 11 (55.0%) patients had stable disease, 2 (10.0%) patients had regression of RA-ILD and 7 (35.0%) patients had progressive disease. Sex, age, seropositivity and radiographic patterns were not associated with progression. In total, 23 adverse events were detected in 11 (42.3%) patients. Five of them were serious infections requiring hospitalization, mostly pneumonia. Other adverse events were simple infections and surgeries such as arthroplasty. RTX was stopped in 4 (15.4%) patients due to infections secondary to hypogammaglobulinemia in 2, malignancy in 1 and allergic reaction in 1.Conclusion:RTX seems to achieve stabilization/improvement of RA-ILD with fewer adverse events. However, given that RA-ILD develops post-RTX, it is not a panacea; therefore, we need more effective treatment modalities in the case of RA-ILD.Table 1.Characteristics of 26 patients with RA-ILD treated with rituximabAge at first RTX infusion, median (IQR), years61.2 (57.1-65.1)RA disease duration at first RTX, median (IQR), years10.1 (4.3-29.7)ILD disease duration at first RTX, median (IQR), years1.9 (0.1-4.5)Age at RA diagnosis, median (IQR), years51.1 (40.0-60.6)Age at ILD diagnosis, median (IQR), years58.3 (53.9-63.3)Male patient, n (%)16 (61.5)RF positivity, n (%)25 (96.2)ACPA positivity, n (%)20 (90.9)CRP levels,mg/L, mean (SD)40.3 (58.9)ESR levels, mean (SD)37.7 (18.2)Smoking status, n (%)16 (64.0)Prior TNF inhibitor treatment, n (%)5 (19.2)DAS28 at first RTX infusion, mean (SD)5.3 (1.5)Radiographic pattern, n (%)UIP7 (26.9)NSIP8 (30.8)OP2 (7.7)Indeterminate8 (30.8)Others1 (3.8)Follow-up duration, median (IQR), years2.5 (1.2-3.7)RA-ILD= Rheumatoid arthritis-related interstitial lung disease, RTX= rituximab, RA= rheumatoid arthritis, RF= rheumatoid factor, ACPA= anti-citrullinated protein antibody, TNF= tumor necrosis factor, CRP= C-reactive protein, ESR= erythrocyte sedimentation rate, UIP= usual interstitial pneumonia, NSIP= non-specific interstitial pneumonia, OP= organizing pneumoniaDisclosure of Interests:None declared

Objective Children born preterm have lower lung function compared with term-born children. Intrauterine growth restriction (IUGR) may predispose individuals to chronic obstructive pulmonary disease. The purpose of this observational study was to investigate the role of IUGR as predictor of lung function at school age in children born very preterm. We further studied the difference in lung function between term-born and preterm-born children with distinct morbidities. Design Preterm-born children and age-matched and sex-matched term-born comparison groups (88 of each) were studied at the mean age of 11 years. Spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded. All preterm-born subjects with IUGR (n=23), defined as birth weight less than −2 SD, were compared with preterm-born subjects without IUGR (n=65). Results In the preterm-born children exposed to IUGR, the forced expiratory volume in 1 s (FEV 1 ) was 5.7 (95% CI −10.2 to −1.3) and DLCO 9.2 percentage points lower (95% CI −15.7 to −2.7) than in the preterm-born children with appropriate in utero growth (expressed as percentage of predicted values). The effect of IUGR in decreasing FEV 1 and DLCO remained significant after adjustment for bronchopulmonary dysplasia (BPD). Further study indicated that after adjustment with IUGR and BPD, prematurity explained reduction in FEV 1 but not in DLCO. Conclusions In children born very preterm, IUGR is an independent risk factor for a lower lung function in school age. We propose that IUGR and BPD are the major early factors predisposing the children born very preterm to lower lung function.

Background:A proportion of patients with Interstitial Lung Disease (ILD) show autoimmune characteristics but do not completely meet the classification criteria for a definitive connective tissue disease. In order to unify the nomenclature and criteria to define this condition, the classification of patients with Interstitial Pneumonia with Autoimmune Features (IPAF) has recently been adopted (Fisher, et al).Objectives:To describe the sociodemographic, clinical, functional characteristics and therapeutic management of IPAF patients in clinical practice and to evaluate the incidence rate of functional respiratory impairment over time.Methods:A longitudinal observational study was performed. Patients with IPAF classification criteria (Fischer et al) were included from the time of ILD diagnosis (Feb 2017 to Sept 2018) and followed until loss of follow-up or end of the study (Oct 2019), in a multidisciplinary team, carried by a pneumologist and a rheumatologist in a Tertiary Hospital in Madrid. Main outcome: relative functional respiratory impairment: defined as decline in percent predicted forced vital capacity (FVC%) of ≥ 5% compared to the previous visit. Respiratory function was measured at baseline and every 6 months. Covariates: a) sociodemographic, b) clinical, c) radiological pattern (non-specific interstitial pneumonia [NSIP]; usual interstitial pneumonia [UIP], others); d) FVC%, DLCO%; e) laboratory tests; f) therapy used (glucorticosteroids, disease modifying antirheumatic drugs (DMARDs) and Biologic Agents). Statistical analysis: description of the sociodemographic, clinical, radiological, functional and treatment characteristics of the patients. Survival techniques were used to estimate the incidence rate (IR) of relative functional respiratory impairment, expressed per 100 patient-semester with their respective confidence interval [95 % CI].Results:17 patients were included with a mean follow-up of 3 ± 1.5 years, 70.6% were women with a mean age of 65±10 years. The most frequent IPAF classification criteria were: a) clinical: arthritis (50%), Raynaud`s phenomenon (33%) and mechanical hands (17%); b) serological: 65% had ANA ≥1/360; 31% FR> 40; 30% Anti-Ro positive; c) morphologic: 59% presented NSIP pattern and 29.4% was UIP. The baseline median FVC% and DLCO% were 89 [83-107.7] and 63 [50-79.8] respectively. During the study period, 94% received treatment: 87.5% glucorticosteroids, 68.5% mycophenolate, 56% azathioprine, 18.7% cyclophosphamide iv and 33% antifibrotics. During the follow-up (104.6 patient - semester), 15 patients presented relative functional respiratory impairment, with an IR of 23.8 [16.1-35.3]. After 14 months from IPAF diagnosis 50% of the patients had relative functional respiratory impairment. At the end of the follow-up, 50% showed a worsening of the DLCO%.Conclusion:IPAF patients are mostly women in their sixties. The most frequent clinical criteria are arthritis and Raynaud`s phenomenon and the serological were FR and ANAs. The most frequent radiological pattern was NSIP. The therapeutic management is mainly with glucorticosteroids, mycophenolate and azathioprine. At the beginning, patients have a slightly diminished lung function. These patients have significant functional impairment over time that will impact in their prognosis. Longitudinal and multicenter studies are necessary to advance in the knowledge and management of these patients.References:[1]Fischer A, Antoniou KM, Brown KK, Cadranel J, Corte TJ, du Bois RM, et al. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J [Internet]. 2015 Oct;46(4):976–87. Available from:http://www.ncbi.nlm.nih.gov/pubmed/26160873Disclosure of Interests:None declared

Background: Interstitial lung disease (ILD) and pulmonary arterial hypertension carry a negative impact on SSc prognosis. Chest CT is the gold standard in assessing ILD and helps in evaluating associated vascular involvement. Objectives: As qualitative analysis of CT scans is limited by low reproducibility and time constraints, we aimed at evaluating parenchymal and vascular features in SSc-ILD by quantitative analysis (QA) of CT scans and testing the relationship with clinical-functional data. Methods: We prospectively enrolled 80 patients who underwent PFTs and chest CT scan spirometry gated at TLC on the same day. Clinical, lung functional and diffusion data, as well as disability indexes were collected. CT images were analyzed by a computational platform for texture analysis of ILD patterns (CALIPER), through Imbio LTA. It quantified the extent of normal pattern (NP %), ground glass opacities (GG %), reticulation (RET %), honeycombing (HC %), total ILD extent (ILD EXT %) and hyperlucent (HL %). Low density areas, representing emphysematous area, were also quantified (LDA %). For lung vessel analysis, a software program developed by the Ludwig Boltzmann Institute for Lung Vascular Research was used. This software determined total, arterial, and venous vascular volumes (TV, AV, VV), and relative volumes (TV%, AV%, VV%), as well as density and number for total, arterial and venous vessels. Results: 43/80 patients/CT scans were eligible for both software analyses, while 36/43 for arterial and venous separation. TV% and total vessel density were correlated positively with mRSS and negatively with %FVC (r=-0.537 and r=-0.382) and %TLC (r=-0.511 and r=-0.648), while vessel tortuosity correlated positively with %DLco. This was confirmed when separately analyzing arterial vessels, while VV% negatively correlated with %FVC, %TLC and %DLco. There was a positive correlation between %ILD patterns and %vascular volumes, being significant for TV%-AV%, total vessels and arterial density. Conversely, %ILD patterns were negatively correlated with VV and number of veins detected, despite positive correlation between VV% and ILD_EXT%. When clustering patients according to %FVC and %DLco with 80% normal cutoff, %FVC allowed clustering according to significantly different ILD patterns extents and vascular features, while %DLCO for vascular features only. Moreover, the consecutive addition of functional impairment and worsening of ILD (from both normal %FVC and %Dlco, to %DLco impairment only to both %FVC and %Dlco impairment), there was a significant increase in %TV, % AV and %VV, with the exception of decrease in %VV and venous density in patients with double impairment versus DLco single impairment. Conclusion: This is the first study showing in SSc a direct correlation between ILD and the increase in lung vascular volume, which is characterized by increase in arterial volume and density and reduction in venous volume and number. These results might be explained by the reduction of pulmonary volume due to fibrosis. However, also a para-physiological mechanism of redistribution of blood flow in lung areas, less involved by ILD, might be considered. Further studies on lung vessel quantification and distribution are ongoing. Disclosure of Interests: Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Mariaelena Occhipinti Consultant of: Imbio, Gianna Camiciottoli: None declared, Maurizio Bartolucci: None declared, Michael Pienn: None declared, Gemma Lepri: None declared, Alessio Fabbrizzi: None declared, Alessandra Tottoli: None declared, Giuglia Ciardi: None declared, Dilia Giuggioli: None declared, Giovanna CUOMO: None declared, Francesco Masini: None declared, Horst Olschewski: None declared, Federico Lavorini: None declared, Linda Calistri: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim

Objectives:This study aims to assess prevalence, severity and clinical correlates of symptoms of autonomic dysfunction in patients with SScMethods:Fifty five consecutively recruited SSc patients were included in this study. Thirty seven (67.3%) patients had limited (lcSSc), whilst 18 (32.7%) patients had diffuse cutaneous SSc (dcSSc). Anticentromere antibodies (ACA) were positive in 31 (56.4%) of patients, whilst 20 (26.4%) patients had anti-topoisomerase I antibodies (ATA). All patients completed the Composite Autonomic Symptom Score (COMPASS-31) questionnaire, which consists of 31 items, quantifying six autonomic domains: orthostatic intolerance (OI), vasomotor (VD), secretomotor (SD), gastrointestinal (GD), bladder (BD) and pupillomotor dysfunction (PD). The total score ranges from 0 to 100, whilst scores for particular domains range as follows: 0-40 for OI, 0-5 for VD, 0-15 for SD, 0-25 for GD, 0-10 BD, and 0-5 for PD. Higher values representing more severe symptoms. Differences in total COMPASS-31 score and domain-specific scores were assessed with respect to disease form, antibody status, capillaroscopic findings, lung diffusing capacity and joint involvement. Moreover, we assessed the correlation between COMPASS-31 scores, disease status (assesed using the Scleroderma Assessment Questionnaire – SAQ) and severity of gastrointestinal symptoms (assessed using the UCLA SCTC GIT 2.0 questionnaire)Results:Percentage of SSc with a score >0 in particular domains of the COMPASS-31 were as follows: OI – 32/55 (58.2%), VD – 49/55 (89.1%), SD – 36/55 (65.5%), GD – 40/55 (72.7%), BD - 26/55 (47.3%), PD – 30/55 (54.5%). The COMAPSS-31 score did not correlate with age or disease duration. There was no relationship between the COMPASS-31 total or subdomain scores and SSc subtype or autoantibody status. Similar mean values for total and subdomain scores were found among patients with different capillaroscopic patterns. Patients with DLCO < 80% had significantly higher mean values of GD, BD and PD scores, compared to patients with DLCO≥80% (4.42 vs 2.75, 1.51 vs 0.38, 1.93 vs 1.09, respectively). Moreover, the total COMAPSS-31 score was significantly higher in patients with decreased DLCO (16.24 vs 11.34, p=0.008). Patients with joint involvement had higher COMPASS-31 score than patients without (17.74 vs 9.85, p=0.012). We have found a statistically significant (pConclusion:Symptoms of dysautonomia are common in SSc patients. Patients with a more severe disease, especially decreased lung diffusing capacity, joint pain, and severe gastrointestinal involvement, report more symptoms of autonomic dysfunction.Disclosure of Interests:None declared

Background:In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. LUS allows the detection of artifacts (B-lines) characteristic of ILD, without the need to use ionizing radiation. However, it is not yet well defined how to interpret the LUS findings under suspicion of RA-ILD.Objectives:To determine the cut-off number of LUS B-lines that identifies a significant RA-ILD.Methods:A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence.Patients underwent LUS, chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of HRCT using a computer-aided method (CaM). The 10% of fibrosis, measured with this method, was considered as a cut-off for the presence of significant RA-ILD. The LUS was carried out in 14 defined intercostal spaces using a linear multifrequency probe 6-18 MHz (MyLab Class C, Esaote S.p.A., Genoa, Italy) and the number of B-lines present in each intercostal space was counted and summed up (Figure 1). The discriminating validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Figure 1.LUS B-line illustrative.Results:72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years), a mean ACPA titre of 327.6 (SD 633.3) U/ml and a rheumatoid factor of 324.6 (SD 748.7) U/ml. The mean estimate of pulmonary fibrosis using the CaM was 11.2% (SD 7.5) at HRCT, while at LUS the mean number of B-lines was 10.6 (SD 15.1). Pulmonary fibrosis of 10% as measured by the CaM at HRCT was detected in 25 patients (34.72%). Applying this HRCT cut-off point as an estimate of significant fibrosis, the presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant fibrosis with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4 (Figure 2).Figure 2.Area under the ROC curve to determine the number of B-lines at LUS to define a significant RA-ILD, applying the 10% of fibrosis at chest HRCT measured by OsiriX as external criterion.Conclusion:The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.References:[1] Tardella M, et al. Ultrasound B-lines in the evaluation of interstitial lung disease in patients with systemic sclerosis: Cut-off point definition for the presence of significant pulmonary fibrosis. Medicine (Baltimore). 2018;97(18):e0566.[2] Salaffi F, et al. High-resolution computed tomography of the lung in patients with rheumatoid arthritis: Prevalence of interstitial lung disease involvement and determinants of abnormalities. Medicine (Baltimore). 2019;98(38):e17088.Disclosure of Interests:Marco Di Carlo: None declared, Marika Tardella: None declared, Emilio Filippucci Speakers bureau: Dr. Filippucci reports personal fees from AbbVie, personal fees from Bristol-Myers Squibb, personal fees from Celgene, personal fees from Roche, personal fees from Union Chimique Belge Pharma, personal fees from Pfizer, outside the submitted work., Fausto Salaffi: None declared

Background:Systemic sclerosis (SSc) is a systematic and rare autoimmune disease that affects many organs. N-acetylcysteine (NAC), thiol containing compound, can act both as the precursor of reduced glutathione and direct scavenger of reactive oxygen species.Objectives:We assessed the clinical effect of NAC on pulmonary function test of patients with diffuse scleroderma.Methods:This study is a randomized double blind clinical trial that was done on 25 patients with diffuse SSc without lung involvement on primary chest high-resolution computed tomography. Placebo was administered for 13 patients and 1200 milligram NAC for 12 patients. Body plethysmography parameters were assessed at the beginning of the study and after 24 weeks.Results:Patients in the two groups were matched in the basic demographic data like age, duration of disease, and modified Rodnan skin score. The analysis showed no significant differences in parameters of plethysmography between the two groups. After importing the data of 2 patients in the placebo-treated group, who developed interstitial lung disease, DLCO in the placebo-treated group was 90.69 ± 21.29 milliliter at the end of the study, which significantly decreased compared with the beginning of the study (102.30 ± 13.83 ml). Also, changes of DLCO between the two groups were significantly different.Conclusion:In this trial, sensitivity of DLCO as the first marker in evaluation of pulmonary function in patients with SSc was confirmed. On the other hand, NAC had no effect versus placebo in a period of 24 weeks. We recommend that more studies with larger sample size and longer duration should conduct for further evaluation.References:No reference.Acknowledgments:The present article was extracted from the thesis written by Maryam Mazidi Moradi. The authors would like to thank Shiraz University of Medical Sciences, Shiraz, Iran and also Center for Development of Clinical Research of Nemazee Hospital and Dr. Nasrin Shokrpour for editorial assistance.Disclosure of Interests:None declared

Background:Interstitial lung disease(ILD) is one of the major contributor to morbidity and mortality in primary Sjögren’s syndrome(pSS)1. However, the clinical features and prognosis were various in literatures1-3; and the optimal management were still under investigationObjectives:To characterize the clinical feature, treatment and prognosis predictor of ILD of pSS in a tertiary medical center in Taiwan.Methods:Patients who had pSS and ILD confirmed with HRCT of lung between 1999-2019 were retrospectively identified. Demographic data, autoimmune feature, complementary examinations and treatments were recorded. Change in pulmonary function tests compared with pre-rituximab or pre-cyclophosphamide levels was assessed at 6–12 months post-treatment. Secondary analyses included acute exacerbation(AE), infection, and survival between different treatment groups.Results:112 patients (mean age 68(56-80); 67% female) were analyzed with the median pSS duration 3.1 (0.8-8.0) years. Most patients presented dyspnea and cough. NSIP was the most common radiological pattern (42.9%), followed by UIP (31.3%). Rituximab was used in 11(9.8%) patients, cyclophosphamide(CYC) was used in 28(25%) patients, and combination was used in 20(17.9%) patients. The FVC level and DLCO% were stable after 6-12month post-treatment in these groups. During the median 3.4(1.3-7.7) years ILD follow up, 88 patients (78.6%) had been hospitalized because of AE or infection; with 34(30.4%) of them experiencing respiratory failure. 1-year and 5-year survival was 88.6% and 67.1%. No significant overall survival was distinguished between different treatment groups(p=0.36). Frequent AE (HR=2.17, 95% CI: 1.36-3.5) and respiratory failure (HR=29, 95% CI: 4.61-191) contributed to mortality, while UIP pattern did not (HR=1.6, 95% CI: 0.77-3.3).Figure 1.Kaplan-Meier survival plot of different treatment group: R, E+R, EConclusion:Rituximab or CYC may stabilize pulmonary function but may not benefit on overall survival. Frequent ILD AE and respiratory failure are risk factors of mortality in pSS-ILD.References:[1] McCoy SS, Sandbo N. Sjögren’s Syndrome-Associated Lung Disease.Clinical Pulmonary Medicine.2017;24(6):232-238.[2] Parambil JG, Myers JL, Lindell RM, Matteson EL, Ryu JH. Interstitial Lung Disease in Primary Sjögren Syndrome.Chest.2006;130(5):1489-1495.[3] Flament T, Bigot A, Chaigne B, Henique H, Diot E, Marchand-Adam S. Pulmonary manifestations of Sjögren’s syndrome.European Respiratory Review.2016;25:110-123.Acknowledgments:Thanks to Dr. Ting-Yuan Lan, Dr. Ko-Jen Li, Dr. Hsieh Song-Chou, Dr. I-Hsien Lee, Dr. Chen-Yen Lin, Dr. Wang Hao ChienDisclosure of Interests:None declared

