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BackgroundCurrent COVID-19 pandemic poses an unprecedented threat to global health and healthcare systems. At least in western countries, the most amount of the death toll is accounted by old people affected by age-related diseases. In this regard, we proposed that COVID-19 severity may be tightly related to inflammaging, i.e. the age-related onset of inflammation, which is responsible for age-related diseases. It has been reported that systemic hyper-inflammation may turn to be detrimental in COVID-19 patients.ObjectiveHere, we exploited a recently closed clinical trial (NCT04315480) on the anti-IL-6 drug tocilizumab to assess whether microRNAs regulating inflammaging can be assessed as biomarkers of drug response and outcome.MethodsSerum levels of miR-146a-5p, −21-5p, and −126-3p were quantified by RT-PCR and Droplet Digital PCR by two independent laboratories on 30 patients with virologically confirmed COVID-19, characterized by multifocal interstitial pneumonia confirmed by CT-scan and requiring oxygen therapy, and 29 age- and gender-matched healthy control subjects. COVID-19 patients were treated with a single-dose intravenous infusion of 8 mg/kg tocilizumab and categorized into responders and non-responders.ResultsWe showed that COVID-19 patients who did not respond to tocilizumab have lower serum levels of miR-146a-5p after the treatment (p=0.007). Moreover, among non-responders, those with the lowest serum levels of miR-146a-5p experienced the most adverse outcome (p=0.008).ConclusionOur data show that blood-based biomarkers, such as miR-146a-5p, can provide a molecular link between inflammaging and COVID-19 clinical course, thus allowing to enlarge the drug armory against this worldwide health threat.

Impaired hand function is a major contributor to overall disability and reduced health-related quality of life in scleroderma patients. A relevant issue concerns interaction of scleroderma subjects with touchscreen interfaces. This study aims at investigating this problem assessing scleroderma patients’ performance with a novel, aptly designed, touchscreen application in order to identify critical items of touchscreen technology which may impair or facilitate the use by scleroderma subjects. Eighty scleroderma patients performed this novel application including three games, each of which tested a different gesture: tapping, dragging/dropping, and pinching-to-zoom. Eighty healthy subjects without hand impairments were recruited as controls. Scleroderma patients performed worse than healthy users in each game, and statistically significant negatively impacting items were identified. In the second phase of the study, the 10 worst touchscreen performers within the scleroderma cohort were recruited for a physio-rehabilitation trial based on the daily use at home of a modified version of the software application downloaded into the personal devices of patients. The results of this study allow introduction of guidelines to design accessible touchscreen interfaces for subjects with scleroderma and suggest that touchscreen technology may be included in self-administered physio-rehabilitation programs for scleroderma hand.

Aims Cardiac involvement in patients with systemic sclerosis (SSc) is frequent and represents a negative prognostic factor. Recent studies have described subclinical heart involvement of both the right ventricle (RV) and left ventricle (LV) via speckle-tracking-derived global longitudinal strain (GLS). It is currently unknown if SSc-related cardiomyopathy progresses through time. Our aim was to assess the progression of subclinical cardiac involvement in patients with SSc via speckle-tracking-derived GLS. Methods This was a prospective longitudinal study enrolling 72 consecutive patients with a diagnosis of SSc and no structural heart disease nor pulmonary hypertension. A standard echocardiographic exam and GLS calculations were performed at baseline and at follow-up. Results Traditional echocardiographic parameters did not differ from baseline to 20-month follow-up. LV GLS, despite being already impaired at baseline, worsened significantly during follow-up (from –19.8 ± 3.5% to –18.7 ± 3.5%, p = .034). RV GLS impairment progressed through the follow-up period (from –20.9 ± 6.1% to –18.7 ± 5.4%, p = .013). The impairment was more pronounced for the endocardial layers of both LV (from –22.5 ± 3.9% to –21.4 ± 3.9%, p = .041) and RV (–24.2 ± 6.2% to –20.6 ± 5.9%, p = .001). A 1% worsening in RV GLS was associated with an 18% increased risk of all-cause death or major cardiovascular event (p = .03) and with a 55% increased risk of pulmonary hypertension (p = .043). Conclusion SSC-related cardiomyopathy progresses over time and can be detected by speckle-tracking GLS. The highest progression towards reduced deformation was registered for the endocardial layers, which supports the hypothesis that microvascular dysfunction is the main determinant of heart involvement in SSc patients and starts well before overt pulmonary hypertension.

The epithelial-to-mesenchymal transition (EMT) is a complex transcriptional program induced by transforming growth factor β1 (TGF-β1). Histone lysine-specific demethylase 1 (LSD1) has been recognized as a key mediator of EMT in cancer cells, but the precise mechanism that underlies the activation and repression of EMT genes still remains elusive. Here, we characterized the early events induced by TGF-β1 during EMT initiation and establishment. TGF-β1 triggered, 30–90 min post-treatment, a nuclear oxidative wave throughout the genome, documented by confocal microscopy and mass spectrometry, mediated by LSD1. LSD1 was recruited with phosphorylated SMAD2/3 to the promoters of prototypic genes activated and repressed by TGF-β1. After 90 min, phospho-SMAD2/3 downregulation reduced the complex and LSD1 was then recruited with the newly synthesized SNAI1 and repressors, NCoR1 and HDAC3, to the promoters of TGF-β1-repressed genes such as the Wnt soluble inhibitor factor 1 gene (WIF1), a change that induced a late oxidative burst. However, TGF-β1 early (90 min) repression of transcription also required synchronous signaling by reactive oxygen species and the stress-activated kinase c-Jun N-terminal kinase. These data elucidate the early events elicited by TGF-β1 and the priming role of DNA oxidation that marks TGF-β1-induced and -repressed genes involved in the EMT.

Introduction Spondyloarthrits (SpA) share clinical, genetic and immunological features with Inflammatory Bowel Diseases (IBD), and enteropathic SpA (eSpA) represent the clinical evidence of the association between gut and joint diseases. This cross-sectional study aimed to report data of eSpA patients collected from the first Italian database. Patients and methods A specific web-based interface has been created to insert and collect the main clinical, serologic and imaging data from patients with eSpA, as well as disease activity, comorbidities and treatment, in a real-life scenario. Results Data were collected in 14 Italian centers (7 rheumatology and 7 gastroenterology units). A total of 347 eSpA patients were enrolled in the study. Type 1 peripheral eSpA was the most frequent form. Crohn’ Disease (CD) was the most represented IBD. CD activity was similar among eSpA, whereas UC activity was slightly higher in the axial and mixed form than in the peripheral eSpA. The disease was active in less than half of axial eSpA patients and in only 18% of patients with peripheral eSpA. Furthermore, most of the patients had an inactive IBD. Nineteen percent of the total eSpA patients were free of therapy at the time of the enrollment and 61% of the patients were receiving biotechnological agents. Conclusions The multidisciplinary management of eSpA patients, favored by this ad hoc created web-based platform, allowed to obtain data from the largest eSpA cohort. The information coming of this database might advance knowledge of eSpA and improve their standard of care.

Clinica Medica and Ematologica in Ancona stemmed some 30 years ago from one originator medical team dedicated to Internal Medicine practice with a special interest towards immunological and hematological studies. This original scientific interest has spread over a multitude of fellows, some of whom have reached outstanding academic and clinical results, maintaining and extending the excellent reputation of the founding group over the years and until the present time. The best scientific achievements have been obtained in the field of systemic sclerosis and chronic graft versus host disease, whereas the clinical activity has been successfully dedicated to the management of autoimmune diseases and hematological disorders, with particular attention to innovative immunomodulatory therapies and stem cell transplantation.

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

Objective To investigate predictors of response, remission, low disease activity, damage, and drug discontinuation in patients with systemic lupus erythematosus (SLE) who were treated with belimumab. Methods In this retrospective study of a multicenter cohort of SLE patients who received intravenous belimumab, the proportion of patients who achieved remission, low disease activity, and treatment response according to the SLE Responder Index 4 (SRI-4) was determined, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) was used to score disease damage yearly over the follow-up. Predictors of outcomes were analyzed by multivariate logistic regression with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Results The study included 466 patients with active SLE from 24 Italian centers, with a median follow-up period of 18 months (range 1-60 months). An SRI-4 response was achieved by 49.2%, 61.3%, 69.7%, 69.6%, and 66.7% of patients at 6, 12, 24, 36, and 48 months, respectively. Baseline predictors of response at 6 months included a score of ≥10 on the SLE Disease Activity Index 2000 (SLEDAI-2K) (OR 3.14 [95% CI 2.033-4.860]) and a disease duration of ≤2 years (OR 1.94 [95% CI 1.078-3.473). Baseline predictors of response at 12 months included a score of ≥10 on the SLEDAI-2K (OR 3.48 [95% CI 2.004-6.025]) and an SDI score of 0 (OR 1.74 [95% CI 1.036-2.923]). Baseline predictors of response at 24 months included a score of ≥10 on the SLEDAI-2K (OR 4.25 [95% CI 2.018-8.940]) and a disease duration of ≤2 years (OR 3.79 [95% CI 1.039-13.52]). Baseline predictors of response at 36 months included a score of ≥10 on the SLEDAI-2K (OR 14.59 [95% CI 3.54-59.79) and baseline status of current smoker (OR 0.19 [95% CI 0.039-0.69]). Patients who were in remission for ≥25% of the follow-up period (44.3%) or who had low disease activity for ≥50% of the follow-up period (66.1%) accrued significantly less damage (P = 0.046 and P = 0.007). A baseline SDI score of 0 was an independent predictor of achieving low disease activity in ≥50% of the follow-up period and remission in ≥25% of the follow-up period. Our findings suggest that the lower the baseline damage, the greater the probability of achieving remission over the course of ≥25% of the follow-up. Further, there was a negative association between the number of flares reported prior to belimumab initiation and the frequency of belimumab discontinuation due to inefficacy (P = 0.009). Conclusion In patients with active SLE and low damage at baseline, treatment with belimumab early in the disease may lead to favorable outcomes in a real-life setting.

Objectives The prevalence and clinical implications of small airways involvement in SSc are still to be fully elucidated. The goal of the present work is to assess the prevalence of small airways dysfunction by impulse oscillometry and to determine whether it correlates with selected disease-related features and respiratory-related quality of life. Methods Ninety-four SSc patients and 93 healthy controls were studied by impulse oscillometry measurements. Small airways dysfunction was defined as the difference between resistance at low frequency, i.e. 5 Hz, and resistance at high frequency, i.e. 20 Hz, termed ‘R5-R20’, ⩾0.07 kPa/l/s. The St George’s Respiratory Questionnaire was used to measure health impairment in SSc patients. Radiological features of small airways disease and parenchymal abnormalities on high resolution CT chest scans were jointly assessed by two thoracic radiologists. Results Small airways dysfunction was present in 21.5% of the SSc patient cohort, with a prevalence almost 5-fold higher compared with controls, and it was significantly associated with worse respiratory-related quality of life. Radiological features consistent with small airways abnormalities were detected in 25% of SSc patients, mostly in the absence of interstitial lung changes. Combining functional and radiological evaluations, one-third of the SSc cohort showed at least one feature of small airways involvement, which was associated with the lcSSc phenotype and with longer disease duration. Conclusion The current study strengthens the hypothesis that small airway dysfunction might be a feature of SSc-related lung involvement, providing the first data on its significant impact on respiratory-related quality of life. A full assessment of lung function in SSc patients should include impulse oscillometry as a complementary technique, due to potential clinical and therapeutic implications.

Background Immune checkpoint inhibitors are a new promising class of antitumor drugs that have been associated with a number of immune-related Adverse Events (AEs), including musculoskeletal and rheumatic disease. Methods We searched Medline reviewing reports of musculoskeletal and rheumatic AEs induced by immune checkpoint inhibitors. Results Several musculoskeletal and rheumatic AEs associated with immune checkpoint inhibitors treatment are reported in the literature. In particular, arthralgia and myalgia were the most common reported AEs, whereas the prevalence of arthritis, myositis and vasculitis is less characterized and mainly reported in case series and case reports. Other occasionally described AEs are sicca syndrome, polymyalgia rheumatica, systemic lupus erythematosus and sarcoidosis. Conclusion Newly induced musculoskeletal and rheumatic diseases are a frequent adverse event associated with immune checkpoint inhibitors treatment.

In our study, we aimed to demonstrate whether a complex iatrogenic clubfoot really exists; identify the causative mechanisms; and determine the outcome if properly treated. We observed 54 clubfeet previously treated unsuccessfully by manipulation and casting elsewhere. All the feet had been classified at diagnosis as typical clubfeet. In 26 cases, the cast had slipped down, entrapping the foot in a plantar-flexed position. Nine clubfeet out of those 26 cases presented the clinical features of a complex iatrogenic deformity. These were treated with the modified Ponseti protocol and evaluated at follow-up according to the International Clubfoot Study Group Score. The length of follow-up averaged 7.2 years. Two feet showed an excellent result, five feet showed a good result, and two feet showed a fair result. The relapse rate was 55% in complex clubfeet. Relapsed clubfeet were treated by Achilles tenotomy or lengthening and anterior tibial tendon transfer. We believe that faulty manipulation and a poor casting technique may convert a typical clubfoot into a complex iatrogenic deformity. Risk factors include severe clubfoot, short and stubby foot, and unmolded casts slipping down.

Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune arthritis, occurring in patients with psoriasis (Pso), that may affect the whole musculoskeletal system but also nails, eye, and gastrointestinal tract. Dermatologists and rheumatologists usually manage Pso and PsA separately, but early diagnosis and integrated management could achieve better outcomes of both skin and musculoskeletal manifestations, thus improving the health-related quality of life (HRQoL) of patients. In this work, we have described a model of integrated dermo-rheumatologic approach for the early diagnosis of PsA and to present the outcomes of the multidisciplinary management of PsA patients after 48 weeks of follow-up. Pso patients complaining musculoskeletal symptoms were enrolled in a DErmo-Rheumatologic Clinic (DERC) in order to screen, classify, and treat patients with PsA, employing an operative working procedure and a specific flowchart. The integrated dermatologic and rheumatologic management of PsA patients allowed a prompt establishment of the diagnosis and the best therapeutic approach in these patients, with a significant improvement of skin and articular diseases and, eventually, a consistent amelioration of HRQoL. Dermatologists and rheumatologists usually manage the "psoriatic disease" in separated outpatient clinics. In our study, we have demonstrated that a combined DERC, by means of a tight cooperation between the dermatologist and the rheumatologist, which use a specific working procedure and treatment flowchart, may achieve the optimal clinical management of these patients, with a consistent clinical remission of the disease and a significant amelioration of the HRQoL.

Background Systemic sclerosis is characterised by progressive cutaneous and organ fibrosis. Among all organs, a subclinical heart involvement is difficult to detect through conventional imaging. Design We evaluated whether speckle tracking-derived global longitudinal strain could help detect early subclinical systolic dysfunction in systemic sclerosis patients without overt clinical involvement. Methods A case–control, single-centre study on 52 systemic sclerosis patients and 52 age and gender-matched controls. Patients with structural heart disease, heart failure, atrial fibrillation and pulmonary hypertension were excluded. For every patient, standard echocardiographic and speckle tracking-derived variables for the systolic and diastolic function of the left ventricle and right ventricle were acquired. Results Traditional parameters of left and right systolic function did not differ between systemic sclerosis patients and controls (all P = ns). Left and right ventricular global longitudinal strain was significantly impaired in patients with systemic sclerosis when compared to controls (–19.2% vs. –21.1%; P = 0.009 and –18.2% vs. –22.3%; P = 0.012, respectively). Systemic sclerosis patients had a 2.5-fold increased risk of subclinical left ventricular systolic impairment (odds ratio 2.5, 95% confidence interval 1.1–5.5; P = 0.027) and a 3.3-fold increased risk of subclinical right ventricular systolic impairment when compared to controls (odds ratio 3.3, 95% confidence interval 1.4–7.7; P = 0.004). Alterations in the myocardial deformation pattern of systemic sclerosis patients were homogeneous in the right ventricle and eccentric in the left ventricle. Conclusions While traditional echocardiographic parameters are ineffective in detecting subclinical systolic impairment, reduced global longitudinal strain is common in patients with systemic sclerosis and significant for both ventricles. Global longitudinal strain could become a low-cost, non-invasive and reliable tool in order to detect early cardiac involvement in systemic sclerosis patients.

Systemic sclerosis (SSc) is an autoimmune disease of unknown aetiology characterized by vascular lesions, immunological alterations and diffuse fibrosis of the skin and internal organs. Since recent evidence suggests that there is a link between metabolomics and immune mediated disease, serum metabolic profile of SSc patients and healthy controls was investigated by 1H-NMR and GC-MS techniques. The results indicated a lower level of aspartate, alanine, choline, glutamate, and glutarate in SSc patients compared with healthy controls. Moreover, comparing patients affected by limited SSc (lcSSc) and diffuse SSc (dcSSc), 6 discriminant metabolites were identified. The multivariate analysis performed using all the metabolites significantly different revealed glycolysis, gluconeogenesis, energetic pathways, glutamate metabolism, degradation of ketone bodies and pyruvate metabolism as the most important networks. Aspartate, alanine and citrate yielded a high area under receiver-operating characteristic (ROC) curves (AUC of 0.81; CI 0.726–0.93) for discriminating SSc patients from controls, whereas ROC curve generated with acetate, fructose, glutamate, glutamine, glycerol and glutarate (AUC of 0.84; CI 0.7–0.98) discriminated between lcSSc and dcSSc. These results indicated that serum NMR-based metabolomics profiling method is sensitive and specific enough to distinguish SSc from healthy controls and provided a feasible diagnostic tool for the diagnosis and classification of the disease.

Oesophageal dilatation (OD) has been implicated in the pathogenesis of interstitial lung disease (ILD) in systemic sclerosis (SSc). The aims of this study were to explore the association of the OD and SSc-ILD on chest high-resolution computed tomography (HRCT), and to establish a cutoff point for the OD suggestive for the presence of a significant lung involvement.The widest oesophageal diameter (WOD) was obtained on axial HRCT images. The parenchymal abnormalities on HRCT were coded and scored according to Warrick method. Patient-centred measures, pulmonary function tests and the single breath carbon monoxide diffusing capacity of the lung (DLco) were also obtained. Multivariate regression analysis was performed to identify factors associated with oesophageal diameter.126 subjects with SSc were included. The mean (± SD) WOD was 13.5 (± 4.2) mm, and in 76 (60.3%) participants WOD was ≥ 11 mm. SSc patients with ILD had larger oesophageal diameters than those without lung disease (19.4 vs. 14.1 mm, p 0.001). We observed a high correlation between WOD and gastro-oesophageal reflux disease questionnaire (GerdQ) (r = 0.886, p 0.001), Borg score (r = 0.705, p 0.001), and Warrick score (r = 0.614, p 0.001). WOD negatively correlated with DLco (r = - 0.508, p 0.001). Multivariate analysis demonstrated positive associations between WOD and GerdQ (p 0.0001), Borg score (p 0.0005), and total Warrick score (p = 0.019).An increased oesophageal diameter ( 11 mm) on chest HRCT is associated with pulmonary and oesophageal symptoms, more severe ILD, and lower DLco.

Background The use of biologic agents in systemic immune-mediated diseases has dramatically increased in recent years, replacing conventional immunosuppressive strategies that are characterized by unspecific mechanisms of action and burdened with serious adverse effects. Biologic drugs have selective action towards specific targets, with considerable steroid-sparing effect. They are used nowadays to induce remission or treat specific organ involvements in systemic autoimmune diseases. Conclusion In this review, we will discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the conventional drugs.

BACKGROUND Biologic drugs, introduced in clinical practice almost twenty years ago, represent nowadays a prominent treatment option in patients with chronic inflammatory arthritis, such as Rheumatoid Arthritis, Psoriatic Arthritis and Spondyloarthritis, that include ankylosing spondylitis and non-radiographic axial spondyloarthritis. METHODS Several compounds targeting different pathways have been marketed and approved for the treatment of inflammatory arthritis, with a significant impact on the clinical outcomes and the natural history of the diseases. RESULTS There are currently seven classes of biologics that are available for the treatment of inflammatory arthritis, each inhibiting a different aspect of the immune-driven inflammatory pathway. They include: • Tumor Necrosis Factor (TNF) inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol); • Interleukin-1 (IL-1) receptor antagonists (anakinra); • Interleukin-6 (IL-6) inhibition (tocilizumab); • Interleukin-12/23 (IL23) inhibition (ustekinumab); • Interleukin-17 (IL-17) inhibition (secukinumab); • B-cell inhibition (anti-CD20, rituximab); • T-cell costimulation inhibition (anti-CTLA-4, abatacept). CONCLUSION In this review, we will focus on the role of biologic drugs in the treatment strategies for inflammatory arthritis.

Systemic sclerosis (SSc) is characterized by microangiopathy, excessive fibrosis, and the presence of circulating autoantibodies to several cellular and extracellular components. The role of autoimmunity in generating the clinical and pathologic phenotypes in SSc has been long debated and is still matter of controversy. Distinct specificities of antinuclear antibodies (ANAs) are selectively detected in SSc patients and are associated with unique disease manifestations, but do not have a proven pathogenic role. A new group of autoantibodies reactive with cell surface receptors have been identified in SSc patients. They have been shown to directly activate pathways that may contribute to tissue and vascular damage. As such, they are proposed to have a role as agonistic autoantibodies in SSc. According to Koch's third postulate, the autoantibodies in question should cause disease when introduced into a healthy subject. Therefore, our review will focus on those autoantibodies for which agonistic activity has already been demonstrated not only in vitro, but, at least partly, also in vivo. These include the antibodies anti-endothelial cells (AECA), anti-Platelet-Derived Growth Factor Receptor (PDGFR), anti-Angiotensin II type 1 receptor (AT1R) and anti-endothelin-1 type A receptor (ETaR). In this review, we will discuss also a class of antagonistic autoantibodies, the anti-muscarinic-3 receptor (M3R) antibodies, since they seem to fulfill the aforementioned requirements.

Lartruvo® (olaratumab) is a fully human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that inhibits platelet-derived growth factor receptor alpha (PDGFRα). The antitumor activity of olaratumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in cancer cell lines, including glioblastoma and leiomyosarcoma cells. It represents the first-in-class antibody to be approved by regulatory authorities for the treatment of advanced soft-tissue sarcomas (STSs) in combination with doxorubicin, based on the results of the Phase Ib/II trial by Tap et al. The median progression-free survival (PFS), which was the primary end point of the study, was improved for patients treated with olaratumab plus doxorubicin compared to those treated with doxorubicin monotherapy (6.6 vs 4.1 months, respectively; HR 0.672, 95% CI 0.442–1.021, p=0.0615). Moreover, final analysis of overall survival (OS) showed a median OS of 26.5 months with olaratumab plus doxorubicin vs 14.7 months with doxorubicin, with a gain of 11.8 months (HR 0.46, 95% CI 0.30–0.71, p=0.0003). In October 2016, olaratumab was admitted in the Accelerated Approval Program by the US Food and Drug Administration (FDA) for use in combination with doxorubicin for the treatment of adult patients with STSs. In November 2016, the European Medicines Agency (EMA) granted conditional approval for olaratumab in the same indication under its Accelerated Assessment Program. A double-blind, placebo-controlled, randomized Phase III study (ANNOUNCE trial, NCT02451943) is being performed in order to confirm the survival advantage of olaratumab and to provide definitive drug confirmation by regulators. The study is ongoing, but enrollment is closed. The purpose of this review was to evaluate the rationale of olaratumab in the treatment of advanced STSs and its emerging role in clinical practice.

Background:Nintedanib has shown to slow FVC decline by 41ml over 52 weeks in systemic sclerosis-associated interstitial lung disease (SSc-ILD). However, the long-term effect of nintedanib treatment on ILD progression and mortality in SSc patients is so far unknown.Objectives:Here, the 52-week treatment efficacy of nintedanib was modeled and extrapolated on the long-term FVC course and survival in SSc-ILD patients from the European Scleroderma Trial and Research (EUSTAR) database.Methods:SSc patients from the EUSTAR database fulfilling the inclusion criteria of the SENSCIS trial (SSc classification criteria, ILD confirmed by imaging, disease duration of Results:Of the 236 included patients, 75% were females, 65% had diffuse cutaneous SSc. Mean age was 50.6 years, mean FVC 78.2%pred and DLCO 56.3%pred at time of inclusion. Mean FVC change after 12±3 months was -2.3 ±6.9%pred. These parameters were largely similar to the characteristics of the SENSCIS population.In the longitudinal follow up of this population, the natural course of FVC showed a total FVC decline of -16.3%pred over 5 years. With assumed SENSCIS effects (effects of nintedanib treatment reported in SENSCIS), the 5-year FVC decline was reduced to -10.3%pred (Figure 1).The reduced FVC progression translated into an improved survival. The natural 5-year survival of this SSc-ILD population was 88.2%. When extrapolating also a severe FVC decline early in the course, frequently terminated by early mortality of SSc patients excluding them from long-term outcome assessment, the estimated 5-year survival was reduced to 81.6%. When the SENSCIS effects on FVC were considered, the 5-year extrapolated survival was increased to 86.3% (Figure 2).Conclusion:Long-term experience of nintedanib treatment in SSc-ILD patients is lacking so far, therefore we modeled and extrapolated the 52-week treatment efficacy of nintedanib on the long-term FVC course and survival in SSc-ILD patients from the EUSTAR database. We could demonstrate a significant reduction of FVC decline by extrapolating the annual treatment effects of nintedanib from the SENSCIS trial from 1 to 5 years in EUSTAR. Translating these reductions of FVC decline into survival, the 5-year mortality rate was reduced from 18% to 13%.Disclosure of Interests:Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Merck Sharp & Dohme, Lilly, Consultant of: Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX, Lilly and Medscape, Grant/research support from: Boehringer Ingelheim, Dörte Huscher: None declared, Paolo Airò Speakers bureau: Boehringer Ingelheim, Consultant of: Bristol-Myers-Squibb, Novartis, Elisabetta Zanatta Speakers bureau: Boehringer Ingelheim, Actelion, GSK, Paid instructor for: GSK, Consultant of: Boehringer Ingelheim, GSK, Patricia Carreira Speakers bureau: Actelion, Boehringer Ingellheim, Janssen, GSK, Paid instructor for: Boehringer Ingelheim, Consultant of: AbbVie, Boehringer Ingelheim, VivaCell, Emerald Health Pharmaceuticals, Gesynta Pharma, Sanofi Genzyme, Grant/research support from: Roche, GSK, Yannick Allanore Consultant of: Honorarium received from Boehringer, MedsenicSanofi, Menarini, Grant/research support from: Grants received from Alpine, Ose Immunogenetics, Ulf Müller-Ladner Speakers bureau: Boehringer Ingelheim, Consultant of: Boehringer Ingelheim, Alessandro Giollo: None declared, Maria Rosa Pozzi: None declared, CAROLINA SOUZA MULLER Speakers bureau: Boehinger Ingelheim, Janssen, Roche, LIBBS, Bristol-Myers-Squib, Radim Bečvář Consultant of: Actelion, Boehringer Ingelheim, Michele Iudici: None declared, Dominik Majewski Speakers bureau: Boehringer Ingelheim - 2 x paid as a speaker, Armando Gabrielli Grant/research support from: Pfizer, CSL Behring, Margarida Alves Employee of: Boehringer Ingelheim, Nils Schoof Employee of: Boehringer Ingelheim International GmbH, Oliver Distler Speakers bureau: Boehringer Ingelheim, Medscape, IQone, Roche, Consultant of: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, Kymera Therapeutics, Lilly, Medac, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB, Grant/research support from: Kymera Therapeutics, Mitsubishi Tanabe

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

Background:There is renewed interest in the role of autoantibodies to predict outcomes in systemic sclerosis (SSc). Among the newly identified subsets, patients with limited cutaneous form (lcSSc) but anti-topoisomerase I antibodies (Scl70) positivity draw particular attention, and namely, assessing the risk of developing interstitial lung disease (ILD) —the main cause of death in SSc—to improve the management of Scl70-lcSSc patients.Objectives:We aimed to characterize patients with Scl70-lcSSc in the large multicenter European Scleroderma Trial and Research (EUSTAR) cohort.Methods:The EUSTAR database was locked in July 2019. We included all patients fulfilling 1980 ACR and/or 2013 ACR/EULAR criteria for SSc, with disease duration at database entry ≤3 yrs and known and stable skin form during the first 3 yrs. Patients with lcSSc were compared: Scl70-lcSSc (target group) vs. ACA-lcSSc and ANA-lcSSc (Step 1); and Scl70-lcSSc vs. Scl70-dcSSc (Step 2). In the ANA subgroup we included ANA+ patients with negative SSc-specific antibodies (Scl70, ACA, RNA polymerase III). In each step, we performed 5 generalized mixed models (GMM) for the risk of the new onset of ILD (defined by imaging), primary myocardial involvement (PMI), pulmonary hypertension (PH), “any severe” (ILD+PMI+PH+scleroderma renal crisis) and all-cause-mortality. An additional GMM assessed the risk of forced vital capacity (FVC) decline ≥10% vs. FVC value at ILD onset. Each GMM was adjusted for age, sex and confounders.Results:Overall, 1285 SSc patients were included: 1068 (83%) females, 860 (67%) lcSSc and 425 (33%) dcSSc. Among patients with lcSSc, 537 (62%) had ACA+, 194 (23%) Scl70+ and 129 (15%) ANA+; 425 patients had dcSSc and Scl70+. Median follow-up was similar in all 4 groups: 7.2 to 8.1 yrs.Step 1: At baseline, Scl70-lcSSc patients had significantly shorter time from Raynaud’s phenomenon (RP) to SSc onset, higher mRSS (5.8±4.8 vs. 4.3±4, p=0.001), and higher rate of articular and muscular involvement vs. ACA-lcSSc patients (Figure 1). No differences were found between Scl70-lcSSc and ANA-lcSSc comparing the aforementioned variables. ILD was more frequent in Scl70-lcSSc (46%) than in ACA-lcSSc (10%) and ANA-lcSSc (25%), as well as restrictive lung disease. GMM showed that Scl70-lcSSc carries a higher risk of ILD than both ACA-lcSSc (HR 4.55, 95%CI 3.23-6.67) and ANA-lcSSc (HR 2.17, 95%CI 1.39-3.45), with a rate of FVC decline ≥10% over time similar to the other limited forms. In Scl70-lcSSc patients the risk of “any severe” organ involvement was similar to ANA-lcSSc and higher than ACA-lcSSc (HR 1.89, 95%CI 1.40-2.50). In particular, Scl70-lcSSc shows a risk of PMI similar to ANA-lcSSc and lower than ACA-lcSSc; no differences regarding PH risk. The mortality risk in patients with Scl70-lcSSc was similar to the other limited forms’.Step 2: At baseline, time from RP to SSc onset was longer in patients with Scl70-lcSSc, with less frequent joint synovitis and tendon friction rubs vs. patients with Scl70-dcSSc. Conversely, the frequency of muscular, cardiac and pulmonary involvement was similar. The risk of ILD in Scl70-lcSSc patients was similar to Scl70-dcSSc, with a lower risk of FVC decline ≥10% over time. The risk of “any severe” involvement (HR 0.66, 95%CI 0.49-0.83), PMI and PH was lower and the mortality risk tended to be lower (HR 0.57, 95%CI 0.33-1.01, p=0.053) vs. Scl70-dcSSc.Conclusion:In our large multicenter EUSTAR cohort one quarter of lcSSc patients were Scl70+. We show a ranking for major organ involvement within lcSSc: Scl70 the most severe, ANA+ intermediate and ACA the milder form. Scl70-dcSSc patients present the most severe phenotype, and Scl70 positivity, more than the cutaneous subset, is strongly predictive of ILD, whereas other variables may influence progression. These results may provide new insight to improve the management of Scl70-lcSSc patients.Disclosure of Interests:Elisabetta Zanatta: None declared, Dörte Huscher: None declared, Paolo Airò: None declared, Alexandra Balbir-Gurman: None declared, Elise Siegert: None declared, Augusta Ortolan: None declared, Marco Matucci-Cerinic: None declared, Franco Cozzi: None declared, Gabriela Riemekasten: None declared, Anna-Maria Hoffmann-Vold: None declared, Oliver Distler Speakers bureau: has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Consultant of: has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: Kymera Therapeutics, Mitsubishi Tanabe, Armando Gabrielli: None declared, Stefan Heitmann: None declared, Nicolas Hunzelmann: None declared, Carlomaurizio Montecucco: None declared, Jadranka Morovic-Vergles: None declared, Camillo Ribi: None declared, Andrea Doria: None declared, Yannick Allanore: None declared

Background:LN is still a severe manifestation of Systemic lupus erythematosus (SLE) and multitarget therapy is needed to control the disease especially in refractory cases.Objectives:To evaluate renal response in SLE patients with glomerulonephritis (GN) treated with Belimumab in real-life setting.Methods:Patients with proteinuria >0.5 g/24 h and/or active sediment at baseline enrolled in a multicentre Italian cohort of SLE patients (BeRLiSS study), treated with monthly iv Belimumab 10 mg/kg plus standard of care were considered in this study. Complete renal response (CRR) was defined as proteinuria 2 and no rescue therapy. Primary efficacy renal response (PERR) was defined as proteinuria ≤0.7 g/24 h, eGFR ≥60ml/min/1.73m2 and no rescue therapy. Prevalence and predictive factors of CRR and PERR at 12 and 24 months after Belimumab initiation were analyzed by multivariate logistic regression analysis.Results:A total of 91 patients were considered in this study, 79 female, mean age 40.51±9.03 years, mean disease duration 12.18±8.15 years, median follow-up time after Belimumab initiation 22 months. Twenty patients had baseline proteinuria ≥0.5 2 at baseline. Immunosuppresants were taken by 70 (76.9%) patients: 47 micofenolate, 15 azathioprine and 5 ciclosporine. Sixty patients (65.9%) were on antimalarials. During follow-up 34 (37.4%) patients achieved CRR. Among them 5 (14.7%) patients relapsed and 29 (85.3%) patients maintained remission. Mean time to achieved CRR was 9.71±5.91 months.High levels of baseline proteinuria were a negative independent predictor of CRR and PERR at 6 months (OR 0.044 CI95% 0.006-0.320 p=0.002 and OR 0.232 CI95% 0.091-0.596 p=0.002) and 12 months (OR 0.029 CI95% 0.002-0.556 p=0.019 and OR 0.056 CI95% 0.009-0.327 p=0.001). High levels of baseline creatinine were a negative independent predictor of renal response. Renal response at 6 months was a strong predictive factor of renal response at 12 and 24 months.Conclusion:Belimumab is an effective add-on therapy in the treatment of GN in real-life practice setting.Disclosure of Interests:None declared

Background:In SSc, ILD is a major cause of morbidity and mortality. High resolution computed tomography (HRCT) is the gold standard for the diagnosis. Predictors of ILD onset are eagerly awaited to improve SSc-ILD management. Pulmonary function test (PFTs) are routinely performed to measure lung function changes.Objectives:Our aim was to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) in predicting the development of SSc-ILD.Methods:The longitudinal data of DLCO, FVC and ILD on HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0), after 12 (±4) (t1) and 24 (±4) (t2) months. Patients with negative HRCT for any sign of ILD both at t0 and t1 were included. Patients who presented or developed pulmonary hypertension during the study period were excluded. At baseline, demographic data, disease duration from Raynaud’s onset, disease subsets, autoantibodies and other laboratory and instrumental data were recorded.Results:474/17805 patients were eligible for the study (403 females, 71 males): 26.0% dcSSc, 58.3% lcSSc, 220 (48.0%) patients with positive anticentromere antibodies (ACA) and 117 (25.4%) with positive antitopoisomerase I antibodies (Topo-I abs). Among all enrolled patients, 46 (9.7%) developed HRCT signs of ILD at t2. Patients with Topo-I abs showed an association with ILD development at t2 (16.7% vs 7.8%, p=0.0031), contrarily ACA positive patients were negatively associated with ILD appearance after 2 years of follow-up (4.4% vs 14.4%, p=0.0001). Positive t2 HRCT patients had a significant lower value of DLCO and FVC at all three assessments when compared to patients with a negative HRCT at t2 (Table 1) and both t0 DLCO and FVC values negatively correlated with ILD development (Table 1). The mean t0 to t1 change (Δ) of DLCO in patients with negative t2 HRTC and positive t2 HRCT were -0.5 (±12.6) and -1.0 (±15.1), respectively. The mean t0 to t1 ΔFVC in patients with negative t2 HRTC and positive t2 HRCT were -0.2 (±10.6) and 0.1 (±11.5), respectively. None of them predicted the appearance of ILD at t2 (ΔDLCO: OR (IC) 0.997 (0.97-1.02), p=0.8024; ΔFVC OR (IC) 1.002 (0.97-1.03), p=0.8664). The data showed an association between t0 DLCO value0 FVC value0 DLCOConclusion:Our data suggest that an impaired baseline DLCO (Table 1.DLCO and FVC values at t0, t1 and t2 values in patients with positive or negative HRCT for ILD at t2 and their statistical differences.Patients without ILD at t2 (mean±SD)Patients with ILD at t2 (mean±SD)OR (95%CL)p-valueDLCO at t079.0 ± 16.669.9 ± 17.40.97 (0.95 - 0.99)0.0006DLCO at t178.4 ± 16.868.9 ± 18.60.97 (0.95 - 0.98)0.0005DLCO at t278.0 ± 17.065.1 ± 19.10.95 (0.93 - 0.97)FVC at t0102.2 ± 17.394.6 ± 16.20.97 (0.96 - 0.99)0.0052FVC at t1101.9 ± 17.994.7 ± 16.50.98 (0.96 - 0.99)0.0092FVC at t2101.6 ± 17.694.5 ± 20.00.98 (0.96 - 1)0.0126Disclosure of Interests:Gemma Lepri: None declared, Cosimo Bruni Speakers bureau: CB reports personal fees from Actelion, personal fees from Eli Lilly, Grant/research support from: CB reports personal fees from Actelion, personal fees from Eli Lilly, grants from European Scleroderma Trial and Research (EUSTAR) group, grants from New Horizon Fellowship, grants from Foundation for Research in Rheumatology (FOREUM), grants from Fondazione Italiana per la Ricerca sull’Artrite (FIRA), outside the submitted work, Lorenzo Tofani: None declared, Alberto Moggi Pignone: None declared, Martina Orlandi: None declared, Tomasetti Sara Speakers bureau: Speaker’s fees for Roche and Boehringer Ingelheim, Mike Hughes: None declared, Francesco Del Galdo: None declared, Rosaria Irace: None declared, Oliver Distler Grant/research support from: OD (last three years) has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Valeria Riccieri: None declared, Yannick Allanore Speakers bureau: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Grant/research support from: YA received personal fees from Boehringer, Sanofi, Menarini and Medsenic and grants from Alpine with regards to the management of systemic sclerosis, Ana Maria Gheorghiu: None declared, Elise Siegert: None declared, Jeska de Vries-Bouwstra: None declared, Eric Hachulla: None declared, Mohammed Tikly: None declared, Nemanja Damjanov: None declared, Francois Spertini: None declared, Luc Mouthon: None declared, Anna-Maria Hoffmann-Vold Speakers bureau: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Consultant of: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Grant/research support from: AMHV: received consulting fees from Actelion, ARXX, Bayer, Boehringer Ingelheim, Lilly, Medscape, Merck Sharp & Dohme and Roche; and grants from Boehringer Ingelheim., Armando Gabrielli: None declared, Serena Guiducci: None declared, Marco Matucci-Cerinic Speakers bureau: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Grant/research support from: has received consulting fees or honorarium from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche, Daniel Furst: None declared, Silvia Bellando Randone: None declared

Objective.Subclinical heart disease occurs in up to 50% of patients with idiopathic inflammatory myopathies (IIM) and is difficult to detect through conventional imaging. We investigated the usefulness of global longitudinal strain (GLS) measurement to detect a subclinical systolic ventricular dysfunction in patients with IIM.Methods.We enrolled 28 patients with IIM and 28 matched controls in a 1:1 fashion. Standard variables for the left ventricle (LV) and right ventricle (RV) systolic and diastolic function were measured and compared between cases and controls, along with speckle-tracking GLS of the LV and RV. A possible correlation between GLS and muscle strength, disease activity, cardiovascular risk factors, and other organ systems involvement was searched.Results.Standard variables of systolic and diastolic dysfunction were similar between patients and controls. GLS was significantly lower in patients when compared with controls for both LV (−18.7 ± 4.2% vs −21.2 ± 2.1%, p = 0.006) and RV (−19.3 ± 6.3% vs −22.5 ± 3.8%, p = 0.033). Patients with IIM had a 4.9-fold increased risk for impaired left GLS [relative risk (RR) 4.9, 95% CI 1.5–15.8, p = 0.006], which involved usually basal and mid-segments of the anterior, anterior-septal, and lateral wall. Patients with IIM had a 3.4-fold increased risk for impaired right GLS (RR 3.4, 95% CI 1.1–11.7, p = 0.04) with the basal segment of the free RV wall most frequently involved. Muscle strength, disease activity, damage and duration, other organ system involvement, and previous treatment were not associated with reduced GLS.Conclusion.Subclinical systolic impairment is common in patients with IIM without overt LV dysfunction. In this context, GLS is a potentially useful variable.

Psoriasis is a chronic immunomediated and inflammatory disease involving mainly skin and joints, often associated with several metabolic and non-metabolic comorbidities. TNF-alpha inhibitors have shown long-term efficacy and safety/tolerability in psoriasis, and preliminary data support the use of certolizumab pegol (CZP) as well. Areas covered: The authors review the pharmacological properties of CZP, as well as its safety data and efficacy profile. They also review the quality of life outcomes related to CZP in psoriasis. The authors also provide their expert opinion on the subject. Expert opinion: CZP is a promising treatment for psoriasis owing to its rapid reduction of disease activity, long-term therapeutic efficacy - both in bio-naive and non-bio-naive patients, long term safety and low rate of site injection reactions. CZP seems to be a promising therapeutic option for psoriasis patients, although further evidence supporting the continuing clinical program for development of CZP in psoriasis is needed.

Background:There is a paucity of epidemiological data in Early Arthritis. SIRENA is an Italian prospective observational study in SpA patients, naïve to conventional, targeted and biological DMARDs.Objectives:To present the baseline data, including demographic characteristics and patterns of clinical presentation, for the population enrolled between June 2017-February 2019.Methods:At the study entry, patients are diagnosed, newly or confirmed, according to ASAS criteria and classified in subjects with predominant axial (AX) or with mainly peripheral (PER) manifestations. Diagnostic delay, subtypes of SpA are evaluated as well as clinical features (i.e. presence of dactylitis, enthesitis, involvement of skin/nails/other organs).Results:In 23 italian sites, 282 patients were enrolled. Baseline data are shown in Table 1. 18% of the patients were obese (maximum BMI=39.7), 22% overweight. Diagnostic delay was registered for 58.1% patients with a mean delay of 57.1 months. Main reasons of the delay were incorrect referrals (44%) and previous misdiagnosis (27%). The most frequent type of SpA was psoriatic arthritis (54.3%), followed by ankylosing spondylitis (18.5%), undifferentiated SpA (11.5%), non-radiographic axial SpA (8.2%), and enteropathic SpA (7.5%). The majority of patients reported as first symptom peripheral arthritis and inflammatory back pain, followed by enthesitis. The most frequently reported comorbidities were psoriasis (50.4%) and cardiometabolic and gastrointestinal diseases (30.1% and 15.7%,respectively) - Table 2. To the 154 psoriatic arthritis (PsA) patients, CASPAR classification criteria were also applied, with a performance of 95% and a mean score of 3.64.Conclusion:SIRENA is the first Italian Disease Registry for SpA patients. The above results are in line with the few evidences found in literature (1), confirming the representativeness of our sample. In case of PsA, our results confirm that the accordance between ASAS and CASPAR criteria is very high.References:[1]Tayel et al. Rheumatol Int 2012; 32:2837-42.Table 1.Patient Characteristics (baseline)MeanN=282Age50.8 yearsSex (%)49 F/51 MWeight73.7 KgBMI25.3Smoking Status (never/ongoing/past - %)56.8/22/21.2Alcohol consumption (not/occasional/usual drinker - %)50.0/44.9/5.1SpA type (%)35.8 AX/64.2 PERDiagnostic Delay (yes - %)58.1Months of diagnostic delay (mean)57.1 monthsNewly diagnosis (%)68.4Table 2.A) First SymptomNumber of PatientsN=282, more than 1 symptom referredArthritis145Enthesitis70Dactylitis35Inflammatory Back Pain114Psoriasis skin67Psoriasis nails21Uveitis5IBD16B) ComorbiditiesPercentage of PatientsN=282, more than 1 comorbidity referredCardiometabolic30.1% - Hypertension27.0% - Dyslipidemia13.8% - Diabetes7.1% - MetS6.0% - CHD3.2%Psoriasis50.4%Gastrointestinal15.7% (5.3% Crohn’s disease)Endocrine9.6%Depression/Anxiety5.7%Osteoporosis4.6%Hepatic4.3% (2.5% NAFLD)Infections3.9%Malignancies2.8%Kidney1.8%Acknowledgments:This study was sponsored by Janssen Italy.We thank the Investigators and their staff at all of the study sites.Disclosure of Interests:Alen Zabotti Speakers bureau: Celgene, Novartis, Janssen, Armando Gabrielli Grant/research support from: Pfizer, Speakers bureau: Pfizer, Actelion, Carlo Selmi Grant/research support from: AbbVie, Janssen, MSD, Novartis, Pfizer, Celgene, and Leo Pharma, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and Sanofi-Regeneron, Speakers bureau: AbbVie, Aesku, Alfa-Wassermann, Bristol-Myers Squibb, Biogen, Celgene, Eli-Lilly, Grifols, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB Pharma, Rosa Daniela Grembiale: None declared, Roberta Ramonda Speakers bureau: Novartis, Celgene, Janssen, Pfizer, Abbvie, Lilly, 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, Salvatore D’Angelo Speakers bureau: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi, and UCB, Roberto Gerli: None declared, Salvatore De Vita Consultant of: Roche, Human Genome Science, Glaxo Smith Kline and Novartis, Silvia Marelli Employee of: Janssen, Daniela Frigerio Employee of: Janssen, Ennio Favalli Speakers bureau: BMS, Eli-Lilly, MSD, UCB, Pfizer, Sanofi-Genzyme, Novartis and Abbvie

Interstitial lung disease (ILD) in systemic sclerosis (SSc) is a major cause of morbidity and mortality, mostly presenting as non-specific interstitial pneumonia. Little is known about the prevalence of pleuroparenchymal fibroelastosis (PPFE), a specific entity affecting the visceral pleura and subpleural parenchyma. We set out to estimate PPFE prevalence in two large cohorts of SSc patients and to assess its impact on survival and functional decline.A total of 359 SSc patients, derived from two referral centres in two different countries (UK and Italy), were included. The first available high-resolution computed tomography scan was independently evaluated by two radiologists blind to clinical information, to quantify ILD extent, freestanding bronchial abnormalities, and lobar percentage involvement of PPFE on a four-point categorical scale. Discordant scores were adjudicated by a third scorer. PPFE extent was further classified as limited (≤2/18) or extensive (>2/18). Results were evaluated against functional decline and mortality.The overall prevalence of PPFE in the combined SSc population was 18% (11% with extensive PPFE), with no substantial difference between the two cohorts. PPFE was significantly linked to free-standing bronchial abnormalities (61% versus 25% in PPFE versus no PPFE; pIn the current study, we provide an exhaustive description of PPFE prevalence and clinical impact in the largest cohort of SSc subjects published so far. PPFE presence should be carefully considered, due to its significant prognostic implications.

MGD and CG were responsible for the study's conception and design. VP and DM contributed to data acquisition. VP and DB planned and performed the statistical analyses. All Authors contributed to data interpretation. MGD, CG, VP and DM drafted the manuscript. AG and DB revised the manuscript critically for intellectual content. All authors gave their final approval of the version of the manuscript to be published.

Depression is often under-recognized in older patients, even if antidepressants (AD) are commonly prescribed, with a prevalence of use that increase with ageing [ 1 ]. Nevertheless, even if a diagnosis of depression is established, inappropriate treatment can occur [ 2 ]. Beers criteria are the most widely screening tools used to detect inappropriate prescription of drugs in people aged 65 years or more [ 3 ]. Since 2010, attempts to adapt the Beers' criteria have been made in Europe [ 4 , 5 ]. Tricyclic drugs are the ADs to be always avoided in the elderly, owing to their anticholinergic side effects, such as cognitive impairment, delirium, urinary retention and falls [ 3 ]. Selective serotonin reuptake inhibitors (SSRIs) should be used with caution because they can cause or exacerbate hyponatraemia [ 3 ]. To our knowledge no studies have been conducted on recent data collected in hospitalized older patients in order to assess the appropriateness of prescription of ADs. With this background, the objectives of this study were to investigate the prevalence of AD use and prescription appropriateness, according to the above-cited criteria, in a large cohort of older patients hospitalized in Italian internal medicine and geriatric wards from 2010 to 2017.

The aim of our study was to assess the role of videofluorography (VFG) in the evaluation of swallowing and oesophageal peristalsis in patients with systemic sclerosis (SSc).From June 2014 to September 2017, 55 consecutive SSc patients, defined according to the 2013 ACR/EULAR classification criteria, underwent VFG study using a remote-controlled digital device. In order to evaluate possible abnormalities, 18 dynamic parameters were chosen, dividing the act of swallowing into three phases: oral, pharyngeal and oesophageal phases. The following dynamic radiological findings were considered: veil motility in phonation, leakage, drooling, salivation and presence of residues in the oral cavity, pharyngeal residues, penetration, aspiration, altered motility of the upper oesophageal sphincter, efficacy of primary peristaltic contractions, oesophageal clearance capacity, reflux, oesophagitis and motility of the lower oesophageal sphincter.The VFG study was well tolerated in all patients. Dysfunctions of oesophageal motility were common and included abnormal motility of UES (12.7%) and LES (76.4%), inadequate primary peristalsis (52.7%), abnormal secondary peristalsis (29.1%) and non-peristaltic contractions (40%). A defective oesophageal clearance was observed in 69.4% of patients. Moreover, most patients presented signs of oesophageal reflux (63.6%), oesophagitis (81.8%) and hiatal hernia (80%). Pharyngeal abnormalities were less common and involved up to 50% of patients. Oesophageal dysfunction and defective clearance were associated with dcSSc and pulmonary involvement.The VFG study is a useful technique for the morphological and functional evaluation of swallowing in SSc patients.

Background Belimumab is the unique biologic therapy available for patients with SLE. Objectives To investigate effectiveness and safety of belimumab in SLE patients in clinical practice. Methods 458 active SLE patients (ACR criteria) from 24 Italian Centers, mean±SD age 43.5±11.3 years; mean±SD disease duration 12.3±8.7 years, were treated with belimumab (10 mg/kg day 0, 14, 28 and then every 28 days), as add-on therapy. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24H proteinuria, CLASI, PGA, Fatigue (VAS 0-10) were recorded at baseline and every 6 months. Flares were defined according to SFI. Response was evaluated according to SRI-4. Statistics were performed by pairs T-test, chi-square test and multiple logistic regression (SPSS, version 22.0). Results Mean±SD follow-up was 21.2±15.3 months (range 3-60). Most common features treated with belimumab were articular in 67%, mucocutaneous in 55%, and renal in 17% of cases. Improvement of clinical and serological variables, including daily prednisone dosage, was observed (Table). SRI-4 is summarized in the Figure. At the end of follow-up 293 patients (66%) were still on belimumab. Most common cause of discontinuation were inadequate response (36%), AEs (31%), and pregnancy (8%). Mean number of flare during belimumab treatment compared with the corresponding period before belimumab initiation decreased (p 9,998 infusions were analyzed. 784 AEs were observed in 330 patients, SAEs were 43 in 36 patients. No severe infusion reactions were observed; 16 patients had infective SAEs, and 22 non infective SAEs. Conclusion We confirmed the effectiveness, the steroid sparing effect and good safety profile of belimumab in our cohort. Disclosure of Interests Luca Iaccarino: None declared, Francesca Saccon: None declared, Alessandro Mathieu: None declared, Matteo Piga: None declared, Angela Ceribelli: None declared, Carlo Selmi Grant/research support from: Abbvie, Janssen, MSD, Novartis, Pfizer, Consultant for: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Speakers bureau: Abbvie, Alfa-Sigma, Biogen, BMS, Celgene, Eli-Lilly, GSK, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Roche, Sanofi-Genzyme, YCB, Paolo Cardinaletti: None declared, Armando Gabrielli: None declared, Andrea Di Matteo: None declared, Rossella De Angelis: None declared, Paola Faggioli: None declared, Antonella Laria: None declared, Micaela Fredi: None declared, Francesca Regola: None declared, Laura Andreoli: None declared, Giulia Pazzola: None declared, Carlo Salvarani: None declared, Francesco Puppo: None declared, Simone Negrini: None declared, Marcella Prete: None declared, Vito Racanelli: None declared, Elisa Gremese Consultant for: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Speakers bureau: BMS, Speakers bureau: Roche, Speakers bureau: AbbVie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Sanofi, UCB, Roche, and Pfizer, Maria Gerosa: None declared, Tania Ubiali: None declared, Enrica Bozzolo: None declared, Valentina Canti: None declared, Fabrizio Conti: None declared, Fulvia Ceccarelli: None declared, Elena Bartoloni Bocci: None declared, Roberto Gerli: None declared, Antonio Lobasso: None declared, Amato De Paulis: None declared, Ginevra De Marchi: None declared, Salvatore De Vita Grant/research support from: Roche, Pfizer, Abbvie, Novartis, BMS, MSD, Celgene, Janssen, Consultant for: Roche, Alessandra Bortoluzzi: None declared, Marcello Govoni Paid instructor for: Pfizer, Roche, Speakers bureau: Pfizer, Abbvie, MSD, Roche, Eli-Lilly, Celgene, Sanofi, Janssen, Francesco Benvenuti: None declared, Margherita Zen: None declared, Marta Mosca Paid instructor for: GlaxoSmithKline, Lilly, UCB, Chiara Tani: None declared, Maurizio Rossini: None declared, Giovanni Orsolini Speakers bureau: Grunenthal, Mariele Gatto: None declared, Salvatore Scarpato: None declared, Enrico Brunetta: None declared, Aurora Zumbo: None declared, Gabriele Valentini: None declared, SERENA FASANO: None declared, Giacomo Emmi: None declared, Maria Letizia Urban: None declared, Giacomo Tanti: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Andrea Doria: None declared

Pulmonary fibrosis is a hallmark of several human lung diseases with a different etiology. Since current therapies are rather limited, mouse models continue to be an essential tool for developing new antifibrotic strategies. Here we provide an effective method to investigate in vivo antifibrotic activity of human mesenchymal stromal cells obtained from whole umbilical cord (hUC-MSC) in attenuating bleomycin-induced lung injury. C57BL/6 mice receive a single endotracheal injection of bleomycin (1.5 U/kg body weight) followed by a double infusion of hUC-MSC (2.5 x 105) into the tail vein, 24 h and 7 days after the bleomycin administration. Upon sacrifice at days 8, 14, or 21, inflammatory and fibrotic changes, collagen content, and hUC-MSC presence in explanted lung tissue are analyzed. The injection of bleomycin into the mouse trachea allows the direct targeting of the lungs, leading to extensive pulmonary inflammation and fibrosis. The systemic administration of a double dose of hUC-MSC results in the early blunting of the bleomycin-induced lung injury. Intravenously infused hUC-MSC are transiently engrafted into the mouse lungs, where they exert their anti-inflammatory and antifibrotic activity. In conclusion, this protocol has been successfully applied for the preclinical testing of hUC-MSC in an experimental mouse model of human pulmonary fibrosis. However, this technique can be easily extended both to study the effect of different endotracheally administered substances on the pathophysiology of the lungs and to validate new anti-inflammatory and antifibrotic systemic therapies.

The aims of this study were to assess the prevalence of use and prescription appropriateness of drugs for peptic ulcer and gastrooesophageal reflux disease (GERD) at hospital admission and discharge. Patients aged 65 years or more hospitalized from 2010 to 2016 in 101 Italian internal medicine and geriatric wards in the context of the REPOSI register were scrutinized to assess if they were prescribed with drugs for peptic ulcer and GERD at hospital admission and discharge. Appropriateness of prescription was assessed considering the presence of specific conditions (i.e., history of peptic ulcer or gastrointestinal hemorrhages, advanced age, Helicobacter Pylori) or gastro-toxic drug combinations, according to the criteria provided by the reimbursement rules of the Agenzia Italiana del Farmaco (NOTA 1 and 48). Among 4715 enrolled patients, 3899 were discharged alive. At hospital discharge, 2412 (61.9%, 95%CI: 60.3–63.4%) patients were prescribed with drugs for peptic ulcer and GERD, a 12% of increase from hospital admission. Almost half of the patients (N = 1776, 45.6%, 95%CI: 44.0–47.1%) were inappropriately prescribed or not prescribed: among the drugs for peptic ulcer and GERD users, about 60% (1444/2412) were overprescribed, and among nonusers, 22% (332/1487) were underprescribed. Among patients newly prescribed at hospital discharge, 60% (392/668) were inappropriately prescribed. The appropriateness of drugs for peptic ulcer and GERD therapy decreased by 3% from hospital admission to discharge. Hospitalization missed the opportunity to improve the quality of prescription of this class of drug.

ObjectivesTo investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) Methods601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5–4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed.ResultsDuring 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF ConclusionsThe present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

Natural history and outcomes of patients with pulmonary embolism (PE) without typical symptoms (atypical PE) remain unclear. The aim of the study is to compare the clinical characteristics and the prognosis between typical PE and atypical PE.We retrospectively analyzed data from consecutive patients admitted to the Emergency Department (ED) because of a diagnosis of PE and classified them in two groups: typical PE and atypical PE. We defined PE to be typical in presence of almost one of the following symptoms or signs: dyspnea, chest pain, hemoptysis or signs of deep vein thrombosis.Of the 191 patients with PE, 154 (81%) had typical PE and 37 (19%) had atypical PE. Patients with atypical and typical PE seemed to had similar prognostic factor such as high risk sPESI (73% vs 65%, p=0.3), right ventricular dysfunction (30% vs 26%, p=0.6) and central PE at chest CT scan (38% vs 36%, p=0.8). The rate of 30 day mortality was 7% in the typical group and 8% in the atypical group (p=0.8). The length of stay in hospital was the same in the two groups (6 days; p=0.2).We found that atypical and typical PE seem to be related diseases with a similar short term prognosis. Therefore, we could speculate that a missed diagnosis of PE in ED could expose the patients to a worsen prognosis. Further perspective studies are required for better investigate this diagnostic challenge.

Objective: To produce recommendations for the design of reliable and informative clinical investigations in chronic wound infection. Method: A multidisciplinary panel of international experts from four countries (Italy, UK, Ireland and the US) were involved in a detailed, semi-structured discussion on how to better select and describe a target population, interventions and outcomes, and which infection-related criteria to apply in order to achieve a high-quality trial. Consent among the experts was measured using the Delphi method and GRADE Working Group suggestions. The project was fully supported by AISLeC 2016 (Italian Nursing Society for Wound Care Study). Results: In total, 37 recommendations achieved substantial agreement among the experts; 10 concerned the most appropriate description and selection of a target population, four related to interventions and 15 to outcomes. A further eight statements about critical methodological points were approved. Conclusion: Developing recommendations in a systematic manner through a representative group of experts could generate tools for improving the design of clinical trials in this challenging area.

Inflammatory bowel disease-associated spondyloarthritis is a systemic disease characterized by the chronic inflammation of both the gastrointestinal tract and the musculoskeletal system. Since inflammatory bowel disease-associated spondyloarthritis has been associated with a significant diagnostic delay, which may lead to poor quality of life and progression of joint damage, efforts to discover new reliable and noninvasive diagnostic biomarkers have been made. We reviewed the state of the art of biomarker research in inflammatory bowel disease-associated spondyloarthritis, showing that to date it has been largely unsatisfactory. Only a few of the biomarkers that have been investigated are likely to enter the clinical practice upon further validation in independent cohorts. The research of new and innovative biomarkers for inflammatory bowel disease-associated spondyloarthritis is warranted.

Benzodiazepines (BDZs) are widely prescribed in older people. The aims of the study are to assess the prevalence of inappropriate prescription of BZDs and the associated factors in acutely hospitalized older patients. Patients aged 65 years or more hospitalized from 2010 to 2017 in more than 100 Italian internal medicine and geriatric wards in the frame of the REPOSI register were included if prescribed with BDZs at hospital admission or discharge. Appropriateness of prescription was assessed according to the 2015 Beers criteria and their modified French and German versions. Among 4681 patients discharged from hospital, 15% (N = 710) were discharged with BDZs, and 62% of them (N = 441, 95% CI: 58.5%–65.6%) were inappropriately prescribed, being prescribed with BDZ to be always avoided in the elderly (45%), at higher doses than recommended (31%) or with no appropriate clinical conditions (19%). From admission to discharge the prevalence of inappropriate BDZ prescription decreased by 4%, but 62% of patients inappropriately prescribed at admission were still inappropriately prescribed at discharge. Among the 179 patients first prescribed at the time of discharge, half were inappropriately prescribed. Being female (OR 1.32, 95%CI 0.95–1.85), enrolled in REPOSI during the years 2016 and 2017 (OR 1.94, 95%CI 1.10–3.39; OR 1.57, 95%CI 0.95–2.58) and living in nursing homes (OR 2.04, 95%CI 0.95–4.37) were associated with an increased risk to be inappropriately prescribed. This study shows a high prevalence of inappropriate use of BDZ in acutely hospitalized older patients both at hospital admission and discharge.

Objectives We aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes. Design Data were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged ≥65 years. Setting and Participants Older hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD. Measures We evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodilators and corticosteroids in COPD patients. We also evaluated the occurrence of outcomes and its association with COPD and guideline adherence. Results At hospital admission, COPD was diagnosed in 1302 (21.5%) of 6046 registered patients. COPD patients were older, with more impaired clinical and functional status and multiple comorbidities. Overall, 34.3% of COPD patients at admission and 35.6% at discharge were adherent to the GOLD guidelines. Polypharmacy (≥5 drugs) at admission [odds ratio (OR): 3.28, 95% confidence interval (CI): 2.24-4.81], a history of acute COPD exacerbation (OR: 2.65, 95% CI: 1.44-4.88) at admission, smoking habit (OR: 1.45, 95% CI: 1.08-1.94), and polypharmacy at discharge (OR: 6.76, 95% CI: 4.15-11.0) were associated with adherence to guidelines. COPD was independently associated with the risk of cardiovascular and respiratory death and rehospitalization occurrence compared to patients without COPD during follow-up. Adherence to guidelines was inversely associated with the occurrence of death from all causes (OR: 0.12, 95% CI: 0.02-0.90). Conclusions/Implications COPD was common in older patients acutely hospitalized, showing an impaired functional and clinical status. Prescriptions for older COPD patients were often not adherent to GOLD guidelines. Poor adherence to guidelines was associated with a worse clinical status. There is a need to improve adherence to guidelines in treating COPD patients, with the ultimate goal of reducing clinical events.

Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sj&ouml, gren&rsquo, s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p &lt, 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p &le, 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc&ndash, CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.

Objective The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

Background:High-resolution computed tomography (HRCT) is the gold standard diagnostic test for Interstitial lung disease (ILD), a significant cause of morbidity and mortality in systemic sclerosis (SSc). Different algorithms have been proposed for the screening of SSc-ILD, including the use of pulmonary function tests (Forced Vital Capacity - FVC, Lung Diffusion of Carbone Monoxyde - DLCO). A prior survey reported that 50-66% of general rheumatologists and SSc experts ordered HRCT for ILD screening in newly diagnosed SSc patients (1).Objectives:Given the recent availability of on-label treatment for SSc-ILD (2), the publication of consensus recommendations for the identification of SSc-ILD (3) and recent awareness programs for the use of HRCT to detect SSc-ILD, we aimed to re-evaluate the use of HRCT for screening, re-screening and follow-up of SSc-ILD.Methods:An invitation was sent to the European Scleroderma Trials and Research (EUSTAR) and Scleroderma Clinical Trials Consortium (SCTC) members, also advertised through social media. Answers were recorded between Nov 25th and Dec 31st 2020. Questions were asked on the use of chest HRCT at baseline, the re-screening of patients with a negative baseline HRCT and the follow-up of HRCT positive SSc-ILD patients. When HRCT was not routinely requested, additional details were collected about the parameters guiding its use. The results of the survey were tested for association with geographical origin, medical specialty, working environment, SSc referral institute and scientific group membership of the responders, using Chi-squared test.Results:205/630 (32.5%) physicians replied to the survey. Participants were widely distributed in terms of geographical origin (130 Europe, 23 Asia, 23 North America, 31 other continents), medical specialty (156 rheumatology, 21 internal medicine, 14 clinical immunology, 14 other), working environment (176 University Hospital, 12 community hospital, 17 other), SSc dedicated clinic (179 referral and 26 non-referral) and scientific group membership (98 EUSTAR, 42 SCTC, 42 EUSTAR and SCTC, 23 not declared).At SSc diagnosis, 95.7% of responders would perform HRCT: 66.7% as routine screening for ILD (67,4% of SSc referral and 62% for non-referral physicians) and 29% for diagnostic purposes (among the latter, if crackles on auscultation – 92.5%, FVCDuring follow-up, 78.8% of responders would repeat an HRCT in baseline negative cases: 20.3% as a yearly routine screening and 64.5% for diagnostic aims (decision on the latter group was more frequently driven by FVC±DLCO relative decline indicative of ILD progression– 90.6%, new onset or worsening of dyspnoea at rest/exercise – 80.5/86.6%, new onset or worsening of lung crackles on auscultation – 82.6%).Finally, 94.5% of responders would repeat a chest HRCT after SSc-ILD diagnosis: 36.8% as a yearly routine and 56.7% according to clinical evaluation (driven by new FVC±DLCO relative decline based ILD progression – 90.8%, new onset or worsening of dyspnoea at rest/exercise – 83.2/81.7%; 5.2% to evaluate treatment effects). We found no difference in the distribution of answers among groups.Conclusion:The use of baseline HRCT for the screening of SSc-ILD has slightly increased in non-referral and remained stable in referral centers compared to previous surveys, indicating that the implementation of guidelines might be successful and awareness programs should be continued. In addition, we provide new data on use of HRCT in re-screening and follow-up. The development of validated algorithms to further support the appropriate application of HRCT at follow-up is highly needed.References:[1]Bernstein EJ et al. Arthritis Rheumatol. 2018 Jun;70(6):971-972.[2]Distler O et al. N Engl J Med. 2019 Jun 27;380(26):2518-2528.[3]Hoffmann-Vold AM et al. The Lancet Rheumatology, Volume 2, Issue 2, e71 - e83.Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Foundation for Research in Rheumatology (FOREUM), Gruppo Italiano Lotta alla Sclerodermia (GILS), Fondazione Italiana per la Ricerca sull’Artrite (FIRA), New Horizon Fellowship, European Sclerodermia Trial and Reserach (EUSTAR) Group., Lorinda Chung Consultant of: Boehringer Ingelheim, Eicos, Mitsubishi Tanabe, Reata., Anna-Maria Hoffmann-Vold Consultant of: Actelion, ARXX therapeutics, Bayer, Boehringer-Ingelheim, Medscape, MSD, Lilly, Roche, Shervin Assassi Speakers bureau: Integrity Continuing Education, Consultant of: Boehringer Ingelheim, Novartis, and Corbus, Armando Gabrielli: None declared, Dinesh Khanna Consultant of: Acceleron, Actelion, Abbvie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead, Galapagos, Genentech/Roche, GSK, Horizon, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis, and United Therapeutics Leadership, Grant/research support from: NIH, Immune Tolerance Network, Bayer, BMS, Horizon, Pfizer, Employee of: Equity position – Chief Medical Officer, Eicos Sciences, Inc., Elana Bernstein Consultant of: Boehringer Ingelheim, Oliver Distler Consultant of: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB., Grant/research support from: Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143).

Background:Hydroxychloroquine (HCQ) is a well-tolerated drug that contributes to downregulating the immune response against autoantigens and it has been used in several autoimmune diseases. In systemic sclerosis (SSc) it is used to treat inflammatory arthritis without proof of efficacy.Objectives:Our aim was to evaluate the use of HCQ and its impact on Health Assessment Questionnaire disability index (HAQ-DI) and the Cochin Hand Function Status (CHFS). in a large SSc cohort compared to a propensity matched group of SSc patients not using HCQ.Methods:SSc patients from the European Scleroderma Trials and Research (EUSTAR) data base treated with HCQ for at least 6 months were evaluated. Demographic and clinical data, concomitant drugs, duration of HCQ treatment and reasons for its discontinuation, HAQ-DI and CHFS (at least 2 evaluation) were recorded and were the outcome variables of interest. Statistical analysis was performed using propensity score matching for age, gender, disease duration, corticosteroids, immunosuppressives, vasoactive drugs, DMARDs in a 3:1 control:HCQ ratio. Standard descriptive statistics and Student’s t-test and Chi-square test were used to assess the propensity-matched groups.Results:1,636 of 17,805 SSc patients (9.2%) were treated with HCQ for at least 6 months; out of these 3% (50/1636). had at least a baseline and follow-up HAQ-DI evaluation, (and 44/1636 (2.7%) had at least a baseline and follow-up CHFS evaluation. Propensity matching assured that pts were matched for demographic variables such as gender (mean on HCQ vs no HCQ:femals:92.0 vs 85.3), age(49.8 vs 49.97yrs) disease duration(8.3 vs 9.1 yrs), limited disease(55.3 vs 62.6%) as well as background medications (P>0.1-0.9). We did not find any significant changes in HAQ or CHFS (difference in slope) over 365 days of treatment, comparing the HCQ-treated group to the non-HCQ treated patients (p=0.240 for both (Figure 1).Conclusion:Results from the EUSTAR registry showed that HCQ was used by 9.2% of SSc patients. HCQ use did not improve the HAQ or CHFS, comparing HCQ users to non-HCQ users.Disclosure of Interests:Silvia Bellando Randone: None declared, Holly Wilhalme: None declared, Cosimo Bruni: None declared, Elise Siegert: None declared, Paolo Airò: None declared, Rosaria Irace: None declared, Oliver Distler: None declared, Andrea Doria: None declared, Lidia P. Ananieva: None declared, László Czirják: None declared, Christopher Denton: None declared, Yannick Allanore: None declared, Valeria Riccieri: None declared, ALESSANDRA VACCA: None declared, Ivan Foeldvari Consultant of: Gilead, Novartis, Pfizer, Hexal, BMS, Sanofi, MEDAC, Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, Lilly and Medscape, Consultant of: Actelion, Boehringer Ingelheim, Roche, Bayer, ARXX, and Medscape, Grant/research support from: Boehringer Ingelheim, Armando Gabrielli: None declared, Marco Matucci-Cerinic: None declared, Daniel Furst: None declared

Background:Current treatments for systemic sclerosis-associated interstitial lung disease (SSc-ILD) are characterised by different attributes such as mode of administration, adverse events (AE) and efficacy. Physicians and patients often have different perspectives on treatments, thus shared decision-making between patients and physicians is essential. An understanding of patients’ decision processes when weighing treatment attributes and the trade-offs they are willing to make is important for shared decision-making.Objectives:The study aimed to 1) identify relevant treatment attributes, 2) elicit patient preferences for these attributes and 3) quantify preference as relative attribute importance (RAI; a higher RAI indicates that more of the variability in patients’ responses may be explained by changes in the attribute); and maximum acceptable risk (MAR) of diarrhoea, nausea and/or vomiting (MAR is a trade-off measure that evaluates attributes in risk-equivalences as a unit of measurement).Methods:A discrete choice experiment (DCE) was created, based on a literature review, a patient advisory board, qualitative patient interviews, and a workshop involving SSc-ILD expert physicians. Seven SSc-ILD treatment attributes were identified: 1) mode of administration; 2) shortness of breath; 3) skin tightness; 4) cough; 5) tiredness; 6) risk of gastrointestinal tract (GIT) AEs; and 7) risk of serious and non-serious infections. The levels of AE risk were informed by frequencies observed in clinical trials and patient input during the interviews. The DCE was integrated into an online survey, which asked patients to make repeated choices between two alternatives described by varying levels of included attributes. Patients with SSc-ILD were recruited by physician referral from Switzerland, Norway, France, Germany and the USA. DCE data were analysed using a logit model, and RAI and MAR measures were calculated.Results:A total of 231 patients with physician-confirmed SSc-ILD (mean age 52.6±13.2 years; 54% diagnosed for >5 years) completed the survey. Patients with SSc-ILD mostly preferred twice-daily oral treatments (pPatients accepted an additional 21% risk (95% CI 13–29%) of GIT AEs if they could reduce the frequency of infusions from monthly to 6–12 monthly, or accepted an extra 15% (95% CI 7–23%) increase in risk if changing to an oral treatment twice daily. Among symptoms, an additional 28% (95% CI 20–36%) risk of GIT AEs was considered acceptable if the severity of patients’ persistent cough was reduced to a level that was easier to tolerate, even if it remained persistent. Similarly, a 37% (95% CI 28–46%) increase in the risk of GIT AEs was acceptable if it resulted in breathlessness during routine activities rather than breathlessness at rest. Finally, patients were willing to accept an additional 36% risk (95% CI 27–45%) of GIT AEs if it reduced their risk of non-serious infections from 30% to 15% and of serious infections from 10% to 5%.Conclusion:This is the first study to quantitatively elicit patients’ preferences for attributes of SSc-ILD treatments. Preferences were driven by safety, efficacy and technical considerations. Patients showed willingness to make trade-offs, providing a firm basis for shared decision-making in routine clinical practice.Disclosure of Interests:Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Gruppo Italiano Lotta alla Scleroderma (GILS), Fondazione Italiana per la Ricerca sull’Artrite (FIRA), New Horizon Fellowship, European Scleroderma Trial and Research (EUSTAR), Foundation for Research in Rheumatology (FOREUM)., Sebastian Heidenreich Consultant of: Sebastian Heidenreich, PhD is employed by Evidera Inc, a business unit of PPD. Evidera is a CRO that offers paid research services to pharmaceutical companies., Ashley Duenas Consultant of: Yes. I am an employee of Evidera which received funding from Boehringer Ingelheim for work related to this study., Anna-Maria Hoffmann-Vold Speakers bureau: Boehringer Ingelheim, Actelion, Roche, Merck Sharp & Dohme, Lilly, Consultant of: Actelion, Boehringer Ingelheim, Roche, Bayer, Merck Sharp & Dohme, ARXX, Lilly and Medscape, Grant/research support from: Boehringer Ingelheim, Armando Gabrielli Grant/research support from: Pfizer Bhering, Yannick Allanore Consultant of: Honorarium received from Boehringer, Medsenic,Sanofi, Menarini, Grant/research support from: Grants received from Alpine, Ose Immunogenetics, Emmanuel Chatelus: None declared, Jörg H.W. Distler Shareholder of: JHWD is stock owner of 4D Science, Consultant of: JHWD has consultancy relationships with Actelion, Active Biotech, Anamar, ARXX, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi and UCB, Grant/research support from: JHWD has received research funding from Anamar, Active Biotech, Array Biopharma, ARXX, aTyr, BMS, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GSK, Inventiva, Novartis, Sanofi-Aventis, RedX, UCB, Eric Hachulla: None declared, Vivian Hsu Speakers bureau: I am a speaker for Boehringer Ingelheim Pharmaceuticals, Consultant of: with Boehringer Ingelheim Pharmaceuticals, Grant/research support from: Principal Investigator for several clinical trials, currently with Genentech, Corbus Pharmaceutical, and EICOS, Nicolas Hunzelmann Speakers bureau: Boehringer, Roche, Sanofi, Dinesh Khanna Shareholder of: Eicos Sciences, Inc (less than 5%), Consultant of: Paid Consultant for: Acceleron, Actelion, Abbvie, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, Corbus, Gilead, Galapagos, Genentech/Roche, GSK, Horizon, Merck, Mitsubishi Tanabe Pharma, Sanofi-Aventis, and United Therapeutics, Grant/research support from: Research Grant support from: Immune Tolerance Network, Bayer, BMS, Horizon, Pfizer, Employee of: Leadership/Equity position – Chief Medical Officer, CiviBioPharma/Eicos Sciences, Inc – recieves a stipend for role as Chief Medical Officer, which would technically qualify as emplyoment., Marie-Elise Truchetet Speakers bureau: Abbvie, Lilly, Sobi, Boehringer, Paid instructor for: Lilly, Consultant of: UCB, Sobi, Abbvie, Grant/research support from: UCB, Gilead, Ulrich Walker Shareholder of: Bayer, NASDAQ, MSCI-World ETF’s, Speakers bureau: All companies producing pharmaceuticals used in AIDS, Paid instructor for: Roche, Abbvie, Novartis, Consultant of: All companies producing pharmaceuticals used in AIDS, Grant/research support from: Gilead, Abbvie, (in the last two years). Other companies in previous years., Margarida Alves Employee of: Boehringer Ingelheim, Nils Schoof Employee of: Employee of Boehringer Ingelheim International GmbH, Lesley Ann Saketkoo Speakers bureau: Boehringer Ingelheim, Actelion, Janssen, Mallinckrodt, United Therapeutics, Consultant of: Actelion, Boehringer Ingelheim, Bayer, Bristol Meyer Squibb, Corbus, EICOS, Janssen, Horizon, United Therapeutics, Inc, Grant/research support from: Mallinckrodt, United Therapeutics, Oliver Distler Speakers bureau: Boehringer Ingelheim, Medscape, IQone, Roche, Consultant of: OD has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years):Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx Therapeutics, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, ChemomAb, Corbus Pharmaceuticals, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Italfarmaco, iQone, Kymera Therapeutics, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Grant/research support from: Kymera Therapeutics, Mitsubishi Tanabe

Background:Coronavirus disease-19 (COVID-19) has been a major clinical challenge worldwide. Sex, age and comorbidities have been associated with worse outcome in the general population. Systemic sclerosis (SSc) is a severe, autoimmune disease with frequent multi-organ involvement.Objectives:To assess the impact of COVID-19 and to determine factors associated with worse outcome in SSc patients from the European Scleroderma Trial and Research (EUSTAR) database.Methods:SSc patients from the EUSTAR database with COVID-19 were prospectively collected between 15.03.-31.12.2020. Two outcomes were chosen: (1) hospitalization; and (2) severe outcome defined as either non-invasive ventilation, mechanical ventilation/extracorporeal membrane oxygenation (ECMO) or death. General risk factors assessed were sex, age and number of comorbidities. SSc related risk factors were SSc subtype, autoantibodies, disease duration, SSc associated organ manifestations including interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), cardiac, gastrointestinal (GI), and musculoskeletal involvement; digital ulcers (DU), CRP at last visit, renal disease (scleroderma renal crisis and SSc associated renal insufficiency), modified Rodnan skin score (mRSS) and immunosuppressive treatment. Descriptive statistics and logistic regression models were applied.Results:In total, 178 European SSc patients with COVID-19 were registered with a median observation time of 5.5 weeks (Table 1). 95 patients (53%) could recall SAR-Cov-2 contact, while 47 (26%) had no contact. 156 (88%) were symptomatic at COVID-19 onset with fever, cough, malaise and dyspnea being most prevalent. Over the disease course, 63 (36%) developed pneumonia. In total, 67/176 (38%) were hospitalized which were in 84% due to COVID-19. 41/170 (24%) had a severe outcome including 21 (12%) deaths. 128 (72%) recovered completely, while 14 (8%) complained of sequela, with 7 (50%) stating respiratory complications. Age, non-SSc comorbidities, presence of ILD, PAH and SSc associated renal or cardiac disease were numerically associated with hospitalization and severe outcome (Table 1). Univariable logistic analyses for hospitalization and severe outcome are shown in Figure 1. In multivariable logistic regression, age (OR 1.03, 95%CI 1.01-1.07, p=0.019), presence of non-SSc comorbidities (OR 2.52, 95%CI 1.16-5.47, p=0.019) and SSc-related renal disease (predicting success perfectly) were associated with hospitalization and for severe outcome age (OR 1.05, 95%CI 1.01-1.08).Conclusion:SSc patients at older age, with non-SSc comorbidities, SSc related renal disease or ILD are at risk of a more severe outcome and should follow precautions to avoid COVID-19 infections and need careful monitoring in case of COVID-19.Table 1.SSc disease characteristics of COVID-19 patientsAll(n=172)Hospitalized(n=67)Severe outcome(n=41)Age at COVID-19, yrs (SD)57 (14.0)63 (13.8)65 (12.2)Male sex, n (%)38 (21)18 (27)12 (29)≥1 comorbidity, n (%)63/176 (36)37 (55)30 (58)SSc disease duration at COVID, yrs (SD)11.5 (8.8)13.3 (9.7)12.7 (10.2)Diffuse cutaneous SSc, n (%)74 (42)29 (43)19 (46)mRSS, median (IQR)5 (8)5 (9)5 (7)ILD, n (%)90/175 (51)36/65 (55)26/40 (65)PAH, n (%)21/175 (12)11/65 (17)8/40 (20)GI disease, n (%)112/176 (64)45 (67)30 (73)Cardiac disease, n (%)37/166 (22)19/59 (32)16/36 (44)Musculoskeletal disease, n (%)40/175 (23)15/65 (23)6/40 (15)Renal disease, n (%)8/175 (5)7/65 (11)5/40 (13)Ever DU, n (%)69/175 (39)27/65 (42)14/40 (35)CRP, ng/ml (SD)35/177 (20)14 (21)9 (22)Immunosuppressive treatment, n (%)104/177 (59)41/66 (62)26 (63)Figure 1.Univariable logistic analyses for hospitalization and severe outcomeDisclosure of Interests:Anna-Maria Hoffmann-Vold Speakers bureau: Actelion, Boehringer Ingelheim, Roche, Merck Sharp & Dohme, ARXX, Lilly and Medscape, Consultant of: Actelion, Boehringer Ingelheim, Bayer, ARXX, and Medscape, Grant/research support from: Boehringer Ingelheim, Cathrine Brunborg: None declared, Francesca Tirelli: None declared, Patricia Carreira: None declared, Nicoletta Del Papa: None declared, Arsene Mekinian: None declared, Madelon Vonk: None declared, Alessandro Giollo: None declared, Giacomo De Luca: None declared, Maria De Santis: None declared, Corrado Campochiaro: None declared, Carina Mihai: None declared, Paolo Airò Speakers bureau: Bristol Myers Squibb, Bohringer Ingelheim, Consultant of: Bristol Myers Squibb, Bohringer Ingelheim, non-financial support from CSL Behring, SOBI, Janssen, Roche, Sanofi, Pfizer, Maria Grazia Lazzaroni: None declared, Elisabetta Zanatta: None declared, Rosario Foti: None declared, Yannick Allanore: None declared, Daniel Furst: None declared, Marco Matucci-Cerinic: None declared, Armando Gabrielli: None declared, Oliver Distler Speakers bureau: Actelion, Kymera Therapeutics, Mitsubishi Tanabe Pharma, Abbvie, Acceleron, Alexion, Amgen, AnaMar, Arxx Therapeutics, Baecon, Discovery, Blade Therapeutics, Corbus Pharmaceuticals, Drug Development International, Ltd, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Kymera Therapeutics, Lilly, Novartis, Pfizer, Topadur and UCB, Consultant of: Actelion, Kymera Therapeutics, Mitsubishi Tanabe Pharma, Abbvie, Acceleron, Alexion, Amgen, AnaMar, Arxx Therapeutics, Baecon, Discovery, Blade Therapeutics, Corbus Pharmaceuticals, Drug Development International, Ltd, CSL Behring, Galapagos NV, Glenmark Pharmaceuticals, GSK, Horizon (Curzion) Pharmaceuticals, Inventiva, iQvia, Kymera Therapeutics, Lilly, Novartis, Pfizer, Topadur and UCB, Grant/research support from: Boehringer Ingelheim.

Idiopathic hypereosinophilic syndrome (HES) is a rare disorder characterized by peripheral eosinophilia exceeding 1500/mm3, a chronic course, absence of secondary causes, and signs and symptoms of eosinophil-mediated tissue injury. One of the best-characterized forms of HES is the one associated with FIP1L1-PDGFRA gene rearrangement, which was recently demonstrated as responsive to treatment with the small molecule kinase inhibitor drug, imatinib mesylate. Here, we describe the case of a 51-year-old male, whose symptoms satisfied the clinical criteria for HES with cutaneous and cardiac involvement and who also presented with vasculitic brain lesions and retroperitoneal bleeding. Molecular testing, including fluorescence in situ hybridization, of bone marrow and peripheral blood showed no evidence of PDGFR rearrangements. The patient was initially treated with high-dose steroid therapy and then with hydroxyurea, but proved unresponsive to both. Upon subsequent initiation of imatinib mesilate, the patient showed a dramatic improvement in eosinophil count and progressed rapidly through clinical recovery. Long-term follow-up confirmed the efficacy of treatment with low-dose imatinib and with no need of supplemental steroid treatment, notwithstanding the absence of PDGFR rearrangement.