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We read with interest the letter by Bozzalla Cassione et al 1 about the role of telemedicine in their clinic during COVID-19 time. Telemedicine represents a useful tool not only in regions with limited access to healthcare2 but also in different settings like quarantine, when healthcare personnel became essential. Since the Italian National lockdown decision3 and the WHO announcement of the COVID-19 pandemic,4 enormous demand to handle the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disease challenged the Italian healthcare system. Indeed, in the Fondazione Policlinico Universitario A. Gemelli (FPG) Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) in Rome, the delegated taskforce (Gemelli against COVID-19) gradually opened 14 COVID-19 dedicated wards, in accordance to the progressive increase of serious cases. Concomitantly, several clinics were remodulated to optimise the staff use and to avoid patient exposure to the hospital environment. The Division of Rheumatology of the FPG-IRCCS is a high-flux rheumatological centre, with almost 16 000 visits performed in the last year for chronic inflammatory arthritis (38%), connective tissue diseases (CTDs) (34%) and other rheumatic diseases (27%) (ie, osteoarthritis and fibromyalgia) from all Italian regions. Before the spread of COVID-19, our rheumatology service was organised to …

Background:The Italian Society for Rheumatology (SIR) comprises committees for Rheumatologists under the age of 40 (SIRyoung) and for Women in Rheumatology (Reumatologhe Donne – ReDO). As female representation is increasing in rheumatology worldwide [1], there has been interest in assessing gender-related issues.Objectives:To describe the gender distribution among young members of SIR and academic positions in Rheumatology in Italy. To assess the expectations and needs of young rheumatologists with regard to their career.Methods:SIRyoung members developed a web-based survey which was distributed among SIR members under the age of 40 during the spring of 2019. Responses were collected and analysed anonymously. ReDO retrieved and analysed the data regarding academic positions in Italy in September 2019 from official data by “Ministry of Education, University and Research” (www.miur.it).Results:Out of 478 SIR members under 40 (66.5% F), 113 (23.7%) completed the SIRyoung survey (62.1% F). Regarding career plans, male and female members responded: hospital physician (36.9% vs 37.8%), outpatient clinic physician (18.5% vs 28.3%), academic career (23.9% vs 22.8%), private practice (16.3% vs 9.4%), and industry (4.3 vs 1.6%), respectively. When asked about their interest in doing a fellowship in another national center or abroad, 60.8% of male and 72.8% of female respondents were interested but thought they could not afford it. Reasons reported by males and females were: working reasons, namely barriers to temporarily leave the workplace (61.3% vs 50.7%), family reasons (16.1% vs 25.4%), financial reasons (22.6% vs 16.5%), respectively. As for academic rheumatology in Italy, 113 positions were retrieved. Men held 64 positions (57%) and women 49 (43%). Full professors were mostly men (92%), while assistant professors were women in 65% of the cases (58% of those with a permanent position; 72% of those with a temporary position) (Figure) [2].Conclusion:Our study explored for the first time gender distribution and related issues in Rheumatology in Italy. Female representation accounts for two thirds of SIR members under 40. This could reflect the general trend of medical school being chosen more often by women than men. No differences were observed in the career expectations of male and female rheumatologists. Interestingly, nearly one fourth of female respondents were interested in academic career, confirming the trend toward female predominance observed for assistant professors. Therefore, it is likely that the next generation of full professors will have a balanced gender distribution, as it is already for associate professors. The choice of a fellowship is still hampered by several problems, but it seems that reasons for not pursuing such opportunities are similarly distributed in males and females. Although family reasons tend to be more frequent in female rheumatologists, this is not significant as compared to men. This could indicate that family affects career choices of both male and female rheumatologists. It is important that national societies promote surveys for the assessment of gender specific issues among their members, in order to identify unmet needs and design interventions for career support regardless of gender.References:[1]Andreoli L, et al. Joint, Bone, Spine: Revue du Rhumatisme. 2019;86(6):669-672.[2]Bosello SL, et al. Reumatismo 2020; in press.Acknowledgments:SIRyoung and ReDO wish to thank the Steering Committee of SIRDisclosure of Interests:Laura Andreoli: None declared, Stefano Alivernini: None declared, Alessia Alunno: None declared, Silvia Laura Bosello: None declared, Cecilia Chighizola: None declared, Paola Conigliaro: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Cristina Iannuccelli: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Marta Vadacca: None declared, Maria Sole Chimenti: None declared

Background:Several studies have showed that antiphospholipid antibodies (aPL) positivity represents a predictor of worse renal outcome in patients with Lupus Nephritis (LN). In addition, an association between aPL positivity and the histological data of vascular lesions on the renal biopsies has been reported.Objectives:To determine the prognostic role of aPL and vascular renal lesions in the assessment of clinical outcome during the follow up period, in terms of time to achieve remission, number of renal flares and development of chronic renal damage in patients affected by LN.Methods:Among 120 patients affected by LN from our Rheumatology Unit, 91 patients (age 43.8 ± 12 years, 74 (81.3%) female, disease duration 7.1 ± 7.9 years) have been evaluated and the follow-up data have been collected at the baseline and at 6, 12, 24 months and at the last follow-up visit. Histopathological data of 41 patients were evaluated according to the 2016 revision of ISN/RPS classification.Results:Among the 91 LN patients, 31 (34.1%) were aPL positive (aPL+), 10 (32.2%) of them were affected by Antiphospholipid Antibodies Syndrome (APS), 53.3% showed a single aPL positivity, 23.1% double aPL positivity and 15.4% triple aPL positivity. At the last follow up visit a significant higher number of aPL+ patients showed a persistent complement consumption than aPL negative (aPL-) patients (p=0.001). Evaluating clinical outcome, we observed that aPL- patients showed a remission achievement time slightly earlier than aPL+ patients (13.6 ± 1.0 months vs 16.5 ± 1.5 months; log-rank test: p=0.06, Breslow test: p=0.08) and as expected, patients with a persistent complement consumption achieve remission later (18.2 ± 1.5 months vs 13.0 ± 1 months; log-rank test: p=0.002, Breslow test: p=0.003). Furthermore at the last follow up, a significant higher percentage of aPL+ patients developed persistent proteinuria (p=0.02) and chronic renal failure (p=0.04). Considering histologic features (activity and chronicity index, glomerulonephritis class, presence of mesangiolysis, glomerular wrinkling, glomerular thrombi, interstitial inflammatory infiltrates, interstitial fibrosis and tubular atrophy,tubulitis and vascular lesions) we didn’t observe significant differences between aPL+ and aPL- patients but we found two typical vascular lesions (mesangiolysis and vascular thrombi) only in aPL + patients.Conclusion:aPL positivity is a predictor of worse renal outcome but in our cohort of LN patients we didn’t find an association between aPL positivity and vascular renal lesions at renal biopsy. The worse renal outcome and the late time to achieve remission in aPL+ group can be related to a cumulative vascular damage over time as observed in other organ and systems.Disclosure of Interests:None declared

Background:cytokine dysregulation plays an important role in the pathogenesis of Lupus Nephritis (LN) representing an attractive field of research aiming to find new pathways for new targeted therapies. IL-17, IL-23 axis seems to have a great influence in the development of LN.Objectives:to evaluate the strongest prognostic factors in a cohort of patient with LN focusing on of the impact of IL-17, IL 23 axis as new pathogenetic pathway on renal outcome.Methods:91 patients with active LN at disease onset or disease flare were enrolled. Laboratory, immunological and disease activity data were collected at the baseline and at 6(T6),12(T12),24(T24) months and at the last follow-up(FU). 84 renal biopsies were evaluated according to ISN/RPS classification, assessing the activity and chronicity indexes and the active interstitial infiltrate using the BANFF score system. Baseline serum levels of IL-17 and IL-23 were assessed by ELISA in 37 patients.Results:among the 84 renal biopsies evaluated 77% belonged to class III and IV according to ISN/RPS; 41,8% of patients had an active interstitial infiltrate5% at renal biopsy and with the development of persistent proteinuria. The analysis of IL-17 could not let us to find a cut off value for renal damage progression since a too much high number of patients had a null value. Nevertheless patients with more elevated serum levels of IL-17 at the baseline showed more elevated level of interstitial infiltrate at renal biopsy and a worse renal outcome overall. Finally we conducted an univariate and multivariate analysis for each renal outcome considered. We found that an inflammatory interstitial infiltrate>5% at renal biopsy and APL+ were associated with worse renal outcome in terms of early and persistent remission, chronic damage, persistent proteinuria, and renal flare both in univariate and multivariate analysis. Higher serum level of IL-23 was associated with persistent proteinuria, renal flare and tended to be associated to chronic renal damage and persistent renal activity.Conclusion:interstitial inflammatory infiltrate and APL+ represent in our study the strongest predictors of worse renal outcome. An higher serum level of IL-23 was found to be a negative prognostic factor pointed out the possibility to consider the IL-17-IL 23 axis as a biomarkers of a more aggressive renal disease.Disclosure of Interests:None declared

Background:Rheumatoid Arthritis (RA) is characterized by synovial tissue (ST) heterogeneity at disease onset in terms of inflammatory degree and microanatomical organization being related to treatment response.Objectives:To develop a multiparametric tool for baseline treatment response prediction including disease characteristics and histopathologic features of ST biopsies, using a large single center (SYNGem Unit) naive to treatment RA cohort.Methods:240 naive to treatment RA who underwent US-guided ST biopsy, at the first clinical evaluation, were enrolled. Clinical and immunological characteristics were recorded for each patient. All ST FFPE specimens were stained with H&E and classified by a pathologist, blinded to clinical characteristics, using the Krenn score [1] to assess the degree of ST inflammation. All naive to treatment RA were treated according to the T2T scheme and DAS remission rate at 6-12 months was recorded. On the basis of the regression analysis, a nomogram was constructed that incorporated the significant factors predicting the “achievement of DAS-Remission at 6 months follow-up” in naive RA. The performance of the nomogram was assessed by discrimination and calibration.Results:Univariate analysis showed that RA who achieved early (6 months) DAS-remission had, at baseline, significantly lower total Krenn score (pLogistic regression analysis revealed that, at baseline, being VERA, not having HDA and having a total Krenn score Conclusion:Krenn score is a reliable tool for the semi-quantitative assessment of ST inflammation on US-guided ST biopsies being contingent to baseline disease characteristics and can be integrated within a nomogram to better predict the therapeutic response in naive to treatment RA.References:[1] Krenn V, et al. Histopathology 2006Disclosure of Interests:Stefano Alivernini: None declared, Barbara Tolusso: None declared, Marco Gessi: None declared, Maria Rita Gigante: None declared, Alice Mannocci: None declared, Luca Petricca: None declared, Simone Perniola: None declared, Clara Di Mario: None declared, Anna Laura Fedele: None declared, Laura Bui: None declared, Annunziata Capacci: None declared, Dario Bruno: None declared, Giuseppe La Torre: None declared, Francesco Federico: None declared, Gianfranco Ferraccioli: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

Background:Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis often affect the kidney and renal involvement has a considerable clinical impact on patient’s prognosis. Currently used histopathological classifications are basically focused on the glomerular damage and assessing chronic damage progression, but their prognostic role presented some limitations.Objectives:To combine the Berden Classification, the ANCA Renal Risk Score (ARRS) and the Mayo Clinic-Renal Chronicity Score (RCS) with the inflammatory interstitial infiltrate and to evaluate the prognostic value of the combined assessment in patients with AAVMethods:We included 19 AAV patients with renal involvement (mean age 63±13.2 years; disease duration 4.9±5.2 months) who underwent renal biopsy. Patients were classified according to age, sex, disease duration, ANCA positivity. The histopathological evaluation was performed assessing the Berden category, Risk group (low, medium, high) according to the ARRS and Chronicity class according to the RCS; we also assessed the % of inflammatory interstitial infiltrate. Each patient was followed-up for 12 months; we considered the stage IV (eGFR < 30 ml/min/m2) of theKDIGO CKDClassification as renal outcome.Results:8 (42.1%) AAV patients were p-ANCA and 11 (57.9%) c-ANCA. 12 months after renal biopsy, 8 patients (42.1%) had a GFR 2=9.0 e p=0.01) as well as the chronicity Score (χ2=8.1; p=0.017). Finally, we built a matrix combining the different histopathological scores and the % of inflammatory infiltrate to predict the outcome; we found that an inflammatory infiltrate wider than 22.5% characterizes most of patients developing stage IV chronic renal failure at the 12th month. In fact, more than 75% of patients with eGFR < 30 ml/min had inflammatory infiltrate wider than 22.5% at biopsy, despite they were in the low risk class (ARRS) and in minimal changes class (RCS).Conclusion:Our results underline the importance of the inflammatory infiltrate in renal outcome and histology. Despite the limited number of patients, our data suggest that a combined histological score assessing the chronicity and activity of renal disease from both glomerular and interstitial perspective could better predict patients’ global and renal prognosis.References:[1]Berden, J Am Soc Nephrol, 2010 Berti, Nephrol Dial Transplant 2018 Brix, Kidney Int. 2018Disclosure of Interests:Laura Gigante: None declared, Pier Giacomo Cerasuolo: None declared, Gisella Vischini: None declared, Francesco Federico: None declared, Dario Bruno: None declared, Alessia Musto: None declared, Stefano Costanzi: None declared, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