Background:Cardiac involvement in systemic sclerosis (SS) is common and one of the leading causes of mortality (up to 31%). Usually, it appears early and in a silent way. It can affect any cardiac structure and present with various manifestations. Cardiac disease worsens the prognosis and increases mortality, so it should be kept in mind in these patients.Objectives:Study the prevalence of arrhythmias in patients with SS, not affected with pulmonary arterial hypertension (PAH) or other cardiac diseases, and establish its association with left ventricular (LV) dysfunction and heart dysautonomia (HD), as well as with other variables that could predict the development of this complication.Methods:Prospective study of a cohort of patients with SS, excluding those with heart disease, PAH or cardiovascular risk factors. All underwent a clinical assessment, blood test with cardiac biomarkers, electrocardiogram (ECG), Holter 24h (HLT) and echocardiogram (TTE), interpreted by an expert cardiologist blind about the patients. Arrhythmias were classified as clinically significant arrhythmias (CSA) or clinically nonsignificant arrhythmias (CNSA) by ECG and HLT. LV diastolic dysfunction (LVDD) was defined as E/e’> 8, LV systolic dysfunction (LVSD) as a global longitudinal strain Results:36 patients were included: age 56.7 ± 12.3 years (y), male / female 35/1, disease duration 7 ± 4.1 y. 66% belonged to the limited SS subtype, 66.6% were anti-centromere+, 25% anti-topoisomerase, 2.7% anti-PM/Scl and 2.7% anti-RNA polymerase III+. Raynaud was present in a 100%, telangiectasia in 55.6% and interstitial lung disease in 36.1%. The modified Rodnan skin score (mRSS) was ≤ moderate (0-29 points) in 55.6%; 27.8% had presented digital ulcers that required prostaglandins.27.8% had LVDD, 22% LVSD, 11.1% LVDD + SD and 16.7% HD. 50% (18/36) of patients had ECG alterations, of which 44% corresponded to CSA (Table 1) and, 55.6% (20/36) HLT alterations, of which 75% were CSA (Table 2). 3/36 patients had both HLT and ECG CSA. In 1 patient, impaired LV ejection fraction was detected; in none, valvular disease. 38.8% had elevated NT-proBNP and 13.9% troponin T (TnT). No correlation was found between any parameters and CSA.Table 1.ECG abnormalities.*CSA.Alterations# PatientsMajorComplete Left Bundle Branch Block (BBB)*1MinorAbnormal QRS prolongation in precordial leads1Nonspecific ST-T wave changes3Incomplete Left BBB*3Incomplete Right BBB*4OtherQT prolongation11Table 2.HLT alterations.*CSA.AlterationsSubtype# PatientsSupraventricular ExtrasystolesUncommon7Frequent*3Mono/Polymorphic0Nonsustained Supraventricular Tachycardia*7Ventricular ExtrasystolesBenign4No Benign*4Doublets1Two Morphologies2Accelerated Idioventricular Rhythm11st-degree Atrioventricular Block1Sinus Tachycardia2A correlation was found between mRSS and DLCO (p=0.002), DLCO and digital ulcers (p=0.001), and mRSS and digital ulcers (p=0.005). A correlation was also found between elevated NT-proBNP and TnT (p=0.006) and between elevated NT-proBNP and LVDD (p=0.049).At follow-up after 6.2 ± 0.9 y, 2 patients had died: 1 of neoplasia and 1 of severe biventricular dysfunction 5.2 y after the study.Conclusion:Our data confirm a high prevalence of ventricular arrhythmias and left dysfunction in patients with SS, without heart disease, cardiorespiratory symptoms or HAP, being up to 75% of the arrhythmias CSA. The lack of correlation between CSA and LVSD or DD indicates that arrhythmias could be due, not only to a supposed structural alteration of the myocardium, but to a primary and early cardiac involvement in SS. In addition, the lack of correlation between CSA in ECG and HLT reinforces the importance of a complete cardiac evaluation in these patients to rule out silent cardiac involvement.Disclosure of Interests:LILIAN LÓPEZ-NÚÑEZ: None declared, Irene Carrión Barberà Grant/research support from: I received a grant from the Spanish Rheumatology Foundation (FER) and laboratories KERN PHARMA for a brief stay abroad., Isabel Padró: None declared, Lluis Molina: None declared, Ana Pros: None declared

Background:Lung involvement remains the main cause of morbidity and mortality in SSc. In 1 year clinical trials to assess lung involvement, FVC is usually evaluated and changes while the DLCO usually remains unchanged. In longer term observational studies, the DLCO often changes more than the FVC.Objectives:To examine, through a systematic literature review(SLR) and meta-analysis, whether DLCO%pred or FVC%pred (both to be designated solely as DLCO and FVC henceforth), responds more in assessing SSC interstitial lung disease in first year and longer term follow-up(FU).Methods:PubMed, EMBASE and COCHRANE databases were searched for english language articles on SSc published between 1960 and 31st October 2018. Any study that made reference to FVC and DLCO evaluation in SSc and reported their changes over the years was included. Reviewers double extracted articles to obtain agreement on>95% of pre-defined critical outcomes:DLCO and FVC at baseline,1 yr of FU and at the last assessment interstitial lung disease by HRCT of the lungs study design, duration of FU. Other variables included demographics. In all cases I^2 test for heterogeneity was used and a result from 75 to 100% was considered as high heterogeneity.A random effects meta-analysis was used. Differences in the degree of change in FVC and DLCO were tested with t-test without compensation for repeated analysis.Results:1870 articles were screened for eligibility and 21 were selected for the SLR and meta-analysis The analysis used 21 studies to evaluate changes of FVC and DCLO at 1 yr of FU. Only 5 studies were eligible to evaluate changes during longer FU (24.7 months(SD=20.4)). Heterogeneity was high at baseline and FU, (at 1 yr and >1 yr),both for the 21 studies at 1 yr (FVC:I^2 99.74%, 99.78%; DLCO: I^2=99.91%99.92%) and the 5 studies at > 1 year (FVC:I^2 92.86%;DLCO:I^2=99.54%), diminishing the confidence in the results. Table 1 gives the results of the random effects meta-analysis both for 21 and for the 5 studies evaluated. Regarding changes over 1 yr in the 21 studies, change of mean FVC was 2.7 (78.8vs81.5) while change in mean DLCO was 3.07(SE 8.20) (59.7vs 63.4). Considering the 5 studies during long term follow up, change in mean FVC was 2.0(7.36)(81.1vs83.1), and change in mean DLCO was -0.96 (16.95)(55.6vs54.7). Comparing the 1 yr changes in the 21 studies, change in mean FVC was 2.7(5.2)and change in mean DLCO was 3.07(8.2); difference in changes was not statistically significant (p=0.5791). During long term FU (24.7 months), change in mean FVC was 2.0(7.36)and change in mean DLCO was -0.96 (16.95); difference in changes was not statistically different (p=0.4698).Table 1.Results from Random Effect Meta-Analysis21 studies5 studiesFVC % predmean valueSEDLCO % pred mean valueSEFVC % predmean valueSEDLCO % pred mean valueSEBASELINE78.83.4359.75.5281.15.6855.611.591 YEAR FOLLOW UP81.53.8563.46.07---->1 YEAR FOLLOW UP----83.44.6854.712.37Conclusion:Our data are limited by great heterogeneity. Given this limitation, this SLR and meta-analysis indicates that there is no difference in the changes comparing FVC to DLCO at either 1 yr or during longer term follow-up. Corroboration of these results in prospective studies and in registries to make clear, comparable comparisons will be needed.Disclosure of Interests:Silvia Bellando Randone: None declared, Eleonora Cappellini: None declared, Letizia Nidiaci: None declared, Gemma Lepri: None declared, Maria Grazia Lazzaroni: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Gianluca Bagnato: None declared, Domenico Sambataro: None declared, Gianluca Sambataro: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Daniel Furst Grant/research support from: AbbVie, Actelion, Amgen, BMS, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Consultant of: AbbVie, Actelion, Amgen, BMS, Cytori Therapeutics, Corbus Pharmaceuticals, the National Institutes of Health, Novartis, Pfizer, and Roche/Genentech, Speakers bureau: CMC Connect (McCann Health Company)

Background:in SSc, PAH has a high morbidity and mortality burden. Therefore, screening and early detection are pivotal to achieve an early diagnosis of PAH.Objectives:to search the literature for all screening modalities for SSc-PAH in reference to right heart catheterization as diagnostic gold standard.Methods:papers from 2 previously published SLRs [22 fromGlaude et al(1) – from inception to 19/06/2012 - and 22 fromYoung et al 2018– from 20/06/2012 to 02/10/2017] were included. The articles’ database was integrated with a systematic search on Pubmed, EMBASE, Web of Science for papers published from 03/10/2017 to 31/12/2018. A total of 199 papers were reviewed and 32 were finally extracted. Bias risk was assessed through QUADAS2 tool.Results:167 papers were excluded from data extraction mainly for PAH screening non as main focus or for non-including SSc patients. The 32 papers extracted presented a low bias risk according to QUADAS2. Screening methods reported were:Echocardiographic parameters in 31/32 studies, in particular systolic pulmonary arterial pressure (sPAP) in 22 papers; 40 mmHg was the most frequently used cut-off (in 12/22 papers); sPAP was part of a composite algorithm in 9/22 papers. Among others, tricuspid regurgitation velocity (TRV) was used in 6/31 (as part of composite 5/6) and right atrial pressure (RAP) in 3/31 papers.Pulmonary function tests parameters in 22/32 papers, with % predicted Lung diffusion for carbon oxyde (DLco) in 21 papers, with a 50% cut-off in 11/21 and as part of composite algorithm in 13/21 studies. Moreover, walked distance at six minutes walking test was a screening parameter in 3/32 papers.Serum biomarkers in 12/32 papers, with anti-centromere antibodies (6/12), NT-proBNP (6/12) and uric acid (5/12) being the most frequently reported.Clinical parameters in 15/32 papers, with unexplained dyspnoea in 9/15 and telangiectasias in 5/15 papers.Composite algorithms were used in 18/32 manuscripts: among them, DETECT (5/18), ESC/ERS 2009 (4/18) or 2015 (3/18) guidelines, ASIG (2/18) e ITINER-air (1/18). In different cohorts, DETECT and ASIG showed higher sensitivity and negative predictive value than ESC/ERS 2009.Conclusion:in the literature, the screening of SSc-PAH is largely investigated by echocardiographic parameters. In particular, sPAP and TRV, both as single items or part of a composite algorithm, including also serum biomarkers, clinical and functional parameters, are the most frequent parameters evaluated.(supported by an Actelion Pharmaceuticals unrestricted research grant)References:[1]Gladue H, et al. Screening and diagnostic modalities for connective tissue disease-associated pulmonary arterial hypertension: a systematic review. Semin Arthritis Rheum. 2014 Feb;43(4):536-41.[2]Young A, et al. Update of screening and diagnostic modalities for connective tissue disease-associated pulmonary arterial hypertension. Semin Arthritis Rheum. 2019 Jun;48(6):1059-1067.Acknowledgments:(supported by an Actelion Pharmaceuticals unrestricted research grant)Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Maria Grazia Lazzaroni: None declared, Elisabetta Zanatta: None declared, Gemma Lepri: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim

Background:Systemic sclerosis (SSc) is a chronic immune-mediated connective tissue disease with heterogeneous organ involvement that reduces the life expectancy of this patients. In particular cardiopulmonary manifestations, such as pulmonary arterial hypertension (PAH), are currently the primary cause of death and stabilizing this condiction may represent an important therapeutic goal (1,2). An increased NT-proBNP is predictors of PAH in SSc and use this markers should result in improved PAH risk stratification (3)Some studies have suggested the role of intravenous iloprost in preventing the incidence of most severe vascular complications in long term treated patients (4).Objectives:The aim of our study is to evaluate the evolution of the disease, with particular focus on cardiopulmonary function, in a group of consecutive patients chronically treated with iloprost at the Rheumatology Unit of Catania Hospital, Italy, from 2006 to 2019.Methods:68 SSc patients (58F, 52.88 ± 12.6 years). At baseline, 67.6%, 25% and 5.9% had a limited, diffuse and early scleroderma type respectively and 20,6% had interstitial lung disease. The follow-up period of the study was of 9.9 ± 2.9 years. Iloprost was administered with a regimen of 6 infusions per month (6 hours/day, 0.5-2.0 ng/kg/min) to treat secondary Raynaud’s phenomenon (RP), diagnosed at an average age of 46.6 ± 13.7 years. We evaluated: skin score (SS), systolic pulmonary arterial pressure (PAPs), plane tricuspid annular systolic excursion (TAPSE), lung diffusing capacity of carbon monoxide (DLCO), forced vital capacity (FVC), alveolar volume (VA), DLCO/VA, pro-brain natriuretic peptide (pBNP), and NYHA class.We analyzed the patients as a whole group (68 subjects), as a group who continued the treatment (57 subjects) and as a group who stopped the treatment during the follow-up (11 patients).Results:After the long follow up period in the study (almost 10 years) in the whole group of patients, PAPs and pBNP showed statistically significant improvement from baseline (30.91 ± 6.4 vs 27.36 ± 7.1 and 97.20 ± 69.3 vs 66.65 ± 44.3 respectively, p < 0.0001 for both) while the other parameters showed no significant changes: SS (4.70 ± 5.3 vs 3.86 ± 4.2 mm), TAPSE (22.07 ± 2.4 vs 22.06 ± 3.8 mm), DLCO (83.68 ± 13.5 vs 77.70 ± 14.6 mmol/kPa.min), FVC (107.09 ± 14.5 vs 107.72 ± 18.7 liters), VA (91.12 ± 13 vs 90.30 ± 14.4 liters), DLCO/VA (88.48 ± 13.5 vs 89.5 ± 16.3) and NYHA class (1.0 ± 0.0 vs 1.0 ± 0.0). A subgroup analysis indicated a significant improvement in addition to PAPs and pBNP also for skin score for 57 patients who continued the treatment (5.09 ± 5.7 vs 3.30± 4.2, p < 0.0001) and a significant worsening of this parameter as early as the first year of suspension (p Conclusion:Cardiac involvement is recognised as a poor prognostic factor among systemic sclerosis (SSc) patients, significantly to mortality and N-TproBNP peptide may represent a surrogate marker for cardiac involvement in SSc, selectively identifying patients with severe impairment of cardiac function. Our intensive (6 infusions/month) and chronic regimen of iv iloprost administration seems improve the long-term evolution of disease in SSc patients, as suggested by the improvement of cardiopulmonary parameters and the significant improvement of SS.References:[1]Rheumatology 51, 1027-36 2) Best Pract Res Clin Rheumatol.32, 223-240 3) Arthritis Rheum. 2008 58, 284-9 4) Rheumatol Int 2012;32:1933-8.Disclosure of Interests:Rosario Foti Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, elisa visalli Consultant of: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Speakers bureau: lilly, sanofi, MSD, Janssen, Abbvie, BMS, celgene, roche, Giorgio Amato: None declared, Alessia Benenati: None declared, Salvatore Bellofiore: None declared, Massimiliano Mule’: None declared, Marcella Di Gangi: None declared

Background:Interstitial lung disease (ILD) represents the most frequent pulmonary manifestation of primary Sjogren’s syndrome (pSS), with a prevalence ranging between 6-70% in different retrospectives studies. Non-specific interstitial pneumonia (NSIP) is recognized as the most common ILD disorder, followed by organizing pneumonia (OP), usual interstitial pneumonia (UIP) and lymphocytic interstitial pneumonia (LIP), specifically associated with pSS but less frequent.Objectives:To investigate the prevalence of fibrosing patterns in a monocentric cohort of pSS patients evaluated for lung involvement in a cross-sectional study.Methods:In a cross-sectional study all patients fulfilling ACR/EULAR classification criteria for pSS and with a known diagnosis of ILD were enrolled; the other patients were carefully investigated for signs or symptoms suggestive for ILD (including the search for velcro crackles with a digital device); when suspect, patients underwent to high resolution computed tomography (HRCT). An expert radiologist re-evaluated all HRCT for classifying the ILD pattern as: UIP, fibrotic NSIP, fibrotic OP, NSIP, OP, LIP, indeterminate.Results:One hundred and eighty-five pSS patients were enrolled; among them 34 showed ILD (18.4%) with the following features: M/F 3/31, median age 57 (range 24-80), median FVC 90% (39-127%), median DLCO 49% (20-84%). Patients were classified in two groups according to radiologic classification: the group 1 (18 pts 52,9%) included UIP (13 patients, 38.2%), fibrotic NSIP (4, 11.8%), fibrotic OP (1 2.9%); the group 2 (16 pts, 47.1%) included NSIP (6, 17.6%), OP (4, 11.8%), indeterminate (4, 11.8%), LIP (2, 5.9%). No significant differences were observed between the two groups with the exception of anti-SSB positivity more frequently detected in non-fibrosing pattern (p0,043).Conclusion:Despite previous observations, our data suggest a high prevalence of fibrosing ILD pattern in pSS patients. We participate at a multidisciplinary team with expert pulmonologists and radiologists and some patients of our cohort firstly referred to pulmonologist for appearance of ILD before the diagnosis of pSS, contributing to the possible selection of more severe lung disease. However, these data suggest first of all that pSS should always be considered in differential diagnosis of fibrosing ILD; moreover, since fibrosing ILD is thought to have a worse response to immunosuppressive drugs, the role of new possible therapeutic strategies such as anti-fibrotic could represent an important field of interest.Disclosure of Interests:None declared

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

Background:Systemic sclerosis (SSc) have various organ involvements including pulmonary hypertension (PH), digital ulcers (DU), and interstitial lung disease (ILD). On the other hand, Nailfold capillary (NFC) abnormalities (enlarged/giant capillaries, fresh or old hemorrhages, avascular areas, ramified/bushy capillaries) detected by capillaroscopy are included in ACR/EULAR classification criteria for SSc as one of important findings. In addition, many studies have reported the relationship between NFC abnormalities and organ involvements (DU, PH) [1][2]. However, there are a few reports about the relationship between NFC abnormalities and ILD.Objectives:We clarify the association with NFC abnormalities and ILD in SSc patients.Methods:We enrolled SSc patients without PH from January 2016 to December 2019 in our institution. SSc patients were diagnosed according to EULAR classification criteria in 2013. ILD was detected by chest CT scans. We assessed severity of ILD with pulmonary function tests (PFT). Abnormal PFT was defined as vital capacity (%VC) or diffusion capacity (DLCO) < 70%. NFC abnormalities were detected with “OptiPiX capillaroscopy Clinic 1.7.x” and the number of capillaries was measured per 1mm in 2nd to 5th fingers of both hand. We defined enlarged and giant capillaries as >30 µm and >50 µm, respectively.Results:We enrolled 59 SSc patients (54 females, 5 males). Mean age is 65.0 ± 8.0 years. Thirty-one patients (52.5%) were complicated with ILD. Mean capillary counts are 6.6/mm. The number of patients with each NFC abnormalities (enlarged capillaries, giant capillaries, microhemorrhages, ramified, avascular areas) are 42, 32, 48, 38, and 33 cases, respectively. Two cases did not have NFC abnormalities. SSc patients with giant capillaries had fewer ILD complications (p Conclusion:We investigated the relationship between NFC abnormalities and ILD conplications in SSc patients. NFC abnormalities are associated with ILD complicacion and severity of ILD. It was suggested that no giant capillary in SSc patients may predict ILD complication. Moreover, no enlarged capillary may predict the severe ILD.References:[1]Valeria Riccieri et al. Systemic sclerosis patients with and without pulmonary arterial hypertension: a nailfold capillaroscopy study. Rheumatology, Volume 52, Issue 8, 1 August 2013, Pages 1525–1528[2]Maurizio Cutolo et al. Nailfold Videocapillaroscopic Features and Other Clinical Risk Factors for Digital Ulcers in Systemic Sclerosis: A Multicenter, Prospective Cohort Study. Arthritis Rheumatol. 2016 Oct; 68(10): 2527–2539.Disclosure of Interests:None declared

Background:Systemic sclerosis (SSc) is a clinically complex and heterogeneous disease. Interstitial lung involvement (ILD) is the main cause of mortality, but progression of skin fibrosis has also been associated with pulmonary dysfunction and mortality. Recently, Rituximab (RTX) has been postulated as a promising therapeutic alternative to cyclophosphamide (CF) or mycophenolate (MFM), but long-term experience is scarce.Objectives:Describe the effectiveness, safety and long-term use of RTX, in a series of cases with SSc.Methods:Retrospective observational study of patients with SSc (EULAR/ACR 2013 criteria) treated with RTX in a university hospital from 2010 to 2019. Sociodemographic data related to SSc and treatments were collected. The effectiveness of RTX was evaluated at 6-12 months and at the end of follow-up, by means of these main outcomes: Rodnan’s modified cutaneous index (mRSS) for skin fibrosis; CK leves for myopathy, variation >10% in forced vital capacity (FVC) and >15% in lung diffusion capacity of carbon monoxide (DLCO) for ILD. Adverse events (AE) were recorded. Statistical analysis performed with Stata v.14 and statistical significance set for p≤0.05.Results:14 women with SSc (mean age 47±13 years, mean evolution 6.2±4.5 years) were treated with RTX for ILD (n=9), skin involvement (n=11) and/or inflammatory myopathy (n=3). The mean±SD of follow-up was 3.36±2.17 years. SSc type: diffuse cutaneous 35.71%, limited cutaneous 21.44%, overlap 35.71% and sine scleroderma 7.14%. Type of antibodies: 50% anti-Scl-70, 14.3% anti-centromere, 21.4% anti-RNA polymerase III and 7.14% anti-Ku. ILD was classified as NINE in 8 patients and NIU in 1. The first cycle of RTX included 2 infusions of 1g and was initiated a mean of 3.36±2.17 years after diagnosis. The retreatments were initially fixed every 6 months and later on demand in 4 patients, and in the rest on demand from the beginning, according to duration of clinical response. A mean of 3.9±2.5 cycles/patient (range: 1-11) were administered. 30% of patients had previously received CF and 21.5% MFM. RTX was administered in association with other DMARDs (MTX 64.29%, hydroxychloroquine [HCQ] 35.71%, MFM 57.14%, others 14.28%), CF (14.29%), intravenous immunoglobulins (7,14%) and prednisone (78.57%). In the final visit, the percentage use of DMARDs (50% MTX, 50% MFM and 28.57% HCQ) and prednisone (62.5% patients, 30% doses) was reduced. mRSS improved significantly. Muscle weakness disappeared in 3/3 with normal CK levels in 2/3 patients with myopathy. The FVC improved or stabilized in 22% and 56% of ILD, respectively, and the DLCO stabilized in 66.70% (not significant). TACAR stabilized in 55.56% of ILD, with some degree of worsening in the rest. Outcomes evolution in the Table:Functional ParametersBasal (mean±SD)6-12 m (mean±SD)CI 95%PFinal (mean±SD)CI 95%PFVC (n=9)63.2±16.870.3±18.6[-13.3–6.1]0,4071.9±21.1[-14.4–5.9]0.36DLCO (n=9)46.3±18.546.1±20.30,3445.2±22.03[-3.9–12.8]0.24Clinical ParametersBasal (mean±SD)Final (mean±SD)CI 95%PmRSS (n=11)13.1±7.28.8±7.1[0.9–9.4]0.02CK (n=3)1786.7±1483.8134.7±119[-2181.9 –5485.9]0.2CK: Creatine kinase; SD: Standard deviation; CI: Confidence interval; m: months.The AE were mostly mild: 13 infusional reactions (6 patients), 1 uncomplicated herpes zoster and 2 serious infections that required admission. There were no exitus.Conclusion:Our results, with a limited sample, suggest that the long-term use of RTX in real world clinical practice may be beneficial for the cutaneous, pulmonary and myopathic manifestations of SSc, with an acceptable security profile.Disclosure of Interests:Esther Vicente Speakers bureau: BMS, Roche., Javier Fernández: None declared, Irene Llorente Speakers bureau: Gebro, Janssen, Sanofi, Lilly., Lorena Vega: None declared, Santos Castañeda: None declared, Alberto García-Vadillo: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Alicia Humbría: None declared, Ana Ortiz: None declared, Esther Patiño: None declared, Eva Tomero Muriel: None declared, Rosario Garcia de Vicuna Grant/research support from: BMS, Lilly, MSD, Novartis, Roche, Consultant of: Abbvie, Biogen, BMS, Celltrion, Gebro, Lilly, Mylan, Pfizer, Sandoz, Sanofi, Paid instructor for: Lilly, Speakers bureau: BMS, Lilly, Pfizer, Sandoz, Sanofi

