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Background: Although mood disorders have been well characterized by immune-mediated inflammatory diseases, physical function and satisfaction with social roles have not yet been defined as independent domains. Objective: The study aims to assess satisfaction with social roles and physical function alterations in a population with immune-mediated inflammatory diseases and identify associated characteris-tics. Methods: Physical function and social role satisfaction were evaluated through the Patient-reported Outcomes Measurement System. Besides comparison between groups, univariate and multivariable logistic regression analyses were performed to identify independent predictors. Results: Two hundred sixty-five patients with immune-mediated inflammatory diseases and 206 controls were recruited. Compared to controls, patients with inflammatory bowel diseases had impaired physical function (p Conclusion: Immune-mediated inflammatory diseases determine alterations in physical function and social life satisfaction. Gender and treatment are independently associated factors. Patient-reported outcomes should be considered in clinical management to define patients’ real needs.

Objectives: To evaluate the impact of obesity in patients with adult onset Still's disease (AOSD) and to assess their clinical characteristics and disease outcomes. Methods: The clinical features of AOSD patients with a body mass index (BMI) ≥ 30 were assessed among those included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort. Results: Out of 139 AOSD patients, who had BMI registered in our database, 26 (18.7%) had a BMI ≥ 30. A lower rate of sore throat (P

Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory disease, frequently associated with cardiovascular (CV) comorbidities. Our aim was to compare the prevalence of CV comorbidities between two groups of PsA patients from different European countries: Belgium and Italy. Methods: This is a cross-sectional analysis of two longitudinal cohorts in which 803 PsA patients were enrolled (463 from Belgium and 340 from Italy). All enrolled patients were ≥18 years old and fulfilled the ClASsification criteria for Psoriatic Arthritis (CASPAR criteria). For each patient, demographics, clinical assessments, smoking habits, the presence of arterial hypertension (AH), obesity (BMI ≥30), type 2 diabetes (T2D), CV diseases (acute myocardial infarction, stroke or transient ischaemic attack), dyslipidaemia (Italy only) and hypercholesterolaemia (Belgium only) were collected. Results: The most prevalent comorbidities among Italian patients with PsA were: AH (45.1%), dyslipidaemia (38.6%) and obesity (30.8%), and among Belgian patients were: hypercholesterolaemia (30.9%), obesity (27%) and AH (26.4%). Moreover, the prevalence of T2D and CV diseases was respectively 14.2% and 7.1% among Italian patients and 7.6% and 3.5% among Belgian patients. When comparing the two groups, AH, T2D and CV diseases were significantly more prevalent in Italian PsA patients. After controlling for different confounders, Italian patients, regardless of age, sex, smoking habits, PsA duration, other CV comorbidities, therapy, disease activity and function, had a higher risk to be hypertensive (OR 2.00, p=0.007). Instead of the country in which patients lived was not a predictor for the risk of T2D and CV diseases. Obesity prevalence was not different between the two groups. The lipid profile was unfavourable in both populations (even if not comparable between the two groups, due to the different way of collection), as is often the case in PsA. Conclusions: The prevalence of AH, T2D and CV diseases were higher in Italian patients rather than Belgians. Moreover, among patients with PsA, the risk of AH was higher in the Italian cohort compared to the Belgian cohort. These results suggest that further research is needed to evaluate potential extrinsic factors (geography and sociocultural aspects) that may contribute to CV risk.

We aimed to investigate the health-related quality of life (HRQoL) in Adult onset Still disease (AOSD) patients, a rare systemic auto-inflammatory disorder of unknown etiology usually affecting young adults. In this multicentre cross-sectional study, AOSD patients and age and gender matched healthy controls (HCs) were included. All patients had a low or absent clinical expressiveness, they were categorized as having a monocyclic pattern or a chronic disease course. The Health Assessment Questionnaire (HAQ), European Quality of Life Questionnaire (EUROQoL), 36-Items Short-Form Healthy Survey (SF-36), Functional Assessment of Chronic Illness Therapy Fatigue subscale (FACIT-F), 100 mm-visual analogue scale (VAS) of pain, fatigue, and global health assessment, were used to evaluate HRQoL. The results were compared between patients and HCs, analyzed according to clinical course, and correlated with clinical features at the time of diagnosis. HRQoL resulted to be altered in 53 AOSD patients compared to 53 age and gender matched HCs. Many SF-36 domains differed between the 2 groups, mainly those of physical functioning which were reduced in AOSD respect to HCs. Furthermore, HAQ, FACIT-F, EuroQoL, VAS state of health, VAS pain, and VAS fatigue significantly differed between AOSD and HCs. No substantial differences were found comparing monocyclic pattern with chronic disease course. AOSD patients showed an impairment of many SF-36 domains, HAQ, FACIT-F, EuroQoL, VAS state of health, VAS pain, and VAS fatigue when compared to matched HCs, despite a low or absent clinical expressiveness; these findings were similarly retrieved in both monocyclic pattern and chronic disease course.

Objective In this study, we aimed to describe the clinical characteristics, life-threatening complications occurrence, and mortality of adult-onset Still's disease (AOSD) patients with elderly onset. Methods A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was performed. Results Out of 221 assessed patients, 37 (16.7%) had an onset of the disease aged over 60 years. When compared with younger patients, these were characterised by a higher prevalence of pericarditis (p=0.008), comorbidities (p < 0.0001), and mortality (p=0.023). Age predicted the presence of serositis in both univariate (HR: 1.02, 95%CI: 1.01-1.03, p=0.007) and multivariate analyses (HR: 1.02, 95%CI: 1.01-1.04, p=0.007). Age was also a significant predictor of parenchymal lung disease in both univariate (HR: 1.03, 95%CI: 1.01-1.05, p=0.017) and multivariate analyses (HR: 1.03, 95%CI: 1.00-1.05, p=0.048). Furthermore, age resulted to be a negative predictor of polycyclic pattern only in univariate analysis (HR: 0.99, 95%CI: 0.97-1.00, p=0.048). Finally, age significantly predicted the mortality in both univariate (HR: 1.03, 95%CI: 1.00-1.06, p=0.034) and multivariate analyses (HR: 1.05, 95%CI: 1.01-1.08, p=0.012). Conclusion Clinical features of AOSD patients in the elderly were described in our cohort. Although the main clinical characteristics were similar comparing older and younger patients, patients aged over 60 years at disease onset were characterised by an increased prevalence of serositis, comorbidities, mostly cardiometabolic, and a higher mortality rate. Age predicted the presence of parenchymal lung disease and mortality, and it could be considered a negative prognostic factor in AOSD.