Background:Gastrointestinal involvement(GI) is a common feature of systemic sclerosis(SSc) and can be highly disabling, representing a major cause of morbidity and reduced quality of life(QoL). The impact of dietary habits on GI symptoms, mood and QoL has not been extensively evaluated.Objectives:To evaluate the adherence to the Mediterranean Diet(MD) in an Italian multicenter cohort of SSc patients, and its impact on GI symptoms and other disease features, depression, anxiety and overall QoL.Methods:Consecutive SSc(ACR/EULAR2013) patients from 4 Italian cohorts were enrolled. Dietary habits and adherence to the MD were assessed using the 14-item MEDAS and QueMD questionnaires. Presence and severity of depressive/anxious symptoms and QoL were evaluated with the Hospital Anxiety and Depression Scale(HADS) and the SSc-HAQ(S-HAQ). GI symptoms were assessed with the Reflux Disease Questionnaire(RDQ) and the UCLA SCTC GI Tract 2.0 questionnaire(USG). Associations with patients’ lifestyle, disease characteristics, and nutritional status were explored.Results:265 patients (94.7% females; age 55.8±13.6years; disease duration 9.1±7.0years; diffuse SSc 31.8%; Scl70 + 35.8%;ulcers 23.4%;ILD 29.4%;BMI 23.7±4.4 Kg/m2; obese 11.3%,overweight 23.4%,underweight 4.9%) were enrolled.Overall MD adherence was moderate(7.5±1.9) according to MEDAS and it correlated with QueMD score(4.53±1.96)(R=.371,pGI symptoms were moderate/severe according to USG in 37(14.0%) patients(USG:0.41±0.40), and heartburn was the most common GI symptom(35.2%). The prevalence of significant anxiety and depression was 24.1% and 17.0%.An inverse correlation was found between MD adherence and mood disturbances at HADS(MEDAS; R=-0.181,p=0.04), work impairment(QueMD;R=-0.247,p=0.005) and reduced QoL, both for GI (constipation at USG: R=-0.133,p=0.032) and general S-HAQ items(bowel:R=-0.181,p=0.04;severity R=-0.202,p=0.01;Raynaud:R=-0.217,pConclusion:Unsatisfactory MD adherence is associated with a low mood, impaired QoL, work impairment, GI and vascular symptoms in Italian SSc patients. The promotion of a healthy lifestyle could positively impact on QoL and disease status of SSc patients.References:[1]Gnagnarella P, et a. NMCD 2018. DOI: 10.1016/j.numecd.2018.06.006[2]Jaeger VK et al. PLoS One, 2016.[3]Dinu M et al. Eur J Clin Nutr 2018. doi: 10.1038/ejcn.2017.58.[4]Khanna D, et al.Arthritis Rheum. 2009. doi: 10.1002/art.24730.Acknowledgments:GILSDisclosure of Interests:Giacomo De Luca Grant/research support from: SOBI, Speakers bureau: SOBI, Novartis, Pfizer, MSD, Celgene, Gerlando Natalello: None declared, Giuseppina Abignano: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Duygu Temiz Karadağ: None declared, Maria De Santis: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Lorenzo Dagna Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, SG, SOBI, Consultant of: Abbvie, Amgen, Biogen, BMS, Celltrion, Novartis, Pfizer, Roche, SG, and SOBI

Background:SpA patients experience a decreased quality of life due to social, emotional and relational life impairment in addition to pain, fatigue and joint damage. Sexual dysfunction (SD) is often neglected by both patients and clinicians, although articular and extra-articular manifestations of the disease can decrease the quality of sexual life. Previous findings showed that SD can affect from 27% to 67% of patients with rheumatic diseases. Data available on SD in rheumatic patients are poor and primarily focus on male ankylosing spondylitis patientsObjectives:The aim of this study is to evaluate, in a group of female SpA patients, the presence of SD, its relationship with extra-articular manifestations and to estimate the correlation between disease activity and sexual activity.Methods:52 SpA patients (including PsA, IBD-SpA and undifferentiated SpA-un-SpA) and 50 healthy controls (HC) were administered the Female Sexual Function Index (FSFI) questionnaire for the analysis of sexual function (score from 0 to 100). SD is defined by a score lower than 26. Disease activity was evaluated through DAPSA and BASDAI. SpA-HAQ and BASFI was also performed to assess functional statusResults:There was a trend for a significantly greater proportion of SD in the patients (21%) than the controls (8%), χ2(1,N =102) = 3.52,p= .06). Within the different groups, the percentage of those with SD according to the FSFI cut off were 23% of PsA patients, 25% of IBD-SpA patients, 11% of un-SpA patients, and 8% of healthy controls, however, when the patient groups were analysed separately these differences were not significant, χ2(3,N =102) = 4.43,p= .22. Mean scores on the FSFI were lower for the total SpA patients group t(100) = 2.47, p = .02 compared to HC. When scores on the FSFI were analysed separately for each patient group, there was a trend for a significant difference between the groups,F(3,98) = 2.43,p= .07, and follow up t-tests showed that only the PsA group scored significantly lower than the HC,t(100) = 2.56,p= .01 (see Fig. 1). Among the items of the questionnaire, questions regarding sexual desire, lubrication and discomfort were statistically significantly lower scores in patients compared to HC (p= 0.001,p= 0.009,p= 0.02, respectively). For the overall patient group, the FSFI was significantly negatively correlated with the DAPSA (r= -.37,p= .008), the SpA-HAQ (r= -.30,p= .03) and the BASFI (r= -.30,p= .03). Additionally, the PsA group showed a negative correlation between DAPSA scores and FSFI score (r= -.38,p=.03) and the IBD-SpA group had a negative correlation between FSFI score and BASFI (r= -.80,p= .002).Conclusion:Overall, the data generally show that SD is more common in SpA patients compared to HC and that SpA patients score lower on the FSFI. The negative correlations between the FSFI and scores on DAPSA, SpA-HAQ and BASFI suggest that sexual function may be poorer for patients with greater disease activity and poorer functional status. These findings could be due to the number of tender and/or swollen joints as well as chronic pain or fatigue patients often experience. A key limitation of this study is the small sample size. Future research will include a larger sample size. SD in patients with rheumatic disease is still a neglected field in clinical practice, however, its assessment could contribute to improved quality of life for patientsTable 1.Clinical characteristics of patients and healthy controlsPsAun-SpAIBD-SpAHCAge (mean ± SD)50.6 ± 4.043.9 ± 3.646.3 ± 2-052.5 ± 0.5Distribution (N%)31 (59%)9 (17%)12 (24%)50Age at diagnosis (mean ± SD)40.0 ± 2.535.6 ± 4.140.8 ± 1.2/DAPSA15.1 ± 9.912.2 ± 9.9/HAQ0.6 ± 0.50.8 ± 0.51.0 ± 0.7/BASDAI0.6 ± 0.90.6 ± 0.85.1 ± 2.8/BASFI16 ± 16.037.8 ± 26.846.7 ± 21.7/Disclosure of Interests:erica de martino: None declared, Paola Conigliaro: None declared, Maria Sole Chimenti: None declared, Paola Triggianese: None declared, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Cristina Iannuccelli: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Marta Vadacca: None declared, Roberto Perricone: None declared

Background:Systemic lupus erythematosus (SLE) patients are at high risk for CV events, and EULAR recommends assessing the 10-year CV-risk using the Systematic Coronary Risk Evaluation (SCORE) [1]. The QRISK3, another score to assess CV-risk in UK population, considers different factors among which also SLE. The Progetto Cuore score (PCS) is validated to estimate CV risk in Italian people and largely replicates the SCORE project [2].Objectives:This cross-sectional study aimed to estimate CV-risk using SCORE, QRISK3 and, for the first time, PCS in a multicentric cohort of Italian SLE patients.Methods:During 2019 we evaluated 173 SLE patients (87.7% female; age 40±16 years; disease duration 138±105 months), fulfilling the 1997 ACR classification criteria. Clinical and laboratory data were registered, and individual CV-risk was calculated using suitable algorithms for the SCORE, QRISK3 and PCS. Statistical analysis was performed using Graphpad Instat 8.0 (San Diego, CA-USA).Results:In 13 (7%) SLE patients a previous CV event was recorded. Hypertension was present in 60 (37.5%) and diabetes in 27 (16.9%) patients. Mean total cholesterol was 184±39 mg/dL, HDLc 58±18 mg/dL, LDLc 124±37 mg/dL, triglycerides 105±63 mg/dL; dyslipidaemia was reported in 58 (36.2%) patients and 29 (18.1%) were on statin. Mean BMI was 24.9±5.3 Kg/sm, 60 (37.5%) and 23 (14.3%) patients were overweight and obese, while 25 (15.6%) patients were smokers. 87 (54.3%) SLE patients had a SLEDAI7.5 mg/day. The CV-risk of SLE patients according to SCORE, QRISK3 and PCS was 1.1±2.1%, 10.5±12.3% and 3.7±5.4%, respectively. Stratifying patients at low, moderate or high CV risk according to the PCS and SCORE a double proportion of patients was at moderate (8% vs 3.9%) or high (1.9% vs 0.9%) CV risk (p=0.03). Finally, CV-risk according to QRISK3 was higher than 20% (high risk) in 32/160 (20%) patients.Conclusion:This multicentre study demonstrated that the mean estimated CV-risk in SLE patients is globally low using the SCORE, QRISK3 and PCS. The PCS seems to better intercept those patients at moderate/high risk, at least in Italian SLE patients, while QRISK3 predicts the highest CV risk. The lack of disease-specific CV-risk factors (such as autoantibodies profile or organ involvement) probably account for the underestimation of CV risk using the SCORE and PCS.References:[1]ARD 2019;78(6):736-745.[2]ARD 2019;0:1–2.doi:10.1136/annrheumdis-2019-215715Disclosure of Interests:Fabio Cacciapaglia Speakers bureau: BMS; Roche; Pfizer; Abbvie, Andreina Manfredi: None declared, Gianluca Erre: None declared, Elena Bartoloni Bocci: None declared, Garifallia Sakellariou Speakers bureau: Abbvie, Novartis, MSD, Ombretta Viapiana: None declared, Sergio Colella: None declared, Anna Abbruzzese: None declared, Marco Fornaro: None declared, Giacomo Cafaro: None declared, Maria Antonietta Fenu: None declared, Bianca Lucia Palermo: None declared, Martina Dessì: None declared, Adalgisa Palermo: None declared, Alessandro Giollo: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fabiola Atzeni: None declared, Matteo Piga: None declared

Background:Systemic Sclerosis (SSc) is characterized by an increased incidence of macro- and microvascular complications. Current evidences on efficacy, safety and tolerability of acetylsalicylic acid (ASA) in SSc patients are limited, and the indication to this treatment is based on the experience of each single centre or physician. Esophagus and stomach are the portions of the digestive tract that are more frequently affected by adverse events due to ASA exposure.Objectives:We evaluated the incidence of adverse events associated with low-dose ASA treatment in a cohort of patients affected by SSc.Methods:Demographic data and disease features of 302 patients affected by SSc treated with low-dose ASA were collected and patients were followed-up for a median period of 6.9 years (range: 0-20 years). The proportion of patients taking ASA for secondary prevention for cardiovascular disease was also noted. The incidence of discontinuation of the drug, gastrointestinal intolerance, bleeding and death in the observation period was recorded.Results:Patients had a median age of 54.0 years (19.6-89.4); 91.9% were female, 13.2% were smokers and 44.0% had a BMI≥30Kg/m2. The prevalence of ischemic heart disease, peripheral vascular disease and stroke was of 8.6%, 5.3% and 3.3%, respectively; 48.7% of the patient took ASA in primary cardiovascular prevention. Therapy started after a median disease duration of 4.8 years (range: 0.0- 30.1 years) since the first non-Raynaud symptom and 56.6% of patients had an early disease (less than three years of disease duration). During the observation period, 30 patients (14.3 per 1000 person-years) discontinued ASA after an average period of assumption of 4.6 years (range: 0.3-18.0 years). The main adverse events were heartburn, dyspepsia and hematochezia, recorded in 18 patients (8.6 per 1000 person-years). Eight of them (3.8 per 1000 person-years) had evidence of digestive tract bleeding. Five patients (2.4 per 1000 person-years) discontinued ASA due to recurrent epistaxis. Twenty-eight patients (13.4 per 1000 person-years) died in the follow-up period, 16 of these (7.6 per 1000 person-years) because of SSc-related causes. None of them had evidence of major bleeding. We used Kaplan-Meier analysis to evaluate the incidence of ASA discontinuation. The history of digital ulcers (Log rank test X24.7, p=0.037) and male sex (Log rank test X24.3, p=0.03) were associated with a higher cumulative ASA discontinuation rate due to gastrointestinal intolerance.Conclusion:In our cohort of SSc patients, ASA resulted safe and well tolerated in most cases, despite the risk of gastroesophageal abnormalities due to disease. Although this comforting results, taking in account the lack of controlled-randomized trials about efficacy and safety, the choice to start antiplatelet therapy with ASA should be mandatorily preceded by a careful evaluation of risks and benefits. Furthermore, an attentive monitoring for possible adverse effects is needed during ASA treatment. Patients with digital ulcers and male sex could present less drug tolerability.References:[1]Valentini G et al. Ann Rheum Dis 2019. Beckett VL et al. Arthritis Rheum 1984. Kavian N et al. Vascul Pharmacol 2015. Lavie CJ et al. Curr Probl Cardiol 2017.Disclosure of Interests:Lucrezia Verardi: None declared, Enrico De Lorenzis: None declared, Gerlando Natalello: None declared, Laura Gigante: None declared, Umberto La Porta: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer

Background:The regulation of inflammation is a dynamic process involving several molecules as lipid mediators. The Specialized Pro-resolving Mediators (SPMs), such as Resolvin (RvD and RvE), Protectins, Maresins and Lipoxin A4 (LXA4), are bioactive metabolites of omega-3 and omega-6 fatty acids which drive inflammatory resolution phase and promote tissue repair. ERV, ALX/FPR2 and BLT1 are SPM receptors. Although in Rheumatoid Arthritis (RA) lipid mediators role within pathophysiology is under definition, studies on SPMs receptors role are still lacking in this disease.Objectives:Purpose of this study is to define ERV, ALX/FPR2 and BLT1 expression in blood derived leukocytes and synovial cells and to correlate it to disease activity to define SPM receptors ad inflammatory resolution biomarkers in RA patients.Methods:A cohort of 52 RA patients was enrolled in the study of which 40 with active disease (DAS28= 5,35 (5,18-6,40)) and 12 in sustained remission status (DAS28= 2,1 (1,83-2,42)). Each enrolled patient underwent peripheral blood (PB) drawing and 46 of them underwent US-guided synovial tissue (ST) biopsy. FACS gating strategy was used for PB and ST processing to evaluate percentage of positive cells and the mean fluorescence intensity (MFI) of ERV+, ALX/FPR2+and BLT1+in CD45+CD3+, CD45+CD19+for PB and ST, CD45+CD14+and neutrophils for PB only and CD45-CD90+, CD45+CD64+CD11b+macrophages (distinct in CD206+and CD206-subpopulations) for ST only. Each included ST was stained with haematoxylin/eosin and categorized by a pathologist, blinded to clinical characteristics, using the Krenn Score (KS) to assess ST inflammation degree. As control group, 11 undifferentiated peripheral inflammatory arthritis (UPIA) patients were enrolled in the study.Results:Considering the whole RA cohort, DAS28 inversely correlated with BLT1+positive cells on ST-derived CD45+(r= -0.48; p= 0.048), CD3+(r= -0.56; p= 0.019) and CD19+(r= -0.49; p= 0.042) cells, in contrast with CD90+(r= 0.50; p= 0.041) cells. Similarly, both DAS28 and KS inversely correlated with ALX/FPR2+positive cells in ST-derived CD45+(r= -0.42, p= 0.050 and r= -0,41, p= 0,046 respectively) cells. Evaluating the MFI levels of the SPM receptors along all RA stages (naïve-to-treatment, resistant-to-treatment, sustained remission) compared with UPIA control group, interestingly ST-derived CD45+cells of remission RA were depleted of ERV1 compared to naïve-to-treatment RA (p=0.04), despite comparable ST inflammation. Furthermore, highest ERV1 expression was found in ST-derived CD45+CD3+and CD45+CD19+cells in naïve-to-treatment RA compared with UPIA patients (p= 0,045 and p= 0,012 respectively). Moreover, the lowest BLT1 level was found in remission RA CD3+cells compared with UPIA and naïve-to-treatment RA patients (p= 0,008 and p= 0,023 respectively).Conclusion:SPM receptors expression seem to be tightly related to disease activity in the synovial tissue, suggesting an important involvement in the inflammatory process in RA patient.References:[1]Serhan CN. Nature, 2014.[2]Alivernini S, et al. Arthritis Res Ther 2016[3]Krenn V et al. Histopathology, 2006.Disclosure of Interests:Simone Perniola: None declared, Stefano Alivernini: None declared, Barbara Tolusso: None declared, Maria Rita Gigante: None declared, Marco Gessi: None declared, Clara Di Mario: None declared, Luca Petricca: None declared, Annunziata Capacci: None declared, Anna Laura Fedele: None declared, Gianfranco Ferraccioli: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

Background:Secukinumab (SEC) is the first interleukin-17A inhibitor showing efficacy in both ankylosing spondylitis (AS) and psoriatic arthritis (PsA) in randomised trials, but real-life data are lacking.Objectives:In this prospective observational study, we evaluated the effectiveness and safety of SEC in patients with AS and PsA in a real-life setting.Methods:From September 2018 to September 2019, data were collected from 168 consecutive outpatients at baseline (T0) and at 6 (T6) and 12 months (T12) after starting SEC (39 AS, 23%; 129 PsA, 77%).Results:Significant improvement was seen at T6 and T12 for all clinical variables, including TJC, SJC, ESR, CRP, DAPSA, ASDAS-CRP, and BASDAI, as well as in patient-reported outcomes such as VAS-pain. By multivariable regression analysis, in AS patients high BASDAI at T0 correlated with diagnostic delay (R2=0.4; p=0.009) and peripheral joint involvement (R2=0.4; p=0.04). During follow-up, reduction of BASDAI positively correlated with high ESR (R2=0.65; p=0.04). ASDAS-CRP at T0 positively correlated with high ESR (R2=0.34; p=0.004). Reduction of ASDAS-CRP from T0 to T6 correlated with current smoking status (R2=0.42; p=0.0005). In PsA patients, reduction of DAPSA score from T0 to T12 negatively correlated with the presence of metabolic syndrome (R2=0.41; p= 0.0025). Retention rate showed good drug survival and an influence of female sex (Figure 1) in the survival curve in only AS patients, but no differences based on BMI, gender and lines of treatment were observed (Figure 2). SEC was well tolerated: Eleven patients discontinued treatment for non-severe adverse events.Conclusion:We demonstrated the effectiveness and safety of SEC in patients with AS and PsA in a real-life setting for the first time. No gender differences were observed; however, less clinical improvement was seen in smokers and in patients with metabolic syndromeReferences:No references.Disclosure of Interests:Maria Sole Chimenti: None declared, giulia lavinia fonti: None declared, Paola Conigliaro: None declared, flavia sunzini: None declared, Rossana Scrivo: None declared, luca navarini: None declared, paola triggianese: None declared, giusy peluso: None declared, Palma Scolieri: None declared, rosalba caccavale: None declared, Andrea Picchianti-Diamanti: None declared, erica de martino: None declared, simonetta salemi: None declared, domenico birra: None declared, Alessio Altobelli: None declared, marino paroli: None declared, Vincenzo Bruzzese: None declared, Bruno Laganà: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Antonella Afeltra: None declared, Roberto Perricone: None declared

Background:Janus kinase Inhibitors (JAKis) are approved for the treatment of Rheumatoid Arthritis (RA) in over 40 countries. The updated EULAR recommendations for RA treatment revised the preference of bDMARDs over tsDMARDs based on the new data related to JAKis long-term efficacy and safety. [1].Objectives:To evaluate the efficacy and safety of JAKis molecules in an observational single center cohort of RA patients in a real life outpatient clinical setting.Methods:76 RA patients [mean age: 55.7±12.5 years, 64(84.2%) female, disease duration: 120.7±97.2 months, 43 (61.4%) seropositive (AB+) for ACPA and/or IgM-RF, 34(44.7%) with BMI ≥25.0 kg/m2] were followed after starting JAKis treatment monotherapy or in combination with conventional synthetic DMARDs (csDMARDs). At study entry, and every 3 months, the ACR/EULAR core data set variables were recorded for each patient. Clinical improvement and remission rate were evaluated according to Disease Activity Score (DAS) and Clinical Disease Activity Index (CDAI) and any therapy-related adverse effect was reported. Among the whole RA cohort, 20 patients underwent US-guided synovial tissue (ST) biopsy before JAKis treatment and classified using the Krenn score for the semiquantitative assessment of ST inflammation[2].Results:Among the whole RA cohort who started JAKis [mean follow-up (FU) duration: 6.1±3.7 months], 22(28.9%) showed DAS-defined high disease activity. 54(71.1%) patients were previously treated with at least 1 csDMARD and 33(43.4%) were naive to biologic DMARDs (bDMARDs). Among RA previously exposed to b-DMARDs, 23(30.3%) were using anti-TNF and 14(18.4%) anti-IL6R, whereas 6(7.9%) patients received other bDMARD. In particular, 11(14.5%) patients were previously treated only with one bDMARD.During the FU, 12(15.8%) patients discontinued JAKis [7 due to treatment failure and 5 to adverse events (1 anemia, 2 gastrointestinal intolerance, 2 H.Zoster infection)]. All RA who discontinued JAKis for incomplete or no-response were previously exposed to bDMARDs.DAS Remission was achieved in 29 of 65(44.6%) patients during the FU, of whom 21(32.5%) achieved remission at 3 months. Similarly, 16(24.6%) patients reached CDAI remission of whom 12(18.5%) patients achieved remission at 3 months.At baseline, there were no differences of DAS-remission rate based on age, gender, disease duration, BMI and high disease activity. Similarly, concomitant steroid and csDMARDs therapy did not impact on the rate of DAS and CDAI Remission. However, RA reaching DAS remission during FU had more likely a shorter disease duration (p=0.01) and were less previously exposed to bDMARDs (p=0.001) than patients not achieving DAS remission. Conversely, the DAS Remission rate was higher in AB+ (55.3%) than in AB- RA patients (27.3%, p=0.04).Furthermore, bDMARDs naive RA showed higher probability to reach remission compared to bDMARD previously exposed RA [DAS remission: 66.7% vs 28.9%, respectively, p=0.003; OR(95%): 4.90 (1.69-14.3) and CDAI-remission: 37.0% vs 15.8%, p=0.05; OR(95%CIs): 3.12(0.97-10.10)], regardless to the type of the previous bDMARDs used.Finally, considering the baseline ST features, RA achieving clinical improvement did not differ in terms of Krenn score and microanatomical organization compared to RA not achieving the clinical improvement.Conclusion:The efficacy rate of JAKis therapy is not influenced by BMI and baseline high disease activity. Previous exposure to bDMARDs impacts both on the clinical response and on the rate of JAKis therapy discontinuation. Therapy-related adverse effects mainly occurred in bDMARD previously exposed RA patients.References:[1]Smolen JS, et al. Ann Rheum Dis 2020[2]Krenn V, et al. Histopathology 2006Disclosure of Interests:Dario Bruno: None declared, Maria Rita Gigante: None declared, Luca Petricca: None declared, Anna Laura Fedele: None declared, Simone Perniola: None declared, Marco Gessi: None declared, Barbara Tolusso: None declared, Stefano Alivernini: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

Background:Rheumatoid arthritis (RA) patients present high cardiovascular (CV) morbidity and mortality and EULAR recommends estimating their CV-risk [1]. The Systematic Coronary Risk Evaluation (SCORE) algorithm is suggested if National Guidelines are lack, but few data are available about different strategies.Objectives:To estimate the 10-years CV-risk using different algorithms in RA compared to osteoarthritis (OA) patients, as control group.Methods:A total of 1467 RA patients (78.3% female; mean age 59.8±11.5 years; mean disease duration 131±109 months), fulfilling the 2010 EULAR/ACR classification criteria, and 342 age and sex matched patients with OA (79.8% female; mean age 58.7±11.5 years) were enrolled in this multicentre cross-sectional study during 2019. Clinical and laboratory data were registered, and individual CV-risk was calculated using: SCORE chart, “Progetto Cuore” model (PCM), QRisk3, Reynolds Risk Scores (RRS) and Expanded Risk Score in RA (ERS-RA), as stated by suitable algorithms. Statistical analysis was performed using the Statistical System Graphpad Instat 8.0 (San Diego, CA-USA).Results:In 46 (3%) RA patients a previous CV event was observed. Among traditional CV-risk factors, RA patients presented higher frequency of diabetes (9.9% vs 6.4%; p=0.04) and lower prevalence of dyslipidaemia (21.7% vs 32.5%; pConclusion:Our study demonstrates a higher estimated CV-risk in RA compared to OA patients. The commonly used algorithms to estimate CV-risk in clinical practice perform differently, evaluating different traditional CV-risk factors and disease specific characteristic, as for QRisk3 or ERS-RA. Rheumatologist should impact on both traditional and RA related modifiable CV-risk factors.References:[1]Agca R, et al. Ann Rheum Dis 2017;76:17–28.Disclosure of Interests:Fabio Cacciapaglia Speakers bureau: BMS; Roche; Pfizer; Abbvie, Matteo Piga: None declared, Gianluca Erre: None declared, Andreina Manfredi: None declared, Elena Bartoloni Bocci: None declared, Garifallia Sakellariou Speakers bureau: Abbvie, Novartis, MSD, Ombretta Viapiana: None declared, Sergio Colella: None declared, Anna Abbruzzese: None declared, Martina Dessì: None declared, Caterina Vacchi: None declared, Floriana Castagna: None declared, Giacomo Cafaro: None declared, Bianca Lucia Palermo: None declared, Alessandro GIollo: None declared, Marco Fornaro: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Fabiola Atzeni: None declared