Background:Interstitial lung disease (ILD) and pulmonary arterial hypertension carry a negative impact on SSc prognosis. Chest CT is the gold standard in assessing ILD and helps in evaluating associated vascular involvement.Objectives:As qualitative analysis of CT scans is limited by low reproducibility and time constraints, we aimed at evaluating parenchymal and vascular features in SSc-ILD by quantitative analysis (QA) of CT scans and testing the relationship with clinical-functional data.Methods:We prospectively enrolled 80 patients who underwent PFTs and chest CT scan spirometry gated at TLC on the same day. Clinical, lung functional and diffusion data, as well as disability indexes were collected. CT images were analyzed by a computational platform for texture analysis of ILD patterns (CALIPER), through Imbio LTA. It quantified the extent of normal pattern (NP %), ground glass opacities (GG %), reticulation (RET %), honeycombing (HC %), total ILD extent (ILD EXT %) and hyperlucent (HL %). Low density areas, representing emphysematous area, were also quantified (LDA %). For lung vessel analysis, a software program developed by the Ludwig Boltzmann Institute for Lung Vascular Research was used. This software determined total, arterial, and venous vascular volumes (TV, AV, VV), and relative volumes (TV%, AV%, VV%), as well as density and number for total, arterial and venous vessels.Results:43/80 patients/CT scans were eligible for both software analyses, while 36/43 for arterial and venous separation. TV% and total vessel density were correlated positively with mRSS and negatively with %FVC (r=-0.537 and r=-0.382) and %TLC (r=-0.511 and r=-0.648), while vessel tortuosity correlated positively with %DLco. This was confirmed when separately analyzing arterial vessels, while VV% negatively correlated with %FVC, %TLC and %DLco. There was a positive correlation between %ILD patterns and %vascular volumes, being significant for TV%-AV%, total vessels and arterial density. Conversely, %ILD patterns were negatively correlated with VV and number of veins detected, despite positive correlation between VV% and ILD_EXT%. When clustering patients according to %FVC and %DLco with 80% normal cutoff, %FVC allowed clustering according to significantly different ILD patterns extents and vascular features, while %DLCO for vascular features only. Moreover, the consecutive addition of functional impairment and worsening of ILD (from both normal %FVC and %Dlco, to %DLco impairment only to both %FVC and %Dlco impairment), there was a significant increase in %TV, % AV and %VV, with the exception of decrease in %VV and venous density in patients with double impairment versus DLco single impairment.Conclusion:This is the first study showing in SSc a direct correlation between ILD and the increase in lung vascular volume, which is characterized by increase in arterial volume and density and reduction in venous volume and number. These results might be explained by the reduction of pulmonary volume due to fibrosis. However, also a para-physiological mechanism of redistribution of blood flow in lung areas, less involved by ILD, might be considered. Further studies on lung vessel quantification and distribution are ongoing.Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Mariaelena Occhipinti Consultant of: Imbio, Gianna Camiciottoli: None declared, Maurizio Bartolucci: None declared, Michael Pienn: None declared, Gemma Lepri: None declared, Alessio Fabbrizzi: None declared, Alessandra Tottoli: None declared, Giuglia Ciardi: None declared, Dilia Giuggioli: None declared, Giovanna CUOMO: None declared, Francesco Masini: None declared, Horst Olschewski: None declared, Federico Lavorini: None declared, Linda Calistri: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim

Background:Reduced bone mineral density (BMD) leads to fragility fracture which is associated with a significant morbidity and excess mortality [1,2]. Patients with idiopathic inflammatory myopathies (IIM) should be at a heightened risk of reduced BMD as a result of the systemic inflammation, reduced mobility and corticosteroid use [3]. A previous cross-sectional study demonstrated a high prevalence of osteoporosis (23.7%) and osteopenia (47.4%) in a cohort of IIM patients [4]. However, longitudinal data are lacking.Objectives:To assess the BMD of IIM patients longitudinally and to investigate the factors associated with accelerated bone loss.Methods:This is a single centered observational study. Existing adult Chinese patients with IIMs who had serial BMD measurements done were recruited. The diagnosis of IIMs was based on the Bohan and Peter’s criteria with definite or probable cases being included [5]. Patients with clinically amyopathic disease must have the typical Gottron’s papules or heliotrope rash as determined by rheumatologists or dermatologists, and with no symptoms or signs of muscle involvement according to Sontheimer [6]. BMD was measured by dual energy X-ray absorptiometry (DEXA). Clinical variables thought to be associated with bone health were documented.Results:All together 28 patients were studied. The mean age of the patients at disease onset was 46.1 years (S.D. 12.2). There was a female predominance (92.9%). The subgroups of IIMs were: dermatomyositis (39.3%), polymyositis (25.3%), clinically amyopathic dermatomyositis (21.4%) and immune mediated necrotising myopathy (14.3%). Only a minority of the patients smoked (7.1%) and none of them drinks regularly. About one fifth of the patients were underweight. All patients have been exposed to systemic corticosteroid, while 82.1% of them were still on it between the two scans with 32.1% even on high dose (>0.5mg prednisolone/kg/day). Three out of the 28 patients (10.7%) was found to be osteoporotic at baseline and 17 patients (60.7%) were osteopenic. Follow-up DEXAs were performed mostly 5 to 10 years after the initial scan. Despite 8 patients (28.6%) were given active anti-osteoporotic medications, the bone health deteriorated significantly. The mean baseline neck of femor BMD dropped from 0.711 to 0.657 g/cm2 (p=0.042) on follow-up, while the total lumbar BMD from 0.951 to 0.905 g/cm2 (p=0.036). The T-score in 11 patients (39.3) reached osteoporotic range at the second DEXA. Together with the patients with osteopenia, 78.6% of the IMM patients had reduced BMD at the follow-up scan. Actually, 5 patients (17.9%) already had one episode of fragility fracture. The use of high dose corticosteroid in between the 2 scans was found to be associated with a greater degree of mean BMD loss in the hip (-0.171 vs -0.007 g/cm2, p=0.007).Conclusion:Reduced BMD is prevalent in patients with IIM. Follow-up study revealed significant worsening of bone health. High dose corticosteroid use might be especially detrimental. Liberal assessment of BMD and use of anti-osteoporotic drugs in IIM patients are advisable. Prompt use of steroid-sparing agents to minimize steroid exposure may also be helpful.References:[1]Falch J, Aho H, Berglund K, et al. Hip fractures in Nordic Cities: difference in incidence. Ann Chir Gynaecol 1995;84:286-90.[2]Dennison E, Mohammed MA, Cooper C. Epidemiology of osteoporosis. Rheum Dis Clin North Am 2006;32:617-29.[3]Luigi S, Massimo V, Giuseppe G. Epidemiology of osteoporosis in rheumatic disease. Clin Exp Rheumatol 2006;32:631-58.[4]So H, Yip ML, Wong KM. Prevalence and associated factors of reduced bone mineral density in patients with idiopathic inflammatory myopathies. Int J Rheum Dis 2016;19:521-8.[5]Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med 1975;292:344-7.[6]6. Sontheimer RD. Clinically myopathic dermatomyositis: what can we now tell our patients? Arch Dermatol 2010;146:76-80.Disclosure of Interests:None declared

Background:The staging of interstitial lung disease (ILD) is important to monitor disease progression and for prognostication. A disease severity scale of Systemic Sclerosis (SSc)-related lung disease has long been proposed (i.e. Medsger’s severity scale). This scale was mostly developed by discussion and consensus and stage thresholds were not computed by a data-driven approach. Hidden Markov models (HMM) are methods to estimate population quantities for chronic diseases with a staged interpretation which are diagnosed by markers measured at irregular intervals.Objectives:To build a SSc-ILD specific disease severity scale with prognostic relevance via HMM modeling.Methods:A total of 358 SSc patients at risk for or with ILD were enrolled in a discovery (207 cases, Milan1) and in a validation (151 cases, Milan2, Pavia and Rome) cohort. Patients were included if satisfied the following criteria: 1) Diagnosis of SSc according to the EULAR/ACR 2013 criteria, 2) absence of anticentromere antibodies, 3) dcSSc subset or 4) other subsets with either 4a) ILD-related antibodies (Scl70, PmScl, Ku) or 4b) evidence of ILD on HRCT, 5) disease duration < 5 years at the time of the first pulmonary function test (PFT). Serial PFTs were retrieved and the time up to the last available visit -if the patient alive-, or to death due to pulmonary complications, was recorded. HMM were used to estimate the threshold of a 3-stage model (SL3SI, Scleroderma Lung 3-Stage Index) based on PFT functional values (normal/mild, moderate, severe involvement) in the discovery cohort. Survival estimates of the SL3SI model were compared to Medsger’s severity classes estimates and their predictive capability evaluated via the explained residual variation (R2) of prediction errors (the higher the better). One-hundred random replicates were generated to simulate the prediction effort in patients with different disease duration and lung severity.Results:Patients characteristics are summarized in the Table. Fifteen-years survival estimates for Mesdger’s classes in the discovery set were: normal=0.88, mild=0.86, moderate=0.84 and severe=0.71. The SL3SI was defined by the following thresholds: normal/mild, FVC and DLco >=75%; moderate FVC or DLco 74-55%; severe, FVC or DLco 2values at 15 yrs for the SL3SI compared to Medsger’s classes, providing evidence for a better predictive capability of the former (discovery: 0.31 vs 0.25; validation: 0.28 vs 0.19).Conclusion:The SL3SI, a simplified 3-stage functional model of SSc-ILD, yields better survival estimates and long-term prognostic information than Medsger’s classes. Its reproducibility and ease of use make it a useful tool for the functional and prognostic evaluation of SSc patients at risk for or with ILD.Table:VariablesDiscovery (n=207)Replication (n=151)DcSSc62 (30%)98 (64%)Age at first PFR48.6±1249.1±14.4Disease duration at first PFR1.7±1.61.3±2.4FVC90.5±18.191.1±20.2DLco70.7±19.861.3±20.1ILD on HRCT179 (86%)125 (80%)Scl70157 (76%)153 (78%)SSA63 (30%)32 (21%)n of visits38571473Follow-up time, yrs11±5.610.6±5.7Deaths27 (13%)23 (15%)Disclosure of Interests:Alessandro Santaniello: None declared, Chiara Bellocchi: None declared, Luca Bettolini: None declared, Marcello Cassavia: None declared, Gaia Montanelli: None declared, Adriana Severino: None declared, Monica Caronni: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Paolo Delvino: None declared, Claudio Tirelli: None declared, Lorenzo Cavagna: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Silvia Laura Bosello: None declared, Lorenzo Beretta Grant/research support from: Pfizer