Objective To compare clinical features and treatments of patients with systemic JIA (sIJA) and adult-onset Still’s disease (AOSD). Methods The clinical charts of consecutive patients with sJIA by International League of Association of Rheumatology criteria or AOSD by Yamaguchi criteria were reviewed. Patients were seen at a large paediatric rheumatology referral centre or at 10 adult rheumatology academic centres. Data collected included clinical manifestations, inflammation biomarkers, systemic score, macrophage activation syndrome (MAS), parenchymal lung disease, disease course, disability, death and medications administered. Results A total of 166 patients (median age at diagnosis 5 years) with sJIA and 194 patients with AOSD (median age at diagnosis 41 years) were included. The frequency of fever, rash, arthralgia, abdominal pain, MAS, parenchymal lung disease and increased acute phase reactants and ferritin were comparable between the two cohorts. Patients with sJIA had a higher prevalence of arthritis, whereas patients with AOSD had experienced leucocytosis and extra-articular organ involvement more frequently. Patients with AOSD were given more commonly low-dose corticosteroids, whereas biologic DMARDs were administered first-line more frequently in patients with sJIA. Conclusion We found remarkable disparities in the prevalence of clinical manifestations between the two illnesses, which may partly depend on their classification by different criteria.

Giant cell arteritis (GCA) is a quite common panarteritis of the elderly that affects medium- and large-size arteries. Despite the increasing role of imaging with advancing technology, the gold standard for the diagnosis of GCA is still the temporal artery biopsy. A described complication of superficial temporal artery biopsy (STAB), for which incidence is not clear, is the accidental damage of the frontal branch of the facial nerve. In this paper, we described the short-scar facelift surgical approach for STAB on 23 consecutive patients who underwent unilateral superficial temporal artery biopsy for GCA suspicion. We collected data in terms of postoperative complications, biopsy specimen length, biopsy result and cosmetic appearance of the scar. In our experience, this surgical approach combines the advantage of avoiding incisions within the dangerous anatomical area, minimizing the risk of facial nerve damage, with an acceptable complication rate and a good final aesthetic result which avoids visible scarring.

The objective of this study is to describe the possible prognostic impact of smoking habit on adult-onset Still’s disease (AOSD) patients, by the assessment of clinical characteristics, life-threatening complications occurrence, and mortality in smokers than non-smokers. A multicentre retrospective study of prospectively followed-up AOSD patients included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort was conducted. Out of 185 AOSD assessed patients, 45 smokers were identified. These showed a higher frequency of pericarditis (35.5% vs 16.4%, p = 0.011), pleuritis (33.3% vs 14.3%, p = 0.008), and abdominal pain (17.7% vs 6.4%, p = 0.035). Furthermore, smokers showed higher values of systemic score (6.4 ± 2.2 vs 5.4 ± 1.8, p = 0.004), an increased rate of macrophage activation syndrome (MAS) (28.9% vs 6.4%, p < 0.0001) and of parenchymal lung disease (17.7% vs 12.6%, p = 0.035). Although not significant, these patients more frequently experienced a poor prognosis (13.3% vs 4.3%, p = 0.074). Smoking habit predicted MAS occurrence in both univariate (HR: 5.98, 95% CI: 2.45–14.57, p < 0.0001) and multivariate regression models (HR: 6.21, 95% CI: 2.46–15.70, p < 0.0001). Smokers had a significant higher risk of parenchymal lung disease in both univariate (HR: 3.97, 95% CI: 1.43–11.02, p = 0.008) and multivariate regression models (HR: 3.90, 95% CI: 1.36–11.23, p = 0.012). Smoking habit also increased the risk of mortality in univariate regression model (HR: 4.25, 95% CI: 1.33–13.55, p = 0.015). Smoking habit resulted to be a negative prognostic factor on AOSD patients. Smokers were characterised by a higher frequency of serositis and higher values of systemic score. Additionally, these patients were more frequently burdened by MAS and parenchymal lung disease associated with a poor prognosis.Key points•Smoking habit resulted to be a negative prognostic factor on AOSD.•Smokers were characterised by an increased frequency of serositis and higher values of systemic score.•Cigarette exposure was associated with MAS and parenchymal lung disease in AOSD.

Objectives To assess the efficacy of the novel anti-IL-23 monoclonal antibody guselkumab in a real-life observational cohort of patients with early PsA. Methods We conducted an observational study on patients with early PsA followed by the joint dermatology-rheumatology clinics of two Italian centres starting therapy with guselkumab for severe skin involvement. Each patient was evaluated at baseline and every 24 weeks for one year, recording Disease Activity Index for PsA (DAPSA), PASI, VAS Pain, VAS Prutitus, Patient's Global Assessment (PtGA) and assessing DAPSA response. Results Twenty-four patients were recruited (16 women). The mean duration of skin disease was 12.5 years (CI 8; 17), but all patients had a shorter articular disease duration, 21.29 months (CI 15.9; 26.68). At baseline, all patients displayed a moderate cutaneous disease with a mean PASI of 15.2 (CI 11.7–18.6) and high disease activity, characterized by mean DAPSA of 26.84 (CI 22.49–31.19). An inflammatory low back pain was reported by five patients (20%) with a mean BASDAI 5.1 (CI 4,38–5,85) at baseline. The majority of guselkumab-treated patients (n = 18; 75%) reached DAPSA remission or DAPSA low disease activity after six months. Seventeen out of 24 patients completed 12 months of treatment, 11 of them (65%) in low disease activity, six (35%) in remission. All patients with axial disease reported improvement of inflammatory low back pain at week 24 with a mean BASDAI 2.98 (CI 2,18– 3,77). No significant side effects were reported. Conclusions Real-life data on a cohort of early PsA patients confirm the efficacy and safety of guselkumab on peripheral and axial manifestations.

Objectives To stratify adult-onset Still’s disease (AOSD) patients in distinct clinical subsets to be differently managed, by using a multi-dimensional characterization. Methods AOSD patients were evaluated by using a hierarchical unsupervised cluster analysis comprising age, laboratory markers systemic score and outcomes. The squared Euclidean distances between each pair of patients were calculated and put into a distance matrix, which served as the input clustering algorithm. Derived clusters were descriptively analysed for any possible difference. Results Four AOSD patients clusters were identified. Disease onset in cluster 1 was characterized by fever (100%), skin rash (92%) and arthritis (83%), with the highest ferritin levels [mean (S.D.) 14 724 (6837) ng/ml]. In cluster 2, the onset was characterized by fever (100%), arthritis (100%) and liver involvement (90%), together with the highest CRP levels [288.10 (46.01) mg/l]. The patients in cluster 3 presented with fever (100%), myalgia (96%) and sore throat (92%). The highest systemic score values [8.88 (1.70)] and the highest mortality rate (54.2%) defined cluster 3. Fever (100%) and arthritis (90%) were the symptoms at the onset in cluster 4, which was characterized by the lowest ferritin and CRP levels [1457 (1298) ng/ml and 54.98 (48.67) mg/l, respectively]. Conclusion Four distinct phenotypic subgroups in AOSD could be suggested, possibly associated with different genetic background and pathogenic mechanisms. Our results could provide the basis for a precision medicine approach in AOSD in an attempt to find a clinical and laboratory multidimensional stratification and characterization, which would drive a tailored therapeutic approach in these patients.