Background:Cardiovascular complications are the leading cause of death in patients with psoriatic arthritis (PsA), but current strategies for reducing cardiovascular risk are still inadequate. Depression is a common comorbidity in PsA patients and it is recognized as an independent cardiovascular risk factor in the general population. Endothelial dysfunction, assessed as a reduction in brachial artery Flow Mediated Dilation (FMD), is a predictor of major cardiovascular events in high and low risk populations.Objectives:To investigate the relationship between endothelial function and depressive symptoms in a cohort of patients with PsA.Methods:Sixty consecutive patients with PsA, aged between 30 and 79 years, with no history of major cardiovascular events, were characterized for traditional cardiovascular risk factors and features of psoriatic disease. The risk of cardiovascular events according to traditional risk factors was calculated using the Framingham Risk Score (FRS) and the presence of depressive symptoms was defined through the Hospital Anxiety and Depression Scale (HDS) using the validated cut-off of 8. Endothelial function was assessed by FMD. Serum IL-6 was quantified by ELISA, IL-17 and TNF-α levels by Luminex method.Results:Patients had an average age of 52.1±11.0 years, 43.3% of them were male, 23.3% obese and 25.0% active smokers; 38.3%, 25.0% and 11.7% were treated for high blood pressure, dyslipidemia and diabetes mellitus, respectively. The 10-year risk of major cardiovascular events estimated by FRS was 10.4%. The mean duration of PsA was 9.4 years, 30.0% of patients were in minimal disease activity (MDA) and 61.7% and 46.7% were treated with conventional and biotechnological DMARDs, respectively. The mean HDS value was 6.9±3.2 and 43.4% of patients had significant depressive symptoms. The severity of depressive symptoms according to HDS correlated with disease activity according to DAPSA (r=0.449, p=0.001). The mean FMD was 7.8±3.8%, this value correlated inversely with age (r=-0.408,p2=0.23) and FRS normalized through logarithmic transformation (β=-0.32, p=0.009, R2=0.22).Conclusion:The degree of endothelial dysfunction quantified by FRS correlates with the severity of the depressive symptoms in patients with PsA, independently of the cardiovascular risk attributable to classical risk factors. The weak relationship between FRS and serum levels of IL-6, IL-17 and TNF-alpha suggests a role of factors independent of inflammation in the regulation of endothelial function in patients with PsA. Systematic research and treatment of depressive symptoms could contribute to a more complete stratification and a better management of cardiovascular risk in patients with PsA.Disclosure of Interests:Enrico De Lorenzis: None declared, Angela Di Giorgio: None declared, Gerlando Natalello: None declared, Antonio Nesci: None declared, Dario Bruno: None declared, Donatella Lucchetti: None declared, Giacomo Tanti: None declared, Clara Di Mario: None declared, Pietro Rubortone: None declared, Maria Rosaria Magurano: None declared, Barbara Tolusso: None declared, Angelo Santoliquido: None declared, Giusy Peluso: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer

Background:Systemic sclerosis (SSc) is one of the connective tissue diseases with the poorer prognosis and disease-related causes, particularly pulmonary fibrosis, PAH and cardiac involvement, accounting the most deaths.Objectives:This multicentre study aimed to evaluate the global survival and any predictor of mortality in a large multicentric cohort of SSc patients.Methods:We performed a retrospective analysis examining the medical records of our longitudinal SSc cohorts with a median (IQR) follow-up of 11 (6-18) years from 3 Scleroderma Units since January 2009. All clinical, laboratory and instrumental findings have been recorded and analyzed using Chi-squared tests, Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models.Results:Data from 750 SSc patients (91.9% female; mean (SD) age at first Non-Raynaud symptom 48.4 (15.3) years, median (IQR) disease duration 3 (0-8) years; diffuse cutaneous involvement 162 (21.6%) patients) fulfilling the 1980 ARA and/or 2013 ACR/EULAR classification criteria, were collected. All patients were positive for ANA, anti-Topo-I Abs were found in 235 (31.3%) and Cenp-B Abs in 300 (40%) patients. 98 (13.1%) patients were positive to other Abs (Anti-RNA polymerase III, anti-Pm/Scl) and anti-ENA were negative/unknown for 117 (15.6%) patients. Interstitial lung disease (ILD) was present in 202 (26.9%), pulmonary arterial hypertension (PAH) was found in 29 (3.9%), and 50/750 (6.7%) patients presented pulmonary hypertension combined with ILD (PH-ILD). The overall 10-years survival was 93.1% and, it was significantly impaired by the presence of ILD, PAH or PH-ILD [Figure]. The univariate analysis showed that female gender, higher age at first Non-Raynaud symptom, earlier referral to a tertiary Scleroderma center, absence of any ENA antibodies, and PH-ILD presence were survival predictors. After multivariate analysis the significance of PH-ILD was lost [Table]. Disease duration, basal Rodnan skin score, smoking, renal or gastrointestinal comorbidities, NYHA functional class, steroid or immune-suppressive treatments did not reach the statistically significance.Conclusion:Our study demonstrated a global 10-years survival rate over 93%. Male patients and rapid evolution of Non-Raynaud symptoms represent the main death predictors in our SSc cohort. A rapid referral to a tertiary rheumatological centre and early treatment with effective agents are associated to a better prognosis.Figure.Kaplan-Meier curves for 5-years survival in SSc patients (Log-rank 8.96, p=0.03).Table.Prognostic factors for 10-years survival at univariate and multivariate analysis.UNIVARIATE ANALYSISMULTIVARIATE ANALYSISHR95%ICPHR95%ICPFemale gender0.350.15-0.810.010.310.15-0.660.002Age at first Non-Raynaud symptom1.071.04-1.10.0011.081.05-1.110.001Time referral to a tertiary SSc centre0.830.76-0.920.0010.840.77-0.930.001Absence of any ENA antibodies0.080.01-0.620.010.090.01-0.710.02PH-ILD presence2.61.01-6.820.042.40.93-6.10.069Disclosure of Interests:Fabio Cacciapaglia Speakers bureau: BMS; Roche; Pfizer; Abbvie, Enrico De Lorenzis: None declared, Addolorata Corrado: None declared, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Marco Fornaro: None declared, Fabio Montini: None declared, Livio Urso: None declared, Lucrezia Verardi: None declared, Alberto Altomare: None declared, Francesco Paolo Cantatore: None declared, Elisa Gremese Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Sanofi, UCB, Roche, Pfizer, Florenzo Iannone Consultant of: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD, Speakers bureau: Speaker and consulting fees from AbbVie, Eli Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, MSD

Background:Predicting clinical outcomes in ANCA-related glomerulonephritis remains a major challenge. To date, there is no reliable biomarker able to predict renal prognosis in patients with ANCA-associated vasculitis (AAV). Micro-RNA (miRNA) are non-coding RNAs involved in the fine tuning of immune cells biology and this epigenetic modulation associates with different phenotypes and prognosis in several diseases.Objectives:To investigate the expression of miR-155 and miR-34a in kidney biopsies of AAV patients according with renal outcome.Methods:Fifteen patients with AAV and renal involvement (mean age 63.0 ±13.3 years, disease duration 4.9±2.2 months), who underwent renal biopsy. Demographic, clinical and autoimmune parameters were recorded for each patient. Each kidney biopsy was classified according to the Berden Classification, Risk group (according to the ANCA Renal Risk Score) and the chronicity Classification of the Mayo Clinic’s proposed score.MiR-155 and miR-34a expression was investigated on kidney biopsy tissue using the miRNeasy FFPE kit (Qiagen). The quantitative expression of miR-155, miR-34a and housekeeping gene U1, used as control, was assessed by Real Time-PCR. MiR-155 and miR-34a expression was correlated with histopathological and clinical-laboratory parameters.Each patient was followed for 12 months and renal outcome was considered according toKDIGO CKDClassification. Markers of inflammation (ESR, CRP) and urine analysis data were recorded at baseline and after 12 months.Results:Six (40%) patients were p-ANCA positive and 9 (60%) c-ANCA positive. Eight patients (53%) also had pulmonary involvement. The mean baseline GFR was 30.7±28.8 ml/min/1.73 m2and 10 patients (66%) showed an active urinary sediment.At disease onset, the mean expression of miR-155 was 9.5±21.1, while the expression of mir-34a was 13.1±46.2. Considering the autoimmune profile, kidney tissue of p-ANCA positive patients was enriched of mir-155 (19.6±30.6 fold) compared to c-ANCA positive patients (1.9±2.9 fold; p=0.001). Particularly, considering the renal function, kidney tissue of patients with greater impairment of renal function (KDIGO stage 5) was enriched of miR-155 (21.5±38.3 fold) compared to patients with less renal impairment (KDIGO stage 1-4) (4.72±8.16 fold, p=0.004).Tissue expression of miR-155 and miR-34a did not correlated with the abovementioned histopathological classifications.After 12 months from kidney biopsy, 3(20%) patients had a worsening of renal function, 5 (33%) still presented elevated markers of inflammation and 3 (20%) still had proteinuria at urine analysis. At baseline, kidney tissue of patients with higher CRP plasma levels and proteinuria at follow-up presented higher expression of miR-155 (p=0.002 and p=0.001), whereas no significant differences were found about miR-34a kidney tissue expression.Conclusion:MiRNAs may play a potential role in the pathogenesis of ANCA-related glomerulonephritis. MiR-155 kidney enrichment seems to mirror the disease inflammatory burden and activity at the onset and after 12 months representing a possible biomarker in ANCA vasculitis with renal involvement. This finding may represent the basis for further studies on miRNA expression in blood samples, aiming to identify a non-invasive biomarker of kidney damage, predicting disease’s relapses and patients’ prognosis.References:[1]Renauer et al, Clin Rev Allergy Immunol. 2016Disclosure of Interests:Dario Bruno: None declared, Pier Giacomo Cerasuolo: None declared, Clara Di Mario: None declared, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Laura Gigante: None declared, Alessia Musto: None declared, Gisella Vischini: None declared, Stefano Costanzi: None declared, Stefano Alivernini: None declared, Barbara Tolusso: None declared, Giuseppe Grandaliano: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

Background:Glucocorticoids (GC) are associated with serious side effects in giant cell arteritis (GCA). Immunosuppressive therapies (IT) gave conflicting results in GCA, regarding GC sparing effect. Recently, tocilizumab by blocking IL-6, has been licensed as first biologic treatment for GCA, being clinically effective and saving GC (1).Objectives:To evaluate the usefulness of IT for GCA in: 1) minimizing the rate of GC-induced adverse events (AEs) and 2) reducing the risk of relapse.Methods:A multicenter retrospective case-control study included 165 GCA was performed. The first group of patients (GCA-IT) included 114 patients who were treated with at least one IT given ab initio or within 3 months from the start of GC. The control group included 51 GCA who received only GC or an IT later than 3 months (GCA-steroid). The primary endpoints were the rate of GC-related side effects: infections, hospitalized infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures.Results:Methotrexate up to 20 mg/week (138 patients), followed by cyclophosphamide (48 patients) and tocilizumab (27 patients) were the most frequently used IT. No difference was observed as concerns the follow-up time between the two groups [48.5 (IQR 26-72) vs 40 (IQR 24-69), p=0,3, rank-sum test)]. The two groups were similar as concerns sex (p=0,13), while the first group (69±8 yrs) was slightly younger than the second one (72±7 yrs) (p=0,005). Comorbidity was similar between groups. Patients in the GCA-IT group showed a significant lower incidence of GC-induced diabetes (8/114, 7% vs 12/51, 23,5%; p=0,003, chi-square test), while no differences were documented for rate of infections (p=0,64), including hospitalized infections (p=0,44), new onset systemic arterial hypertension (p=0,68), or osteoporotic fractures (p=0,32). Forty-four patients in the GCA-IT group (38,6%), while 34 patients in the GCA-steroid group (66,7%) experienced at least one relapse (p=0,001, chi square test). There was no difference in terms of time to first relapse between the two groups (p=0,53, log-rank test). GCA-IT group was exposed to lower dose of GC at first (pConclusion:Very early introduction of IT in GCA provided a greater steroid sparing in the first 3 months of treatment, leading to a lower incidence of diabetes. Relapse rate was even lower. IT was usually well tolerated without an increase incidence of infections. A randomized prospective trial is required to support this strategy in the management of GCA.References:[1]Hellmich B, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020;79:19-30.Disclosure of Interests:Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Miriam Isola: None declared, Dario Bruno: None declared, Elena Treppo: None declared, Laura Gigante: None declared, Francesca Angelotti: None declared, Riccardo Capecchi: None declared, Gianfranco Vitiello: None declared, Elena Cavallaro: None declared, Antonio Tavoni: None declared, Silvia Laura Bosello: None declared, Daniele Cammelli: None declared, Salvatore De Vita Consultant of: Roche, GSK, Speakers bureau: Roche, GSK, Novartis, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