Background:Neointima proliferation is a key pathologic feature of Systemic Sclerosis (SSc), causing arterial vessel narrowing and being the recognised culprit pathological lesion in Digital Ulcers (DUs), pulmonary artery hypertension and renal crisis. Nevertheless, there are no validated imaging techniques to assess the severity of vascular involvement in SSc. Digital Artery Volume index (DAVIX ©) is an MRITime of flight angiographybased quantitative score of digital arteries flow, without the need to administer contrast.Objectives:To determine the value of DAVIX in predicting the onset of digital ulcers (DUs), the worsening of patient reported outcomes (PROs) and clinical parameters in SSc patients.Methods:We enrolled 91 consecutive patients affected by Raynaud’s phenomenon, 63 of which fulfilled the 2013 ACR/EULAR classification criteria for SSc and 28 had a score Results:78/91 patients were females and median disease duration was 4 years (IQR1.91-9). Complete historical and prospective follow-up data were available for 68 patients. DAVIX© correlated with mRSS (r=-0.258, p=0.017), DLCO% (r=0.338, p=0.008) and capillaroscopy pattern (r=-0.388, p=0.001). In patients with DUs, DAVIX© showed a stronger correlation with DLCO% (r=0.786, p=0.048). DAVIX© predicted the worsening of HAQ-DI (r=-0.295, p=0.029), sHAQ (r =-0.333, p=0.029) and VAS pain (r=-0.269, p=0.038) independently of the presence of DUs. In the context of DU, 7 patients had DUs at baseline (5 with a positive history for DUs). 12 patients developed DUs within 12 months, 3 of them had DUs at baseline. 38 patients did not have either previous or current DUs, neither did they develop new DUs within 12 months. DAVIX of patients with current DUs was 3-fold lower than DAVIX of patients without DUs (0.18 vs 0.63 p=0.0093). Further, DAVIX of patients with positive history of DUs was 50% lower than in patient with a negative history (median 0.34 vs 0.64, p=0.0052). In patients without current DUs, DAVIX of patients who developed new DUs within 12 months of follow-up was 3-fold lower than in patients who didn’t develop DU (0.21 vs 0.65, p=0.0156). ROC curve analysis indicated that DAVIX threshold Conclusion:Outcome measures of vascular involvement in SSc are scanty. We demonstrated that DAVIX© is a promising and feasible surrogate outcome measure of neointima proliferation in SSc and a useful imaging biomarker of vascular disease activity. The predictive value of DAVIX for the future onset of DU could be employed as a useful stratification tool in clinical trials. The value of DAVIX in predicting the worsening of PROs and clinical parameters in overall patients, may offer insights on the role of vascular disease activity in the overall progression of SSc.References:[1]Lettieri G, Abignano G, et al Digital artery volume index: the first objective, automated, non-invasive imaging diagnostic of macrovascular involvement in ssc.Annals Rheum Dis2018Disclosure of Interests:Klodian Gjeloshi: None declared, Fiammetta Danzo: None declared, Giovanni Lettieri: None declared, Giuseppina Abignano: None declared, Mark Hinton: None declared, Anne-Maree Dean: None declared, Giovanna CUOMO: None declared, Olga Kubassova Shareholder of: IAG, Image Analysis Group, Consultant of: Novartis, Takeda, Lilly, Employee of: IAG, Image Analysis Group, Francesco Del Galdo: None declared

Background:The main clinical associations of anti-PM/Scl in Systemic Sclerosis (SSc) so far reported include calcinosis, myositis and interstitial lung disease (ILD). Nevertheless, data regarding the long-term outcome of ILD in these patients are lacking. A single centre Spanish cohort reported a better functional outcome in 14 SSc-ILD patients anti-Pm/Scl+ as compared to 49 anti-Topo I after a mean follow-up of 7 years (1).Objectives:To analyze the long-term outcome of ILD in a large multicentre EUSTAR study dedicated to anti-Pm/Scl SSc patients.Methods:A case-control study within the EUSTAR cohort collected 165 anti-PM/Scl+ SSc cases and 257 anti-PM/Scl- SSc controls, matched for sex, cutaneous subset, disease duration, and age at onset. Data for ILD at HRCT were available for 162/165 cases and 249/257 controls. Data for pulmonary function tests (PFT) at the baseline (T0), 1 year after diagnosis (T1) and at the last visit (LV) were analyzed.Results:A significantly higher frequency of ILD was reported in anti-Pm/Scl+ cases vs anti-Pm/Scl- controls (62.3% vs 39.4%, p:In ILD cases, %pFVC tended to improve from T0 (85.1±18.3) to T1 (89.5±16.5, p:0.045) and to LV (87.9±16.9, p:0.057), while in ILD controls remained stable from T0 (90.4±18.5) to T1 (91.1±16.5, p:0.38) and significantly declined to LV (85.0±18.0, p:0.0002). %pDLCO remained stable from T0 (60.5±16.8) to T1 (60.1±17.6, p:0.87) and to LV (60.4±16.9, p:0.77) in ILD cases, while significantly declined from T0 (67.0±18.9) to T1 (62.7±18.2, p:0.0016) and to LV (59.6±18.4, pDelta %pFVC (LV-T0) was 2.85±11.3 for the anti-Pm/Scl+ group vs -5.42±13.4 in the control group (p:0.0004) with a significant smaller proportion of patients with FVC loss ≥10% from T0 to LV in the anti-PM/Scl group (12.3% vs. 39.7%, p:0.0001). Delta %pDLCO (LV-T0) was -0.13±10.8 for the anti-PM/Scl+ group vs -7.38±14.6 in the control group (p:0.0015), with a significant smaller proportion of patients with DLCO loss ≥10% from T0 to LV in the anti-PM/Scl+ group (13.6% vs. 42.3%, pConclusion:In this multicenter real-life study, the long-term pulmonary functional outcome in SSc-ILD patients with anti-Pm/Scl positivity seems to be more favorable than in patients without anti-Pm/Scl antibodies.References:[1]Guillen-Del Castillo A, Semin Arthritis Rheum 2014, 44 (3), 331-7.Disclosure of Interests: :Maria Grazia Lazzaroni: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Emiliano Marasco: None declared, Jeska de Vries-Bouwstra: None declared, Franco Franceschini: None declared, Francesco Del Galdo: None declared, 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, Lorenzo Cavagna: 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, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Paolo Airò: None declared

Background:Interstitial lung disease (ILD) can be the first manifestation of connective tissue disease (CTD) and rheumatoid arthritis (RA). Pulmonologists are usually the first referral in these patients.Objectives:To determine: 1) the prevalence of ILD as initial manifestation of CTD or RA 2) clinical characteristics of such patients.Methods:From a database of consecutive patients with CTD or RA referred to our academic hospital from 2009 and 2017, we selected all the patients with ILD as initial manifestation of the disease. Periodic multidisciplinary evaluations were performed during a median follow-up of 48 (35-50) months.Results:1) Fifty-four of the 427 patients with CTD or RA (12.6%) had ILD as initial manifestation (mean age: 63.9±12.9 yrs, F/M ratio: 20/34). Autoimmune myositis was diagnosed in 16/54 patients (29.6%), systemic sclerosis in 11 patients (20.4%), RA in 9 patients (16.7%), Sjogren syndrome in 9 patients (16.7%) and SLE in 3 patients (5.5%). Six patients remained classified as IPAF (11.1%). Among the Rheumatology patients we followed-up in the same period, autoimmune myositis had the highest prevalence of ILD as initial manifestation (63.6%), followed by Sjogren syndrome (20.5%), systemic sclerosis (20.0%), RA (3.4%), and SLE (3.3%). 2) Patients with initial ILD were all firstly evaluated by the Pulmonologist and the main reasons for Rheumatology referral were positivity for one or more autoantibodies (57.4%), mainly ANA≥1:320, and joint pain (29.6%). Thirty-six patients (66.7%) received steroid and/or immunosuppressive therapy in the six months before the first Rheumatology visit to relieve respiratory symptoms. Twenty of these patients (58.8%) had rheumatic manifestations during steroid tapering. ILD CT patterns were NSIP (25 patients, 52.1%), UIP (18 patients, 33.4%), and organizing pneumonia (5 patients, 9.3%). In four patients (4.5%), autoantibodies became positive during the follow-up. The final diagnosis of CTD- or RA-ILD was made after a median period of 16.5 (6-39) months from the clinical onset. At the time of diagnosis, average FVC was 90.4±18.7% of predicted, DLCO 55.4±20.2% and the median GAP index was 3 (2-3). During the median follow-up of 48 months, eight patients (14.8%) had a decline in DLCO of ≥ 15% predicted and/or a decline in FVC of ≥ 10% despite immunosuppressive drugs. Nine patients (17%) died and six of these patients (11.1%) for causes related to ILD.Conclusion:In our study population, the prevalence of ILD as initial manifestation of CTD or RA was 12.6%. Autoimmune myositis, systemic sclerosis and Sjogren syndrome were the most frequent diagnosis. As our data confirmed, ILD is a major cause of death in patients with systemic autoimmune diseases and can progress despite immunosuppression [1]. Furthermore, clinical features may become evident even months after the disease onset. A multidisciplinary evaluation is therefore essential, not only at the time of diagnosis but also during the follow-up [2].References:[1] A. Fischeret al.Progressive fibrosing interstitial lung disease associated with systemic autoimmune diseases.Clin Rheum(2019); 38:2673-81[2] F. Furini,et al. The role of the Multidisciplinary Evaluation of Interstitial Lung Diseases: Systematic Literature Review of the Current Evidence and Future Perspectives.Front Med(2019); 6:246Disclosure of Interests:None declared