Background Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder of unknown aetiology usually affecting young adults. Interestingly, recent evidence from the juvenile counterpart of AOSD suggested the emergent high fatality rate of lung disease (LD) in these patients. In this work, we aimed to characterise LD in AOSD, to identify associated clinical features and predictive factors, and to describe long-term outcomes of the disease comparing patients with LD and those without. Methods A retrospective assessment of prospectively followed patients, from January 2001 to December 2019, was provided to describe the rate of LD in AOSD, associated clinical features and predictive factors, and long-term outcomes. Patients with AOSD, who were included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort, were assessed. Results Out of 147 patients included in GIRRCS cohort, 18 (12.25%) patients were reported to be affected by LD, at the time of diagnosis of AOSD, who were characterised by older age, a higher prevalence of myalgia, of lymph node involvement, of pleuritis, and abdominal pain. Furthermore, patients with LD showed higher values of systemic score and ferritin. Among those clinical variables, older age and systemic score were also independently predictors of LD. Chest CT scans were also obtained, and the most common finding was the peripheral consolidations in 8 (44.4%) patients. Finally, a higher mortality rate, of 38.9%, was registered in patients with LD than others, since it was associated with a significant decreased survival rate. Conclusions The presence of LD could suggest an emergent cause of mortality in AOSD, as observed in juvenile counterpart recognising a further marker of severity and poor prognosis to be careful evaluated. Patients with LD were also characterised by some clinical features, higher values of systemic score and ferritin than the others, identifying a subset of patients mostly burdened by systemic signs and symptoms. Although specific designed future studies are needed to fully elucidate the significance of LD in AOSD, a more accurate evaluation and management of this feature could improve the long-term outcomes of these patients.

A growing body of evidence suggests the usability of biologic disease-modifying anti-rheumatic drugs (bDMARDs) in treating adult-onset Still's disease (AOSD). In a multicentre "real-life" cohort, the physicians' prescribing motivations and patients' predictive characteristics of being treated with bDMARDs were assessed. Patients with AOSD, who were included in GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort and treated with bDMARDs, were retrospectively assessed. Relevant data were collected by a review of clinical charts. Forty-four patients treated with bDMARDs were analysed, with slight male preponderance (52.3%) and a mean age of 39.3 ± 15.2years. All patients were treated with corticosteroids (CCSs) (38.6% with low dosage) and 93.2% were treated with synthetic DMARDs (sDMARDs). Regarding the effectiveness of the first-line bDMARD, 65.6% of patients experienced a complete remission, defined as complete disappearance of both systemic and joint symptoms and normalisation of laboratory evidence of disease. The physicians' prescribing motivations for bDMARDs were inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and occurrence of macrophage activation syndrome (MAS). Analysing patients' characteristics, chronic disease course (OR 3.09; 95%CI 1.22-7.80, p = 0.017), defined as disease with persistent symptoms, was predictive of being treated with bDMARDs, whereas age (OR 0.97, 95%CI 0.93-0.99, p = 0.048) was negatively associated, suggesting younger age as a further predictive factor. Patients with AOSD were treated with bDMARDs for inadequate response to CCSs and/or sDMARDs, CCS-sparing effect and MAS occurrence. Younger age and chronic disease course were patients' predictive characteristics of being treated with bDMARDs.

We read with interest the recently published paper from McGonagle et al 1 analysing the role of interleukin (IL)-17A in axial spondyloarthritis and psoriatic arthritis (PsA). The meta-analysis and functional study provided by the authors highlighted the efficacy of IL-17A block by secukinumab in the treatment of PsA. However, there is no mention of the role of body mass index (BMI), if any, in influencing the clinical response to secukinumab, given the lack of published data. PsA is a chronic inflammatory arthritis burdened by a series of metabolic comorbidities. Among them, obesity is very common in PsA, with a prevalence of 27%, as confirmed by a recent Spanish work.2 Obesity in PsA has been associated with higher disease activity and a worse effectiveness of biologic treatment in PsA. This has been certainly proven for anti-tumour necrosis factor (TNF)-α as demonstrated by different studies reporting, in obese patients, a reduced treatment response and adherence. In particular, …

ObjectiveTo assess the predictive role of ferritin and C-reactive protein (CRP) on occurrence of macrophage activation syndrome (MAS) and mortality in patients with adult onset Still's disease (AOSD), a rare and severe disease, included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort.MethodsThe predictive role, at the time of diagnosis, of serum levels of ferritin and CRP on occurrence of MAS and mortality, was evaluated by logistic regression analyses and receiver-operating characteristic (ROC) curves were built to identify patients at high risk of MAS and mortality, respectively.ResultsIn assessed 147 patients with AOSD, levels of ferritin were predictive of MAS (OR: 1.971; P: 0.002; CI 95%: 1.280-3.035). The ROC curve showed that the best cut-off for ferritin was 1225 ng/ml in predicting MAS (sensitivity 88%; specificity 57%). Levels of CRP were predictive of mortality in these patients (OR: 2.155; P: 0.007; CI 95%: 1.228-3.783). The ROC curve showed that the best cut-off for CRP was 68.7 mg/L in predicting mortality (sensitivity 80%; specificity of 65%).ConclusionsWe reported the predictive role of ferritin and CRP on MAS and mortality, respectively, in a large cohort of patients with AOSD, identifying subsets at higher risk of poor prognosis. Considering that the analysis of CRP and ferritin is widely available, these results could be readily transferable into clinical practice, thus improving the management of patients with AOSD.

