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Extracellular vesicles (EVs) are critical in the initiation and progression of cardiovascular calcification, and immune cell infiltration and inflammation have a central role in this process. EVs egress from various cardiovascular cell types, which when acquiring specific properties, become calcifying. These calcifying EVs form nidi for microcalcification, which can progress to the macrocalcification lesions that are visualized clinically. We make the distinction between inflammatory-driven and mineral dysregulation-driven calcification, which both share EVs as a central initiator. In inflammation-mediated calcification, inflammation precedes microcalcification and results from EV release from macrophages. Local cellular crosstalk mediated by EVs as well as circulating EVs and other inflammatory nanoparticles, such as calciprotein particles and lipoproteins, are also critical in the progression of cardiovascular calcification. It is imperative that future work links the already established and to be discovered roles of inflammation and innate immunity in cardiovascular calcification to these key signaling and functional roles of these nanoparticles. It remains an understudied area with high potential to unravel mechanistic roles and has important implications in drug target research.

Patients and health workers were at high risk of infection during the Sars-Cov-2 pandemic lockdown. For this reason, other medical and clinical approaches such as Telemedicine were necessary. Despite Telemedicine was born before COVID-19, the pandemic was the opportunity to accelerate a process already underway for at least a decade and to blow all the barriers away. Our aim is to describe the experience of Telemedicine during and immediately after the first lockdown to assure the follow-up in a 'virtual' outpatient clinic dedicated to Rheumatic and Musculoskeletal Diseases (RMDs) and to give an overview of Telemedicine in the rheumatology field. We retrospectively evaluated the patient flow to our rheumatology division from March to September 2020 and, in accordance with local restrictions, three periods were selected. In the 1st period, 96.96% of the outpatient clinic cases were shifted to Telemedicine; these decreased to 52.45% in the 2nd period, while the 3rd period was characterized by the return of the patients at the clinic (97.6%). Diagnostic procedures were postponed during the 1st period, reduced drastically during the 2nd and performed regularly during the third period. Intravenous infusions were maintained as much as possible during the three periods, to assure therapeutic continuity. Shifting stable patients to Telemedicine has the potential to allow continuity of care, while reducing the risk of contagion during a pandemic. In the next future, the integration of Telemedicine as standard of care for specific clinical applications might assure assistance for RMDs patients also in non-pandemic conditions.

Introduction: Inflammation is causally related to atherothrombosis. Interleukin-1β (IL-1β) and interleukin-18 (IL-18) require NLRP3 inflammasome for activation and have downstream effects on interleukin-6 (IL-6), a marker previously associated with high risk of coronary artery and cerebrovascular disease (CCVD). However, data pertaining to peripheral artery disease (PAD) are sparse and could offer druggable targets in this disease. Methods: We conducted a prospective cohort study of 4248 patients with type 2 diabetes or metabolic syndrome and prior coronary artery disease who participated in the NIH-funded Cardiovascular Inflammation Reduction Trial (CIRT). Participants were followed for up to 5 years for incident CCVD and symptomatic PAD events. Randomized treatment with low-dose methotrexate (vs. placebo) had no effect on event rates or plasma levels of inflammatory biomarkers. Baseline levels of IL-1β, IL-18, and IL-6 were tested for association with incident vascular events. Kaplan-Meier curves and Cox proportional hazards models (adjusted for traditional risk factors) were estimated. Results: In multivariable adjusted analyses, hazard ratios for the lowest (referent) to highest baseline quartiles of IL-6 were 1.0, 1.5, 1.8, and 2.0 (p-trend Conclusion: In this contemporary cohort of secondary prevention patients, elevated IL-6 was associated with both incident CCVD and PAD. These data support exploration of direct IL-6 inhibition for PAD prevention, a strategy currently being pursued to reduce risk of coronary artery and cerebrovascular disease.

Objectives aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria (‘criteria aPL’) and at titres lower than thresholds considered by classification criteria (‘low-titre aPL’) on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM). Methods Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations. Results EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-β2-glycoprotein I (β2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-β2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-β2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-β2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly. Conclusion EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.

This paper studies the effect of credit constraints on the choice by small and medium-sized enterprises to export goods of higher quality relative to their domestically sold output (quality differentiation). The empirical analysis employs detailed firm-level data on product characteristics and credit scores. Credit constraints are found to be negatively associated with export quality differentiation. Firms reporting a deterioration of the credit score by a standard deviation are 36% less likely to pursue quality differentiation. The negative relation between credit constraints and quality differentiation is stronger for firms exporting to distant markets.

In refractory inflammatory joint diseases (IJDs) biological disease-modifying anti-rheumatic drugs (bDMARDs) may achieve remission. EULAR recommends bDMARD tapering when remission persists. However, guidelines on tapering modalities and criteria for patient selection are lacking. We aimed to evaluate remission persistency after lengthening the time between injections of golimumab in patients affected by IJD and to identify any patient or disease characteristics associated to flare after lengthening.Patients affected by rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and juvenile idiopathic arthritis (JIA) treated with golimumab were enrolled in a retrospective observational study. Demographic data, ESR, cRP, DAS28/ BASDAI, were collected at baseline and during the follow-up (T1- defined as a medical check-up after 1 year of treatment or, for patients with longerg exposure, the first medical check-up in 2016, when at our unit we began to experience drug tapering- and T2- 12 months after the lengthening was started). In 22/80 patients in remission at T1, injection time was lengthened.Eighty patients were enrolled, 34 AS, 33 PsA, 9RA and 4 JIA. At baseline, all had an active disease. At T1, 60/80 patients reached remission and 22/60 patients started tapering. At T2, 20/22 pts (91%) were in remission. At T1 BASDAI was higher (2.2, SD 0.28 vs. 0.58, SD 0.47; p0.001) in patients who lost remission at T2.Patients who flared recovered remission once taken back to a 28-day interval. 4/38 patients maintained at the standard dose flared up and switched/swapped bDMARD. The difference in retention rate toward patients on reduced dose was not significant.Results show that golimumab lengthening is safe and successfully maintains remission. In patients who experienced a flare after lengthening, the standard regimen promptly restored remission.

Introduction: Calcific aortic valve disease is a multifaceted disease in which pathogenic mineralisation of the valvular tissue occurs in tandem with fibrocalcific remodelling of the aortic valve, resulting in a wide variety of clinical presentations. Immunity, both innate and adaptive have been shown to play important roles in chronic cardiovascular diseases. Noteably, 15% of cells within healthy aortic valves are up to hematopoietic origin and these populations are further increased within calcified valves however, the role of the immune system within CAVD remains to be elucidated. Objectives: Investigate the prevalence and distribution of immune cells within CAVD. Methods & Results: Human calcified aortic heart valves were obtained from valve replacement surgeries. Immunohistological assessment of immune cells within the tissue was conducted, with the presence of T cells, B cells, macrophages and dendritic cells detected in the vicinity of calcific nodules. Flow cytometry analysis of cells isolated from the valve was conducted. 69% of cells isolated from the valve were CD45+, with 57% and 42% of CD45+ CD3+ presenting as CD8+ and CD4+ respectively. Within the CD8+ population, 56% of these were central memory CD8+ T cells, with 24% as activated CD8+ T cells. Likewise, within the CD4+ population 29.5% CD4+ cells were activated T cells and 55% central memory T cells. Small populations of naïve CD4+ and CD8+ T cells; 9% and 13% respectively, were present within the valve. CD45+, CD3+, CD4+/CD8+ cells were isolated via FACS and their global proteomic profile was analysed on the Thermo Scientific Lumos orbitrap mass spectrometer. IL-31RA was present within the T cell population, alongside MAPK pathway mediators were also present. Network analysis of T cell proteomics showed increased IL-4 and IL-13 pathways (p Conclusions: Prevalence of immune cells within the valve suggests an inflammatory role in the development of calcific aortic valve disease, with the prevalence of T cells within the valve suggesting an adaptive immune response may be central to the pathology of CAVD.

RATIONALE. Calcific Aortic Valve Disease (CAVD) affects more than 5.2 million people in the US. The only effective treatment is surgery and this comes with complications and no guarantee of long-term success. OBJECTIVE. Outcomes from pharmacological initiatives remain unsubstantiated and therefore the aim of this study is to determine if repurposing a selective XPO1 inhibitor drug (KPT-330) is beneficial in the treatment of CAVD. METHODS AND RESULTS. We show that KPT-330 prevents, attenuates and mitigates calcific nodule formation in heart valve interstitial cells (VICs) in vitro, and prevents CAVD in Klotho(−/−) mice. Using RNA-sequencing and Mass Spectrometry we show that KPT-330’s beneficial effect is mediated by inhibiting nuclear export of the transcription factor C/EBPβ in VICs, leading to repression of canonical Wnt signaling, in part through activation of the Wnt antagonist Axin1, and a subsequent decrease in pro-osteogenic markers and cell viability. CONCLUSIONS. Our findings have met a critical need to discover alterative, pharmacological-based therapies in the treatment of CAVD.

BACKGROUND Phosphaturic mesenchymal tumors are rare neoplasms, frequently presenting with osteomalacia. These neoplasms usually grow at a slow rate and are associated with unspecific symptoms. CASE In this study, we present the case of a 70-year-old woman who had been suffering from musculoskeletal pain, hypophosphatemia, and spontaneous fractures. Positron emission tomography with Gallium showed increase uptake in a subpleural lesion. CONCLUSION The patient underwent surgical excision of the subpleural lesion with a non-intubated uniportal video-assisted thoracoscopic surgery approach.

Aortic aneurysm/dissection (AAD) is a life-threatening disorder lacking effective pharmacotherapeutic remedies. Aldehyde dehydrogenase 2 (ALDH2) polymorphism is tied with various risk factors for AAD including hypertension, atherosclerosis, and hypercholesterolaemia although direct correlation between the two remains elusive.Two independent case-control studies were conducted involving 307 AAD patients and 399 healthy controls in two geographically distinct areas in China. Our data revealed that subjects carrying mutant ALDH2 gene possessed a ∼50% reduced risk of AAD compared with wild-type (WT) alleles. Using 3-aminopropionitrile fumarate (BAPN)- and angiotensin II (Ang II)-induced AAD animal models, inhibition of ALDH2 was found to retard development of AAD. Mechanistically, ALDH2 inhibition ablated pathological vascular smooth muscle cell (VSMC) phenotypical switch through interaction with myocardin, a determinant of VSMC contractile phenotype. Using microarray and bioinformatics analyses, ALDH2 deficiency was found to down-regulate miR-31-5p, which further altered myocardin mRNA level. Gain-of-function and loss-of-function studies verified that miR-31-5p significantly repressed myocardin level and aggravated pathological VSMC phenotypical switch and AAD, an effect that was blunted by ALDH2 inhibition. We next noted that ALDH2 deficiency increased Max expression and decreased miR-31-5p level. Moreover, ALDH2 mutation or inhibition down-regulated levels of miR-31-5p while promoting myocardin downstream contractile genes in the face of Ang II in primary human VSMCs.ALDH2 deficiency is associated with a lower risk of AAD in patients and mice, possibly via suppressing VSMC phenotypical switch in a miR-31-5p-myocardin-dependent manner. These findings favour a role for ALDH2 and miR-31-5p as novel targets for AAD therapy.

Calcific aortic valve disease (CAVD), and its clinical manifestation that is calcific aortic valve stenosis, is the leading cause for valve disease within the developed world, with no current pharmacological treatment available to delay or halt its progression. Characterized by progressive fibrotic remodelling and subsequent pathogenic mineralization of the valve leaflets, valve disease affects 2.5% of the western population, thus highlighting the need for urgent intervention. Whilst the pathobiology of valve disease is complex, involving genetic factors, lipid infiltration, and oxidative damage, the immune system is now being accepted to play a crucial role in pathogenesis and disease continuation. No longer considered a passive degenerative disease, CAVD is understood to be an active inflammatory process, involving a multitude of pro-inflammatory mechanisms, with both the adaptive and the innate immune system underpinning these complex mechanisms. Within the valve, 15% of cells evolve from haemopoietic origin, and this number greatly expands following inflammation, as macrophages, T lymphocytes, B lymphocytes, and innate immune cells infiltrate the valve, promoting further inflammation. Whether chronic immune infiltration or pathogenic clonal expansion of immune cells within the valve or a combination of the two is responsible for disease progression, it is clear that greater understanding of the immune systems role in valve disease is required to inform future treatment strategies for control of CAVD development.

Objectives The level of detail included when describing nailfold videocapillaroscopy (NVC) methods varies among research studies, making interpretation and comparison of results challenging. The overarching objective of the present study was to seek consensus on the reporting standards in NVC methodology for clinical research in rheumatic diseases and to propose a pragmatic reporting checklist. Methods Based on the items derived from a systematic review focused on this topic, a three-step web-based Delphi consensus on minimum reporting standards in NVC was performed among members of the European League against Rheumatism (EULAR) Study Group on Microcirculation in Rheumatic Diseases and the Scleroderma Clinical Trials Consortium. Results A total of 319 articles were selected by the systematic review, and 46 items were proposed in the Delphi process. This Delphi exercise was completed by 80 participants from 31 countries, including Australia and countries within Asia, Europe, North America and South America. Agreement was reached on items covering three main areas: patient preparation before NVC (15 items), device description (5 items) and examination details (13 items). Conclusion Based on the available evidence, the description of NVC methods was highly heterogeneous in the identified studies and differed markedly on several items. A reporting checklist of 33 items, based on practical suggestions made (using a Delphi process) by international participants, has been developed to provide guidance to improve and standardize the NVC methodology to be applied in future clinical research studies.

Cellular heterogeneity of aortic valves complicates the mechanistic evaluation of the calcification processes in calcific aortic valve disease (CAVD), and animal disease models are lacking. In this study, we identify a disease-driver population (DDP) within valvular interstitial cells (VICs). Through stepwise single-cell analysis, phenotype-guided omic profiling, and network-based analysis, we characterize the DDP fingerprint as CD44

Aims: Switching from originator to biosimilar is part of current practice in inflammatory rheumatic musculoskeletal diseases (iRMDs) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA), with evidences derived from both etanercept (ETN) to SB4-switching randomized controlled trials and real-life registries. We investigated the safety and treatment persistence of ETN/SB4 in a multi-iRMD cohort derived from two rheumatology departments in our region. Methods: Adult patients with iRMDs, treated with ETN for at least 6 months and switched to SB4 in stable clinical condition, were eligible for this retrospective evaluation. Retrospective data on adverse events, loss of efficacy and persistence on treatment were collected until latest available follow-up. Results: A total of 220 patients (85 RA, 81 PsA, 33 axSpA, 14 juvenile idiopathic arthritis and seven other conditions; 142 females, mean age 58 ± 7 years, disease duration 12 ± 4 years, ETN duration 7 ± 4 years) were enrolled, with median follow-up of 12.1 (9.7–15.8) months. A total of 50 patients (22.7%) presented with at least one adverse event, with 36 (16.4%) disease flares and 30 (13.6%: 11 for safety and 19 loss of efficacy) SB4 withdrawals. Cumulative SB4 treatment persistence was 99.1%, 88.6% and 64.6% at 6, 12 and 18 months respectively. Back-switch to ETN was performed in 17/30 cases, the remaining cases were managed with change of biologic disease modifying or conventional synthetic anti-rheumatic drug. Age was the only significant predictor of SB4 interruption at 6 months. Conclusion: Our real-life data confirm the safety profile of switching from ETN to SB4, with slightly higher treatment persistence rates compared with other real-life registries.

Aims Vascular calcification is a recognised predictor of cardiovascular risk in the diabetic patient, with DNA damage and accelerated senescence linked to oxidative stress associated pathological calcification. Having previously shown that systemic SIRT1 is reduced in diabetes, the aim was to establish whether SIRT1 is protective against a DNA damage-induced senescent and calcified phenotype in diabetic vascular smooth muscle cells (vSMCs). Methods and results Immunohistochemistry revealed decreased SIRT1 and increased DNA damage marker expression in diabetic calcified arteries compared to non-diabetic and non-calcified controls, strengthened by findings that vSMCs isolated from diabetic patients show elevated DNA damage and senescence, assessed by the Comet assay and telomere length. Hyperglycaemic conditions were used and induced DNA damage and enhanced senescence in vSMCs in vitro. Using H2O2 as a model of oxidative stress-induced DNA damage, pharmacological activation of SIRT1 reduced H2O2 DNA damage induced calcification, prevented not only DNA damage, as shown by reduced comet tail length, but also decreased yH2AX foci formation, and attenuated calcification. While ATM expression was reduced following DNA damage, in contrast, SIRT1 activation significantly increased ATM expression, phosphorylating both MRE11 and NBS1, thus allowing formation of the MRN complex and increasing activation of the DNA repair pathway. Conclusions DNA damage induced calcification is accelerated within a diabetic environment and can be attenuated in vitro by SIRT1 activation. This occurs through enhancement of the MRN repair complex within vSMCs and has therapeutic potential within the diabetic patient. Translational perspective Our study provides the first evidence that DNA damage is enhanced in the vasculature of the diabetic patient and that this process, in tandem with loss of SIRT1, exacerbates pathological smooth muscle cell calcification. We propose that current SIRT1 activators and their analogues may be useful as investigational tools, and further elucidation of downstream mechanisms of SIRT1 will aid the development of novel and more precise drug regimens.

SB5 showed comparable efficacy and safety profile in respect to adalimumab originator (ADA) in randomized clinical trials of rheumatoid arthritis (RA) and psoriasis. We aimed to describe the efficacy and safety of SB5 after switching from ADA in RA, axial spondyloarthritis (axSpA), psoriatic arthritis (PsA) and juvenile idiopathic arthritis (JIA) patients.Adult RA, PsA, axSpA, JIA patients treated with ADA for at least 6 months, switched to SB5 in stable clinical conditions, were eligible. Data on safety, activity indexes and patient-reported outcomes were collected at baseline, 3 and 6 months after switching.Eighty-two patients (19 RA, 28 PsA, 32 axSpA and 3 JIA; 45 females, mean age 54 ± 14 years, disease duration 13 ± 7 years, ADA duration 6 ± 3 years) were enrolled. RA patients showed stable conditions, while PsA patients showed an increase in both HAQ, DAS28(CRP) and DAPSA and axSpA patients an increase in VAS pain, VAS patient disease activity and ASDAS, both at 3 months. There were changes in the concomitant medications profile, with regression of activity indexes increases at 6 months. Adverse events were reported by 33.7% patients at 3 months and 16.6% patients at 6 months, mostly disease flares and infectious events. Two patients stopped SB5.Despite temporary changes in the concomitant medication profile for mild disease flares, our real-life data replicate the safety profile of switching from ADA to SB5 in RA, with additional data for its applicability in PsA and axSpA patients, further supporting switching to biosimilars in treating inflammatory rheumatic conditions. Key Points • Switching from adalimumab originator to SB5 is feasible in real life rheumatic inflammatory joint diseases. • Mild disease flares can present after switching from originator adalimumab to SB5, in particular in axial spondyloarthritis and psoriatic arthritis. • Changes in concomitant medications profile allows the control of minor disease flares presenting after switching from adalimumab originator to SB5.

INTRODUCTION Interleukin-6 (IL-6) is well-known for its pro-inflammatory properties, has been proven to target a wide range of cells in the joint, and has been implicated in extra-articular and articular manifestations in rheumatoid arthritis (RA). Tocilizumab (TCZ) is now widely used in patients with active RA and a number of additional agents that target the IL-6 pathways are under development, including sirukumab (SRK). Areas covered: SRK is an IgG1κ human anti-IL-6 monoclonal antibody which binds to IL-6 and prevents IL-6-mediated downstream effects. Initial trial results in phase-III studies in patients with RA seemed promising, showing improved results in patients with moderate-to-severe RA. Data derive from the phase-II study and the various SIRROUND studies (phase III). Expert commentary: The available data show that SRK50 mg every 4 weeks or 100 mg every 2 weeks will be effective in treating the RA population, with clinical improvements as early as week 2 and sustained over time. The adverse-event profile seems to be similar to TCZ, except for an increased mortality post open-label studies due to infections and cardiovascular events, our knowledge of which will be deepened with post-marketing surveillance and registry data.

Background:Biologic and target synthetic disease modifying anti-rheumatic drugs (bDMARDs and tcDMARDs) are recommended to control RA disease activity, pain and steroid use. Following randomized clinical trials (RCTs) and their post-hoc analyses, the Janus Kinase Inhibitor tsDMARDs BARI was superior to reference bDMARD Adalimumab in reducing disease activity, pain and functional disability. In addition, BARI monotherapy also determined more significant pain reduction and functional improvement when compared to Tocilizumab monotherapy (3).Objectives:to confirm RCT results in a real-life clinical setting, with focus on disease activity, pain, functional disability and steroid tapering, when comparing BARI to bDMARDs for the treatment of active RA.Methods:RA patients starting BARI or a bDMARD for active RA were retrospectively evaluated from June 2019 to June 2020. Disease activity (DAS28CRP, SDAI, CDAI), pain visual analogic scale (pain_VAS), functional disability (HAQ) assessments and mean prednisone dosage (pred_dose) were collected at baseline (BL), 3 months (3M) and 6 months (6M) after BARI/bDMARD initiation. The changes of the outcome measures were evaluated between BL-3M, 3M-6M and BL-6M, as well as between BARI and bDMARDs groups. Finally, we assessed the variables associated with prednisone tapering in the whole population.Results:90 out of 100 RA patients evaluated (baseline: age 57±12 years, disease duration 131±100 months, DAS28PCR 4.8±1.0, pain_VAS 61±23 mm, prednisone dose 5.5±5.3 mg) were eligible for the study; 49 received BARI and 41 bDMARDs (17 abatacept, 12 TNF inhibitors, 11 tocilizumab, 1 rituximab). At BL, the two groups did not differ statistically in terms of age, sex, disease duration, disease activity, pain_VAS, previous bDMARD failure or ts/bDMARD naive, concomitant conventional synthetic DMARDs treatment, pred_dose. Both BARI and bDMARDs determined a significant reduction in activity scales and HAQ when comparing BL-3M and BL-6M, with only pain_VAS and pred_dose showing a significant decrease in the 3M-6M interval. When comparing the two groups, BARI showed a significantly higher reduction of pred_dose (-3.2±5.1 vs -1.7±3.7 mg at BL-3M, and -4.1±5.3 vs -1.9±4.6 mg at BL-6M), which was not significant after adjusting for BL pred_dose. No other difference was seen when the two groups, including the numerically higher reduction of pain_VAS in the BARI group (-29±28 vs -20±27 mm at BL-3M and -35±25 vs -30±28 mm at BL-6M comparison). The analysis of the predictors for steroid tapering (Δmean_pred) in the two intervals, showed that BL DAS28PCR, DAS28PCR BL-3M change and BL pred_dose were associated with BL-3M Δmean_pred, while 3M pain_VAS and 3M pred_dose were associated with 3M-6M Δmean_pred.Conclusion:Although limited by the small samples and the retrospective nature, our real-life comparison shows similar efficacy of BARI and bDMARDs in terms of disease activity control, functional disability and pain. In addition, the treatment with BARI or bDMARD did not influence the steroid tapering, which was driven mostly by its initial dose, disease activity and pain. Larger real-life multi-center studies are warranted to confirm our results.References:[1]Taylor PC et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662.[2]Fautrel B et al. Effect of Baricitinib and Adalimumab in Reducing Pain and Improving Function in Patients with Rheumatoid Arthritis in Low Disease Activity: Exploratory Analyses from RA-BEAM. J Clin Med. 2019 Sep 5;8(9):1394.[3]Fautrel B et al. Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment withDisclosure of Interests:Laura Cometi: None declared, Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Fondazione Italiana Ricerca sull’Artrite (FIRA), Gruppo Italiano lotta alla Sclerodermia (GILS), New Horizon Fellowship, European Scleroderma Trials and Research (EUSTAR) group, Foundation for Research in Rheumatology (FOREUM)., Lorenzo Tofani: None declared, Giulia Tesei: None declared, Francesca Nacci: None declared, Ginevra Fiori: None declared, Francesca Bartoli: None declared, Marco Matucci-Cerinic Speakers bureau: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Consultant of: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Grant/research support from: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly

Background:Remission or low disease activity (LDA) are the ultimate goals of both conventional synthetic (csDMARD), target synthetic and biologic disease-modifying anti-rheumatic drugs (bDMARD) in treating RA. Janus Kinase (JAK) inhibitors are nowadays part of tsDMARDs, with BARI as an oral selective JAK1-2 inhibitor. Ultrasound (US) is a valuable imaging tool for detecting inflammatory joint changes and monitoring RA patients. The US7 score (US7) is a semiquantitative score including grayscale (GS) and power Doppler (PD) measurements of synovitis and tenosynovitis in 7 joints of the clinically dominant hand and foot.Objectives:to evaluate real life efficacy and safety of BARI 4 mg in RA patients using clinical, clinimetric and US evaluation.Methods:adult RA patients starting BARI were eligible. DAS28ESR, CDAI, SDAI, painVAS, HAQ, COCHIN, laboratory parameters and US7 were performed/collected at baseline (BL) and after 3 and 6 months. Adverse events (AE) and concomitant medications were recorded. Responder/non responder status was determined using DAS28ESR improvement according to the EULAR Response Criteria at 3 months. Moreover, SDAI clinical remission or LDA (remission: SDAI≤3,3; LDA:3,3Results:43 patients (12 csDMARD and 31 bDMARD failure) were enrolled, with 30 patients starting BARI in combination with a csDMARDs. BL painVAS was 68±23mm and disease activity was moderate to severe according to DAS28VES, CDAI and SDAI. BARI determined a significant improvement of every disease activity composite score and US7 components, except tendon PD; steroid daily dosage was significantly reduced.28 patients were considered Responders at 3 months: responders used to have higher disease activity levels and synovitis scores at baseline.Table 1.Comparisons demographics and renal pathologies of responder and non-responder groupsBL3Mp value6Mp valueRNRRNRRNRpainVAS67,88±23,3758,18±22,7230,19±23,5245,64±25,48p=0.004030,19±20,4229,73±22,15p=0.2105Daily prednisone equivalent5,97±5,575,45±4,302,96±3,023,95±3,63p=0.22481,63±2,103,03±3,59p=0.1247GSS8,50±5,257,00±3,813,69±3,632,33±2,45p=0.93343,56±3,014,22±2,64p=0.2452GST2,88±2,333,11±2,090,88±0,891,56±1,59p=0.65011,00±1,372,78±1,72p=0.0831PDS8,00±7,113,33±3,463,00±3,482,44±3,36p=0.00663,25±3,135,00±4,56p=0,0006PDT2,81±2,462,44±3,360,88±1,541,33±1,50p=0.449901,06±1,533,78±3,19p=0.0156Erosions1,25±2,050,44±0,731,50±2,030,44±0,73p=0.07361,31±2,091,11±1,27p=0.0902Interestingly, painVAS and steroid dosage significantly decreased both in responders and non-responders, achieving similar value at 6 months. Non-responders showed both synovial and tendon involvement relapse at 6 months, with significantly higher PD score compared to responders. Remission was reached by 12,8% patients at 3 months and 21,6% at 6 months, while LDA patients were respectively 53,8% and 51,3%; combination with csDMARD was the only factor positively associated with remission/LDA at 3 months.The percentage of dropped-out patients due to AE was aligned with literature data (5% in 6 months) whereas the percentage of Herpes Zoster Virus (HZV) infections was higher (4,6% in 6 months in our population vs 4,3% in 1 year in RCTs). Corticosteroid dosage was directly associated with AE development at 6 months.Conclusion:Real life data confirmed BARI RCTs efficacy and safety data. Non responders showed both synovial and tendon PD disease relapse, despite painVAS and steroid reduction were comparable to responders. In our population, HZV infection prevalence was higher than in RCTs and corticosteroid dosage was positively associated with AE development at 6 months.Disclosure of Interests:Giulia Tesei: None declared, Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Laura Cometi: None declared, Francesca Nacci: None declared, Marco Capassoni: None declared, Riccardo Terenzi: None declared, Lorenzo Tofani: None declared, Francesca Bartoli: None declared, Ginevra Fiori: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments.

In the present study we evaluated how systemic arterial hypertension (SAH), dyslipidemia and diabetes mellitus influence the efficacy, safety and retention rate of biological disease-modifying anti-rheumatic drug (bDMARD) treatment in rheumatic musculoskeletal disorders (RMDs). The charts of RMD patients treated with the first-line bDMARD were reviewed, collecting data on safety, efficacy and comorbidities at prescription (baseline, BL), after 6 months (6M) and at last observation on bDMARD (last observation time, LoT). In 383 RMD patients, a higher rate of adverse events at 6M (p = 0.0402) and at LoT (p = 0.0462) was present in dyslipidemic patients. Patients who developed dyslipidemia or SAH during bDMARD treatment had similar results (dyslipidemia p = 0.0007, SAH p = 0.0319) with a longer bDMARD retention as well (dyslipidemia p &lt, 0.0001, SAH p &lt, 0.0001). SAH patients on angiotensin converting enzyme inhibitors (ACEis) or angiotensin-II receptor blockers (ARBs) continued bDMARDs for longer than non-exposed patients (p = 0.001), with higher frequency of drug interruption for long-standing remission rather than inefficacy or adverse reactions (p = 0.0258). Similarly, dyslipidemic patients on statins had a better bDMARD retention than not-exposed patients (p = 0.0420). In conclusion, SAH and dyslipidemia may be associated with higher frequency of adverse events but a better drug retention of first-line bDMARD in RMDs, suggesting an additional effect of ACEis/ARBs or statins on the inflammatory process and supporting their use in RMD bDMARD patients with SAH/dyslipidemia.

Background: Hydroxychloroquine is an anti-malarial drug that not only exerts immunomodulatory and anti-thrombotic properties, but also has been shown to reverse several effects mediated by anti-phospholipid antibodies (aPL) in models of obstetric anti-phospholipid syndrome (APS). Not surprisingly, HCQ, whose prescription during gestation is perfectly safe, has been proposed as an additional therapeutic tool in obstetric APS, but evidence of ist efficacy is still scant. Objectives: This study investigates how treatment with HCQ, prescribed in different combinations with low-dose aspirin (LDASA) and low-molecular weight heparin (LMWH), affects the probability of pregnancy morbidity (PPM). Methods: Data on pregnancies in women with persistent aPL positivity at any titre, with or without autoimmune diseases, were retrospectively collected at a single centre. A weigthed generalized estimated equation (GEE) model was applied to quantify the effect of treatment with HCQ on PPM, allowing to: i) evaluate pregnancy outcomes over time using available longitudinal data; ii) account that pregnancies of the same woman are not independent events; iii) consider that women had a different number of pregnancies; iv) estimate the role of several confounders and predictors. The model envisaged as dependent variable pregnancy outcome as a binary outcome, defined for each pregnancy as “obstetric complication yes versus no” (pregnancy loss before 10 weeks, pregnancy loss after 10 weeks, premature birth before 34 weeks, according to updated APS classification criteria). Results: Three-hundred-eighty-one women were recruited in this study: 155 women with aPL positivity (100 women with positivity for criteria aPL and 55 women with low titer aPL) and 226 women with autoimmune diseases but negative aPL. Data were collected on 847 pregnancies: 458 in women with positive aPL (172 in women with criteria aPL and 286 in women with low titer aPL) and 389 in women with autoimmune disease and negative aPL. PPM in untreated patients are presented in Table 1. Table 2 reports PPM in women receiving LDASA+/- HCQ, LDASA + LMWH +/- HCQ. Conclusion: HCQ, when added to LDASA or on the top of standard treatment with LDASA and LMWH, allows to reduce PPM. Most importantly, HCQ plus the combo LMWH + LDASA leads to a significantly reduction of PPM even in women at highest risk, namely those with multiple criteria aPL positivity. References: [1] Miyakis S, et al. J Thromb Haemost. 2006;4(2):295-306 [2] Sciascia S, et al. Thromb Haemost. 2016;115(2):285-90. [3] Ruffatti A, et al. Thromb Haemost. 2018;118(4):639-646. Disclosure of Interests: Cecilia Chighizola Speakers bureau: Inova Diagnostics, Francesca Pregnolato: None declared, Francesca Bartoli: None declared, Maria Gerosa: None declared, Chiara Comerio: None declared, Maria Gabriella Raimondi: None declared, Laura Trespidi: None declared, Maria Orietta Borghi: None declared, Manuela Wally Ossola: None declared, Enrico Ferrazzi: None declared, Pier Luigi Meroni Consultant for: Inova, Thermofisher, Teofarma