Background:Scleroderma (systemic sclerosis; SSc) has high morbidity and mortality. Pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) is common with a high mortality (1). SSc patients are screened with pulmonary function tests (diffusing capacity of the lung for carbon monoxide; DLCO) (2).Objectives:The DLCO%predicted was analyzed comparing patients with and without PAH to determine if it is always low at time of PAH diagnosis.Methods:The Canadian Scleroderma Research Group (CSRG) database was used containing more than 1300 SSc patients with a mean disease duration of 8 years. All patients with at least one follow up visit and DLCO recorded at least twice were eligible for enrolment into this nested case control study. Diagnosis of PH was verified using several algorithms within the database including R heart catheterization, use of PH medications and physician response of ‘yes’ to question has this patient been diagnosed with pulmonary hypertension. Sensitivity, specificity and positive (PPV) and negative predictive values (NPV) were calculated for DLC0%predicted Results:At time of PH diagnosis, the mean DLCO% predicted was 47% (N=30) vs no PH 73% (N=960) PTable 1.DLCO comparison between PH+ and PH- SSc patients and between PAH+ and PAH- SSc patients, at the time of diagnosis.PH+(n=30)PH-(n=960)P-valuePAH+(n=22)PAH- (n=968)P-valuemean±SD47.17±17.5372.74±20.7951.23±17.5572.44±20.99Range18-8113-14725-8113-147Table 2.Sensitivity, specificity and predictive values in SSc-PH and -PAH for DLCO at various cut points.ORPPVSpecificityNPVSensitivityDLCO11.5 (CI 95% 5.4-24.8),p13.2%87.0%98.7%63.3%PHDLCO7.6 (CI 95% 3.3-17.2), p7.9%73.3%98.9%73.3%DLCO>80%0.06 (CI 95% 0.008-0.46), p=0.0070.3%64.5%95.5%3.3%DLCO7.6 (CI 95% 3.2-17.9), p8.3%86.4%98.8%54.5%PAHDLCO4.7 (1.9-11.3), p5.0%72.7%98.9%63.6%DLCO>80%0.1 (0.01-0.7), p=0.0180.3%64.8%96.8%4.5%Conclusion:A low DLCO is associated with a high odds of PH/PAH in SSc and the NPV is very high at both DLCOReferences:[1]Mukerjee D et al (2003) Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis 62(11):1088-93[2]Khanna D et al (2013) Recommendations for screening and detection of connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheum 65(12):3194-201Disclosure of Interests:None declared

Background:Interstitial lung disease (ILD) represents a frequent extra-glandular manifestation of primary Sjögren’s Syndrome (pSS). Limited published data regarding phenotyping and treatment exists. Advances in managing specific ILD phenotypes have not been comprehensively explored in patients with coexisting pSS.Objectives:This retrospective study aimed to phenotype lung diseases occurring in a well-described pSS cohort and describe treatment course and outcomes.Methods:Between April 2018 and September 2019, all pSS patients attending our Outpatient clinic were screened for possible lung involvement. Clinical, laboratory and computer tomography (CT) findings were analysed. Patients were classified according to CT findings into 5 groups: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), combined pulmonary fibrosis and emphysema (CPFE) and unspecific-ILD.Results:Lung involvement was confirmed in 24/240 patients (10%). Clinically manifest pSS occurred later in patients with ILD vs. non-ILD (53.2 [42.0-61.7]vs.62.3 [55.6-68.8] years; p=0.0016). The commonest phenotype was UIP n=10 (41%), followed by NSIP n=7 (29%), DIP n=2 (8%), CPFE n=2 (8%) and unspecific-ILD n=3 (13%). Forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) appeared lower in UIP and DIP, without reaching a significant difference. Treatment focused universally on intensified immunosuppression, with 12/24 patients (50%) receiving cyclophosphamide. No anti-fibrotic treatments were used. Follow-up was median 13.2 [7.9-72.3] months, during which 6/24 (25%) patients exhibited a further decline in FVC. No deaths occurred.Conclusion:Lung involvement in pSS is heterogeneous. Better phenotyping and tailored treatment may improve outcomes and requires further evaluation in larger prospective studies.Disclosure of Interests:None declared

Background:Interstitial lung disease (ILD), is common in patients with idiopathic inflammatory myopathies (IIM) and strongly impact on patients’ morbidity and mortality. Patients with anti-aminoacyl-transfer RNA-synthetases (anti-ARS) antibodies are associated with an increased risk of ILD.Objectives:Defining the radiological characteristics of IIM patients, with special focus on serological groups, through qualitative, semiquantitative and quantitative analysis of lung CT.Methods:This was a prospective study conducted from 2016 to 2019. Ninety-eight IIM patients (35 men, 63 women) were included. Myositis specific autoantibodies (MSA) were assessed with Myositis Prophyle III (Euroimmune, Lubeck).Each patient had a baseline CT; the total score of Warrick (WS) was obtained at semiquantitative analysis. The radiological scores ILD% (interstitial lung disease %) and PVRS% (pulmonary vascular related structure) were the result of quantitative analysis in 61 patients (CALIPER). Pulmonary function tests (PFTs) included TLC%, FVC% and DLCO% (65 patients). The analysis was conducted in the whole group and divided in subgroups based on their MSA pattern: in particular anti-ARS (Group 1) and patients negative to MSA (Group 2) were analysed.Results:Positive correlations between ILD% and PVRS% (Rho=0.916; ρ=0.000), WS and ILD% (Rho=0.663; ρ=0.000) and WS and PVRS% (Rho=0.637; ρThe most relevant inverse correlations were found between ILD% and DLCO% (Rho=-0.590; ρ=0.001), PVRS% and DLCO% (Rho=-0.549; ρStatistically significant higher values of WS, ILD% and PVRS% were found in Group 1 (WS=15, ILD%=11 and PVRS%=3.5), compared to Group 2 (WS=2.5, ILD%=0.84 and PVRS%=2.2). NSIP pattern resulted dominant represented in the two groups (80% Group 1, 75% Group 2). No statistically significant differences of DLCO%, FVC% and TLCO% were found.Conclusion:The inverse correlations between the radiological scores and the functional data TLC% and DLCO% (ρDisclosure of Interests:None declared

Background:Disease activity assessment is crucial in defining the appropriate therapy and to monitor the efficacy of treatment in systemic sclerosis.Objectives:We aimed to test the performance of the ’old’ European Scleroderma Trials and Research Group (EUSTAR) Activity Index (old-AI) (1), the ’new’ EUSTAR activity index (new-AI) (2), and the scleroderma activity index derived from the old-AI (Pecs-AI) (3). We compared the three indices to the disease activity based on the physician’s global assessment (PGA). We also assessed the correlations with the change in modified Rodnan Skin Score (MRSS), FVC and arthritis after one year follow-up.Methods:We evaluated 77 patients (50 diffuse /dcSSc/ and 27 limited cutaneous SSc /lcSSc/ patients) from a single tertiary clinical center. Cohort enrichment was performed to increase the number of patients with early disease and dcSSc. Seventy-two patients were re-evaluated after one year. Nine patients had overlap syndromes: rheumatoid arthritis (n=3), Sjögren syndrome (n=2), polymyositis (n=2), and mixed connective tissue disease (n=2). The overall disease activity was evaluated using both composite indices (old-AI, Pecs-AI, new-AI) and the PGA of disease activity, based on the blinded evaluation of a single physician (LV). In addition to the minimal essential data from the EUSTAR database we also performed detailed assessment of the musculoskeletal involvement evaluating measures of hand function, DAS28 scores, and the Clinical Disease Activity Index (CDAI) (4).Results:Three times more patients with active disease were identified by the new-AI compared to the old-AI at baseline investigation (n=37, 48.7%, vs. n=11, 14.3%). Two patients (18%) with active disease based on the old-AI were missed by the new-AI. Pecs-AI index identified 15 patients (19.5%) with active disease (cut-off >2.75 points). Active disease was equally frequent in dcSSc and lcSSc patients based on old-AI, but was more frequent in dcSSc patients based on the new-AI in the whole cohort, and also after excluding overlap cases.Patients with active disease based on the old-AI had more frequently rheumatoid factor (6/9, vs. 12/45, p=0.047), and DLCOCDAI correlated significantly with the old-AI (rho: 0.345, and rho: 0.283, respectively, pConclusion:The two validated disease activity indices indentify different patient groups. Joint involvement is potentially underrepresented in the new EUSTAR activity index. Active disease is also present in lcSSc and should be assessed regularly in these patients.References:[1]Valentini G, et al. Ann Rheum Dis 2003; 62: 901-3.[2]Valentini G, et al. Ann Rheum Dis 2017;76:270–276.[3]Minier T, et al. Rheumatology (Oxford) 2010;49(6):1133-45.[4]Lorand V, et al. Rheumatology (Oxford). 2016;55(10):1849-58.Acknowledgments:This work was supported by the EU Seventh Framework Program [FP7/2007-2013] under Grant Agreement n° 305495 (DeSScipher), by the Hungarian Scientific Research Fund (contract n°: 112939), and the EU under the Grant Agreement n° PEPSYS GINOP-232-15-2016-00050.Disclosure of Interests:Tünde Minier Speakers bureau: Actelion, Abbvie, MSD, Pfizer, Lilly, Roche, Veronika Lóránd: None declared, Zsófia Bálint: None declared, Dalma Komjati: None declared, Gabriella Nagy Speakers bureau: MSD, Antonietta Kovács: None declared, Orsolya Koncz: None declared, Cecília Varjú Consultant of: Boehringer Ingelheim RCV GmbH & Co KG, Speakers bureau: Lilly, László Czirják Consultant of: Actelion, BI, Roche-Genentech, Lilly, Medac, Novartis, Pfizer, Bayer AG, Gabor Kumanovics Consultant of: Boehringer, Teva, Speakers bureau: Roche, Lilly, Novartis, Balazs Nemeth: None declared