Background:The new coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) is a source of concern for the management of patients suffering from rheumatic and musculoskeletal diseases (RMDs) treated with immunomodulatory therapies (1).Objectives:We aimed to analyze the prevalence of SARS-CoV-2 infection in patients with RMDs living in Italy.Methods:During the first wave (March-May 2020) and during the second wave (October-December 2020) of COVID-19, we conducted a survey to investigate the incidence of SARS-CoV-2 infection in patients with RMDs followed at the Rheumatology Unit of the University of Campania, Italy. The demographic data, medication use, the frequency of respiratory symptoms and the incidence of COVID-19 confirmed by nasopharyngeal swab were collected with questionnaires administered by phone. The prevalence of COVID-19 of our cohort was compared to that of the general population (2).Results:During the first wave, we collected data from 900 patients with RMDs (Table 1): 320 patients with rheumatoid arthritis (RA), 295 patients with spondyloarthropathies (SpA), 283 patients with systemic lupus erythematosus (SLE), 2 patients with vasculitis. 546 (60%) were treated with bDMARD/tsDMARDs. Overall, a total of 11/900 (1%) cases were tested for COVID-19 due to compatible symptoms. 2 (0.2%) adult patients treated with bDMARDs were registered as swab test positive by PCR for COVID-19. 2 patients without confirmed COVID-19 developed pneumonia that required admission to hospital. No deaths occurred among the patients with confirmed COVID-19.During the second wave, data were collected from 470 patients who accepted to take part of the study (Table 1). 49 presented with symptoms that were compatible with COVID-19. 139 patients were tested whereas 30 patients (6%) had a swab confirmation of SARS-CoV-2 infection. Among them, 16 (53%) were treated with bDMARDs and a patient was treated with tofacitinib. we found no increase in COVID-19 prevalence in patients treated with bDMARD/tsDMARDs (p>0.05). A patient with SLE developed pneumonia that required admission to hospital and died.Lacking distinct prevalence data between first and second waves, we found no differences in total COVID-19 prevalence between general population living in Campania (215.752/5.802.000; 3.7%) and patients with RMDs (32/900; 3.5%). However, we had a significant increase in COVID-19 prevalence in our cohort during the second wave compared to the first. Nevertheless, no increase in mortality or hospitalization was recorded, confirming the safety of immunomodulatory therapies in patients with RMDs.Conclusion:In this cohort of patients with RMDs in a geographical region with a high prevalence of COVID-19, the risk of SARS-CoV-2 infection does not appear different from that observed in the general population.References:[1]Wang L., Wang Y., Ye D. Int J Antimicrob Agents. 2020:105948.[2]http://www.protezionecivile.gov.it/ (accessed 28.01.21)Table 1.Demographics and clinical characteristics of 900 patients with rheumatic diseases during the COVID-19 Pandemic.First waveSecond waveWomen, n 660 (73 %) 366(77%)Age, years, median (range)56 (54-57)53 (51-55)Rheumatoid Arthritis320 (35.5%)143 (30%)Spondyloarthritis295 (32%)110 (23%)Systemic Lupus Erythematosus283 (31%)217 (46 %)Vasculitis2 (0.2%)1 (0.2%)Prior ILD56 (6%)22 (4.6%)Smokers220 (24%)118 (25%)Hydroxychloroquine215 (23%)155 (32%)Steroids337 (37%)194 (41%)Prednisone equivalent dose, median (range)5 (0-75)5 (0-50)bDMARD/tsDMARDs546 (60%)247 (52%)csDMARDS387 (43%)185 (39%)Angiotensin-converting enzyme (ACE) inhibitors178 (19.8%)101 (21%)Angiotensin II receptor blockers(ARBs)153 (17%)61 (13%)Fever64 (7%)30 (6.3%)Cough83 (9%)36 (7%)Shortness of breath34 (3%)15 (3%)Sore throat32 (3%)11 (2.3%)Rhinorrhoea36 (3%)11 (2.3%)Headache5 (0.5%)2 (0.4%)Anosmia10 (1%)24 (5%)Myalgia2 (0.2%)1 (0.2%)Gastrointestinal symptoms24 (2.6%)3 (0.6%)Pneumonia2 (0.2%)2 (0.4%)Admission to hospital2 (0.2%)9 (1.9%)Swab confirmation of SARS-CoV-2 infection230Disclosure of Interests:None declared.

Objective.Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE.Methods.Patients consecutively admitted to our center who, at admission, satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus Collaborating Clinics classification criteria for SLE, and had not experienced any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c-HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ associated with a lower incidence of CVE. Cox regression analysis served to identify factors associated with a first CVE.Results.For the study, 189 patients with SLE were enrolled and monitored for 13 years (median). Ten CVE occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047, respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR 18.054) increased the risk of a first CVE.Conclusion.Our results suggest that prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional evidence for its continued use in patients with SLE.

Background The systemic inflammatory process and the “traditional” cardiovascular (CV) risk factors could synergize the enhancement of CV burden in rheumatoid arthritis (RA) [1]. Objectives To assess the occurrence and the predictive factors of subclinical and clinical atherosclerosis in patients with RA. Methods During 2015, consecutive patients, admitted to Italian Rheumatology Units, were assessed in GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort [2]. After that, patients were followed-up in a 3-year, prospective, observational study, assessing the occurrence of subclinical (carotid and/or peripheral arteries atherosclerotic lesions detected by ultrasound imaging) and clinical atherosclerosis (myocardial infarction and/or congestive heart failure and/or cerebrovascular accidents) and possible predictive factors. McNemar test was employed to assess the changes in subclinical and clinical atherosclerosis and regression analyses exploited the ORs for the occurrence of those comorbidities. Results After 3 years of prospective follow-up, 797 patients (82.7% female, median age of 60 years, range 21-89) were assessed. We also observed a median RA duration of 8.35 years (range 0.1-35), 70.9% of patients showed rheumatoid factor and 55.7% ACPA. Among “traditional” CV risk factors, we observed that BMI was 27.21 ± 4.05, 33% of patients reported smoking habit, 49.3% were affected by high blood pressure (HBP) and 12.3% by type 2 diabetes (T2D). Corticosteroids were administered in 75.5% of patients (low dosage 66.8%), methotrexate in 86.8%, hydroxychloroquine in 28.1% and biologic DMARDs in 60.7%. The remission was reached and maintained in 42.6% of patients, during the follow-up. We recorded an increased rate of subclinical atherosclerosis (70 vs 130 patients p Conclusion The maintenance of remission was strongly associated with a reduced risk of clinical and subclinical atherosclerosis in 3-year prospective follow-up. Among “traditional” CV risk factors, T2D was significantly associated with both clinical and subclinical atherosclerosis. References [1] Nurmohamed MT, et al. Nat Rev Rheumatol. 201511:693-704 [2] Ruscitti P, et al. Medicine (Baltimore). 2017;96:e8180. Disclosure of Interests Piero Ruscitti Grant/research support from: PFIZER INNOVARE 2018, Speakers bureau: MSD, BMS, SOBI, LILLY, PFIZER, Paola Cipriani Grant/research support from: ACTELION, Speakers bureau: ACTELION, Vasiliki Liakouli Grant/research support from: PFIZER, Speakers bureau: SANOFI, Daniela Iacono Speakers bureau: PFIZER, Ilenia Pantano: None declared, Giulia Maria Destro Castaniti: None declared, Nicola Maruotti Speakers bureau: N Maruotti has received speaker honoraria from Pfizer outside this work, Domenico Paolo Emanuele Margiotta: None declared, Licia Picciariello: None declared, Francesco Caso: None declared, Rosa Daniela Grembiale Grant/research support from: BMS, Consultant for: JANSSEN, CELGENE, Speakers bureau: PFIZER, JANSSEN, BMS, NOVARTIS, Fabiola Atzeni: None declared, Raffaele Scarpa Speakers bureau: ABBVIE, MSD, PFIZER, LILLY, JANSEEN, CELGENE, Federico Perosa Speakers bureau: OCCASIONALLY, Antonella Afeltra Grant/research support from: MSD, PFIZER, ABBVIE, ROCHE, UCB, Speakers bureau: MSD, PFIZER, BMS, ROCHE, SANOFI, Francesco Paolo Cantatore Speakers bureau: PFIZER, ROCHE, Giuliana Guggino Grant/research support from: Laborest, Pfizer, Consultant for: Novartis, Abbvie, Speakers bureau: Sandoz, Francesco Ciccia Grant/research support from: CELGENE, PFIZER, Consultant for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, Paid instructor for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, Speakers bureau: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, ROCHE, AMGEN, Roberto Giacomelli Grant/research support from: Pfizer, Actelion, Speakers bureau: Actelion, Bristol-Myers Squibb, Merck Sharp & Dohme, Abbvie, Pfizer, Sobi, Roche

Background Current recommendations on the treatment of Rheumatoid Arthritis (RA) are based on a treat to target approach, nevertheless which biologic drug should be used in an unresponsive patient is not clarified (1). Such a strategy is essentially justified by the fact that no biotechnological drug has proved to be superior to any other (2). Recent studies have reported some disease or patient features that are associated with a greater or lesser likelihood of response (3). Nevertheless, an adapted therapy to the single patient and based on physiopathological mechanisms has not been acquired yet. Objectives Aim of this study was to evaluate if the choice of a tailored therapy, based on patient and disease features, would be an effective strategy. Methods From April 1st 2017, at our Department of Rheumatology of the University of Campania, each patient with RA has been characterized, at enrolment, for demographic and disease features, and started a biological Disease-modifying antirheumatic drug based on an established algorithm (Figure 1). Attainment of the targeted end point i.e. remission (R) as assessed by Simplified Disease Activity Index (SDAI) Results Forty-nine patients were admitted to our centre from April 1st2017 to December 31st2018. Out of them, 36 patients have been followed up at least for 3 months and were included in the study (algorithm+ patients). Out of them, 26 (72.2%) reached 6 months of treatment, while 16 (44.4%) 12 months of treatment. Among the 26 patients evaluated at 6 months, 23(88.5%) achieved the targeted end point. At 12 months, 16/16 patients (100%) preserved a status of remission or at least low disease activity. We compared our results to those registered, from January 2015 to September 2016, in a RA cohort of 79 patients (RA general cohort). We found a significant difference in regard to attainment of the target at 6 months (23/26 patients, 88.5% algorithm+ vs 45/67 patients, 67.2% RA general cohort; p=0.04) and at 12 months (16/16 patients, 100% algorithm+ vs 40/57 patients, 70.2% RA general cohort; p=0.01) (Table 1). Notably, 32 out of the 79 patients had undergone a biological drug which didn’t follow the predefined algorithm. These patients (algorithm- patients) presented a further lower incidence of response with regard to those enrolled according to the algorithm: 22/32 patients (68.7%) at 3 months; p=0.4; 17/29 (58.6%) at 6 months; p=0.001; 17/24 (70.8%) at 12 months; p=0.03). Conclusion The choice of a personalized approach toward treatment of RA might be an effective strategy to achieve the targeted end point of remission or at least low disease activity in every patient. References [1] Smolen JS et al. Ann Rheum Dis 2017;76:960–77 [2] Pierreisnard A et al. Joint Bone Spine. 2013;80:386-92. [3] Daien CI et al. Mediators of Inflammation 2014;2014:386148 Disclosure of Interests DANIELA IACONO Speakers bureau: PFIZER company, Ilenia Pantano: None declared, SERENA FASANO: None declared, GIUSEPPE SCALISE: None declared, Francesco Ciccia Grant/research support from: CELGENE, PFIZER, Consultant for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, Paid instructor for: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, Speakers bureau: UCB, NOVARTIS, CELGENE, PFIZER, LILLY, JANSSEN, MSD, ROCHE, AMGEN

Objective. To investigate the role of acetylsalicylic acid (ASA) in reducing the incidence of cardiovascular (CV) events in an Italian multicentre rheumatoid arthritis (RA) inception cohort. Methods. The clinical charts of RA patients consecutively admitted to 4 Italian centres for their 1st visit from November 1, 2000, to December 31, 2015, and followed up till December 2016 were retrospectively investigated for the incidence of CV events. Patients were subdivided into two groups, namely, ASA- and non-ASA-treated groups. The Kaplan–Meier curve and log-rank test were used to investigate differences in event-free survival. Cox regression analysis was carried out to identify factors associated with CV event occurrence. Results. Seven hundred forty-six consecutive RA patients were enrolled and followed up for a median of 5.6 years (range 2.9–8.9 years). The incidence rate (IR) of CV events was 8/1000 person-years (p-ys) in the overall cohort. The IR of CV events was significantly lower in the ASA-treated group with respect to the non-ASA-treated group (IR 1.7 vs. 11.8/1000 p-ys; p=0.0002). The CV event-free rate was longer in ASA-treated patients than in non-ASA-treated patients (log-rank test 12.8; p=0.0003). At multivariable analysis, arterial hypertension (HR 9.3) and hypercholesterolemia (HR 2.8) resulted to be positive predictors and ASA (HR 0.09) and hydroxychloroquine (HCQ) (HR 0.22) to be negative predictors. Conclusion. The IR of CV events in our Italian multicentre cohort was lower than that reported in other European and non-European cohorts. Low-dose ASA may have a role in the primary prophylaxis of CV events in RA patients.

Background Rheumatoid arthritis (RA) is associated with an increased risk of morbidity and mortality, when compared with general population, largely due to enhanced atherosclerotic disease. In this work, we aimed at assessing both occurrence and predictive factors of subclinical and clinical atherosclerosis in RA. Methods From January 1, 2015, to December 31, 2015, consecutive participants with RA, admitted to Italian Rheumatology Units, were assessed in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort. After that, those participants were followed up in a 3-year, prospective, observational study, assessing the occurrence of subclinical and clinical atherosclerosis and possible predictive factors. McNemar test was employed to assess the changes in subclinical and clinical atherosclerosis, and regression analyses exploited the ORs for the occurrence of those comorbidities. Results We analysed 841 participants, mostly female (82.2%) and with median age of 60 years (range 21–90). The remission was achieved and maintained by 41.8% of participants during the follow-up. We observed an increased rate of subclinical atherosclerosis at the end of follow-up (139 vs 203 participants, p

Systemic sclerosis (SSc) is characterized by microangiopathy with impaired reparative angiogenesis and fibrosis. Epidermal Growth Factor Like-domain 7 (EGFL7), firstly described in endothelial cells plays a pivotal role in angiogenesis. Fibroblasts (FBs) are involved in vascular remodeling, under physiological and pathological conditions. In this study, we investigated: (i) the expression of EGFL7 and its miR-126 in patients affected by diffuse cutaneous SSc (dcSSc); (ii) the ability of Transforming Growth Factor-beta (TGF-β) to modulate EGFL7 expression; (iii) the ability of EGFL7 to modulate COL1A1 expression and proliferation/migration, and (iv) the functional role of EGFL7 on angiogenesis. Patients were divided in 2 subsets: patients fulfilling the classification criteria in less than one year from Raynaud’s Phenomenon onset (Early Onset Subset–EOS), and all the others (Long Standing Subset–LSS). We show that EGFL7 expression is increased in EOS dcSSc skin and cultured FBs. EGFL7 is inducible by TGF-β on Healthy Controls (HC) FBs but not in SSc-FBs. EGFL7 decreases COL1A1 expression in EOS SSc-FBs while EGFL7 silencing up-regulates COL1A1 expression. EGFL7 promotes migration/invasion of EOS SSc-FBs but not proliferation. Finally, SSc-FBs, partially inhibit angiogenesis in organotypic coculture assays, and this is reversed by treatment with human recombinant (rh)EGFL7. We conclude that EGFL7 and its specific microRNA miR-126 may be involved in the pathogenesis of SSc vasculopathy and fibrosis.