Background:Sjogren Syndrome (SS) is an autoimmune exocrinopathy, resulting mainly in ocular and oral dryness, with approximately half of patients displaying symptoms from different organ systems, further adding to the heterogeneous clinical phenotype of the disease. Fatigue and pain are common systemic symptoms in patients with primary SS and fibromyalgia is a frequent condition associated with chronic diseases.Objectives:The aim of the study was to evaluate the impact of concomitant fibromyalgia in patients with Sjogren Syndrome in terms of clinical features and disease activity.Methods:50 patients with Sjogren Syndrome were enrolled in the study (100% female, age: 53.7 ± 13.2 years and disease duration: 8.7 ± 5.3 years), 25(50.0%) with concomitant fibromyalgia (SS/Fibro-group) and 25(50.0%) without (SS-group). 36 patients with primary fibromyalgia (Fibro-group) were included as control group. At study entry, demographic, educational, life-style and clinical parameters were recorded for each patient. SS was diagnosed according to the American College of Rheumatology (ACR) classification criteria (1) and fibromyalgia was diagnosed according to criteria for fibromyalgia defined by ACR (2). Moreover, each patient with fibromyalgia, with and without concomitant SS, was asked to fill a self-reported questionnaire to assess the impact of Fibromyalgia on multiple physical and psycological domains (Italian-FIQR).Results:Stratifying the study cohorts based on the demographic and life-style characteristics, no significant differences were found comparing SS-group, Fibro-group and SS/Fibro-group. However, considering the different organ involvement, SS/Fibro-group were more likely reporting arthralgia symptoms (100.0%) than SS-group (76.0% p=0.02), despite similar clinical evidence of arthritis-synovitis among the two groups (12.0% in both groups respectively, p=1.00). Moreover, SS/Fibro-group showed significantly lower ESSDAI score (2.8 ± 1.7) and higher ESSPRI score (7.0 ± 0.9) compared to SS-group (ESSDAI: 7.5 ± 3.7 p0.05 for all the 21 questions included).Conclusion:SS is affected by concomitant fibromyalgia in terms of subjective-dependent parameters (i.e. joint complaints) however the concomitant SS does not affect the impact of fibromyalgia on physical and psycological domains, even if disease activity is higher in SS patients without fibromyalgia.References:[1]Shiboski SC et al. Arthritis Care Res, 2012[2]Wolf F. et al. Arthritis Rheum 1990Disclosure of Interests:Annunziata Capacci: None declared, Pietro Rubortone: None declared, Valentina Varriano: None declared, Annamaria Paglionico: None declared, Simone Perniola: None declared, Maria Rita Gigante: None declared, Barbara Tolusso: None declared, Stefano Alivernini: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

Background:Epigenetic factors such as non-coding RNA (miRNA) have been shown to be deregulated in Systemic Lupus Erythematosus (SLE). In particular, in mouse model (1), different miRNAs have been associated with lupus nephritis (LN), one of the most severe manifestations of the disease.Objectives:The aim of the study was to evaluate the expression of miR-155 and miR-34a in renal tissue as biomarkers of organ involvement and inflammatory tissue activity in patients with LN.Methods:Thirty-two LN patients with active renal involvement were enrolled (age: 32.2 ± 9.2 years). The nephritic onset of the disease (early-SLE) was present in 13 patients (41%), while 19 patients (59%) showed a renal involvement during the follow-up (long-SLE). Clinical, laboratory and demographic data were collected for each patient. Disease activity was recorded using SLEDAI-2K and renal activity, using the total SLEDAI-2K fraction including the items related to the renal involvement. Ultrasound-guided renal biopsy has been performed for each patients for the definition of the nephritic class according to the ISN / RPS classification of 2003 revised in 2018(2). The expression of miR-155 and miR-34a in renal tissue was carried out by extraction of total RNA from paraffin-preserved biopsies and after a retrotrascription protocol was evaluated using SYBR® Green-based real-time PCR by relative quantification considering the ΔCt (Ct miRNA- Ct housekeeping gene)(3).Results:Mir-155 and miR-34a expression in renal tissue were comparable in the different histological classes. Dividing patients on the base of nephritic onset, patients with early SLE showed lower expression of miR-155 (ΔCt 12.8 ± 10.8) and miR-34a (ΔCt 14.6 ± 9.9) than patients with long-SLE (miR-155: ΔCt 6.1 ± 8.7 p = 0.02; miR-34a: ΔCt 7.1 ± 9.0 p = 0.03). Furthermore, a direct correlation was observed between the expression of miR-155 and miR-34a (r = 0.91, p Conclusion:MiR-155 and miR-34a may represent tissue biomarkers of inflammatory activation in patients with LN in particular the higher expression of these miRNA in Long-SLE patients could indicate a possible role of these biomarkers in renal involvement in patients with SLE with later renal onset. The increased expression of miR-34a could give indications of a disease recurrence suggesting a closer monitoring of the patient.References:[1] Leiss H et al. Plosone 2017[2] Bajema IM et al Kidney Int. 2018[3] Alivernini S et al. Nat Commun 2018Disclosure of Interests:None declared

Background:18-FDG PET/CT is a functional imaging method which allows to identify inflammation of vessel walls. The use of PET in large vessels vasculitis(LVV) at disease onset and during follow up is still debate either to confirm clinical remission either to drive the therapy choice. American Society of Nuclear Cardiology (ASNC) recently advanced recommendations aimed to standardize the application of PET in LVV(1).Objectives:The aim of our study was to assess the clinical role of PET performed in patients affected by LVV at the diagnosis and during the follow up.Methods:We retrospectively evaluated PET/CT of 49 patients affected by clinically active LVV according to LVV visual grading (LVG, grading 0-3) and measured the standardized uptake value(SUV) of large vessels. 38 (77,6%) patients were affected by Giant Cells Arteritis and 11(22,4%) by Takayasu Arteritis. 32(65.3%) patients repeated the imaging after a mean follow-up of 11.5±5.4 months.All baseline (T0) and follow up (T1) clinical data of disease activity were collected. Patients were treated according to EULAR LVV management recommendations(2). T0 PET/CT study was performed in patients with a clinically active disease defined by suggestive symptoms/signs and/or high inflammatory markers. The mean disease duration before T1 PET/CT examination was 4 months. T0 PET was performed in 25/49 patients(52%) at the diagnosis of LVV, whereas in 24/49(48%) patients with already diagnosed but active LVV disease.Results:Baseline PET was positive in 21 patients(42.9%). According to ASNC recommendations, 19 patients (38.8%) presented a LVG=3, 2(4.0%) a LVG=2, 6(12.2%) LVG=1 and 22 (44.9%) LVG=0. Patients performing PET at disease onset(75%) had higher LVG score than patients performing PET during the disease course (25%),p=0,002. At T0, aortic, carotid, axillary and subclavian SUV did not correlate with inflammatory markers.Follow up PET/CT studies were performed in 32 patients, 13 (40.6%) with a clinically active disease despite therapy, while 19(59.4%) in clinical remission.Follow up PET was still positive in 8 patients (25%) with a LVG=3, 10 (31.2%) patients presented LVG=1 and 14 (43.8%) LVG=0. T1 PET/CT study showed a significant reduction of SUV values in descending aorta, left and right subclavian arteries, and left and right axillary arteries when compared with first PET/CT study. According to LVG, 12 patients with active PET/CT study at T0 (19 pts) presented a reduction of LVG from score 2 and 3 to grade 1 or 0 (64.2%) at second PET/CT study. Only 3 patients presented an increased LVG score at T1, while in the other 17 patients T1 PET confirmed the previous score. No significant difference was found between LVG scores according with clinical characteristics, but among 8 patients presenting an active T1 PET, 4(50%) were in clinical remission.Conclusion:The use of ASNC recommendations for FDG PET/CT in LVV enables to confirm a metabolically active disease in 40% of patients and in 75% of patients at disease onset, suggesting that post-posing the exam could lead to underrate the real extension of disease. Our data, even if limited, suggest that PET/CT could be crucial in management of patients in clinical remission, detecting patients with still metabolically active LVV. Further prospective studies are necessary to evaluate the role of PET/CT in driving therapeutic strategies.References:[1]Slart R et all - Eur J Nucl Med Mol Imaging, 2018[2]Hellmich et all – Ann Rheum Dis 2018Disclosure of Interests:Laura Gigante: None declared, Dario Bruno: None declared, Vanessa Feudo: None declared, Silvia Laura Bosello Speakers bureau: Abbvie, Pfizer, Boehringer, Lucia Leccisotti: None declared, Alessia Musto: None declared, Pier Giacomo Cerasuolo: None declared, Angelo Zoli: None declared, Alessandro Giordano: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

We read with great interest the paper by Graef and colleagues, ‘Festina lente: hydroxychloroquine, covid-19 and the role of the rheumatologist’.1 As the authors correctly point out, despite firm evidence that their efficacy and safety are lacking,2 antimalarials are being widely prescribed for the treatment of patients with COVID-19. This, as also underlined with some concern by the European League Against Rheumatism President Iain McInness,3 has rapidly led to antimalarial supply shortages worldwide, primarily affecting patients with rheumatic disease, such as those with systemic lupus erythematosus and rheumatoid arthritis (RA). In these groups, low-dose antimalarials (hydroxychloroquine up to 6 mg/kg/day and chloroquine up to 4 mg/kg/day) are the mainstay to control immunological response and to prevent flare in view of their favourable efficacy and safety profile. However, electrophysiological experiments in isolated cardiac preparations and animal models, and some case reports in rheumatic patients, have reported a proarrhythmic effect of antimalarials. Arrhythmias, potentially triggered by hypoxia, metabolic/electrolyte derangement and viral myocarditis, have been reported in 16.7% of hospitalised patients with COVID-19.4 While this suggests that antimalarial use may further …

Background: Consensus among dermatologists and rheumatologists in the diagnosis and assessment of musculoskeletal diseases in psoriasis (PsO) patients is needed. This study assesses characteristics of musculoskeletal pain in patients with PsO for the presence of psoriatic arthritis (PsA) and evaluation of a novel 16-item visual instrument (PsA-Disk). Methods: Data were collected from eight dermatological/rheumatological centres across Italy. Patients with PsO completed PEST (Psoriasis Epidemiology Screening Tool) and PsA-Disk questionnaires during the first visit. A rheumatological visit was performed to confirm the presence of PsA. Both validity and reliability of PsA-Disk were assessed. Results: A total of 573 patients with PsO were examined at the first visit, and 120 (21%) were diagnosed with PsA. Patients with PsA compared with patients with PsO ( n = 119) presented statistically significant differences for: nail involvement, PEST score ⩾3, higher erythrocyte sedimentation rate (ESR), Nail Psoriasis Severity Index (NAPSI)-feet, NAPSI-(hands + feet) and PsA-Disk scores (73.9 ± 32.1 versus 58.1 ± 39.8, p Conclusion: PsA-Disk may be considered a valid novel instrument aiding both dermatologists and rheumatologists in the rapid detection and assessment of musculoskeletal disease characteristics.

BACKGROUND: Data from trials of vedolizumab for inflammatory bowel disease and from real-world studies suggest an exposure-response relationship, such that vedolizumab trough levels may predict clinical and endoscopic outcomes. OBJECTIVE: The purpose of this study was to evaluate in a prospective observational study the utility of an early vedolizumab trough level assay for predicting the first-year vedolizumab therapy outcome. METHODS: This prospective observational study included consecutive inflammatory bowel disease patients. We measured vedolizumab trough levels and anti-vedolizumab antibodies at weeks 6 and 14. Clinical outcome was assessed at weeks 6, 14, 22 and 54. The primary endpoint was the correlation between early vedolizumab trough levels and vedolizumab persistence over the first year of treatment, defined as the maintenance of vedolizumab therapy due to sustained clinical benefit. RESULTS: We included 101 patients initiating vedolizumab. A cut-off vedolizumab trough level of 16.55 µg/ml at week 14 predicted vedolizumab persistence within the first year of therapy, with 73.3% sensitivity and 59.4% specificity (p = 0.0009). Week 14 vedolizumab trough level was significantly higher in patients with clinical remission at weeks 14, 22 and 54; and in patients achieving mucosal healing within 54 weeks. CONCLUSION: High vedolizumab trough level at week 14 was associated with a higher probability of maintaining vedolizumab therapy over the first year due to sustained clinical benefit.

Heart involvement – often asymptomatic – is largely underestimated in patients with systemic autoimmune diseases (SADs). Cardiovascular events are more frequent in patients with SADs compared to the general population, owing to the consequences of inflammation and autoimmunity and to the high prevalence of traditional risk factors. Coronary microvascular disease (CMD) is a form of cardiac involvement that is increasingly recognised yet still largely neglected. CMD, the incapacity of the coronary microvascular tree to dilate when myocardial oxygen demand increases or when there is a microvascular spasm (or subclinical myocarditis), is increasingly reported because of the widespread use of new cardiac imaging tools, even in a subclinical phase. The assessment of myocardial coronary flow reserve (CFR) emerged as the most effective clinical tool to detect microvascular damage. The potential causes of microvascular damage, molecular and cellular inflammation along with a pathological CD39-CD73 axis, need always to be considered because data show that they play a role in the occurrence of acute coronary syndromes, heart failure and arrhythmias, even in the early asymptomatic stage. Data suggest that controlling disease activity by means of methotrexate, biologic drugs, antimalarial medications, statins and aspirin, according to indication, might reduce the cardiovascular risk related to macrovascular and microvascular damage in most patients with SADs, provided that they are used early and timely to control diseases. The need of new biomarkers and a careful assessment of myocardial CFR emerged as the most effective clinical tool to detect microvascular damage.

Background Interstitial lung disease (ILD) is the most severe extra-articular manifestation of rheumatoid arthritis (RA). Although it is responsible of 10-20% of all RA mortality, no controlled studies are available for the treatment of RA-ILD and its therapeutic approach is still debated. Aims To analyse the evolution of ILD in a population of RA patients treated with tocilizumab (TCZ). Methods In this national multicentre study, we retrospectively collected patients with RA-ILD treated with at least one dose of TCZ. For each patient, disease activity and serological data were evaluated. Moreover, we analysed the evolution of high-resolution computed tomography (HRCT) and pulmonary function tests, including forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (DLCO). Results Twenty-eight RA-ILD patients were identified (females/males 18/10, mean age 61.6 years), with a mean follow up for TCZ therapy of 30 months. At the end of follow up, FVC remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%). DLCO remained stable in 14 (56%) patients, improved in 5 (20%) and worsened in 6 (24%), even though in 3 patients DLCO and FVC showed an opposite trend. HRCT remained stable in the majority (25) of cases, worsened in two patients with a usual interstitial pneumonia pattern and improved in only one case with a non-specific interstitial pneumonia pattern. Conclusions The management of RA-ILD patients remains a critical unmet need. TCZ demonstrated a good safety profile in patients with RA-ILD and a potential effect on the stabilisation of lung involvement.

[Image: see text] Autoreactive T cells specific to human collagen type II have a crucial role in the development of rheumatoid arthritis (RA) in the context of MHC class II allele HLA-DRB1-*04. The protein–protein interactions between the T cell receptor (TCR) and the type II collagen bound to the allele MHC of class II may thus represent the target for the development of new drugs against RA. In this study, a structure-based pharmacophore model for potential small molecule inhibitors was developed from protein–protein interface structure. The 3D model obtained was used for a virtual screening workflow, which resulted in three hits for experimental follow up. Three compounds have been identified that interfere with the TCR/collagenII-MHCII (K(i) values below 10 μM) and open up new possibilities in the treatment of RA.

ObjectivesTo evaluate interstitial lung disease associated with systemic sclerosis (SSc-ILD) and its changes during treatment by using quantitative analysis (QA) compared to semi-quantitative analysis (semiQA) of chest computed tomography (CT) scans. To assess the prognostic value of QA in predicting functional changes.Materials and methodsWe retrospectively selected 35 consecutive patients with SSc-ILD with complete pulmonary functional evaluation, Doppler-echocardiography, immunological tests, and chest CT scan at both baseline and follow-up after immunosuppressive therapy. CT images were analyzed by two chest radiologists for semiQA and by a computational platform for texture analysis of ILD patterns (CALIPER) for QA. Concordance between semiQA and QA was tested. Traction bronchiectasis severity was scored. Analysis of ROC curves was performed.ResultsSeventy CT scans were analyzed and QA failed in 4/70 scans. Thus, the final population included 31/35 patients (51.3±12.1 years). QA had a weak-to-good concordance with semiQA (ICC reticular:0.275; ICC ground-glass:0.667) and QA correlated better than semiQA (r = -0.3 to -0.74 vs r = -0.3 to -0.4) with functional parameters. Both methods correlated with traction bronchiectases score and pulmonary artery diameter at CT. A pulmonary artery diameter ≥29mm distinguished patients with lower lung volumes and ILD extent greater than 39% (p0.05) in predicting disease progression as assessed by functional parameters, whereas variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco% (AUC = 0.74; 95%CI: 0.54 to 0.93; p = 0.03).ConclusionsPulmonary QA of CT images can objectively quantify specific patterns of ILD changes during treatment in patients with SSc-ILD. Changes in QA patterns do not correlate with functional changes, but variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco%. Pulmonary artery diameter at CT reflects the interstitial involvement, identifying patients with more severe prognosis.

Background Few data exist regarding the effectiveness of ustekinumab in inflammatory bowel disease (IBD) patients treated for concomitant psoriasis or psoriatic arthritis. Aims to describe the outcomes of IBD patients who received subcutaneous ustekinumab through a dermatological or rheumatological prescription. Methods This multicenter, retrospective study included all IBD patients who were started on ustekinumab for concomitant active psoriasis/ psoriatic arthritis, irrespective of IBD activity. The primary endpoint was overall ustekinumab persistence, defined as the maintenance of therapy because of sustained clinical benefit for IBD. Results Seventy patients (64 Crohn’s disease / 6 ulcerative colitis) were enrolled. The median follow-up on ustekinumab therapy was 10.7 months (range, 1.4–67.3). Twelve patients (17.1%) withdrew the treatment after a median of 7.4 months (range, 0.9–23.8). The cumulative probability of maintaining ustekinumab treatment was 97.1% at 6 months and 77.1% at 12 months. Among the 56 patients with baseline active IBD, 34 (60.7%) were in clinical remission at the last follow-up visit. Their cumulative probability of achieving clinical remission was 84.7% and 63.9% at 6 and 12 months, respectively. Two patients stopped ustekinumab for an adverse event. Conclusions Subcutaneous ustekinumab had a good effectiveness profile for IBD patients treated for concomitant dermatological or rheumatological conditions.

Objectives The aim of our study was to define the role of high-sensitive cardiac troponin T (hs-cTnT) and NT-proBNP in identifying Systemic Sclerosis (SSc) patients with cardiac involvement and at higher risk of cardiac death. Methods Plasma hs-cTnT and NT-proBNP concentrations were measured in 245 SSc-patients. Results hs-cTnT and NT-proBNP levels were higher in SSc-patients than in healthy controls. Hs-cTnT levels were higher than 0.014 ng/ml in 32.3% SSc-patients, while NT-proBNP was above 125 pg/ml in 31.8% of them, irrespective of classical cardiovascular risk factor and of pulmonary arterial hypertension. Elevated hs-cTnT and NT-proBNP were associated with diffuse skin involvement and directly correlated with the skin score. Patients with increased cardiac markers presented a lower left-ventricular ejection fraction (LVEF) and a higher rate of right bundle branch block (RBBB) on electrocardiogram (ECG) compared to patients with normal cardiac enzymes. During the follow-up, 12 SSc-patients experience a disease-related death; 9 of these were directly related to cardiac involvement (sudden cardiac death or heart failure) and the majority of them occurred among patients with increase of at least one cardiac biomarker. Long-term survival was worse in patients with increase of both cardiac biomarkers. Conclusions Evaluation of hs-cTnT and NT-proBNP levels may provide a tool to screen non-invasively SSc-patients for heart involvement. A higher incidence of impaired systolic function, ECG abnormalities and a poor outcome in SSc-patients with elevated cardiac enzymes suggests that they may be valuable screening biomarkers to detect a cardiac damage at early stages and to improve risk stratification.

Purpose Body mass index (BMI) demonstrated to influence the clinical response to different drugs in rheumatoid arthritis (RA). The aim of this study was to investigate the role of BMI in the achievement of remission in active RA patients starting the treatment with abatacept. Methods Data regarding 130 RA patients enrolled in the UltraSound-CLinical ARthritis Activity (US-CLARA) study were retrospectively analyzed. Patients were assessed at baseline (when starting abatacept treatment) and at 3- and 6-months. An extensive clinimetric evaluation, including a new ultrasound (US)/clinical composite disease activity index, termed US-CLARA, was performed at every timepoints. Outcome of interest of the study was the impact of BMI on the achievement of the Disease Activity Score 28-joints erythrocyte sedimentation rate (DAS28-ESR) or the ACR/EULAR Boolean remission criteria at 6 month. Results At 6-month 26 out of 130 patients were defined as responders to abatacept. Comparing the baseline characteristics of responders to non-responders, US-CLARA showed a statistically significant difference between the two groups. The logistic regression analysis showed that the two indipendent variables, predictive of treatment response (keeping the DAS28-ESR and/or Boolean remission criteria as dependent variable), were the self-tender joint count assessment (p = 0.0412) and the ultrasound score (p = 0.0211). No other baseline variable, notably BMI, was associated to 6-month abatacept response. Conclusions BMI does not influence the abatacept response in RA patients with active disease. During abatacept treatment, the clinical response can be achieved despite a condition of overweight or obesity.

In the last years, a dramatic amount of research has been performedincreasing the knowledge about the biological mechanism underpinning Rheumatoid Arthritis (RA) inflammation, putting B lymphocytes in the center of RA pathogenesis. Nowadays, B cell phenotypes and autoantibodies positivity arose as important biomarkers in early and long-standing disease. Moreover, comparative analysis of peripheral blood and synovial tissue compartments enables the identification of novel physiopathological mechanisms promoting inflammation. In this narrative review we will discuss the biological relevance of B cell derived autoimmunity and in RA course, from disease onset to remission achievement.

Low T-cell receptor (TCR)/CD28 signaling lymphocytes are expanded in arthritis. We asked whether the down-expression of TCR-related molecules correlates with specific arthritis characteristics and if it has clinical implications. TCR-ZETA, ZAP-70 and CD28 expression was measured by flow cytometry in synovial fluid (SF) and peripheral blood (PB)-derived T cells. In PB, ZETA-downregulation in CD4+ CD28+ and consequent CD4+ CD28lowZETAlow cell expansion correlate with CRP elevation, leukocyte recruitment into SF and, primarily, disease activity (DAS). In some patients, ZETA-downregulation extends to CD8+ CD28null and/or CD8+ CD28+ cells, and this correlates with enhanced leukocyte recruitment, multiple joint involvement, and disability index (HAQ). ZETA-downregulation in CD4+ CD28+ may also lead to CD4+ CD28+ ZETAnull cell expansion, which strongly correlates with HAQ. In SF, ZETA-downregulation in CD8+ CD28null and consequent CD8+ CD28nullZETAlow/null cell expansion correlate with CRP elevation and neutrophilic influx into SF, whereas ZAP-downregulation in CD8+ CD28+ and consequent CD8+ CD28lowZAPlow cell expansion strongly correlate with HAQ and DAS. ZETA-downregulation is preponderant in SF of seronegative arthritides, with seronegative rheumatoid arthritis showing significant down-regulation in CD8+ CD28null, and non-rheumatoid arthritides showing significant down-regulation in CD4+ CD28+ . Altogether, we identified new molecular and cellular biomarkers of arthritis-related T-cell inflammation, useful for assessing arthritis activity, predicting polyarticular progression and functional impairment, characterizing seronegative arthritides, and possibly tailoring immunotherapies.

Background: Methotrexate (MTX) is generally recommended as first-line treatment of rheumatoid arthritis (RA). Despite its efficacy is well established, a percentage of patients fails the treatment. Few studies investigated the causes of early discontinuation of MTX; a two-year retention rate of about 66% is described for RA patients with lower age and longer disease duration as independent predictors for discontinuation. Objectives: Aim of this study was to detect possible predictive factors for early discontinuation of MTX prescribed as first line treatment in RA patients enrolled in the GISEA (Italian Group for the Study of Early Arthritis) registry. Methods: RA patients who began MTX as first line treatment were included in the study. For all patients age, sex, disease duration, smoking status, the intake of glucocorticoids, clinical and serological data, comorbidities and extra-articular manifestations were collected. Results: We analyzed 612 RA patients (females/males 477/132, mean age 55.73±14.5 years; mean DAS28 5.35±1.5); rheumatoid factor (RF) was positive in 64.9%, anti-citrullinated peptide antibodies (ACPA) in 42.7%. Comorbidities were observed in 17.5% of patients, while extra-articular RA manifestations were recorded in 1.5%; 68.3% of subjects taken low doses of steroids. One hundred and forty-nine (24.3%) patients discontinued MTX during the first year (for inefficacy in 66/149 (44.3%) patients, adverse events in 51/149 (34.2%), and other reasons in 32/149 (21.5). At univariate analysis early discontinuation of MTX was associated to a lower mean age (p=0.041) and a higher mean tender and swollen joints count (p=0.001 and p=0.024, respectively). Age and tender joints count were confirmed at multivariate analysis (OR 1.014, CI95% 1.001–1.027 and OR 0.951, CI95% 0.923–0.981, respectively) as independent predictors of early withdrawal of MTX. Conclusions: More than 75% of RA patients treated with MTX as first-line therapy remained in treatment after 12 months. Age was directly correlated and tender joints count was inversely correlated with early withdrawal of MTX in RA patients. Disclosure of Interest: None declared

Background Polymyalgia Rheumatica(PMR)is an inflammatory disease that affects people over 50 years old, characterised by pain and functional limitation of shoulder and hip, acute phase reactant elevation and a dramatic response to low doses of steroids. Atherosclerosis is a chronic inflammatory process that affects the arterial vessels of multiple districts. Endothelial dysfunction is an early event of the atherogenic process. Chronic inflammatory diseases have an increased risk of accelerated atherosclerosis and cardiovascular disease. A study on 41 subjects with giant cell arteritis with and without PMR showed an increased mean-intimal thickness, suggesting a pro-atherogenic role of PMR. However there are no studies that evaluated endothelial dysfunction which is a more precocious marker of subclinical atherosclerosis in PMR patients Objectives Aim of the study was to compare endothelial function among PMR patients to a control population. Moreover, the trend of endothelial disfuncion was evaluated over time in relationship to the improvement of clinical, laboratory and instrumental parameters. Methods The study involved 16 treatment-naive patients with a new PMR diagnosis. Every 3 months routine visits were performed;at each visit laboratory and clinical data and the endothelial function at the brachial artery were evaluated. The endothelial function was evaluated at the brachial artery level after 15 min of rest; the brachial artery diameter and the basal flow was measured at baseline and after the positioning of sphygmomanometerfor 5 min to induce the forearm ischemia. The flow was measured again 15 s after deflation of the sleeve and 60–90 s after the diameter of the artery reassessed to obtain flow-mediated dilatation (FMD). The FMD, which represents endothelium-dependent vasodilatation was expressed as percentage increase to the starting diameter after stimulation Results 16 PMR patients(mean age 73.9±5.8, 7 Female)were compared with a population of 16 healthy controls age-matched(70.8±8.1,p=ns). The two groups differed for the values of Erythrocyte Sedimentation Rate(ESR)(61.1±28 vs 19.3±16 mm/h, p At the sixth month of follow-up ESR was 31.2±29,9 mm/h while CRP was 8±5.9 mg/L; at the twelve month of follow-up ESR was 22.7±13.6 and CRP was 9.1±8.2 mg/L In PMR patients group 11 patients had hypertension, 5 dyslipidemia, 1 diabetes and 5 patients were smokers, while in control group 9 had hypertension, 10 dyslipidemia, 6 were smokers and no one had diabetes. Healthy subjects matched by age, sex and comorbidity were chosen as controls. At baseline FMD of patients was lower than controls(6.6±3.4 vs 10.7±2.3, p The FMD values show an inverse correlation with values of ESR(R=−0.42 p=0.019)and CRP(R=−0.56 p=0.001)at baseline. Conclusions Endothelial dysfunction in patients with PMR appears early during the course of the disease and is related to levels of acute phase reactant; steroid therapy gradually improves these values;only after a year of therapy comparable values are observed between patients and healthy controls. Disclosure of Interest None declared

Background The use of glucocorticoid (GC) in Rheumatoid arthritis (RA) is recognised by the current treatment approach as a valid adjunct to DMARDs therapy. Despite its efficacy, safety of GC is still an issue and the best strategy of use is still debated, including patients under bDMARDs therapy Objectives To analyse in RA the differences of GC users versus non-users of baseline features, response to therapy and persistence in bDMARDs from the Italian biologics registry GISEA (Italian Group for the Study of Early Arthritis) Methods Consenting patients satisfying 1987 or 2010 ACR criteria for RA included in the Italian GISEA registry were enrolled. Data recorded comprehend demographic and clinimetric variables. Data are collected at baseline and 6 monthly during follow-up. To be included in the study patients needed a minimum follow-up time of 12 months and if data were not updated after 2012 patients were considered lost to follow-up. EULAR and HAQ responses were calculated. Statistical analysis included descriptive measures, parametric and nonparametric comparisons between groups and univariate analysis of survival on therapy Results A total of 8545 patients were enrolled, of them 4193 (49%) using a variable dose of GC. In 3035 (72%) the dose was ≤5 mg. Baseline demographic and disease-specific features at the start of bDMARD therapy were not different between GC users and non-users, both in 1 st and 2nd line bDMARDs RA patients. EULAR response rates were generally better in GC users at 6 and 12 months, but without statistical significance: good/moderate EULAR responses at 6 months were attained in 76,5% of GC users versus 67% in non users, while at 12 months in 81,5% vs 73% respectively (both Ps not significant). Similarly, HAQ responses ( Conclusions Our data show that GC are used in a high percentage of RA patients on bDMARD therapy. GC significantly improve the persistence on bDMARDs therapy in 1 st and 2nd line. No obvious other differences are evident in baseline, EULAR and HAQ response rates. This fact should be kept in mind when evaluating the persistence on bDMARD treatment reported in different registries. Safety evaluations in individual patients should be further analysed to guide the use of GC in this setting Disclosure of Interest None declared

Background Interstitial lung disease (ILD) is the leading cause of death in systemic sclerosis (SSc) but its pathogenesis and the risk factors of pulmonary function deterioration are not fully understood. Esophageal disease is high frequent in SSc and motor activity abnormalities with occult micro-aspiration of both acid and non-acid gastro oesophageal reflux has been implicated in the pathogenesis of ILD. DLCO reduction is considered the earliest sign of microaspiration-induced lung damage1. Cross-sectional studies have demonstrated an association of SSc-ILD and esophageal abnormalities on 24 hours intraesophageal pH-monitoring and esophageal manometry but prospective evaluation of lung deterioration is lacking2,3. Esophagogram was proposed as a useful tool to evaluate disease severity of upper gastrointestinal tract involvement in SSc4. Objectives To assess the role of esophagogram in predicting pulmonary function test deterioration in SSc-patients. Methods We retrospectively evaluated 160 consecutive SSc patients who underwent esophagogram because of suspected upper gastro-intestinal involvement. All patients underwent baseline pulmonary function tests and global clinical evaluation. Eighty-five patients underwent a High Resolution CT within 3 months from esophagogram because of suspected lung involvement. One hundred twenty three patients underwent pulmonary function test every 6 months up to 24 months. Results Seventy five patients (46.9%) presented abnormalities of peristaltic waves, 50 patients (31.2%) showed structural changes (hypotonic oesophagus or dilatation) while indirect signs of cardial incontinence (patent cardia or gastro-esophageal reflux) were present in 36 patients (22.5%). A reduced peristaltic activity with a prolongation of transit time was associated to reduced DLCO (50.16%±19.80% vs 60.36±22.69%, p=0.002) and TLC (87.05%±20.43% vs 95.09±20.59%, p=0.017). An hypotonic oesophagus was reported in 25.2% of patients and it was associated to ILD on CT (72.0% vs 28.0%, p=0.033). Patients with hypotonic oesophagus presented a reduced FVC (84.63%±22.86% vs 102.93±21.40%, p Conclusions The esophagogram is wide available, well tolerated and inexpensive tool to assess upper gastro-intestinal tract involvement and its abnormalities are associated to SSc-ILD severity. Because of a faster deterioration of lung function is associated to esophagogram abnormalities, a complete gastro-intestinal evaluation in ILD-SSc patients is mandatory. References [1] Schachter LM, et al. Chest2003. [2] Christmann RB, et al. Semin Arthritis Rheum2010. [3] Marie I, et al. Arthritis Care Res2001. [4] Medsger TA, et al. Clin Exp Rheumatol2003. Disclosure of Interest None declared

Background the relationship between B cells subsets distribution, clinical and laboratory parameters, therapeutic response and prognosis in lupus nephritis (LN) is still underestimated. Objectives The aim of our study is to establish the value of B cells subsets as biomarkers in patients with active LN than controls, in patients at the onset of renal manifestation than patients with renal flare, and finally in nephritic patients in relation to their clinical and laboratory characteristics at the baseline and during the course of the disease. Methods 50 patients with a diagnosis of LN have been evaluated every tree months. Laboratory, immunological and disease activity data were collected at the baseline and at 6 (T6), 12 (T12), 24 (T24), 36 (T36) months and at the last follow-up (FU). Number of renal flares, time to renal remission and persistent proteinuria at the last FU were evaluated. B cell subsets were obtained through cytofluorimetry and classified using C27/IgD classification. The characterisation of B cells subsets was realised in 50 LN patients and 37 healthy controls. Results LN patients had a lower percentage of CD19 +cells than controls (9.2% vs 10.6%; p=0.01) as well as a lower percentage of memory unswitched cells CD27 +IgD+ (10.7% vs 15.3%; p No significant differences regardless B cells subsets were found between early LN patients and long ones as well as between LN patients at the onset and LN patients during renal flare. We found a correlation between an higher disease activity (assessed with SLEDAI 2K) and lower percentage of memory B cells IgD-CD27+ (p=0.02). Double negative B cells CD27-IgD- tended to be correlated with an higher disease activity. Of interest the correlation between persistent proteinuria detected during the follow-up and a lower percentage of plasmablasts at the baseline (p=0.01). Conclusions The alteration of B cells subsets is an early event in LN without differences regardless the period of renal involvement (nephritic onset or later LN development). The association between persistent proteinuria and a lower percentage of plasmablasts at the baseline could be a negative prognostic factor considering the correlation between persistent proteinuria and worse renal outcome. Disclosure of Interest None declared

Background Despite IL-6R inhibition was found to influence B cell subpopulations distribution in Rheumatoid Arthritis (RA), no data are available on the effect on epigenetic signature of RA B cells by this treatment. It is well known that B cell maturation is under control of the microRNA-155 (miR-155)/PU.1 axis significantly influenced by IL-6 stimulation 1 . Objectives To investigate the effect of IL-6R inhibition on the epigenetic signature of B cells (miR-155/PU.1 axis) in RA patients. Methods Twenty-nine RA patients [18 (62.1%) female; 57.2±14.9 years old; disease duration 1.3±0.7 years] starting IL-6R inhibitor treatment as first b-DMARD, have been enrolled. At study entry and after 3–6–12–18 months follow-up, CD19 + cells were isolated from peripheral blood (PB) by magnetic microbeads (Miltenyi) and B cells subpopulations were assessed through FACS according to the IgD/CD27 classification. MiR-155 and PU.1 endogenous expression was determined in PB-derived CD19 + cells by RT-PCR at baseline and after 3–6–12–18 months follow-up. IL-6 plasma level was assessed by ELISA at study entry for each patient. ACR/EULAR criteria were used to assess the response rate to IL-6R inhibitor treatment for each RA patient. PB-derived CD19 + cells of healthy individuals (HC) were used as comparison group. Results At study entry, RA patients showed higher percentage of IgD - /CD27 - CD19 + cells (p + /CD27 + CD19 + cells (p - /CD27 - CD19 + cells percentage directly correlated with Disease Activity Score (p=0.04) and IL-6 plasma levels (p=0.06) in RA patients. IL-6R inhibition lead to DAS and SDAI remission achievement in 73.9% and 52.2% of RA patients after 18 months follow-up, respectively, and significantly reduced IgD - /CD27 - CD19 + cells percentage after 18 months follow-up (p - /CD27 - CD19 + cells percentage compared to patients not achieving this outcome (p - /CD27 - CD19 + cells percentage comparable to HC (p>0.05). Analysing the epigenetic profile in B cells of RA patients, at baseline, PB-derived CD19 + cells of RA patients showed significantly higher endogenous expression of miR-155 (p=0.04) than HC. Moreover, RT-PCR showed that IL-6R inhibition significantly represses endogenous miR-155 expression in PB-derived RA B cells already after 3 months of treatment (p Conclusions IL-6R inhibitor, used as first b-DMARD treatment, acts restoring B cells homeostasis through epigenetic modulation in RA. In particular, IL6-R inhibition significantly represses endogenous expression of miR-155 in PB-derived CD19 + cells conversely restoring PU.1 expression mirrored by the decrease of IgD - /CD27 - B cell rate in RA patients achieving disease remission. Reference [1] Alivernini S, Kurowska-Stolarska M, Tolusso B, et al. Nat Commun2016. Disclosure of Interest None declared

Background Dendritic cells (DCs) direct the immune response against pathogens while maintaining self-tolerance by instructing T/B cells in lymphoid organs and peripheral tissues. However, their aberrant activation can lead to chronic inflammation and autoimmunity. Based on the distinct transcriptomics, function and distribution, DCs can be broadly categorised as plasmacytoid and myeloid (conventional) DCs. Based on recent single cells sequencing and secretome data, can be divided into CD141+ DCs (DC1), DC2_A (DC2) defined as “CD1chighCD32BhighCD36negCD163neg” and DC2_B (DC3) defined as “CD1clowCD32BnegCD163highCD36high.” In addition, populations of CD1c-CD141-CD16+ DC (named DC4), that shares some gene expression with CD16+monocyte and inflammatory DC (infDC). Most to date studies on Rheumatoid Arthritis patients investigated DCs in circulation or in synovial fluid (SF). This provided important insight into epigenetic changes in DC-precursors before they enter synovial tissue, e.g. RA blood CD1c+have deregulated microRNA-34a driven epigenetic control of anti-inflammatory Axl pathway2 or into the influence of inflammatory milieu on DCs, respectively. However, neither (peripheral blood) PB or SF are major sites for DC regulated T/B cell activation; instead, DCs control immune responses in the appropriate structures of lymph organs and tissues. Objectives In this study, we sought to investigate myeloid DCs in synovial tissue with the prospect of better understanding their role in driving autoimmunity in RA. Methods We developed a flow cytometry sorting strategy to characterise the phenotype of distinct myeloid DC subsets in multiple biological compartments (PB, SF and synovial tissue). Synovial tissue (ST) biopsies (RA n=9; Psoriatic arthritis n=3) were digested with liberase prior the analysis. Peripheral blood DCs (RA n=19, Psoriatic arthritis n=16, healthy donors n=12), and SF DC (n=3) were used as comparators. Synovial tissue, SF and PB DCs were sorted and microRNAs, pro-inflammatory and regulatory cytokine expression analysed by amplified qPCR. In addition, DCs were mapped in synovial tissue in RA (n=8), PsA (n=7) and control non-inflammatory OA (n=5) by immunohistochemistry. Results Myeloid DCs are scarce in control non-inflammatory OA synovial tissues and their number increased substantially in PsA and RA tissues. Phenotyping data revealed that all myeloid DC subsets can be present in inflamed RA and PsA synovium. However, CD1c+ DC populations (DC2/DC3) were the most abundant in RA synovial tissues and the gene expression analysis of CD1c+ sorted from RA synovial biopsies showed an increase in the expression of epigenetic regulator of inflammatory response miR-155 and IL-6, TNF and IL-23 as compared to circulating cells. Conclusions CD1c+DCs from RA synovial tissues had epigenetically regulated activated phenotype (miR-155 and miR-34a2) that through the production of cytokines could maintain tissue activation of autoreactive Th1 and Th17 cells and contribute to inflammation. References [1] Villani AC, et al. Science2017. doi:10.1126/science.aah4573 [2] Kurowska-Stolarska M, et al. Nat Commun2017. doi:10.1038/ncomms15877 Disclosure of Interest None declared

Background The assessment of joint disease in psoriasis (PsO) patients is paramount, particularly where consensus among dermatology and rheumatology specialists is necessary. Objectives To evaluate the prevalence of psoriatic arthritis (PsA) in PsO patients and assess how a novel 16-item visual instrument (PsA-Disk) correlates with the disease and its clinical manifestations. Methods Data were prospectively collected from 8 dermatological/rheumatological centres across Italy. During their first dermatological visit, patients completed both PEST (Psoriasis Epidemiology Screening Tool) and PsA-disk questionnaires. Rheumatological visit was performed in order to confirm presence/absence of PsA. Clinimetric and disease activity variables were recorded. Results From a total of 239 PsO patients, 120 (50.2%) patients were diagnosed with PsA. More PsA-positive patients had nail PsO (54.2% vs. 42%, p=0.05) and a PEST score ≥3 vs. PsA-negative patients (77.5% vs. 37.8%, p Conclusions PsA-Disk is a novel instrument helping both dermatologist and rheumatologist in the rapid assessment PsA, facilitating in the timely therapeutic management of these patients. Disclosure of Interest None declared

Background The antimicrobial peptide LL37 plays a pathogenic role in psoriasis (Pso) due to its adjuvant and auto-antigenic properties. At least a third of Pso patients develop psoriatic arthritis (PsA) but mechanisms that lead PsA development in Pso patients remain elusive. Objectives To understand the role of LL37 in PsA pathogenesis and its relationship with inflammatory molecules IFNa, GMCSF, C5a. Methods Blood samples were collected from 32 biologic-naive PsA, 12 active Pso (without PsA) patients and 8 healthy donors (HD). Synovial fluids (SF) were collected from 17 PsA and 12 osteohartritis (OA) patients. Synovial biopsies from 3 biologic-naive PsA patients were studied by confocal microscopy. Native-LL37 was synthesised and carbamylated LL37 (LL37carb) produced by incubating LL37 with 1 M potassium cyanate and verified by dot-blot assay. Antibodies to native-LL37/LL37carb and levels of LL37, GMCSF, IFNa and complement C5a were measured by in-house and commercial ELISA tests, respectively, in SF and plasma. Results High LL37 levels were detectable in SF of PsA compared to OA. Anti-LL37 [24% in SF (4/17)] and anti-LL37carb antibodies [47% in SF (8/17), 46% in plasma (15/32)] were present in PsA but not in OA and HD. Anti-LL37carb antibodies [41% (5/12)] were also detectable in Pso plasma. IFNa was present in 37% of SF PsA (7/16; not detectable in OA) and correlated with C-reactive Protein (CRP); GMCSF and C5a levels were significantly higher in SF PsA than in SF OA. Notably, GMCSF was also detectable in 40% and 30% of PsA and Pso plasma, respectively, but not in HD; Plasma C5a levels were comparable between PsA and Pso and significantly higher than in HD. SF GMCSF correlated with anti-LL37carb autoantibodies. Anti-LL37carb antibodies correlated with levels of C5a in Pso and PsA plasma. In synovial tissues of PsA the expression of the IFN-related gene MX1 was highly up-regulated in close proximity of neutrophil markers myeloperoxidase and LL37. Conclusions LL37 and, in particular, LL37carb is the target of autoantibodies that correlate with pro-inflammatory GMCSF and C5a in both Pso and PsA, suggesting immunological pathways in common between psoriasis and psoriatic arthritis. Reference ] Lande R, et al. Nature 2007;449:564. ] Lande R, et al. Sci Transl Med 2011;3(73):73ra19. [] Lande R, et al. Nat Commun2014;5:5621. [] Chimenti MS, et al. Autoimmun Rev2015;14(12):1142. Disclosure of Interest None declared

Background The PsABio study (ClinicalTrials.gov Id: NCT02627768) was developed to evaluate the efficacy, tolerability and persistence of TNF inhibitors (TNFi) and ustekinumab (UST) for patients with psoriatic arthritis (PsA) starting 1 st, 2nd or 3rd line biologic disease-modifying antirheumatic drugs (bDMARDs) in real-world routine care. Objectives In this interim analysis, the objective was to describe the profile of patients starting either UST or TNFi in routine clinical care in 8 European countries. Methods Between Dec 2015 and, Aug 2017 patients were enrolled in Italy, Greece, Russia, France, United Kingdom, The Netherlands, Spain and Belgium and had valid baseline data available. Descriptive baseline characteristics for the UST and TNFi cohorts were compared. Results 563 consecutive patients were analysed (278 UST- and 285 TNFi-treated patients): mean (SD) age 49.3 (12.4) years, disease duration 7.2 (7.5) years; 49.6% were men and most had polyarticular disease (Table). Among comorbidities, cardiovascular disease (38.9%) and obesity (30.4%) were most frequent; 11.5% had anxiety or depression. 25.6% of patients were current smokers. TNFis were more often given as 1 st line bDMARD than UST (56.8% vs 39.2%). For patients receiving their 1 st bDMARD, the prevalence of concomitant conventional synthetic (cs) DMARDs at baseline was: UST: 46.8% (39.5% methotrexate [MTX]) and TNFi: 53.7% (39.5% MTX). Among 166 patients who received a 2nd or 3rd bDMARD and had no ongoing csDMARDs at baseline, 66.3% received UST and 33.7% received TNFi. The most prescribed TNFi were etanercept (34.0%), adalimumab (25.3%) and golimumab (19.6%); 12.6% were TNFi biosimilars. The majority of patients on UST received the recommended dose, although 27.8% (10/36) of patients>100 kg started with 45 mg every 3 months. Disease activity was moderate to high with more axial, skin and nail involvement in the UST group. Conclusions European PsA patients starting bDMARDs in 2016/2017 frequently presented with moderate to high disease activity, and overlapping subtypes of PsA, mainly polyarticular disease. Comorbidities, predominantly cardiovascular, were common. Compared to patients treated with TNFi, UST was more often given as 2nd or 3rd line bDMARD and in patients with more axial and skin disease. Among patients who switched to a 2nd or 3rd line bDMARD, those not on concomitant csDMARDs preferentially received UST. Acknowledgements This study was sponsored by Janssen. Disclosure of Interest L. Gossec Grant/research support from: Pfizer, Consultant for: AbbVie, Celgene, Janssen, Lilly, Novartis-Sandoz, Pfizer, Sanofi, and UCB, P. Athanassiou: None declared, P. Bergmans Shareholder of: Johnson and Johnson, Employee of: Janssen, K. de Vlam Consultant for: Johnson and Johnson, E. Gremese Consultant for: AbbVie, Janssen, Lilly, Pfizer, Speakers bureau: AbbVie, Janssen, Lilly, Pfizer, B. Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, AbbVie, and Janssen, T. Korotaeva Consultant for: Pfizer, MSD, Novartis, AbbVie, Celgene, Biocad, Janssen, and UCB, Speakers bureau: Pfizer, MSD, Novartis, AbbVie, Celgene, Biocad, Janssen, and UCB, F. Liote Grant/research support from: Principal investigator or Co-PI for Janssen, MSD, Pfizer, Novartis, AbbVie, and Celgene, Consultant for: Advisory boards for Celgene and MSD, M. Nurmohamed Grant/research support from: Received research support to his institution from Pfizer, AbbVie, Roche, BMS, MSD, Mundipharma, UCB, Janssen, Menarini, Eli Lilly, Sanofi, and Celgene, Consultant for: Pfizer, AbbVie, Roche, BMS, MSD, Mundipharma, UCB, Janssen, Menarini, Eli Lilly, Sanofi, and Celgene, Speakers bureau: Pfizer, AbbVie, Roche, BMS, MSD, Mundipharma, UCB, Janssen, Menarini, Eli Lilly, Sanofi, and Celgene, P. Sfikakis: None declared, S. Siebert Grant/research support from: Receipt of grants/research support to his institution from Pfizer, Janssen, BMS, Celgene, UCB, and Boehringer Ingelheim. participation in clinical trials with AbbVie, Novartis, and UCB, Consultant for: AbbVie, UCB, Pfizer, Janssen, Boehringer Ingelheim, Celgene, and Novartis, Speakers bureau: AbbVie, UCB, Pfizer, Janssen, Boehringer Ingelheim, Celgene, and Novartis, P. Smirnov Employee of: Janssen, E. Theander Employee of: Janssen, J. Smolen Grant/research support from: Received grants for his institution from AbbVie, Janssen, Lilly, MSD, Pfizer, and Roche, Speakers bureau: Provided expert advice to and/or had speaking engagements with AbbVie, Amgen, Astra-Zeneca, Astro, Celgene, Celtrion, GlaxoSmithKline, ILTOO, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB

Background Gastrointestinal (GI) symptoms are seen in majority of patients with Systemic Sclerosis (SSc) and are a common presenting feature of disease. Severe GI involvement may lead to malabsorption which represents a poor prognostic factor. Accordingly, a regular monitoring of gastrointestinal tract involvement and nutritional status appears crucial in SSc patients. Previous studies reported low values of bone mass density (BMD) in SSc patients1. While no specific relationship has emerged between the two conditions, it’s likely that disease related GI involvement may contribute to the alterations in BMD. Objectives To determine if GI-related clinical status was associated to low bone density in our cohort of SSc patients. Methods Two-hundred-ten unselected SSc patients have been enrolled. The 7-items UCLA SCTC GIT 2.0 questionnaire and Malnutrition Universal Screening Tool (MUST) were administered to each patient. A comprehensive medical history was collected. A blood panel for nutritional status was also performed. T-scores and Z-scores at lumbar spine, femoral neck, Ward’s and total hip measured by dual-energy X-ray absorptiometry (GE Lunar Prodigy) were measured. Results In our cohort, 86.7% of patients reported some GI symptoms. The mean UCLA GIT total score was 0.345±0.34 and 51 patients (24.3%) were at risk of malnutrition according to MUST (score ≥1). 53.7% patients had BMD values Patients with spine T-score Femoral neck T-score On the other hand, the comparison of patients with severe, moderate and mild symptoms according to UCLA GIT total score2 showed an association between progressively lower values of spine and total hip T-score and increasing severity of GI symptoms (ANOVA for spine T-score: p=0.015; for total hip T-score: p=0.048). Patients at risk of malnutrition (MUST score ≥1) presented significant lower T-score for all the considered sections (spine and hip) and significant lower total hip Z-score. Conclusions In our SSc cohort gastrointestinal symptoms were frequent and were associated with low BMD. Considering the heterogeneity of GI involvement, UCLA SCTC GIT 2.0 emerged as a useful and feasible tool to assess GI involvement and other associated comorbidities. In particular, SSc patients who report remarkable GI symptoms and are at risk of malnutrition according to MUST may benefit from a stricter control of BMD to promptly detect osteopenia and osteoporosis. References [1] Omair MA, et al. J Rheumatol. 2013 [2] Khanna D, et al. Curr Opin Rheumatol. 2013 Disclosure of Interest None declared

Background Psoriatic arthritis(PsA)is characterised by several comorbidities;among these obesity and overweight have a major impact on patients’ quality of life and on disease treatment. Obesity increases the risk of developing psoriatic arthritis in the general population compared to normal-weight subjects. Obesity increases the risk of developing arthritis in patients with psoriasis, especially for HLA B27 negative and late onset forms. Objectives Aim of the study was to evaluate the incidence of overweight and obesity in a cohort of PsA patients, the differences between disease phenotypes and therapeutic response between patients with normal weight and overweight/obesity. Methods In this retrospective observational study 332 PsA patients, afferent to our unit between 2010 and 2017, were assessed. At each visit data on disease characteristics, BMI, ongoing treatment, joint count and clinimetric indexes were collected. The baseline was defined as the onset of the disease in bio-naive patients or the start of the last bDMARD therapy for patients previously treated with cs or bDMARDS, while the last follow-up is considered the last visit at our unit Results The 332 patients had a mean age of 52.5±7.3 years;35% of the patients were normal weight, 39.5% were overweight and 25.5% obese. No differences were observed in terms of disease characteristics according to BMI cathegory at baseline and during follow-up, with comparable percentages of peripheral arthritis, enthesitis, dactylitis, axial arthritis or uveitis, as well as cutaneous psoriasis among the groups. At baseline, obese patients had more tender(4.4±5.2 vs 2.3±3.6 p=0.003)and swollen joints(mean value 2.3 vs 1 p=0.03)and higher activity indexes, as for DAS28(3.3±1.2 vs 2.7±1.2 p=0.002)and DAPSA(15.6±9.9 vs 11.5±9 p=0.004)compared to normal weight patients. The same difference was observed between normal-weight and overweight patients, with higher values of DAS28(3.04±1,4 vs 2,7±1.2,p=0.17)and DAPSA(13.6±11 vs 11.5±9, p=0.025)in overweight patients. No significant difference was observed in patients treated with NSAIDs, csDMARDs or bDMARDs according to BMI cathegory. In 190 patients followed according to the tight control strategy, with evaluations every 3 months, the disease activity indexes after two years of follow-up became similar in obese patients compared to normal weight patients. Among the normal-weight patients, 69.4% took csDMARDs,48.7% were treated with bDMARDs. 74.7% of obese patients took csDMARDs, while 36.1% took bDMARDs, with no statistically significant differences between the two groups(p=ns). In particular low-disease activity according to DAPSA was achieved in 76% of normal weight patients, compared with 68.9% of obese patients (p=ns), and also the percentage of patients reaching Minimal Disease Activity in the two groups was comparable (28.4% vs 22.7%, p=ns). Conclusions Clinical manifestations of psoriatic disease do not seem to differ according to BMI cathegory:however, at the first evaluation, obese patients appear to have more disease activity than non-obese patients. At the same treatment intensity, obese patients seem to achieve a percentage of remission comparable to normal weight patients, suggesting that the an intensive treatment strategy allows to obtain optimal results also in a more challenging group of patients. Disclosure of Interest None declared