Background:Antisynthetase syndrome is an autoimmune rheumatologic disease characterized by the presence of specific antibodies that are known as antisynthetase antibodies and with a varied clinic, including arthritis, myositis or interstitial lung disease (ILD), among others. ILD is the manifestation that associates the highest morbi / mortality and can occur with different characteristic radiological patterns: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), organized pneumonia (OP)Objectives:Describe the clinical, serological and prognostic characteristics of patients with antisynthetase syndrome with interstitial pulmonary involvement (ILD) based on their radiological pattern.Methods:Retrospective descriptive study of patients with a clinical diagnosis of antisynthetase syndrome in which they show positive for some antisynthetase antibody and with clinical follow-up of at least 6 months in a reference center consultation between the period from January 2008 to September 2019. In those patients who presented interstitial lung involvement clinical, analytical and prognostic variables were evaluated (including spirometry) based on the radiological pattern presented by high-resolution computed tomography (HRCT) of the chestResults:32 patients (24 women and 8 men) were included in the study. 7 cases (21.9%) did not present pulmonary involvement, while the remaining 25 cases (78.1%) presented with interstitial lung involvement. Of the patients diagnosed with ILD, 4 cases (12.5%) had an interstitial pattern UIP, 17 cases (53.1%) had an interstitial pattern of NSIP and another 4 (12.5%) interstitial pattern of OP. From an analytical point of view, the most frequent antisynthetase antibody in our sample was antiJo1 with 29 cases (96.9%) and less frequently the antiPL12 antibody with 2 cases and antiPL7 with 1 case. The specific characteristics depending on the type of EPID pattern are summarized in Table 1.Table 1.CHARACTERISTICSILD PATTERNPattern UIP N=4Pattern NSIP N=17Pattern OP N=4Gender (Female) n (%)4 (100)11 (64.7)3 (75.0)Age at diagnosis47.5 ± 12.952.9 ± 10.542.0 ± 12.9Myositis, n(%)2 (50.0)13 (76.5)4 (100)Arthritis, n (%)3 (75.0)15 (88.2)3 (75.0)Fever, n (%)1 (25.0)9 (52.9)2 (50.0)Mechanic´s hands, n(%)2 (50.0)7 (41.2)2 (50.0)Raynaud´s phenomen, n (%)1 (25.0)8 (47.1)1 (25.0)Skin involvement, n(%)2 (50.0)10 (58.8)4 (100)Treatment, n(%)Glucocorticoids4 (100)16 (94.1)4 (100)Immunosuppresants4 (100)16 (94.1)4 (100)Biological therapy1 (25.0)8 (47.1)2 (50.0)Drug´s number (mean, SD)3 ± 0.85 ± 2.94.7 ± 1.8Antisynthetase antibodies, n(%)Anti Jo13 (75.0)15 (88.2)4(100)PL70 (0)1 (5.9)0 (0)PL121 (25.0)1 (5.9)0 (0)Ro523 (75.0)14 (82.4)2 (50.0)RF positive1 (25.0)4 (23.5)1 (25.0)CK increase2 (50.0)11 (64.7)4 (100)Aldolase increase2 (50.0)12 (70.6)4 (100)Functional respiratory tests: mean(CI95%)Variation DLCOc(%)-4.4 (-12.5, 3.7)-2.5(-6.1, 1.0)7.4 (-10.6, 25.3)Variation FVC(%)-1.1 (-12.8, 9.1)6.0 (3.2, 8.8)7.5 (-9.5, 24.6)Variation FEV1(%)0 (0-2.25)5.0 (1.9, 8.3)7.35 (-18.0, 32.7)Variation FEV1/FVC(%)0.5 (-7.1, 8.2)-1.3 (-2.22, -0.37)-0.4(-12.88, 11.98)Conclusion:ILD is a frequent and serious manifestation that can occur in patients with antisynthetase syndrome, which may have different radiological patterns. In our series, the most observed radiological pattern has been the NSIP pattern with 68%. The pattern most associated with the Ro 52 antibody was the UIP pattern and the NSIP pattern. As for the group that required the largest numbers of drugs (including biological therapy) it was the NSIP pattern. When evaluating changes in respiratory function tests, the pattern that shows a tendency to improve over time is organized pneumonia with improvement of the DLCO, FVC, FEV1, FEV1 / FVC, while the UIP pattern showed a worsening of the DLCO and the FVC.Disclosure of Interests:None declared

Background:Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are the major life-threatening complications in systemic sclerosis (SSc). Data on the impact of PAH and/or ILD in SSc patients (pts) are limited by their low prevalence.Objectives:To assess differences in demographic/clinical characteristics of SSc pts according to presence of PAH and how these are affected by ILD. The impact on characteristics and survival of PAH + ILD was also assessed.Methods:We compared data on SSc pts without PAH from the Spanish registry of patients with SSc (RESCLE) (SSc pts) and SSc pts with PAH from the Spanish registry of pts with PAH (REHAP) (SSc-PAH pts). Only data common in both registries were analyzed. Sub analyses were performed according to the presence/absence of ILD. Transplant-free survival from diagnosis of PAH was estimated using the Kaplan-Meier method.Results:1,579 pts with SSc (RESCLE) and 364 pts with SSc-PAH (REHAP) were analyzed. Compared to SSc pts, SSc-PAH pts had worse functional status (NYHA FC III/IV: 70.6% vs. 8.2% in SSc pts) and pulmonary function (lower mean forced vital capacity [FVC, 81.2±20.6% vs. 93.6±20] and diffusing capacity for carbon monoxide [DLCO, 45.3±17.7% vs. 79.0±36.6%]). More patients had FVC/DLCO ≥1.4 (77.8% vs. 34.8%), tricuspid regurgitation (91.4% vs. 46.1%) or pericardial effusion (30.0% vs. 5.1%). Mean systolic pulmonary artery pressure (sPAP) was higher (70.0±21.3 vs. 27.5±9.1 mmHg) (all respectively; PConclusion:PAH has a profound impact on functional status, pulmonary function and right ventricle function of SSc patients, independently of presence of ILD. Despite the deleterious effect of functional status and pulmonary function, in pts with SSc and PAH, presence of concomitant ILD has no impact on 5-year survival.Disclosure of Interests:Alfredo Guillén-del-Castillo Consultant of: Actelion pharmaceuticals, GSK, MSD., Manuel López-Meseguer Consultant of: Actelion pharmaceuticals, GSK, MSD., Carles Tolosa Consultant of: Actelion pharmaceuticals, GSK, MSD., Antonio Romás Broto Consultant of: Actelion pharmaceuticals, GSK, MSD., Dolores Colunga Argüelles Consultant of: Actelion pharmaceuticals, GSK, MSD., Isabel Blanco Consultant of: Actelion pharmaceuticals, GSK, MSD., Antoni Castro Consultant of: Actelion pharmaceuticals, GSK, MSD., Raquel López Reyes Consultant of: Actelion pharmaceuticals, GSK, MSD., Adela Marín Ballvé: None declared, Isabel Otero González Consultant of: Actelion pharmaceuticals, GSK, MSD., Vicent Fonollosa-Pla Consultant of: Actelion pharmaceuticals, GSK, MSD., Ernest Sala LLinas Consultant of: Actelion pharmaceuticals, GSK, MSD., Pilar Escribano Subías Consultant of: Actelion pharmaceuticals, GSK, MSD., Carmen Pilar Simeón-Aznar Consultant of: Actelion pharmaceuticals, GSK, MSD.

Background:Lung involvement is very common is systemic sclerosis (SSc). Approximately one quarter of patients develops pulmonary problems within the first 3 years of diagnosis and still represents the leading cause of death in these patients. In a recent clinical trail, the reduction of FVC was not accompanied by a benefit with respect to health-related quality of life and patient-reported outcomes (PROs).Objectives:To assess how the change in Pulmonary Function Test (PFTs) parameters correlates with the Patient Reported Outcomes (PROs) in an observational cohort of patients with Systemic Sclerosis (SSc).Methods:We conducted a retrospective study of 330 clinic episodes from 121 unselected patients diagnosed with systemic sclerosis according to EULAR/ACR 2013 criteria, in annual follow-up (for a total of 165 patients/year) with PFTs, Health Assessment Questionnaire Disability Index (HAQ-DI), Scleroderma Health Assessment Questionnaire (sHAQ), Modified Borg Dyspnea Scale (Borg) and Cochin Hand Function Score (CHFS). We assessed the correlation between the HAQ and the Visual Analogical Scale 1-7 at baseline (VAS1 pain, VAS2 disease severity, VAS3 arthritis activity, VAS4 intestinal problems, VAS5 dyspnea, VAS6 Raynaud’s phenomenon, VAS7 digital ulcers). We evaluated the correlation of PFTs with PROs at every time period and the correlation between the change of PFTs parameters (δFVC, δDLCO) with the change of the PROs over a year of follow-up. Following analysis of distribution, Spearman or Pearson Test were used to determine correlation coefficients, as appropiate (Prism 7).Results:The median disease duration was 5 years (IQR 3-10). The median of 12 months δFVC% and δDLCO% were 0 (IQR -5.81 to 3.28) and -2.439 (IQR -8.76 to 5.98), respectively. The analysis evidenced a strong positive correlation between VAS1-7 and HAQ. We observed also significant correlation between FVC%, DLCO% and HAQ-DI (r= - 0.355 and -0.266, respectively; pConclusion:This analysis of a monocentric non-selected population evidenced that the current commonly used PROs in SSc while showing a good correlation with lung function are poorly sensitive to change or to reflect changes in lung function over 12 months. In this sense, prudent interpretation of the lack of correlation between FVC and patient-reported outcomes in studies of phase 3 is warranted.References:[1]Rahimi S., Nintedanib for systemic sclerosis-associated interstitial lung disease, Lancet Respiratory Medicine (2020)Disclosure of Interests:None declared

Background:Pulmonary hypertension (PH) is an important cause of morbidity and mortality in patients with systemic sclerosis (SSc). Different screening algorithms have been proposed for identifying patients who have a high probability of PH and require right heart catheterization (RHC), which is the gold standard for diagnosing PH.Objectives:To compare the performance of PH screening algorithms in our patients with SSc.Methods:Sixty-nine consecutive pts fulfilling ACR/EULAR 2013 SSc criteria have been screened for PH until now, using the 2015 ESC/ERS, DETECT and ASIG algorithms. Pulmonary function tests (PFT), diffusing capacity of the lung for carbon monoxide (DLCO), trans-thoracic echocardiography, serum NT-proBNP and uric acid assay and high-resolution computed tomography (HRCT) were performed as needed. Patients with known PH, severe interstitial lung disease and severe left ventricular dysfunction (LVD) were not included. RHC was performed in all patients with positive screening according to any one of the screening algorithms. Pts with PH were classified according to the updated PH classification criteria. Sensitivity and specificity of the 3 screening algorithms were evaluated according to the established cut-off value of 25 mmHg for mean systolic pulmonary artery pressure and for the recently proposed cut-off value of 20 mmHg.Results:Among the 69 SSc pts, 27 were excluded due to ILD(n=6), LVD(n=6), already diagnosed PH(n=4) no measurable TRV(n=5), lung cancer (n=2), pulmonary embolism (n=1) and nephrotic syndrome (n=1). Among the remaining 42 patients, 17 required RHC according to at least one of the screening algorithms (Table 1). Number of patients who had suspected pulmonary hypertension and required RHC according to ESC/ERS 2015, DETECT and ASIG were 7 (%17), 13 (%31), and 12 (%29) respectively (Figure 1). Among the 17 pts. who had RHC, PH was present in 3 pts according to the 25-mmHg cut-off (Group 2 in 2, Group 3 in 1) and in 9 pts according to the 20-mmHg cut-off (Group 1 in 5, Group 2 in 3, Group 3 in 1). The sensitivity and specificities were presented in Table 2. ASIG and DETECT had better sensitivity for 25-mmHg cut-off and was better with ASIG for 20 mmHg cut-off. The specificity was better with ESC/ERS for both cut-off values.Conclusion:The ASIG algorithm has a better sensitivity and ESC/ERS algorithm has a better specificity for detecting PH in patients with SSc. A limitation of this study was that RHC was not performed in patients who did not fulfill criteria according to any of the screening algorithms. The sensitivities may be lower than what we propose if there are patients with PH who are asymptomatic and not captured with any of the algorithms.Disclosure of Interests:Mustafa Erdogan: None declared, Burcak Kilickiran Avci: None declared, Cansu Ebren: None declared, Yagmur Ersoy: None declared, Zeki Ongen: None declared, Gul Ongen: None declared, Vedat Hamuryudan Speakers bureau: Pfizer, AbbVie, Amgen, MSD, Novartis, UCB, Gulen Hatemi Grant/research support from: BMS, Celgene Corporation, Silk Road Therapeutics – grant/research support, Consultant of: Bayer, Eli Lilly – consultant, Speakers bureau: AbbVie, Mustafa Nevzat, Novartis, UCB – speaker