Background Osteoporosis is a frequent complication of rheumatic muscle-skeletal diseases (RMD), with high impact from steroid treatment. It is known that bDMARD impact positively on patients’ prognosis and this is also known for Denosumab, a monoclonal antibody for osteoporosis. The combination treatment with two monoclonal antibodies, bDMARD & denosumab, has addressed the problem of safety and efficacy, with incomplete answers from the available literature. Objectives: to evaluate the impact of the combination treatment bDMARD+Denosumab (COMBO group), compared to mono-therapy with bDMARD (MONO group), on clinical efficacy, safety and treatment retention of bDMARD in patients with RMD. Methods RMD patients treated with COMBO therapy where enrolled from a single centre rheumatology unit; for each case, at least one MONO therapy control (matched per age±5 years, sex, bDMARD, RMD, without osteoporosis) was enrolled. Data on clinical efficacy (3-points Likert scale for physician and patient – improved/stable/worse), safety (locl reaction, serious and non-serious adverse events) and bDMARD treatment retention at 12, 18 and 24 months. Results Out of 129 eligible patients, 77 were enrolled in the protocol: 49 in the MONO and 28 in the COMBO group. The two groups were different of age (slightly higher in the COMBO group), for tender joint count, erythrocyte sedimentation rate and c-reactive protein (higher in the MONO group). Efficacy analysis showed higher percentage of clinical improvement at 12 months in the MONO group at 12 months, being not significant at 18 and 24 months (possibly explained by a different disease activity at baseline visit, corresponding to the overlap of denosumab on top of bDMARD in the COMBO and to the initiation of bDMARD in the MONO group). Between the 2 groups, no difference about safety and retention rate was found. Conclusion: the efficacy of COMBO treatment is similar to MONO therapy. Moreover, the data show that also safety and retention rate are similar. Therefore, the COMBO treatment with 2 different monoclonals can be safely employed in the treatment of RMDs and osteoporosis. Disclosure of Interests Cosimo Bruni: None declared, Cosimo Cigolini: None declared, Giulia Tesei: None declared, Francesca Bartoli: None declared, Ginevra Fiori: None declared, Maria Letizia Conforti: None declared, Silvia Bellando Randone: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Pfizer, BMS, Chemomab, Sanipedia, Speakers bureau: Actelion, BMS; MSD, Janssen

Introduction Patients with type II diabetes have considerably higher risk of developing cardiovascular disease and often have an elevated prevalence of vascular calcification combined with a loss of SIRT1, which induces osteogenic differentiation within the smooth muscle. This study aims to determine whether the loss of SIRT1 contributes to the enhanced DNA damage associated with vascular calcification and diabetes. Methods Popliteal arteries, harvested from diabetic patients undergoing limb amputation, and non-atherosclerotic internal thoracic arteries, were stained for a range of DNA damage markers. Human coronary artery smooth muscle cells (vSMCs) were used for an in vitro calcification model (5mM βGP and 2.6mM CaCl2) in the presence or absence of a diabetic environment (high glucose (25mM), or control (5mM) DMEM respectively. DNA damage was induced using 200μM H2O2 and SIRT1 was activated or inhibited pharmacologically using SRT1720 or Sirtinol respectively. DNA damage was assessed via a comet assay, γH2A.X and p21 immunocytochemistry, whilst DNA damage-induced SIRT1 activation was assessed via nuclear fractionation and western blotting. Activation of the MRN DNA damage response pathway was confirmed by chIP qPCR and western blot analysis. Results Alizarin red, Alkaline phosphatase activity and RUNX2 and OCN qPCR confirmed development of calcification during H2O2 treatment, which was reduced with SIRT1 activation. Immunohistochemistry demonstrated enhanced DNA damage marker expression in diabetic vessels compared to non-diabetic control ITA tissue, while SMCs harvested from diabetic patients also showed a significant reduction in SIRT1 expression (p Conclusions This study demonstrates that SIRT1 protects against H2O2 induced DNA damage and subsequent calcification within a diabetic environment via activation of the MRN complex. The loss of SIRT1 within the calcified vessels of diabetic patients may contribute to a defective DNA repair mechanism, caused by the absence of SIRT1, resulting in a reduction of MRN deacetylation and thus activation of the DNA damage response, and could be an appropriate target for potential therapeutic intervention for vascular calcification. Conflict of interest N/A

Background:In refractory IJD, remission may be obtained with antiTNFa drugs and other biological disease modifying anti-rheumatic drugs (bDMARDs). The last EULAR recommendations suggest tapering of bDMARD when remission persists1. However, best timing and modality of tapering are uncertain and specific knowledge on patients’ characteristics associated to a better outcome is still lacking.Objectives:To evaluate the persistency of remission after increasing the interval between injections of Golimumab in a group of patients affected by rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and juvenile idiopathic arthritis (JIA) and to identify any variables associated to disease flare after tapering.Methods:Between 2011 and July 2020, 80 patients affected by RA, PsA, AS and JIA treated with Golimumab were enrolled. Their demographic and clinical data, including inflammation (ESR and cRP) and clinimetric indices (DAS28 or BASDAI), were collected at baseline and during the follow up visit (T1). In 22/80 patients that reached clinical remission at T1, the time between Golimumab injections has been prolonged (mean time between injection: 43.7 days); ESR and cRP, DAS28/BASDAI, and time since the start of the tapering (weeks) were evaluated in the next control visit (T2).Results:80 patients were enrolled (32 male, mean age 50.6 years +/- 13.91), 34 AS, 33 PsA, 9 RA and 4 JIA. At baseline they have an active disease with a DAS 28 of 4.74+/-0.85 and a BASDAI of 5.23+/- 1.31. At T1, 60/80 patients were in remission (75%), with a mean DAS 28 of 1.84+/- 0.6 and an average BASDAI of 1.32+/-0.6, and 22/60 patients started drug tapering. At T2, 20/22 patients (91%) were in remission, (DAS 28 1.9+/-0.49, BASDAI of 0.8+/- 0, 67). A significantly higher BASDAI was observed at T1, even though in the range of absence of disease activity (2.2, +/- 0.28 vs 0.58, +/- 0.47; p vs reduced dose was not statistically significative.Conclusion:Tapering of Golimumab was successful in 91% of the cases without flare. Moreover, the prolongation of the increase of the treatment window provided the same result as that obtained in patients that continued in the standard time window. This evidence suggests that the extension of the gap between Golimumab administrations may be feasible and safely applied in practice.References:[1]Smolen JS, Landewé RBM, Bijlsma JWJ, et al EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update Annals of the Rheumatic Diseases 2020;79:685-699.Disclosure of Interests:None declared

Background:In March this year, most of the routine activities were cancelled during the streaming of the pandemic in Italy. This prompted a pragmatic reorganization of the traditional care model of nursing and medicine, to quickly give an efficient clinical response. During the first phase of the pandemic, outpatient visits dropped by more than 60%, forcefully shifting to telemedicine to assure continuity of care despite the lockdown.Objectives:The aim of the present work was to describe the strategy adopted during and immediately after the lockdown to assure the follow up of patients and the maintenance of their treatment in an outpatient “virtual” telemedicine clinic dedicated to RDs.Methods:the patient flow to a rheumatology division during the lockdown was evaluated retrospectively from March to September 2020 in accordance with local restrictions, and three periods are described.Results:653/913 (71.5%), 542/542 (100%) and 1.048/1.048 (100%) infusion activities scheduled were performed at the centre for daily infusion and pre-infusion assessment, respectively during the 1st, 2nd and 3rd period. In the outpatient clinic during the 1st period, 96.96% of the cases was shifted to Telemedicine, which decreased to 52.45% in the 2nd period; while in the 3rd period, 97.6% of the performances were carried out at the clinic. Diagnostic procedures, such as ultrasound, capillaroscopy, and joint injection were generally postponed during the 1st period, reduced drastically during the 2nd and performed regularly during 3rd period. Ulcer treatment and the Clinical Trial Unit never stopped their activity. The flow of the activity of the outpatient clinic and the day hospital is represented as monthly trends in graph 1 (See Graph 1).Conclusion:Our data show the feasibility of Telemedicine in a lockdown condition. Shifting stable patients to Telemedicine has the potentiality to minimize the risk of contagion and allow continuity of care. In the future, the use of Telemedicine for specific clinical uses might assure patient assistance also in non-pandemic conditions.References:[1]Rawaf S, Allen LN, Stigler FL et al. Lessons on the COVID-19 pandemic, for and by primary care professionals worldwide. Eur J Gen Pract. 2020 Dec;26(1):129-133. doi: 10.1080/13814788.2020.1820479. PMID: 32985278.[2]McDougall JA, Ferucci ED, Glover J, et al. Telerheumatology: A Systematic Review. Arthritis Care Res (Hoboken). 2017 Oct;69(10):1546-1557. doi: 10.1002/acr.23153. Epub 2017 Aug 22. PMID: 27863164; PMCID: PMC5436947.[3]Romão VC, Cordeiro I, Macieira C, Oliveira-Ramos F, Romeu JC, Rosa CM, Saavedra MJ, Saraiva F, Vieira-Sousa E, Fonseca JE. Rheumatology practice amidst the COVID-19 pandemic: a pragmatic view. RMD Open. 2020 Jun;6(2):e001314. doi: 10.1136/rmdopen-2020-001314. PMID: 32584782; PMCID: PMC7425193.Characters from table content including title and footnotes:Graph 1.Monthly trend for telemedicine and visits during the SARS Cov2 emergencyAcknowledgements:The project (Telereuma) has been supported by an unrestricted grant of Biogen, BMS, and Novartis.Disclosure of Interests:None declared

Objective.To evaluate pathogenesis and clinical features of lower limb ulcers in systemic sclerosis (SSc) and to propose a classification that could be used in clinical practice.Methods.Charts of 60 patients with SSc who had lower limb cutaneous lesions were reviewed. All patients had videocapillaroscopy and arterial and venous lower limb color Doppler ultrasonography (US). Arteriography was performed if occlusive peripheral arterial disease was suspected.Results.The 554 lesions were classified as hyperkeratosis, ulcers, and gangrenes. There were 341 (61.6%) hyperkeratoses, 208 (37.5%) ulcers, and 5 (0.9%) gangrenes. Ulcers were divided into pure ulcers, ulcers associated with hyperkeratosis, and ulcers secondary to calcinosis. Involvement of arterial and venous macrocirculation as determined by color Doppler US was observed in 17 (18.3%) and 18 (30%) patients, respectively. Seventeen out of 37 patients with pure ulcers (45.9%) presented neither venous insufficiency nor hemodynamically significant macrovascular arterial disease. In these patients, pure ulcers were most likely caused by isolated SSc-related microvascular involvement (pure microvascular ulcers). The only significant risk factor for development of pure microvascular ulcers in the multivariate analysis was the history of lower limb ulcers (OR 26.67, 95% CI 2.75–259.28; p < 0.001).Conclusion.Results of our study indicate that lower limb ulcers in SSc often have a multifactorial pathogenesis that may be difficult to manage. Further studies are needed to validate the proposed classification and to assess the most appropriate management of lower limb ulcers in SSc.

Background:bDMARDs have an effect on glucose homeostasis (1), lipoproteins profile (2; 3) and blood pressure (4). However, with the exception of obesity (5; 6), there are no clear data on how bDMARDs work in patients who already have or develop metabolic comorbidities and whether these conditions can impact on their efficacy and safety profile.Objectives:to evaluate, in chronic inflammatory joint diseases, the effect of arterial hypertension (AH), dyslipidemia (DYS) and diabetes mellitus (DM) on efficacy, safety and retention rate of first-line bDMARDs therapy.Methods:a retrospective observational study on the clinical charts of Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Ankylosing Spondylitis (AS), treated with first on-label bDMARD was performed. Data on adverse events, efficacy and comorbidities at the baseline visit in which the bDMARD was prescribed (BL), the visit performed after 6 months of therapy (6M), and the last visit on treatment (LoT) were collected.Results:383 patients (41,8% RA, 33,4% PsA and 24,8% AS) were included in the study, with the predominance of females (F: 67,36%, M: 32,64%; mean age 51,67 ± 15,11 years). Our data show that the presence of comorbidities had no influence on efficacy of bDMARD, while patients who had DYS at BL manifested a higher rate of systemic adverse events either in the first 6 months of therapy (58,9% vs 43,7%, p=0,040) and also later on (80,36% vs. 66,67%, p=0,046). In addition, patients who developed DYS and AH after the 6M visit reported a higher rate of systemic adverse events at LoT visit, compared to others (DYS: 97,8% vs 66,7%, pConclusion:our data suggest that AH and DYS may be associated with higher frequency of adverse events but a better drug retention. The combination of bDMARD and ACEi/ARB may determine a better control of the inflammatory process by inhibition of angiotensin II, favouring the achievement of remission. In AH patients on bDMARDs, ACEi and ARB could therefore represent an useful anti-hypertensive drug choice. Similarly, statins could be the treatment of choice in DYS patients.References:[1]Gonzalez-Gay MA, et al. Clin Exp Rheumatol. 2006.[2]Pollono EN, et al. Clin Rheumatol. 2010[3]van Sijl AM, et al. Semin Arthritis Rheum. 2011.[4]Yoshida S, et al. J Hum Hypertens. 2014.[5]Gremese E, et al. Arthritis Care Res (Hoboken). 2013.[6]Heimans L, et al. Arthritis Care Res (Hoboken). 2013.Disclosure of Interests:Laura Cometi: None declared, Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Nicolò Chiti: None declared, Lorenzo Tofani: None declared, Francesca Nacci: None declared, Francesca Bartoli: None declared, Silvia Bellando Randone: None declared, Ginevra Fiori: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim

Background:In SSc, skin involvement of the face is frequent and extremely disabling, resulting in limited mouth opening, an altered dentition, difficulty in teeth care, as well as having a strong impact on the emotional and psychological well-being, thus impairing quality of life.Objectives:to evaluate the efficacy of a self-treatment protocol (created by AMURR A Multidisciplinary Association of Rheumatological Rehabilitation) for face and tempomandibular joints (TMJs) rehabilitation with two devices used in the dental field.Methods:40 SSc patients (37 female and 3 male) with a mouth opening ≤ 40 mm, were recruited and randomized in two groups of treatment: Group 1 (20 patients: mean age 50,650 yrs ± 13,937 SD, mean disease duraton 10,45 yrs ± 7,877 SD, opening mouth 32,250 mm ± 5,590 SD) treated with a home self-treatment protocol consisting of 23 exercises carried out at home in front of a mirror, 22/23 exercises were performed once a day, one of these using a device to obtain uniform stretching of the buccal rhyme, another one usingused three times a day to reduce tension of muscles of the TMJs, facilitating the mouth opening; group 2 (20 patients: mean age 58,05 yrs ± 18,103 SD, mean disease duration 17,4 yrs ± 15,017 SD, opening mouth 34,950 mm ± 5,753) without physical rehabilitation, only drugs as treatments of SSc and its complications. All patients underwent a baseline (T0) and 45 days (T1) clinimetric assessment by self-assessment of quality of life with SF-36 (Short-Form 36 Health Survey), of the degree of disability of the mouth with MHISS (of the Mouth Handicap in Systemic Sclerosis scale), Muscle pain evaluated by numerical rating scale (NRS) of the temporomandibular joint with TMD (Temporo mandibular Disorders), evaluation of mouth opening and ROM of the cervical spine. Statistical analysis was performed using the t-test or the Mann-Whitney test for assessing changes in all measurement scales between treatment groups.Results:The protocol of home physiotherapy exercises resulted in a statistically significant improvement in the treated group compared to group 2 both for mouth opening (T0: 32,250 ± 5,590, T1: 35,650 ± 6,046) vs (T0: 34,950 ± 5,753 T1: 34,300 ± 6,001) (pConclusion:The use of the home exercises protocol associated with the two devices has shown a significant improvement of the disability linked to skin involvement of the face. This highlights the fundamental role that home rehabilitation self therapy has in practice. These data will need to be confirmed in a larger cohort of patientsDisclosure of Interests:Mauro Passalacqua: None declared, Cristian Foggi: None declared, Nicola Mauro: None declared, Lorenzo Tofani: None declared, Serena Guiducci: None declared, Cosimo Bruni Speakers bureau: Actelion, Eli Lilly, Gemma Lepri: None declared, Jelena Blagojevic: None declared, Khadija El Aoufy: None declared, Ginevra Fiori: None declared, Francesca Bartoli: None declared, Susanna Maddali Bongi: None declared, Marco Mitola: None declared, Marco Gizduloch: None declared, Marco Matucci-Cerinic Grant/research support from: Actelion, MSD, Bristol-Myers Squibb, Speakers bureau: Acetelion, Lilly, Boehringer Ingelheim, Silvia Bellando Randone: None declared

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

Iloprost (ILO) is employed intravenously for the treatment of severe Raynaud phenomenon (RP) and digital ulcers (DU) in systemic sclerosis (SSc). The aim of this study was to evaluate the safety and tolerability of the intravenous treatment with ILO in different phases of SSc. Eighty-one consecutive non-selected SSc patients, all on nifedipine, with moderate RP, treated with ILO infusion, were retrospectively evaluated. Patients were sub classified according to the edematous or fibrotic/atrophic cutaneous phase of the disease. ILO was infused with a progressive increase of the dosage up to the achievement of patient's tolerance, 1 day/week. In cases of slower infusion regimen due to adverse events (AE) at the beginning of the administration, patients received a lower dose of the drug (not possible to quantify precisely the final cumulative dosage). 16/81 SSc patients presented digital edema, 5 developed diarrhea, and 9 developed transient hypotension during the infusion at 20 ml/h that ameliorated when the drug was withdrawn. Moreover, 10/16 edematous patients experienced significant and painful digital swelling, unlike patients in the fibrotic group (p