Objectives Cardiovascular (CV) morbidity and mortality are significantly greater in SLE patients than in the general population. ASA is known to be associated with a decrease in the incidence of CV events in high-risk patients from the general population, but its efficacy as primary prophylaxis in SLE patients has not yet been investigated. Methods The clinical charts of SLE patients consecutively admitted to a tertiary centre who, at admission, satisfied 1992 ACR and/or 2012 SLICC classification criteria for SLE and had not experienced any CV event, were reviewed. The occurrence of any CV event was recorded at each visit. ASA was prescribed to all patients at first visit. The rate and reasons for ASA discontinuation were also recorded at each visit. Results One hundred and sixty-seven consecutive SLE patients were enrolled and followed up for a median of 8 years (range 1-14 years). Among them, 146 regularly took the medication (ASA-treated patients) and 21 refused to take or discontinued it (non-ASA-treated patients). Five CV events occurred in the 146 ASA-treated patients (4.2 per 1000 person-years) and four in the 21 non-ASA-treated patients (30 per 1000 person-years; P = 0.0007). The CV event-free rate was higher in ASA-treated than in non-ASA-treated patients (log-rank test χ(2) = 15.74; P = 0.0001). No relevant side-effect related to ASA was recorded. Conclusion Low-dose ASA is a safe treatment and may be beneficial in the primary prophylaxis of CV events in SLE patients. Controlled, prospective studies are needed to provide a better definition of its role in these patients.

Background:Psoriatic arthritis (PsA) is a chronic inflammatory arthritis burdened by a series of metabolic comorbidities. Among them, obesity is very common in PsA, with a prevalence of 27%, as confirmed by a recent Spanish work (1). Obesity in PsA has been associated with higher disease activity and a worse effectiveness of biologic treatment in PsA. This has been certainly proven for anti-TNF-α as demonstrated by different studies reporting, in obese patients, a reduced treatment response and adherence. In particular, results coming from DAN-BIO and ICE-BIO registries, (2) point out that obesity is a risk factor for anti-TNF withdrawal due to poor response. Although a recent multi-centric, retrospective study in Spain has shown that obese subjects with psoriasis have a poor therapeutic response to secukinumab, (3) no data are currently available for secukinumab in PsA obese patients.Objectives:Our studies focused on the relationship between BMI and clinical response to secukinumab in PsA.Methods:We, retrospectively, analysed clinical data of 100 patients with PsA (57% female, median age 53 (49.2-55 years)) satisfying CASPAR criteria (4) for PsA, afferent to our clinic, who were treated with secukinumab. Patients were divided into 2 groups based on BMI (BMIResults:In the normal weight group 75% were female, median age was 50.5 (41-54.6), median BMI was 22 (20.2-23.3) and median DAPSA was 19.19 (15.6-24.2). The features of the overweight/obese patients were similar to the normal weight group (48% were female, median age 54 (50-59), median BMI 29 (27.4-30.1) and median DAPSA 21.2 (19-24.4)). Clinical response to therapy, evaluated as the achievement of low disease activity or remission according to DAPSA, was recorded 6 months after starting treatment. After 6 months of treatment, the variation of the DAPSA was inversely related to BMI: overweight/obese patients had in fact a better response to secukinumab compared to normal weight patients. By using a correlation coefficient (SPSS), to analyze the degree of association between BMI and DAPSA, we observed that BMI and DAPSA are inversely related in our PsA patients (p=0.05). Interestingly, analysis of serum levels of IL-17 in 20 obese patients compared to 20 non-obese patients, showed significantly higher serum levels of IL-17 in the former (Figure 1), indicating IL-17 as a key cytokine driving inflammation in PsA obese patients.Conclusion:These are the first data about clinical response to secukinumab in obese PsA patients. Our results support the relevance of IL-17 in driving systemic inflammation in obese PsA patients, also providing evidence that obese patients may have a better response to secukinumab compared to non-obese patients. Interestingly, this effect was notReferences:[1]Rubén Queiro, Lorenzo A, Tejón P et al. Obesity in psoriatic arthritis. Comparative prevalence and associated factors. Medicine 2019 Jul;98(28):e16400[2]Pil Højgaard, Glintborg B, Kristensen LE et al. The influence of obesity on response to tumour necrosis factor-a inhibitors in psoriatic arthritis:results from the DANBIO and ICEBIO registries. Rheumatology (Oxford). 2016 Dec;55(12):2191-2199[3]Jaime Notario, Deza G, Vilarrasa E et al. Treatment of patients with plaque psoriasis with secukinumab in a real-life setting: a 52-weeks, multicenter, retrospective study in Spain. Journ of Derm Treat 2019 Aug;30(5):424-429[4]Taylor W, Gladman D, Helliwell P et al. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006 Aug;54(8):2665-73.[5]Lluís Puig. Cardiometabolic Comorbidities in Psoriasis and Psoriatic Arthritis. Int J Mol Sci. 2017 Dec 25;19(1).Disclosure of Interests:Ilenia Pantano: None declared, DANIELA IACONO Speakers bureau: PFIZER, BRISTOL MAYERS SQUIBB, SANOFI, ENNIO GIULIO FAVALLI: None declared, GIUSEPPE SCALISE: None declared, Luisa Costa: None declared, Francesco Caso: None declared, Giuliana Guggino Grant/research support from: Pfizer, Celgene, Speakers bureau: Celgene, Sandoz, Pfizer, Raffaele Scarpa: None declared, francesco ciccia Grant/research support from: pfizer, novartis, roche, Consultant of: pfizer, novartis, lilly, abbvie, Speakers bureau: pfizer, novartis, lilly, abbvie

Background Rheumatoid Arthritis (RA) is a chronic systemic inflammatory disorder associated with increased mortality, in particular from cardiovascular (CV) disease, infections and cancer. We recently demonstrate a incidence mortality rate (IMR) in 654 RA patients enrolled over a 6 year period in a South-Italian tertiary Rheumatology Centre lower than that reported in the Norfolk Arthritis Registry. 1 Objectives The present study is devoted to investigate differences in IMR between our series and other European tertiary centre cohorts. Furthermore we evaluated the role, if any, of Anticarbamylated protein antibodies (anti-CarP Ab) in modulating the low IMR detected in our patients. Methods Clinical charts of patients consecutively admitted to our centre, from January 1st, 2008 to December 31st, 2014 were reviewed. IMRs and causes of death as assessed at December 31st 2015, were registered. Sera collected at the time of admission to our centre in 61 patients representative of our RA cohort were investigated for the presence and the level of anti-CarP Ab. Demographic and clinical features, mortality rates and prevalence of anti-CarP Ab detected in our series were compared with those reported in the Better Anti-rheumatic Farmaco-therapy (BARFOT) cohort, the Leiden Early Arthritis Clinic cohort (Leiden EAC) and a Spanish cohort. 2 3 Results Six hundred and eight patients were observed for a median of 3.51 years. All causes and cause-specific IMRs were significantly lower in our cohort with respect to the BARFOT and the Spanish cohort, while only all causes and CV IMRs were significantly lower in our series with respect to the Leiden EAC. These discrepancies might depend on demographic and clinical differences among the various cohorts. Nevertheless, we failed to find putative differences with respect to each North European cohort, but we detected a significantly lower prevalence of anti-CarP Ab in our series with respect to that reported in the other European cohorts considered (table 1). Conclusions In conclusion, we confirm that the mortality rate in our South Italian RA cohort is lower than that detected in patients from both North and South European countries. We detected a very low prevalence of anti-CarP Ab in our sample representative of the entire cohort. Whether this is the aspect underpinning the low mortality rate detected in our series, awaits to be furtherly investigated. References [1] Iacono D, et al. Mortality in Italian patients with rheumatoid arthritis: evidence for a low mortality rate from cancer and infections in patients followed up at a tertiary center. Open Access Rheumatol2017. [2] Ajeganova S, et al. Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts. Ann Rheum Dis2016. [3] Vidal-Bralo L, et al. Anti-carbamylated protein autoantibodies associated with mortality in Spanish rheumatoid arthritis patients. PLoS One2017. Disclosure of Interest None declared

Background Cardiovascular (CV) morbidity and mortality are significantly greater in Rheumatoid Arthritis (RA) patients than in the general population. Acetylsalicylic acid (ASA) is known to be associated with a significant decrease in the incidence of CV events in patients at high CV risk, as we have recently demonstrated in patients with Systemic Lupus Erythematosus, but its effectiveness as primary prophylaxis in RA patients has not yet been addressed. Objectives To investigate the role of ASA in reducing the incidence of CV events in an Italian multicentre RA cohort from the GIRRCS ( Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale ). Methods The clinical charts of RA patients consecutively admitted to 4 GIRRCS centres for their 1 st visit from November 1 st 2000 to December 31 st 2015, who, at admission, satisfied 2010 ACR/EULAR criteria for RA and had not experienced any CV event, were analysed. The incidence of CV events during follow-up was recorded at December 2016. Kaplan Meier curve and log-rank test were used to investigate differences in event-free survival. Cox regression analysis served to identify factors associated with CV event occurrence. Results Seven hundred and forty-six consecutive RA patients were enrolled and followed up for a median of 5.6 years (range 2.9–8.9 years). The incidence rate (IR) of CV events was 7.8/1000 person-years (pys) in the overall cohort. Patients were subdivided into two groups, namely ASA- (242 patients) and non-ASA-treated (504 patients). The IR of CV events was significantly lower in the ASA-treated with respect to the non ASA-treated group (IR 1.7 vs 11.5/1000 pys;p=0.0002). Furthermore, the CV event-free rate was longer in ASA-treated than in non-ASA-treated patients (log-rank test 12.3;p=0.0004). Figure 1. At multivariate analysis hypertension and metabolic syndrome (HR 5.6, 95% CI:1.2–26.3;p 0.03 and HR 3.7, 95% CI:1.3–9.8;p 0.009) resulted to be the only positive predictors; ASA treatment (HR 0.04, 95% CI:0.06–0.33;p 0.02) the only negative one. Conclusions The incidence rate of CV events in our italian multicentric cohort was lower than that reported in other European and non European cohorts. Low-dose ASA may have a role in the primary prophylaxis of CV events in RA patients. References [1] del Rincon ID, et al. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum2001;44(12):2737–45. [2] Fasano S, et al. Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus. J Rheumatol2017;44(7):1032–1038. [3] Meek IL, et al. Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective analysis of a current low disease activity rheumatoid arthritis cohort and review of the literature. BMC Musculoskelet Disord2014;15:142. Disclosure of Interest None declared

Daniela Iacono,1 Elvira Favoino,2 Alessia Borgia,1 Serena Fasano,1 Ilenia Pantano,1 Virginia D’Abrosca,1 Giuseppe Picillo,1 Rosa Daniela Grembiale,3 Federico Perosa,2 Gabriele Valentini1 1Department of Clinical and Experimental Medicine, Rheumatology Section, University of Campania “Luigi Vanvitelli”, Naples, Italy; 2Department of Biomedical Sciences and Human Oncology (DIMO), Rheumatologic and Systemic Autoimmune Diseases Unit, University of Bari Medical School, Bari, Italy; 3Department of Medical and Surgical Sciences, University of Magna Graecia, Catanzaro, Italy Background and objective: Anti-carbamylated protein antibodies (anti-CarP Ab) represent a novel kind of autoantibodies specificity detectable in the sera of patients with rheumatoid arthritis (RA). They have been recently reported to be associated with increased mortality in Spanish patients with RA. The aim of our study was to compare the incidence mortality rates (IMRs) detected in RA patients from a tertiary Italian center with those reported in other European tertiary centers and to evaluate the putative role of anti-CarP Ab in modulating the low IMR detected in our patients.Methods: Clinical charts of patients consecutively admitted to our center, from January 1, 2008, to December 31, 2014, were retrospectively reviewed. The mortality rate (expressed as the number of deaths in the cohort divided by the number of years of IMR follow-up) and causes of death were assessed at December 31, 2015. Sera of 61 patients, representative of the whole cohort, collected at the time of admission to our center were investigated for the presence and the level of anti-CarP Ab. Demographic and clinical features, mortality rates and prevalence of anti-CarP Ab in our series were compared with those reported in other European cohorts.Results: We observed 608 patients for a median of 3.51 years. All-cause and cause-specific IMRs in our cohort were significantly lower than the Better Anti-rheumatic Farmaco-therapy and the Spanish cohort, while only all-cause and cardiovascular IMRs were significantly lower in our series with respect to the Leiden Early Arthritis Clinic cohort. Anti-CarP Ab prevalence was significantly lower in our series than in any other European cohorts.Conclusion: We confirm that the mortality rate is lower in our Italian RA cohort with respect to other European cohorts. Whether the low prevalence of anti-CarP Ab might be responsible for this result awaits to be furtherly investigated. Keywords: rheumatoid arthritis, mortality, anti-carbamylated protein antibodies, death causes

Daniela Iacono, Serena Fasano, Virginia D’Abrosca, Ilenia Pantano, Gabriele Valentini Department of Clinical and Experimental Medicine, Rheumatology Section, University of Campania “Luigi Vanvitelli,” Naples, Italy Objectives: Mortality in patients with rheumatoid arthritis (RA) has never been investigated in Italy. This study is devoted to investigating all the distinct causes of mortality in Italian RA patients.Methods: Clinical charts of patients consecutively admitted to an Italian tertiary center, from January 1, 2008 to December 31, 2014, were reviewed. Mortality rates (incidence mortality rate [IMR] and standardized mortality rate [SMR]) and causes of death as assessed at December 31, 2015, were registered. Mortality rates detected in our series were compared to those reported in other European cohorts and in the general Italian population.Results: Six hundred and eight patients were observed for a median of 3.51 years. Overall IMR was 0.79 deaths/100 person-years. No significant difference between our IMR and that reported in Italian population by the National Institute of Statistics was observed. All-cause and neoplasm IMRs in our series were found to be significantly lower than that reported in the Norfolk Arthritis Registry, while no difference was detected in cardiovascular (CV) mortality. On the other hand, all causes and CV SMRs in our series were found to be higher than that reported in the general Italian population, while cancer and infectious SMRs were found to be lower.Conclusion: In our series, RA patients had an increased all-cause mortality, and in particular an increased death rate due to CV. However, a lower death rate due to cancer and infections was observed. This figure might be due to the careful follow-up of RA patients in tertiary centers, and the results underlines the need to improve the management of CV risk. Keywords: rheumatoid arthritis, mortality, cancer, infections, cardiovascular deaths

Objective.High endothelin-1 (ET-1) and transforming growth factor-β (TGF-β) levels may induce in healthy endothelial cells (EC) an endothelial-to-mesenchymal transition (EndMT). The same cytokines are associated with fibrosis development in systemic sclerosis (SSc). Although EndMT has not been definitively shown in SSc, this process, potentially induced by a stimulatory loop involving these 2 cytokines, overexpressed in this disease might contribute to fibroblast accumulation in affected tissues. Macitentan (MAC), an ET-1 receptor antagonist interfering with this loop, might prevent EndMT and fibroblast accumulation.Methods.EC, isolated from healthy controls (HC) and patients with SSc, were treated with ET-1 and TGF-β and successively analyzed for gene and protein expressions of endothelial and mesenchymal markers, and for Sma- and Mad-related (SMAD) phosphorylation. Further, in the supernatants, we evaluated ET-1 and TGF-β production by ELISA assay. In each assay we evaluated the ability of MAC to inhibit both the TGF-β and ET-1 effects.Results.We showed that both TGF-β and ET-1 treatments induced an activation of the EndMT process in SSc-EC as reported in HC cells. The ELISA assays showed a mutual TGF-β and ET-1 induction in both SSc-EC and HC-EC. A statistically significant increase of SMAD phosphorylation after treatment was observed in SSc-EC. In each assay, MAC inhibited both TGF-β and ET-1 effects.Conclusion.Our work is the first demonstration in literature that SSc-EC, under the synergistic effect of TGF-β and ET-1, may transdifferentiate toward myofibroblasts, thus contributing to fibroblast accumulation. MAC, interfering with this processin vitro, may offer a new potential therapeutic strategy against fibrosis.

Background Systemic lupus erythematosus (SLE) is associated with an increased cardiovascular (CV) risk (1). By retrospectively investigating a one centre cohort, we have recently reported that low-dose aspirin (ASA) use is associated with a reduced CV risk in SLE (2) and long-term hydroxychloroquine (HCQ) exposure may have an additive effect (3). Objectives This study was conducted on 2 Italian SLE cohorts to confirm these results and assess the role, if any, of statins. Methods Clinical charts of SLE patients consecutively admitted to 2 University Rheumatology Units from November 2000 to December 2014 who, at admission, had not experienced any CV event, were investigated. ASA, HCQ and statins use and the occurrence of any CV event, were recorded at each visit. Kaplan-Meier analysis was performed to determine the HCQ exposure status associated with a higher CV-free survival. Cox regression analysis was carried out to identify factors independently associated with a first CV event. Results A total of 291 SLE patients were included in the study and followed for a median of 8 years. During follow-up, 16 CV events occurred. Kaplan Meier analysis revealed a greater CV event-free rate in the 120 ASA-treated patients taking HCQ at standard dose for more than 5 years than in the 98 patients treated with ASA alone or with HCQ for less than 5 years (Figure 1). At univariate analysis, patients with a first CV event compared with those without any thrombotic events were antiphospholipid antibody (aPL) positive (P=0.017 HR 2.91) and had significantly higher blood pressure (P=0.017 HR 3.58), hypercholesterolemia (P=0,015 HR 3.40) and higher disease damage at last visit (P=0,032 HR 1.56). Moreover, ASA treatment (P=0,012 HR 0.27) and HCQ use (P=0,012 HR 0.26) for more than 5 years were negative predictors, while statins use did not show any association (P=0.619). All other variables examined, including smoking, obesity, hypertriglyceridaemia, diabetes mellitus, disease activity, severe SLE, other medications (immunosuppressive agents, steroids) were not associated, either positively or negatively, with the occurrence of CV events. At multivariate analysis, taking ASA and HCQ for more than 5 years were protective against thrombosis (HR 0.24 and HR 0.27, respectively), while aPL positivity (HR 4.32) increased the risk of a first CV event. Conclusions Use of antimalarials for more than 5 years is associated with a reduced risk of a first thrombosis in SLE patients and the HCQ-ASA combination seems to synergistically reduce further the CV risk. Larger, prospective studies are needed to provide a better definition of the role of these drugs in CV primary prevention in SLE. References Cervera R, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients.Medicine (Baltimore). 2003. Iudici M, et al. Low-dose aspirin as primary prophylaxis for cardiovascular events in systemic lupus erythematosus: a long-term retrospective cohort study. RheumatolOxfEngl 2016. Fasano S, et al. Long-Term Hydroxychloroquine Therapy and Low-Dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol 2016. Disclosure of Interest None declared

Background Cardiovascular events (CV) i.e. acute myocardial infarction and stroke are recognized as a leading cause of mortality in patients with Rheumatoid Arthritis (RA) [1,2]. Acetylsalicylic acid (ASA) is known to be associated with a significant decrease in the incidence of CV events in patients at high risk for atherosclerosis like patients with diabetes [3] and has been recently reported to play a primary prophylactic role of CV events in Systemic Lupus Erythematosus by our team [4]. Objectives To investigate the so far unexplored role of ASA in reducing CV morbidity in RA. Methods We analysed patients admitted to our Outpatient clinic from January to December 2015. Out of 199, 155 patients, who had been followed from January 2000 and had not experienced any CV event at the first visit, were enrolled. The incidence of CV morbidity was recorded at December 2016. Results The 155 patients had been followed-up for a median of 8 years (range 1–15 years). Out of them, 111 patients had been treated with ASA, that we currently administer to patients undergoing steroid treatment. During the 15-years of follow up, 5 CV events (2 cerebrovascular, 3 acute myocardial infarction) had occurred (Incidence rate 3.93/1000 person/year). Interestingly, only 1 CV event had occurred in ASA treated patients (Incidence rate 1.12/1000 person/year) with respect to 4 in the non-ASA group (44 patients) (Incidence rate 10.48/1000 person/year) (p=0.0146). Conclusions Our study has several limitations including the low number of patients and CV events. Nevertheless, it might suggest a primary prophylactic role of ASA in RA, that awaits to be investigated in large controlled prospective studies. References Arthritis Rheum. 2001 Dec;44(12):2737–45. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditionalcardiac risk factors. del Rincόn ID, