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Fibrosing interstitial lung disease (ILD) is one of the most important causes of morbidity and mortality in patients with connective tissue diseases (CTDs), which include systemic sclerosis, rheumatoid arthritis, Sjogren's syndrome, idiopathic inflammatory myositis and systemic lupus erythematosus. The treatment of CTD-ILDs is challenging due to the paucity of proven effective treatments. Recently, two antifibrotic drugs conditionally approved for use in patients with idiopathic pulmonary fibrosis, nintedanib and pirfenidone, have been trialled in CTD-ILDs based on overlapping pathological and clinical features between the two diseases. In this narrative review, we discuss the experimental evidence and clinical trials investigating the efficacy and safety of antifibrotic drugs in patients with CTD-ILDs and the potential mechanisms of action involved. Results from clinical trials suggest that nintedanib use retards lung function decline in progressive fibrotic CTD-ILDs. By contrast, the evidence for the efficacy of pirfenidone in these groups is not equally compelling. Further, well-designed randomized clinical trials are needed to evaluate the efficacy and safety of individual antifibrotic drugs in specific CTD-ILD subgroups.

Objectives This study aims to investigate the factors associated with early discontinuation (within one year) of etanercept (ETA) in rheumatoid arthritis (RA) patients who began ETA as first biologic disease-modifying antirheumatic drug (bDMARD) and who were entered into the Gruppo Italiano di Studio sulla Early Arthritis (Italian Group for the Study of Early Arthritis; GISEA) registry. Patients and methods This registry-based cohort study included 477 RA patients (95 males, 382 females; median age 53 years; range 18 to 83 years) who began ETA as first bDMARD. Patient demographics, disease features and drugs were re-evaluated after 12 months. Baseline predictors of ETA discontinuation were estimated by univariate and multivariate analyses using Cox regression model. Results Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 55.8%, adverse events in 28.6%, and other reasons in 6.5%). Concurrent conventional synthetic DMARDs (csDMARDs) were reported in 54.3% of patients, mainly methotrexate (MTX), while 52.4% of subjects took low doses of glucocorticoids. Patients stopping ETA more frequently showed one or more comorbidities, mainly cardiovascular diseases (28.6% vs. 15.7% in patients stopping and continuing ETA, respectively, p=0.009). The presence of comorbidities and a combination therapy with csDMARDs other than MTX were independent factors associated with early discontinuation of ETA at multivariate Cox analysis. Conclusion Although ETA demonstrated a high persistence in biologic-naive RA patients, about 15% of patients discontinued the treatment within 12 months. The presence of comorbidities and a combination therapy with csDMARDs other than MTX were the main factors for an early withdrawal of the drug.

Several cardiovascular (CV) risk algorithms are available to predict CV events in the general population. However, their performance in patients with rheumatoid arthritis (RA) might differ from the general population. This cross-sectional multicentre study aimed to estimate the 10-year CV risk using two different algorithms in a large RA cohort and in patients with osteoarthritis (OA).In a consecutive series of RA patients and matched OA controls without prior CV events, clinical and serologic data and traditional CV risk factors were recorded. The 10-year CV risk was assessed with the Systematic COronary Risk Evaluation (SCORE) and the "Progetto Cuore" algorithms.1,467 RA patients and 342 OA subjects were included. RA patients were more frequently diabetic (9.9% vs 6.4%; p=0.04) and smokers (20.4% vs 12.5%; p=0.002) but had lower prevalence of obesity (15% vs 21%; p=0.003). Dyslipidaemia was more prevalent in OA (32.5% vs 21.7%; p0.0001). The 10-year estimated CV risk was 1.6% (95%CI 1.3-1.9) in RA and 1.4% (95%CI 1.3-1.6) in OA (p=0.002) according to SCORE and 6.5% (95%CI 6.1-6.9) in RA and 4.4% (95%CI 3.9-5.1) in OA (p0.001) according to "Progetto Cuore". Regardless of the score used, RA patients had a 3- to-4-fold increased 10-year risk of CV events compared to OA subjects.RA patients have a significantly higher 10-year risk of CV events than OA subjects. In addition to effective disease control and joint damage prevention, specific protective measures targeting modifiable traditional CV risk factors should be implemented in RA.

Rituximab represents a milestone in the treatment of mixed cryoglobulinemic vasculitis. Despite usually well-tolerated, rituximab may induce different types of adverse drug reactions, including exacerbation of vasculitis. Rituximab biosimilar have been recently approved in Europe in the treatment of rheumatoid arthritis, but no data are available about effectiveness and safety of rituximab biosimilar in the treatment of mixed cryoglobulinemic vasculitis. We describe a severe skin vasculitis reactivation in a patient affected by rheumatoid arthritis and mixed cryoglobulinemic vasculitis treated with rituximab biosimilar. After 7 days from the first infusion, a severe purpuric rash at lower limbs appeared, that resolved in about 2 weeks with high dose-corticosteroid. Rituximab-induced vasculitis has also been described since 2001, but its pathophysiology is still controversial due to the anecdotical descriptions in literature and the variability of the time between the rituximab infusion and the onset of skin lesions. Up to date, this is the first report describing a vasculitic flare in a patient affected by mixed cryoglobulinemic vasculitis treated with rituximab biosimilar.

Acute exacerbation (AE) is a possible manifestation of interstitial lung diseases (ILD) associated to very high mortality. It’s defined as clinically significant respiratory deterioration with evidence of new widespread alveolar abnormalities on computed tomography scan. AE is better described in idiopathic pulmonary fibrosis (IPF) but also reported in ILD secondary to connective tissue diseases (CTD) and vasculitis. The main features and the real clinical impact of this severe complication in these patients are not well defined. Aim of our study was to prospectively investigate the incidence, clinical features and outcome of AE in a population of patients with ILD related to CTD and vasculitis. We consecutively enrolled all patients, with ILD secondary to rheumatic systemic diseases, referring to our multidisciplinary outpatient clinic for rare lung diseases. All patients were followed for at least 12 months (range, 12–36 months). At baseline, all patients underwent to a core set of laboratory investigations and periodically followed; data about demographic, disease onset, clinical, serological and therapeutic features were also recorded. AE occurred in 9/78 patients, with an incidence of 5.77/100 patients/year, and 5/9 patients died because of AE. The baseline value of DLCO was significantly associated to the risk of AE at Cox regression. In patients with ILD related to rheumatic systemic diseases AE can occur with an incidence similar to IPF. Rheumatologists should carefully consider this life-threatening complication as a possible natural course of all patients with ILD secondary to systemic rheumatic disease.

Objectives: The recent introduction of direct-acting antiviral agents (DAAs) which can eliminate Hepatitis C virus (HCV) had revolutionized the treatment of HCV infections also in a complex clinical setting such as the patients with rheumatoid arthritis (RA). HCV elimination is also opportune due to the availability of more efficient immunosuppressive drugs, whose effect on the course of HCV infection is largely unknown. Methods: Consensus process was endorsed by the Italian Society of Rheumatology (SIR) and the Italian Society of Infectious and Tropical Diseases (SIMIT) to review the available evidence and produce practical, hospital-wide recommendations. The consensus panel consisted of 18 infectious diseases consultants, 20 rheumatologists and one clinical epidemiologist, who used the criteria of the Oxford Centre for Evidence-based Medicine to assess the quality of the evidence and the strength of their recommendations. Results: A core-set of statements about management of patients with RA and infection by HCV have been developed to help clinicians in their clinical practice. Conclusions: A screening for HCV should be performed in all RA patients and it is mandatory before starting an immunosuppressive therapy. Finally, a DAA treatment should be considered in all HCV-infected patients.Significance and Innovations HCV antibodies should be investigated at the time of diagnosis of RA and, in any case, before starting immunosuppressive therapy with disease-modifying antirheumatic drugs (DMARDs). HCV eradication with DAA should be attempted as soon as possible, depending on patient conditions allowing a continuous oral treatment lasting 8–12 weeks Conventional and biological DMARDs are allowed in patients with HCV infection, but they should be used cautiously in presence of advanced liver disease.

Objective: Despite the well-established efficacy of methotrexate (MTX) in rheumatoid arthritis (RA), monotherapy is not sufficient in almost half of patients. The aim of this registry-based study was to detect possible predictive factors for the early failure of MTX as a first-line treatment in early RA patients. Materials and Methods: Five-hundred and ninety RA patients beginning MTX as the first-line treatment were included. Persistence on therapy was re-evaluated after 12 months. Baseline features of disease were evaluated by means of univariate Cox regression, and parameters significantly associated to the outcome were included in multivariate model. Results: One hundred and forty-nine patients (25.3%) failed MTX during the 1st year, for inefficacy in 43.6% and adverse events in 37.5% of cases, respectively. At univariate analysis, patients who discontinued or failed treatment showed lower mean age, higher prevalence of anti-citrullinated peptide antibodies (ACPAs), and higher number of tender/swollen joints. The dose of MTX was correlated with the efficacy and the tolerance of the drug. In particular, patients treated with 7.5 mg of MTX weekly showed a higher rate of discontinuation for inefficacy than adverse events, and the contrary was detected for higher doses. On multivariate analysis, age, ACPA, and number of tender joints were directly associated with MTX discontinuation or failure. Conclusions: More than 25% of RA patients treated with MTX as a first-line therapy failed treatment at 12 months. ACPA positivity, age, and number of tender joints were associated with early withdrawal of MTX in RA patients, while the dose of MTX was correlated to the efficacy and safety of the drug.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by chronic symmetrical erosive synovitis and extra-articular manifestations, including interstitial lung disease (ILD), whose treatment is nowadays challenging due to high infectious risk and possible pulmonary iatrogenic toxicity. Janus kinase inhibitors, namely, tofacitinib, baricitinib, and upadacitinib, are the latest drug class for the treatment of RA with a good safety profile. We present the case of a patient with RA-ILD successfully treated with tofacitinib. A 52-year-old man was referred to our multidisciplinary clinic for rheumatic and pulmonary diseases for an active erosive seropositive RA and progressive ILD. Previous treatments were GC, hydroxychloroquine, methotrexate, etanercept, withdrawn after ILD detection, and tocilizumab, discontinued due to relapsing infections. After our evaluation, we proposed rituximab in addition to low-dose GC and hydroxychloroquine, ineffective on joint involvement. Therefore, we proposed tofacitinib which allowed us to control joint involvement, stabilize ILD improving respiratory symptoms, and manage the frequent infectious episodes that occurred initially. The short half-life and rapid-acting of tofacitinib are two helpful characteristics regarding this aspect. Despite limited data from randomized trials and real-life, tofacitinib could represent a safe therapeutic option for RA-ILD patients. Longitudinal studies are required to confirm this encouraging report.

Objectives Interstitial lung disease (ILD) represents the main pulmonary involvement in primary Sjogren syndrome (pSS). A proportion of patients with pSS develop a progressive fibrosing form of ILD, but no data are available about the prevalence of these patterns in pSS patients. Aim of this monocentric, cross-sectional study was to investigate the prevalence of fibrosing patterns in pSS patients with ILD. Methods All consecutive patients fulfilling classification criteria for pSS with a new or previous diagnosis of ILD were enrolled in the study. Diagnosis of ILD was always performed by mean of HRCT and specific patterns were identified according to current classification criteria and divided in two groups according to the detection of a fibrotic pattern. Results Thirty-four pSS-ILD patients were enrolled in the study (males/females 3/31, median age 69.5 years, median pSS duration 47.5 months). Fibrotic pattern was detected in 52.9% of patients, namely: UIP (13 patients, 38.2%), fibrotic NSIP (4, 11.8%), fibrotic OP (1 2.9%) and group 2 (16 pts, 47.1%) including NSIP (6, 17.6%), OP (4, 11.8%), LIP (2, 5.9%) and unclassifiable (4, 11.8%). These patients were younger and with a shorter pSS duration at ILD diagnosis, in particular ILD diagnosis was prior or concurrent to pSS in 83.3% of cases compared to 62.5% in the group of nonfibrotic pattern (P Conclusion Our data suggest a high prevalence of this pulmonary clinical phenotype in pSS-ILD patients. Since the course of progressive fibrosing pneumonia generally results in respiratory failure, this result could be worthy of further studies.

Anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (MPO) antibodies, have been frequently identified in patients with idiopathic pulmonary fibrosis (IPF). However, their role remains unclear, and only 7–23% of these patients develops clinically overt vasculitis. We aimed to investigate the clinical, serological, and radiological features and prognosis of anti-MPO-positive interstitial lung disease (ILD) patients. Fifty-eight consecutive patients firstly referred for idiopathic interstitial pneumonia and showing serological positivity of anti-MPO antibodies were retrospectively enrolled. For each patient, clinical data, lung function testing, chest high-resolution computed tomography (HRCT) pattern, and survival were recorded. Thirteen patients developed a rheumatic disease during a median follow-up of 39 months. Usual interstitial pneumonia (UIP) was the most frequent ILD pattern, significantly influencing the patients’ survival. In fact, while the 52-week survival of the overall population was 71.4 ± 7.5%, significantly higher than IPF, survivals of anti-MPO patients with UIP pattern and IPF were similar. Forced vital capacity and diffusion lung capacity for CO significantly declined in 37.7 and 41.5% of cases, respectively, while disease progression at chest HRCT was observed in 45.2%. A careful clinical history and evaluation should always be performed in ILD patients with anti-MPO antibodies to quickly identify patients who are developing a systemic rheumatic disease.

Objectives: This study aims to evaluate the diagnostic accuracy of the VECTOR software in patients with connective tissue diseases (CTDs), compared with the reference standard of high-resolution computed tomography (HRCT). Patients and methods: The study included 98 consecutive patients of CTD (24 males, 74 females; median age: 66 years; range, 24 to 85 years) with a recent HRCT. Patients were evaluated in a blindly manner by VECTOR and the results obtained by the algorithm were compared with the presence of interstitial lung disease (ILD) according to HRCT. Results: Interstitial lung disease was detected in 42.8% of subjects. VECTOR correctly classified 81/98 patients, with a diagnostic accuracy of 82.6%; sensitivity and specificity were 88.1% and 78.6%, respectively. Only 5/42 patients with ILD were not correctly classified by VECTOR, while false positive cases were 21.4%. No significant differences were observed according to the radiologic pattern of ILD. Conclusion: VECTOR showed high sensitivity, specificity and diagnostic accuracy, allowing selecting patients to be investigated with HRCT. The relatively high frequency rate of false positive results is acceptable if compared with the lack of effective screening methods for this complication of CTDs.

INTRODUCTION: Interstitial lung disease (ILD) represents one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA) with a deep impact on both quality of life and overall prognosis. A literature search was performed trough some electronic databases, including PubMed, Embase, Scopus, and Web of Science. Areas covered: Many retrospective studies investigated the possible risk factors for RA-ILD, aiming to early identify patients at risk. Among them, male sex, smoking habit, positivity of anti-citrullinated peptide antibodies have been associated to RA-ILD, such as some genetic haplotypes. Histologic and radiologic patterns detected in idiopathic interstitial pneumonias (IIP) have also been observed in RA; among them, usual interstitial pneumonia is the most frequently observed, followed by nonspecific interstitial pneumonia. Since lung involvement can represent the RA onset, an early differential diagnosis with IIP can be difficult or sometimes impossible. High resolution computed tomography represents the gold standard for ILD diagnosis, while multidisciplinary discussion should be required to assess disease staging, severity and progression. Expert opinion: Management of RA-ILD patients are challenging due to the lacking of evidence-based data regarding both assessment and treatment. Moreover, the high variability of clinical presentation and evolution makes difficult to establish the correct therapeutic strategy. Currently, multidisciplinary approach, including at least rheumatologists, pulmonologists, and radiologists, is desirable to define therapy and follow-up strategies.

Mycophenolate mofetil (MMF) is an antimetabolite with a potent inhibitory effect on proliferation of T and B lymphocytes used since the early 1990s for the prevention of acute allograft rejection after organ transplant. MMF is also widely used for the treatment of a variety of rheumatic diseases (RDs) and their pulmonary involvement. Interstitial lung disease (ILD) is a heterogeneous group of progressive fibrotic diseases of the lung, which is often secondary to RD and represents a major cause of morbidity and mortality. MMF is considered the main alternative to cyclophosphamide as a first-line agent to treat RD-related ILD or as possible maintenance therapy after cyclophosphamide, with a lower rate of side-effects. However, as for other immunosuppressive agents, the use of MMF in RD-ILD is supported by poor scientific evidence. In this narrative review, we describe the available data and recent advances on the effectiveness and safety of MMF for the treatment of ILD related to RD, including rheumatoid arthritis, systemic sclerosis, primary Sjögren syndrome, systemic lupus erythematosus, idiopathic inflammatory myopathies, undifferentiated connective tissue disease, interstitial pneumonia with autoimmune features and antineutrophil cytoplasmic antibody-associated vasculitis.

In 2015 the European Respiratory Society (ERS) and the American Thoracic Society (ATS) “Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease” proposed classification criteria for a new research category defined as “Interstitial Pneumonia with Autoimmune Features” (IPAF), to uniformly define patients with interstitial lung disease (ILD) and features of autoimmunity, without a definite connective tissue disease. These classification criteria were based on a variable combination of features obtained from three domains: a clinical domain consisting of extra-thoracic features, a serologic domain with specific autoantibodies, and a morphologic domain with imaging patterns, histopathological findings, or multicompartment involvement. Features suggesting a systemic vasculitis were excluded. Since publication of ERS/ATS IPAF research criteria, various retrospective studies have been published focusing on prevalence; clinical, morphological, and serological features; and prognosis of these patients showing a broad heterogeneity in the results. Recently, two prospective, cohort studies were performed, confirming the existence of some peculiarities for this clinical entity and the possible progression of IPAF to a defined connective tissue disease (CTD) in about 15% of cases. Moreover, a non-specific interstitial pneumonia pattern, an anti-nuclear antibody positivity, and a Raynaud phenomenon were the most common findings. In comparison with idiopathic pulmonary fibrosis (IPF), IPAF patients showed a better performance in pulmonary function tests and less necessity of oxygen delivery. However, at this stage of our knowledge, we believe that further prospective studies, possibly derived from multicenter cohorts and through randomized control trials, to further validate the proposed classification criteria are needed.

Introduction Main clinical manifestations of SARS-CoV-2 infection are characterized by fever, cough, dyspnoea and interstitial pneumonia frequently evolving in an acute respiratory distress syndrome (ARDS). Areas covered Features of coronavirus disease 2019 (COVID-19) pneumonia presents some common points with interstitial lung disease (ILD) both idiopathic and related to rheumatoid arthritis (RA), typically characterized by a chronic progression over some years and possibly complicated by acute exacerbation. The study of some common pathogenetic mechanisms, such as the involvement of the toll-like receptor 4 (TLR4), could contribute to the knowledge and treatment of idiopathic and RA-ILD. Moreover, the hyper-inflammation, mainly characterized by increase of effector T cells and inflammatory cytokines, and the activation of coagulation cascade, observed in COVID-19 related ARDS have been already shown in patients with acute exacerbation of idiopathic and RA-ILD. A literature search was performed some electronic databases, including PubMed, Embase, Scopus, and Web of Science, together with a manual search in COVID-resource centres of the main journals. Expert opinion Despite the uncertainty about many pathogenetic aspects about COVID-19-related pneumonia, we are probably observing a possible model for other forms of ILD and AE. The great amount of data deriving from studies on COVID-19 could be helpful in proposing a safe therapeutic approach for RA-ILD, in understanding pathogenesis of UIP related to autoimmune systemic diseases and to develop new therapeutic strategies for AE.

Antisynthetase syndrome (ASSD) is a rare autoimmune disease characterized by serologic positivity for antisynthetase antibodies. Anti-Jo1 is the most frequent, followed by anti PL-7, anti PL-12, anti EJ, and anti OJ antibodies. The lung is the most frequently affected organ, usually manifesting with an interstitial lung disease (ILD), which is considered the main determinant of prognosis. Some evidences suggest that non-anti-Jo-1 antibodies may be associated with more severe lung involvement and possibly with poorer outcomes, while other authors do not highlight differences between anti-Jo1 and other antisynthetase antibodies. In a multicenter, retrospective, &ldquo, real life&rdquo, study, we compared lung function tests (LFTs) progression in patients with ILD associated with anti-Jo1 and non-anti-Jo1 anti-synthetase antibodies to assess differences in lung function decline between these two groups. Therefore, we analyzed a population of 57 patients (56% anti-Jo1 positive), referred to the outpatient Clinic of four referral Centers in Italy (Modena, Monza, Siena, and Trieste) from 2008 to 2019, with a median follow-up of 36 months. At diagnosis, patients showed a mild ventilatory impairment and experienced an improvement of respiratory function during treatment. We did not observe statistically significant differences in LFTs at baseline or during follow-up between the two groups. Moreover, there were no differences in demographic data, respiratory symptoms onset (acute vs. chronic), extrapulmonary involvement, treatment (steroid and/or another immunosuppressant), or oxygen supplementation. Our study highlights the absence of differences in pulmonary functional progression between patients positive to anti-Jo-1 vs. non anti-Jo-1 antibodies, suggesting that the type of autoantibody detected in the framework of ASSD does not affect lung function decline.

Interstitial lung disease (ILD) represents a severe pulmonary complication of connective tissue diseases, rheumatoid arthritis (RA), and antineutrophil cytoplasmic antibody-associated vasculitis. Treatment of ILD, mainly based on immunosuppression, remains challenging. Rituximab (RTX), a monoclonal antibody binding to CD20, is considered a valuable therapeutic choice in cases of refractory ILD. Here, we review the available efficacy and safety data on the use of RTX in the treatment of rheumatic disease-related ILD. Despite controversial efficacy data, RTX seems to be able to stabilize or improve ILD related to RA and antisynthetase syndrome and in established and severe ILD complicating systemic sclerosis. Fewer data are available regarding ILD related to Sjogren syndrome, systemic lupus erythematosus, and antineutrophil cytoplasmic antibody-associated vasculitis. To date, few prospective studies are available and randomized trials are still ongoing with the purpose of exploring the role of RTX in this condition, including the supposed relationship between efficacy and ILD radiologic patterns and safety data, up to now derived mainly from RA studies. Despite an overall acceptable safety profile, concerns remain regarding an increased infectious disease risk in patients with ILD as well as possible lung toxicity and the increased rate of immune-mediated reactions in patients with connective tissue diseases. In conclusion, RTX is a relevant therapeutic option for rheumatic disease-related ILD despite the existing uncertainties; ongoing trials are expected to clarify its use.

Primary Sjogren syndrome (pSS) is a systemic autoimmune disease characterised by lymphocytic infiltration of exocrine glands and by a number of systemic manifestations, including those regarding the lung. Pulmonary involvement in pSS includes interstitial lung disease (ILD) and airway disease, together with lymphoproliferative disorders.Patients with pSS-ILD report impaired health-related quality of life and a higher risk of death, suggesting the importance of early diagnosis and treatment of this type of pulmonary involvement. In contrast, airway disease usually has little effect on respiratory function and is rarely the cause of death in these patients.More rare disorders can be also identified, such as pleural effusion, cysts or bullae.Up to date, available data do not allow us to establish an evidence-based treatment strategy in pSS-ILD. No data are available regarding which patients should be treated, the timing to start therapy and better therapeutic options. The lack of knowledge about the natural history and prognosis of pSS-ILD is the main limitation to the development of clinical trials or shared recommendations on this topic. However, a recent trial showed the efficacy of the antifibrotic drug nintedanib in slowing progression of various ILDs, including those in pSS patients.

Background: There is a paucity of head-to-head comparisons of the efficacy and harms of pharmacological treatments for systemic sclerosis-related interstitial lung disease (SSc-ILD). Methods: We conducted a network meta-analysis (NMA) in order to compare the effects of different treatments with the placebo on change in forced vital capacity (FVC), change in diffusion lung capacity for CO (DLCO), serious adverse events (SAEs), discontinuation for adverse events and mortality in SSc-ILD. Standardized mean difference (SMD) and log odds ratio were estimated using NMA with fixed effects. Results: Nine randomized clinical trials (926 participants) comparing eight interventions and the placebo for an average follow-up of one year were included. Compared to the placebo, only rituximab significantly reduced FVC decline (SMD (95% CI) = 1.00 (0.39 to 1.61)). Suitable data on FVC outcome for nintedanib were not available for the analysis. No treatments influenced DLCO. Safety and mortality were also not different across treatments and the placebo, although there were few reported events. Cyclophosphamide and pomalidomide were less tolerated than the placebo, mycophenolate, and nintedanib. Conclusion: Only rituximab significantly reduced lung function decline compared to the placebo. However, direct head-to-head comparison studies are required to confirm these findings and to better determine the safety profile of various treatments.

Background: Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA). Methods: All RA-ILD patients treated with ABA for at least six months were retrospectively evaluated. Serology, previous and concurrent therapies, chest high-resolution computer tomography (HRCT), forced vital capacity (FVC), and lung diffusion of carbon monoxide (CO, DLCO) were collected. Results: Forty-four patients were included, HRCT, FVC, and DLCO were analyzed at baseline, at one year, and at the end of follow-up. A remission or a low disease activity of RA was reached in 41/44 patients. Overall, FVC and DLCO remained stable or increased in 86.1% and 91.7% of patients, respectively, while HRCT was stable or improved in 81.4% of them. Previous and concurrent treatments, in particular, methotrexate, serology, age, sex, joint and lung disease duration were not associated with the outcome at univariate analysis. Conclusion: The management of RA-ILD patients remains a critical unmet medical need. Waiting for prospective controlled studies, ABA has shown a good safety profile in our cohort of Italian RA-ILD patients.

Interstitial lung disease (ILD) is one of the most serious pulmonary complications of connective tissue diseases (CTDs) and it is characterized by a deep impact on morbidity and mortality. Due to the poor knowledge of CTD-ILD’s natural history and due to the difficulties related to design of randomized control trials, there is a lack of prospective data about the prevalence, follow-up, and therapeutic efficacy. For these reasons, the choice of therapy for CTD-ILD is currently very challenging and still largely based on experts’ opinion. Treatment is often based on steroids and conventional immunosuppressive drugs, but the recent publication of the encouraging results of the INBUILD trial has highlighted a possible effective and safe use of antifibrotic drugs as a new therapeutic option for these subjects. Aim of this review is to summarize the available data and recent advances about therapeutic strategies for ILD in the context of various CTD, such as systemic sclerosis, idiopathic inflammatory myopathy and Sjogren syndrome, systemic lupus erythematosus, mixed connective tissue disease and undifferentiated connective tissue disease, and interstitial pneumonia with autoimmune features, focusing also on ongoing clinical trials.

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5–1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10–20% of mortality, with a mean survival of 5–8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.

Rituximab (RTX) represents a milestone in the treatment of mixed cryoglobulinemic vasculitis (MCV). Despite usually well-tolerated, RTX may induce different types of adverse drug reactions, including exacerbation of vasculitis. Recently, RTX biosimilar CT-P10 has been approved in Europe for the treatment of rheumatoid arthritis, but no data are available about effectiveness and safety of CT-P10 in the treatment of MCV. In this multicenter open-label study, we analyzed the safety of CT-P10 in patients with MCV treated in first-line or after a shift by RTX originator. Fifty-one consecutive MCV patients (females/males 35/16, median age 68 years, median disease duration 42 months, 51% HCV positive) were included in the study between July and December 2018 and were treated with CT-P10 (group 1). Safety and effectiveness of CT-P10 were compared with a retrospective group (group 2) including 75 consecutive patients treated with RTX originator between July 2017 and July 2018. Thirty-six patients were treated with CT-P10 for the first time, while the other 15 switched from RTX originator. RTX was administrated with high or dosage schemes (375 mg/m2 four times a week apart/1000 mg twice one week apart or 250 mg/m2 twice one week apart). During a month period after the last infusion, 13/51 adverse events (AE) were observed in group 1 and 17/75 in group 2 (p not significant). Among them, 7/13 and 6/17 (in group 1 and 2, respectively) could be considered immune-mediated AE (p not significant). At univariate analysis patients with IM-AE were more frequently males (p = 0.04) and with a lower disease duration (p = 0.03), but both the parameters were not significant at logistic regression. About clinical response after 6 months by the end of the treatment, no differences were observed between patients treated with originator and CT-P10 regarding the response to the therapy. No differences were observed in safety and effectiveness between patients naive at RTX or switching from originator. Despite the higher prevalence of immune-mediated AE among patients treated with CT-P10 than originator, we have observed no significant differences between the 2 groups. The use of a low-dosage regimen is more common in group 1 than in group 2, representing a possible bias of the study, possibly influencing the appearance of AE. Considering the cost/efficacy ratio of biosimilars, their use could be helpful to treat a large number of MCV patients with an effectiveness and safety comparable to originator. Multicenter studies including a large number of patients and the new RTX biosimilars could be useful to fully elucidate the possible risk of immune-mediated adverse events with biosimilar drugs. Considering the cost/efficacy ratio of CT-P10, its use could help to treat a large number of MCV patients with an effectiveness and safety comparable to originator.

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease characterized by joint and extra-articular involvement. Among them, interstitial lung disease (ILD) is one of the most common and severe extra-articular manifestations, with a negative impact on both therapeutic approach and overall prognosis. ILD can occur at any point of the natural history of RA, sometimes before the appearance of joint involvement. Since no controlled studies are available, the therapeutic approach to RA-ILD is still debated and based on empirical approaches dependent on retrospective studies and case series. Here, we report the case of a 75-year-old patient affected by RA complicated by ILD successfully treated with a combination therapy of an antifibrotic agent, nintedanib, and an inhibitor of IL-6 receptor, sarilumab. We obtained a sustained remission of the joint involvement and, simultaneously, a stabilization of the respiratory symptoms and function, with a good safety profile. To date, this is the first report describing a combination therapy with nintedanib and a disease-modifying antirheumatic drug (DMARD) for the management of RA complicated by ILD. Future prospective studies are needed to better define efficacy and safety of this approach in the treatment of these subjects.

Primary Sjögren syndrome (pSS)-related interstitial lung disease (ILD) involved about 10–20% of patients. In 20% of cases, ILD can be diagnosed before pSS; anyway, few studies have investigated the frequency of ILD as the first clinically relevant manifestation of pSS, generally referred to retrospective studies. Aim of our prospective study was to describe prevalence, clinical, serological, and instrumental features of non-sicca onset pSS patients with interstitial lung involvement. During a period of 48 months, all consecutive patients diagnosed as pSS were enrolled. For all patients, the reason for the first visit was recorded. When present, ILD was categorized as definite, possible, or inconsistent with usual interstitial pneumonia (UIP) pattern, according to the current criteria. ILD was the main presenting symptom in 13/77 new diagnoses of pSS patients; in particular, 6/13 patients were initially diagnosed as idiopathic ILD, and only later developed clinical manifestations suggestive for pSS; ILD-pSS patients were older than others and showed a higher EULAR primary Sjögren’s syndrome disease activity index. A radiologic definite or possible UIP pattern was detected in 12/13 pSS. For the first time, we prospectively observed a prevalence of 16.8% of non-sicca onset pSS patients with ILD. Interestingly, UIP pattern was the most frequently detected, while typical autoantibodies were often absent. These features stressed the importance of differential diagnosis in the first stage of the disease, considering the possible poorer prognosis in this subgroup of patients. Multidisciplinary approach is crucial for a correct and early diagnosis, at both onset and follow-up.

Background:Prevalence of anti-neutrophil cytoplasmic antibody (ANCA) in patient with idiopathic pulmonary fibrosis (IPF) ranges from 1 to 35%, mainly anti-MPO. The presence of ANCA positivity seems to be a poorer prognostic factor in patient with IPF, and some of these patients will develop clinical vasculitis (7-23%).Unfortunately, the majority of the available studies on this topic are retrospective and the real natural history of the disease remains poorly understood.Objectives:Aim of the study was to investigate the clinical, serological and radiologic features of patients with interstitial lung disease (ILD) and positivity for anti-MPO, and to evaluate the survival of this population compared with IPF patients.Methods:We retrospectively analysed 30 patients with ILD and anti-MPO antibodies, without diagnosis of vasculitis, from 3 different rheumatology-pulmonology Italian Center.For each patient, clinical, radiologic and serological data were evaluated. Treatments were also collected, both immunosuppressants or antifibrotic agents.Finally, survival of ILD-MPO patients and of 90 unselected idiopathic pulmonary fibrosis (IPF) patients was compared.Results:Thirty patients were enrolled in the study (see table for the characteristics of the patients).Fibrosing pneumonia was described in 73.3% of patients (usual interstitial pneumonia [UIP] in 19 patients), and 10 patients (33.3%) received antifibrotic drugs, all with UIP pattern. Of interest, 7 patients were treated with immunosuppressants (azathioprine, cyclophosphamide, mycophenolate mofetil), independently by the ILD pattern and 21 (70%) low dosage of steroids.After a median period of 23.5 months (range 11-111), 7 patients developed an ANCA associated vasculitis, while other 3 developed other rheumatic diseases.Finally, when compared with IPF, ILD-MPO patients had a better survival (81.2%±0.9 vs 54.7±0.7 for ILD-MPO and IPF, respectively; p=0.045)Conclusion:ILD positive for anti-MPO antibodies are still a not definite condition. We need larger population to identify possible markers for the evolution in an ANCA associated vasculitis, to define the prognosis of disease and the better therapeutic approach.References: :[1]Mohammad AJ, et al. Pulmonary Involvement in Antineutrophil Cytoplasmic Antibodies (ANCA)-associated Vasculitis: The Influence of ANCA Subtype. J Rheumatol. 2017;44:1458-67Table.Serological, clinical and radiological features of anti-MPO + interstitial lung diseaseNumber30Males/female15/15Median age (years + IQR)68 (17)Median follow-up (months + IQR)39.5 (61)Smoke36.70%ILD pattern Usual interstitial pneumonia63.30% Nonspecific interstitial pneumonia16.70% Hipersensitivity pneumonia10% Other fibrosing pneumonia10%Median FVC (% + IQR)83 (23)Median DLCO (% + IQR)53 (28)Clinical features Raynaud’s phenomenon7.70% Sicca syndrome0 Arthralgias20% Arthritis3.40%Serology Antinuclear antibodies30.80% Anti-extractable nuclear antibodies (ENA)8% Anti-SSA4% Rheumatoid factor21.40%Therapy Immusuppressants23.30% Anti-fibrotic drugs33.30%Disclosure of Interests:None declared

Background and objective Recently the term “interstitial pneumonia with autoimmune features” (IPAF) has been proposed to identify patients with interstitial lung disease and autoimmune characteristics, not fulfilling the criteria for specific connective tissue diseases (CTD). Only few data are available about the clinical and serological features of IPAF patients, their survival and the possible evolution in a CTD. The aims of the study were to investigate the demographic and clinico-serologic features of patients with IPAF, their relationship to survival, and the possible evolution in a definite CTD. Patients and methods Fifty-two patients were consecutively enrolled and prospectively followed for 45 ± 31.6 months. Data about disease onset, serological, clinical and therapeutic features, pulmonary function tests and high-resolution computed tomography were periodically repeated. The survival of patients with IPAF was compared with that of 104 patients with idiopathic pulmonary fibrosis (IPF). Results The clinical domain for IPAF was satisfied in 44 patients, serological domain in 49 and the morphological domain in 29 patients. During the follow-up, a definite CTD was diagnosed in 7 patients, in particular Sjogren's syndrome in 4 patients, rheumatoid arthritis in 2, and polymyositis in the last. The estimated 5-year survival of IPAF patients 69.5 ± 7.8%, significantly higher than survival observed in IPF patients, and the baseline value of FVC and DLCO were the only factors associated to death. Conclusions IPAF seems to a distinct entity, with a low tendency to evolve in a definite CTD. Nevertheless, further studies are needed to better define the clinical evolution and the outcome of IPAF.

Background Recently the term “interstitial pneumonia with autoimmune features” (IPAF) has been proposed to identify patients with interstitial lung disease and autoimmune characteristics, not fulfilling the criteria for specific connective tissue diseases (CTD). Until now, only few data are available about the clinical and serological features of IPAF patients, their survival and the possible evolution in a CTD. Objectives Aim of the study was to investigate the therapeutic choices in IPAF patients, their efficacy and safety. Methods Fifty-two patients (mean age at diagnosis 65.5±11.0 years, female/male ratio 29/23) were consecutively enrolled and prospectively followed for 45±31.6 months. Data about therapies, disease onset, serological, clinical and therapeutic features, pulmonary function tests and high-resolution computed tomography were periodically repeated. A worsening of lung function was defined as a reduction of 10% compared to baseline of forced vital capacity (FVC) and diffusion lung capacity of CO (DLCO). Results An immunosuppressive therapy was prescribed in 15 patients (namely cyclophosphamide in 4, mycophenolate mofetil in 6 and azathioprine in 6, respectively), while 6 patients were treated with anti-fibrotic therapies (pirfenidone or nintedanib). Thirty-three patients taken corticosteroids, associated to other drugs in 18 patients, and alone in 15. Finally, no therapies were prescribed in 16 patients. At the end of follow-up FVC remained stable in 35% of patients, worsened in 50% and increased in 15%; DLCO remained stable in 25.8% of patients, worsened in 58.1% and increased in 16.1%. Mean survival was 94.2±8.5 months, and no differences were recorded according to the kind of therapy, while survival was significantly associated to the lung function at baseline (FVC and DLCO were confirmed to be significantly associated to death at multivariate analysis). The treatment was generally well tolerated. In 7/15 patients treated with immunosuppressive therapy was recorded at least an adverse event, responsible for the treatment discontinuation only in 3 patients. Conclusion The therapeutic strategy in IPAF patients reflects the etherogeneity of the disease. Waiting for specific trial in this population, treatment is empyrical and based on the baseline features of the patients. Despite well tolerated both anti-fibrotic and immunosoppressive therapies seem to not influence the evolution of the disease. References [1] Fischer A, Antoniou KM, Brown KK, eta al. “ERS/ATS Task Force on Undifferentiated Forms of CTD-ILD”. An official European Respiratory Society/American Thoracic Society research statement: interstitial pneumonia with autoimmune features. Eur Respir J. 2015;46:976-87 [2] Ferri C, Manfredi A, Sebastiani M, et al. Interstitial pneumonia with autoimmune features and undifferentiated connective tissue disease: Our interdisciplinary rheumatology-pneumology experience, and review of the literature. Autoimmun Rev. 2016;15:61-70 Disclosure of Interests None declared

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

Background Interstitial lung disease (ILD) represents one of the most frequent pulmonary manifestations in connective tissue diseases (CTD) and it is characterized by severe implications in morbility and overall prognosis. However, a routinely assessment of ILD is not so common in all CTDs. Velcro-type crackles are typical of lung fibrosis and have been proposed for the early diagnosis of the disease. Recently, we validated the algorithm VECTOR (VElcro Crackles detecTOR), developed to detect the presence of velcro-crackles in pulmonary sounds recorded by an electronic stethoscope (ES) in RA-ILD patients as screening for the diagnosis of interstitial lung involvement, showing a diagnostic accuracy, a sensitivity and a specificity of 83.9%, 93.2% and 76.9%, respectively. Objectives The aim of the present study was to evaluate the diagnostic accuracy of VECTOR in a population of CTDs, compared with the reference standard of high-resolution computed tomography (HRCT), in a monocentric study. Methods CTDs patients who underwent HRCT in the last 12 months were enrolled. They were auscultated with an ES (Littmann 3200TM 3M, USA), bilaterally, at dorsal level, in at least 3 pulmonary fields (apical, medium and basal). All tracks recorded were analyzed by suitably developed software (VECTOR) capable of recognizing pathological crackles in lung sounds. Results were compared with HRCT findings detected in a blind manner by an expert radiologist. Results Ninty CTDs patients were enrolled, namely 27.8% systemic sclerosis (SSc), 31.1% primary Sjogren’s syndrome (pSS), systemic lupus erythematosus 11.1%, 7.8% polymyositis, 6.6% dermatomyositis, and 15.5% undifferentiated CTD (UCTD). Male/female ratio was 1/3.1 and a mean age of 63.9±12.7 years; among them 45 (50%) showed ILD at HRCT. The algorithm correctly classified 73/90 patients, with a sensitivity and specificity of 93.3% and 68.9%, respectively, and a diagnostic accuracy of 81.1% (figure 1). Conclusion These data confirm the diagnostic accuracy of VECTOR in detection of ILD in CTDs patients, as previously described also for RA-ILD. In some CTDs such as SSc, a careful evaluation of lung involvement is quite diffused, while for other CTDs, for example pSS or UCTD, ILD remains often underestimated, with a delay in diagnosis and treatment. Since lung complications represent one of the most serious and frequent cause of poor prognosis for all CTDs patients, the search for a simple, repeatable and radiation-free tool for the screening of these patients is mandatory. The routinely employment of an ES and VECTOR, combined to clinical findings (cough, dyspnea) and respiratory lung function tests, could increase our ability to early identify ILD in CTD patients. References [1] Kelly C, Iqbal K, Iman-Gutierrez L, Evans P, Manchegowda K. Lung involvement in inflammatory rheumatic Diseases. Best Pract Res Clin Rheumatol 2016; 30:870-888. [2] Pancaldi F, Sebastiani M, Cassone G, Luppi F, Cerri S, Della Casa G, Manfredi A. Analysis of pulmonary sounds for the diagnosis of interstitial lung diseases secondary to rheumatoid arthritis. Comput Biol Med. 2018; 96:91-7 Disclosure of Interests None declared

Background: Primary Sjogren’s syndrome (pSS) is an autoimmune systemic disease characterized by lymphocytic infiltration of exocrine glands, mainly resulting in dysfunction of salivary and lachrymal glands and symptomatic xerostomia and xerophthalmia. About one third of patients also present extra-glandular manifestations and,among them, interstitial lung disease (ILD) is one the most frequent, occurring in about 10– 20% of patients. ILD is associated with an impaired quality of life and physical capacity and to a reduced 10-year survival. Despite it seems to bemore frequently detected in late stages of thedisease, some authors suggest that ILD can be diagnosed before pSS in 20% of cases. Main predictive factors of progression of pSS-ILD have not been clearly investigated in previous studies and no evidence-based treatment is defined for these patients. Objectives: To describe the clinical and serologic features and the outcome of a monocentric cohort of pSS-ILD and the possible differences between patients treated or not with immunosuppressive treatment Methods: We retrospectively evaluated the 37 pSS-ILD patients followed at our Rheumatology Unit (male/female ratio 1/6.4, mean age 69.6±11.3 years, mean disease duration of pSS 5±5.2 years). Among them, 18 patients (48.6%; group 1) underwent immunosuppressive treatment because of lung disease, namely mycophenolate mofetil (9 patients, 50%), cyclophosphamide (3, 16.7%), azathioprine (5, 27.8%), high dose steroids (1, 5.6%), while 19 patients were not treated (group 2). Results: No significant differences were observed in regard of age, male/female ratio, and disease duration of ILD and pSS, while a significant difference was observed regarding the lung function of the 2 groups; the forced vital capacity (FVC) and the diffusion lung capacity of CO (DLCO) at baseline were significantly lower in the group 1 (FVC 78.6% vs 99.4% p=0.008; DLCO 45.7% vs 56.9%, p=0.025; in group 1 and group 2, respectively). No significant difference was observed between baseline and follow-up for FVC and DLCO in both groups, regardless the immunosuppressive drug (fig. 1). At the end of follow-up FVC increased, decreased and remained stable in 5.3/10.5/84.2% and 16.7/27.8/55.6%, in group 1 and group 2, respectively; DLCO increased, decreased and remained stable in 10.5/21.1/68.4% of group 1, while remained stable or decreased in 61.1 and 38.9 of treated patients, respectively (figure 1). Conclusion: At our knowledge, few studies have investigated the features of pSS-ILD and the role of immunosuppressive drugs in these patients. Our data suggest that the decline of lung function is one of the most significant parameters to guide the prescription of immunosuppressive drugs, but no differences can be observed according to the treatment in term of effectiveness. However, no studies have investigated the correctness of this approach or the efficacy of the MMF or CFX in pSS-ILD. Our study is strongly limited by the retrospective design and the low number of patients evaluated, but these data set attention on this unmet need. Further prospective studies are mandatory to clarify the impact of ILD in pSS patients and the correct therapeutic approach. References [1] Baldini C, Pepe P, Quartuccio L, et al. Primary Sjogren’s syndrome as a multi-organ disease: impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients. Rheumatology. 2014; 53: 839-844 [2] Manfredi A, Sebastiani M, Cerri S, et al.Prevalence and characterization of non-sicca onset primary Sjogrensyndrome with interstitial lung involvement. Clin Rheumatol. 2017;36:1261-1268. Disclosure of Interests: None declared

Impaired diffusing capacity of the lung for carbon monoxide (DLCO) was frequently observed in systemic sclerosis (SSc) patients, generally related to the presence of interstitial lung disease (ILD) and/or pulmonary arterial hypertension (PAH). However, in clinical practice abnormally low DLCO values may be found also in the absence of these SSc complications. The objective was to investigate the prospective clinical relevance of isolated DLCO reduction at baseline in SSc patients. Ninety-seven SSc female patients (age at the diagnosis: 51.3±14.5 years; disease duration: 10.4±6.6 years; limited/diffuse skin subsets: 92/5), without any clinical, radiological (high resolution computed tomography), and echocardiographic manifestations of ILD or PAH at baseline, nor other lung or heart diseases able to affect DLCO, were recruited at our Rheumatology Centre. Patients with DLCO

Background Interstitial lung diseases (ILDs) are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the lungs, varying from idiopathic interstitial pneumonias to secondary variants, including the ILDs associated to connective tissue diseases (CTDs). In addition, a number of patients are recognized as unclassifiable ILD (U-ILD), because of the inability to reach a definite diagnosis; some of them show autoimmune manifestations not fulfilling the classification criteria of a given CTD. The term interstitial pneumonia with autoimmune features (IPAF) has been recently proposed for this particular ILD subset. Methods Here, we report our experience resulting from the integrated — pneumology/rheumatology — approach to patients with suspected ILDs or CTDs referred to our university-based Center for the Rare Pulmonary Diseases and Rheumatology Unit, from January 2009 to June 2015, with particular attention to the above-mentioned U-ILD, IPAF, and undifferentiated connective tissue disease (UCTD). The comparative analysis of these clinical variants was carried out; moreover, the observed findings were compared with the results of the updated review of the literature. Results After the first clinical assessment, the U-ILD were identified in 50 patients; afterwards, on the basis of clinico-serological and radiological findings U-ILD group was subdivided into 2 subgroups, namely U-ILD without any clinical extra-thoracic manifestations and/or immunological alterations (15 pts) and IPAF according to the above-mentioned classification criteria (35 pts). Patients with either IPAF or U-ILD were compared with a series of 52 stable UCTD (disease duration ≥ 3 years), followed at our Rheumatology Unit. Some important differences were evidenced among the 3 series of U-ILD, IPAF, and UCTD: firstly, female gender was more frequent in patients with UCTD (86%) or IPAF (69%) compared with U-ILD (60%) or idiopathic pulmonary fibrosis (24%; p = 0.001). In addition, UCTD patients were younger and showed longer disease duration. More interestingly, both UCTD and IPAF series show a comparable prevalence of various clinical manifestations, with the exception of the interstitial lung involvement detectable in a very small percentage of UCTD patients. Concordantly, the review of the literature evidenced two main subsets of U-ILD, one is characterized by isolated unclassifiable interstitial pneumonia and another one composed by subjects with clinically prevalent lung involvement in the setting of not definite CTD, the recently proposed IPAF. Conclusion We hypothesize that IPAF and UCTD might represent two clinical variants of the same systemic autoimmune disorders. The marked difference regarding the prevalence of ILD, which is the clinical hallmark of IPAF but very rare in UCTD, may at least in part reflect a selection bias of patients generally referred to different specialist centers, i.e. pneumology or rheumatology, according to the presence/absence of clinically dominant ILD, respectively. Well-integrated, interdisciplinary teams are recommended for the assessment and management of these patients in the clinical practice. Finally, the cooperation between multidisciplinary groups with different experiences may be advisable for a validation study of the proposed nomenclature and classification criteria of these indefinable ILD/CTD variants.

We read with interest the paper published by Gianfrancesco et al 1 describing the epidemiological findings associated with hospitalisation for COVID-19 in 600 patients with rheumatic diseases. Multivariate adjusted models proved a significant increased risk of hospitalisation for older age (>65 years), prednisone doses of ≥10 mg/day and presence of comorbidities, such as cardiovascular (CV) and lung diseases or diabetes. The use of biological or targeted synthetic disease-modifying antirheumatic drug (DMARD) appeared to decrease hospitalisation risk. Underlying CV comorbidities seem to increase the susceptibility to SARS-CoV-2 infection and to contribute to myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism also in non-rheumatic patients.2 3 Pathophysiological mechanisms underlying cardiac injury in patients with SARS-CoV-2 infection are poorly understood. However, biological features of SARS-CoV-2 and its interaction with the immune system seem to have a pivotal role in organ damage and, in particular, in CV manifestations.3 Clinical and demographic characteristics of patients with rheumatic disease suffering from COVID-19 have been explored by several Italian groups, with the highest number of COVID-19 cases observed in the North, particularly in Lombardy. In this setting, Fredi et al , on behalf of the Brescia Rheumatology COVID-19 Study Group,4 confirmed that patients with COVID-19 were older and more likely to have arterial hypertension and obesity, while no association with CV …

Background: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Its use has been associated with hypersensitivity pneumonitis and diffuse lung disease. Whether MTX exposure increases the risk of interstitial lung disease (ILD) in patients with RA is disputed. Objectives: We aimed to evaluate the association of antecedent MTX use with development of RA-ILD. Methods: Through a case-control study design with derivation and international validation samples, we examined the association of MTX exposure with ILD in 482 patients with RA-ILD and 741 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. Results: Analysis of the derivation sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.25 to 0.92; P=0.028), which was confirmed in the validation samples (pooled adjusted OR, 0.39; 95% CI, 0.23 to 0.68; P Conclusion: Our results suggest that MTX is not a risk factor for RA-ILD and support a possible disease modifying effect of MTX on development of RA-ILD. Disclosure of Interests: Pierre-Antoine Juge: None declared, Joyce S. Lee Consultant of: Celgene, Genentech, Boehringer Ingelheim, Jessica Lau: None declared, Leticia Kawano: None declared, Jorge Rojas-Serrano: None declared, Marco Sebastiani: None declared, Gouri Koduri: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Karina Bonfiglioli Consultant of: Roche, Abbvie, Pfizer, Janssen and BMS, Marcio Sawamura: None declared, Ronaldo Kairalla: None declared, Lorenzo Cavagna: None declared, Emanuele Bozzalla Cassione: None declared, Andreina Manfredi: None declared, Mayra Mejia: None declared, Pedro Rodriguez Henriquez: None declared, Montserrat I. Gonzalez-Perez: None declared, Ramces Falfan-Valencia: None declared, Ivette Buendia-Roldan: None declared, Glora Perez-Rubio: None declared, Esther Ebstein Consultant of: BMS, Employee of: BMS, Steven Gazal: None declared, Raphael Borie Consultant of: Roche, Boehringer Ingelheim, Sebastien Ottaviani: None declared, Caroline Kannengiesser: None declared, Benoit Wallaert Consultant of: Roche, Boehringer Ingelheim, Yurdagul Uzunhan Consultant of: Roche, Boehringer Ingelheim,, Hilario Nunes: None declared, Dominique Valeyre Consultant of: Astra Zeneca, Roche, Boehringer Ingelheim, Nathalie Saidenberg Kermanac’h: None declared, marie-Christophe Boissier: None declared, Lidwine Wemeau Stervinou Consultant of: Roche, Janssen, BMS, Boehringer Ingelheim, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Sylvain Marchand-Adam Consultant of: Roche, Novartis, Boehringer Ingelheim, Pascal Richette: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi, Claire Dromer: None declared, Marie-Elise Truchetet: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thierry Schaeverbeke: None declared, Huguette Liote: None declared, Gabriel Thabut Employee of: Astra Zeneca, Kevin Deane Grant/research support from: Janssen, Consultant of: Inova, ThermoFisher, Janseen, BMS and Microdrop, Joshua Solomon: None declared, Tracy Doyle: None declared, Jay H. Ryu: None declared, Ivan O. Rosas Consultant of: Boehringer Ingelheim, Gerentech, Three Lakes Partners, V. Michael Holers Grant/research support from: Janssen, Celgene, and BMS, Catherine Boileau: None declared, Marie-Pierre Debray: None declared, Raphael Porcher: None declared, David A. Schwartz Consultant of: NuMedii, Robert Vassallo Shareholder of: Pfizer, BMS, SunPharma, Bruno Crestani Shareholder of: Apellis, Boehringer Inghelheim, Medillune, Roche, Consultant of: Boehringer Ingelhiem, Astra Zeneca, Roche, Sanofi, Philippe Dieude: None declared

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

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

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

Background:Interstitial lung disease (ILD) is one of the more frequent and potentially severe extra-articular manifestation of rheumatoid arthritis (RA). ILD significantly decreases the survival and quality of life of patients and influences the treatment approach to the patient.Despite its clinical relevance, the prevalence, incidence and survival of RA-ILD is unknown and supposed on the base of retrospective data or registry-based studies.Objectives:For the first time, the Lung Involvement in Rheumatoid Arthritis (LIRA) study aims to investigate epidemiology, features and prognosis of RA-ILD patients in a prospective international multicentre study.Methods:All RA patients referring to the involved centres will be evaluated every six months with a digital stethoscope and a software able to identify velcro crackles with a diagnostic accuracy of 83.9% (VECTOR). In fact, velcro crackles are virtually identified in all stages of fibrosing alveolitis like RA-ILD, and their search is as a simple and reliable method to screening patients to be undergone to high resolution computed tomography (HRCT).For each patient, clinical and serological data are recorded at baseline and every six months; when velcro crackles or other conditions suspicious for ILD, such as cough or dyspnoea, are detected, a HRCT is requested to confirm ILD. Patients with ILD periodically perform pulmonary function tests to monitor lung function evolution.Results:At now, 205 RA patients have been enrolled (female/male 161/44, mean age 64.8±12.9 years, mean disease duration 14.2±8.9 years), anti-citrullinated peptides antibodies (ACPA) and rheumatoid factor (RF) were positive in 77.1% and 78.1%, respectively. The prevalence of ILD was 21% (43 patients). In other 13 patients the HRCT is ongoing; therefore, we could suppose up to a prevalence of 27.3%. Patients with ILD were symptomatic in 53.5% of cases (23 patients), they are more frequently males and were older than patients without ILD (mean age 73.2±7.4 and 62.7±13.2; pConclusion:The prevalence and the incidence of RA-ILD is still not well defined. Preliminary data of our study confirm a prevalence of ILD higher than 20%, patients are asymptomatic in almost the half of cases and more frequently males and elderly. Our study can help to define the clinical history of these patients, the possible association with clinical and serological features and the supposed role of some drugs.References:[1]Manfredi A, et al. Diagnostic accuracy of a velcro sound detector (VECTOR) for interstitial lung disease in rheumatoid arthritis patients: the InSPIRAtE validation study (INterStitial pneumonia in rheumatoid ArThritis with an electronic device). BMC Pulm Med. 2019;19:111.[2]Bendstrup E, et al. Interstitial Lung Disease in Rheumatoid Arthritis Remains a Challenge for Clinicians. J Clin Med. 2019:8Disclosure of Interests:Marco Sebastiani: None declared, Caterina Vacchi: None declared, Giulia Cassone: None declared, Fabiola Atzeni: None declared, Martina Biggioggero: None declared, Antonio Carriero: None declared, Gian Luca Erre: None declared, Anna Laura Fedele: None declared, Federica Furini: None declared, Paola Tomietto: None declared, Vincenzo Venerito: None declared, Belén Atienza-Mateo: None declared, Giovanni Della Casa: None declared, Stefania Cerri: None declared, Gilda Sandri: None declared, Adalgisa Palermo: None declared, Elena Galli: None declared, Fabrizio Pancaldi: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Carlo Salvarani: None declared, Andreina Manfredi: None declared

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

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

Background Antisynthetase syndrome (ASSD) is an autoimmune disease characterised by the clinical triad arthritis, myositis, and interstitial lung disease (ILD). Despite Raynaud’s phenomenon (RP) is another typical feature of ASSD, nailfold videocapillaroscopy (NVC) assessment of these patients has been only sporadically described, without the elucidating data for clinicians. Objectives To describe NVC features of ASSD patients and to investigate possible correlations with clinical and serological features of the disease. Methods We retrospectively analysed NVC images of 190 ASSD patients (females/males 3.76, mean age 49.7±12.8 years, mean disease duration 51.2±71.4 months, 133 anti-Jo-1 and 57 non-anti-Jo-1 positive patients). For each patient, we examined number of capillaries, giant capillaries, micro-haemorrhages, avascular areas, ramified capillaries, and the presence of scleroderma (SSc) patterns. Finally, we correlated NVC features with clinical and serological findings of ASSD patients. Results NVC abnormalities were observed in 62.1% of AASD patients compared with 29.3% of a group of 75 patients with primary Raynaud’s phenomenon (p Conclusions NVC abnormalities are commonly observed in ASSD, independently to the occurrence of RP. The presence of a SSc-like pattern should let to identify a more defined ASSD subtype and prospective studies could confirm the association with clinical and serological features of ASSD. Disclosure of Interest None declared

Background: Tumor necrosis factor-α inhibitors (TNFi) are usually the first biologic drugs employed in rheumatoid arthritis (RA) after failure of conventional disease-modifying antirheumatic drugs (DMARDs). Retention rate is a useful surrogate marker of effectiveness and safety in real life, but few studies investigated the causes of early discontinuation of these drugs. Objectives: Aim of the study was to investigate the possible predictors of early discontinuation (within 1 year of treatment) of etanercept (ETA) in RA patients enrolled into the GISEA (Italian Group for the Study of Early Arthritis) registry. Methods: RA patients who began etanercept as first biologic DMARD were included in the study. For all patients age, sex, disease duration, smoking status, the intake of glucocorticoids and DMARD, clinical and serological data, comorbidities and extra-articular manifestations were collected. Results: We analyzed 477 RA patients (females/males 382/95, mean age 51.3±14.1 years; mean DAS28 5.4±1.5); rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA) were positive in 66% and 62.3%, respectively. Comorbidities were observed in 16.6% of patients, mainly cardiovascular diseases, while extra-articular RA manifestations were recorded in 6.3%. Concurrent DMARDs therapies were reported in 54.3% of patients, mainly methotrexate (40.5%), while 52.4% of subjects taken low doses of steroids. Seventy patients (14.7%) discontinued ETA during the first year (for inefficacy in 43 patients, adverse events in 22, and other reasons in 5). The presence of comorbidities and a combination therapy with DMARDs different by MTX were independent predictors of early discontinuation of ETA at multivariate analysis (see table 1). The association with MTX didn’t increase the 1-year retention rate of ETA. No significant associations were observed with steroids, presence of RF or ACPA or the disease activity at baseline. Conclusions: ETA demonstrated a high persistence in RA patients and after 12 months more than 85% of patients continued the treatment. The presence of comorbidities and a combination therapy with DMARDs different by MTX were associated to an early withdrawal of the drug. Disclosure of Interest: None declared

Background Interstitial lung disease (ILD) is a possible manifestation of several rheumatic diseases. Although lung involvement is common in Anti-neutrophil cytoplasmic antibodies (ANCA) vasculitides (AAV), the presence of ILD is relatively rare. Moreover, a very small subgroup of patients may present ILD along ANCA positivity without other systemic signs of AAV. Objectives To describe the phenotypic characteristics of ILD patients with ANCA positivity without a definite diagnosis of AAV. Methods ANCA-ILD patients from 7 tertiary care hospitals (6 from Italy, 1 from Spain – 2 rheumatology centres, 4 pneumology centres, 1 internal medicine) were included. The mean follow-up was of 62.6±49.8 months. We collected epidemiologic, demographic, clinical, serological, pulmonary function test (PFT) data and high resolution computed tomography (HRCT) pattern. Results 19 patients with ANCA-ILD (M:F=9:10, mean age at diagnosis 66.2±8 years) were enrolled. The mean latency between the first respiratory symptom onset and the diagnosis was 26.4±37.0 months. Sixteen patients (84%) had ANCA-MPO positivity while 3 ANCA-PR3. Antinuclear autoantibodies were positive in 12 patients (63%). Usual interstitial pneumonia was the main HRCT pattern (10, 52.6%), followed by non specific interstitial pneumonia (8, 42%, 1 associated with organising pneumonia), 1 combined pulmonary fibrosis and emphysema. Six patients with ILD-ANCA presented also a non-erosive oligoarticular inflammation (n=6). During the follow-up, the majority of the patients (16/19) did not require oxygen therapy at last evaluation. However, 1 patient required continuous O2, 1 intermittent O2, 1 patient underwent lung transplant due to respiratory failure. Five patients required hospitalisation due to respiratory insufficiency. Two patients died, both for respiratory insufficiency. All patients were treated with glucocorticoids as induction therapy (4 intravenous pulses), combined with an immunosuppressant in 11 cases: cyclophosphamide (3, 15%), azathioprine (6, 31%), mycophenolate (2, 10.5%), methotrexate (1, 5.5%) or rituximab (2, 10.5%). Conclusions the observation of ANCA positivity in patients with ILD may open new prospective in the assessment of interstitial lung diseases. Although most of patients had a good prognosis, up to 25% presented unfavourable respiratory outcome. Further prospective studies in larger cohorts and longer follow-up may clarify the prognosis of this particular lung disease and if ILD-ANCA should be classified as a distinct subset or an incomplete form of AAV. Disclosure of Interest None declared

The diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis is fundamental to improving their survival rate. In particular, the average survival time of patients affected by rheumatoid arthritis with pulmonary implications is approximately 3 years. The gold standard for confirming the diagnosis of this disease is computer tomography. However, it is very difficult to raise diagnosis suspicion because the symptoms of the disease are extremely common in elderly people. The detection of the so-called velcro crackle in lung sounds can effectively raise the suspicion of an interstitial disease and speed up diagnosis. However, this task largely relies on the experience of physicians and has not yet been standardized in clinical practice. The diagnosis of interstitial lung diseases based on thorax auscultation still represents an underexplored field in the study of rheumatoid arthritis. In this study, we investigate the problem of the automatic detection of velcro crackle in lung sounds. In practice, the patient is auscultated using a digital stethoscope and the lung sounds are saved to a file. The acquired digital data are then analysed using a suitably developed algorithm. In particular, the proposed solution relies on the empirical observation that the audio bandwidth associated with velcro crackle is larger than that associated with healthy breath sounds. Experimental results from a database of 70 patients affected by rheumatoid arthritis demonstrate that the developed tool can outperform specialized physicians in terms of diagnosing pulmonary disorders. The overall accuracy of the proposed solution is 90.0%, with negative and positive predictive values of 95.0% and 83.3%, respectively, whereas the reliability of physician diagnosis is in the range of 60−70%. The devised algorithm represents an enabling technology for a novel approach to the diagnosis of interstitial lung diseases in patients affected by rheumatoid arthritis.

Resume L’infection par le virus de l’hepatite B (VHB), est largement repandue dans le monde et frequemment retrouvee chez les patients souffrant de polyarthrite rhumatoide (PR). La Societe italienne de rhumatologie (SIR) et la Societe italienne des maladies infectieuses et tropicales (SIMIT) ont approuve un processus de consensus national visant a passer en revue les donnees probantes disponibles sur la prise en charge du VHB chez les patients atteints de PR et a formuler des recommandations pratiques destinees a l’ensemble des hopitaux. Le groupe de consensus etait compose de specialistes des maladies infectieuses, de rhumatologues et d’epidemiologistes et s’appuyait sur les criteres du Centre for Evidence-Based Medicine (medecine fondee sur les preuves) d’Oxford pour evaluer la qualite des donnees probantes et la validite des recommandations edictees. Un ensemble d’enonces ont ete developpes pour aider les medecins dans la prise en charge des patients atteints de PR et souffrant d’une infection au VHB. La vaccination et la prophylaxie des patients PR traites par biotherapies ont egalement ete examinees. L’infection par le VHB n’est pas rare en pratique clinique ; le depistage du VHB chez tous les patients souffrant d’arthrite precoce n’est toutefois pas universellement reconnu alors qu’il est considere comme obligatoire avant l’introduction de tout traitement immunosuppresseur ou hepatotoxique. En fait, il existe un risque specifique associe a l’utilisation des biotherapies chez les patients ayant une infection par le VHB et ce malgre les conclusions generalement rassurantes des etudes longitudinales sur la reactivation virale. Les patients atteints de PR et infectes par le VHB doivent etre orientes vers un hepatologue et correctement identifies comme porteurs actifs ou inactifs. Chez les porteurs actifs du VHB, un traitement antiviral doit etre instaure avant l’introduction des immunosuppresseurs. Les porteurs occultes du VHB doivent faire l’objet d’une surveillance appropriee ou recevoir une prophylaxie en raison du risque de reactivation associe au traitement administre.

Background Skin ulcers (SU) are one of the most frequent manifestations of systemic sclerosis (SSc). SSc-SU are very painful, often persistent and recurrent; they may lead to marked impairment of patient's activities and quality of life. Despite their severe impact on the whole SSc patient's management, the proposed definition, classification criteria, and therapeutic strategies of SSc-SU are still controversial. Objective The present study aimed to elaborate a comprehensive proposal of definition, classification, and therapeutic strategy of SSc-SU on the basis of our long-term single center experience along with a careful revision of the world literature on the same topic. Methods A series of 282 SSc patients (254 females and 28 males; 84% with limited and 16% diffuse cutaneous SSc; mean age of 51.5 ± 13.9SD at SSc onset; mean follow-up 5.8 ± 4.6SD years) enrolled during the last decade at our Rheumatology Unit were retrospectively evaluated with specific attention to SSc-SU. The SSc-SU were classified in 5 subtypes according to prominent pathogenetic mechanism(s) and localization, namely 1. digital ulcers (DU) of the hands or feet, 2. SU on bony prominence, 3. SU on calcinosis, 4. SU of lower limbs, and 5. DU presenting with gangrene. This latter is a very harmful evolution of both DU of the hands and feet needing a differential diagnosis with critical limb ischemia. Results During the follow up period, one or more episodes of SSc-SU were recorded in over half patients (156/282, 55%); skin lesions were often recurrent and difficult-to-heal because of local complications, mainly infections (67.3%), in some cases associated to osteomyelitis (19.2%), gangrene (16%), and/or amputation (11.5%). SSc-SU were significantly associated with lower patients' mean age at the disease onset (p = 0.024), male gender (p = 0.03), diffuse cutaneous subset (p = 0.015), calcinosis (p = 0.002), telangiectasia (p = 0.008), melanodermia (p Therapeutic strategy of SSc-SU included both systemic and local pharmacological treatments with particular attention to complicating infections and chronic/procedural pain, as well as a number of non-pharmacological measures. Integrated local treatments were often decisive for the SSc-SU healing; they were mainly based on the wound bed preparation principles that are summarized in the acronym TIME (necrotic Tissue, Infection/Inflammation, Moisture balance, and Epithelization). The updated review of the literature focusing on this challenging issue was analyzed in comparison with our experience. Conclusions The recent advancement of knowledge and management strategies of SSc-SU achieved during the last years lead to the clear-cut improvement of patients' quality of life and reduced long-term disability.

Cryoglobulinemic vasculitis (CV) involving small- and medium-sized vessels is very frequently associated with hepatitis C virus and may be responsible for multiple organ involvement and skin ulcers (SU). Skin ulcers are often non-healing cutaneous lesions, possibly complicated by local infection and gangrene; they may severely affect the patients׳ quality of life and the overall prognosis. Therefore, the treatment of cryoglobulinemic SU is particularly challenging in the clinical practice. The present work evaluated the prevalence and correlations of cryoglobulinemic SU with other clinico-epidemiological features of CV; moreover, our long-term experience with the management strategies of these cutaneous lesions was compared with the world literature on this topic.The study included 126 CV patients (24 male and 102 female, aged 69 ± 11.2 SD years, disease duration 7 ± 6.9 SD years), followed at our Rheumatology Unit during the past decade. All patients were carefully evaluated regarding the entire cryoglobulinemic syndrome with particular concern for clinical characteristics and treatment of SU.Among 126 CV patients, 36 individuals (29%) experienced at least one episode of SU, more commonly localized at the lower limbs. Patients with complicating SU showed significantly higher percentage of purpuric manifestations (p0.01) and liver (p0.001), peripheral nerve (p0.02), and/or thyroid involvement (p = 0.019). Therapeutic approach to SU included both systemic (immunosuppressors, corticosteroids, and/or plasma exchange) and local treatments. Local treatments consisted of sharp or surgical debridement as well as interactive dressing according to the condition of wound bed, perilesional skin, and the possible presence of infection, detected in 29 of 36 (81%) individuals in our Rheumatology unit. All patients underwent analgesic treatment for SU-related background pain as well as procedural pain, which was critical for an effective local SU management. The large majority of patients with SU healed at a variable time interval according to the severity of the single lesion; only five patients with very severe, non-healing SU needed amputation. The updated review of the literature revealed the presence of SU in around a quarter of CV patients. Among systemic treatments, the anti-CD20 monoclonal antibody rituximab represents one of the most effective and frequently employed therapies; however, the available data focusing on local therapeutic approach are generally limited to anecdotal observations.Overall, the treatment of cryoglobulinemic SU should be tailored to the single patient׳s conditions using combined systemic and local treatments; lesional sharp debridement and interactive dressing as well as procedural pain management were decisive, particularly for more severe, non-healing cutaneous lesions.

Background. Increased incidence of cancer was frequently reported in scleroderma (SSc), but no association with gynaecological malignancies was described in literature.Objectives. To investigate gynaecological neoplasms in SSc patients.Methods. In this cross-sectional analysis, we evaluated 80 SSc patients, living in the same geographical area. We considered all patients undergoing gynaecological evaluation, including pap test as screening for cervical cancer, between January 2008 and December 2014.Results. 55 (68.7%) patients were negative and 20 (25%) presented inflammatory alterations, while cancer or precancerous lesions were found in 5 (6.2%) cases (2 showed cervical cancer (one of them in situ), 1 vulvar melanoma, 1 vulvar intraepithelial neoplasia, and 1 endocervical polyp with immature squamous metaplasia). The frequency of cervical cancer in our series seems higher in comparison to the incidence registered in the same geographical area. The presence of atypical cytological findings correlated with anti-Scl70 autoantibodies (p= 0.022); moreover, the patients with these alterations tended to be older (median 65, range 46–67), if compared to the whole series (p= 0.052).Conclusions. A relatively high frequency of gynaecological malignancies was found in our SSc series. In general, gynaecological evaluation for SSc women needs to be included in the routine patients’ surveillance.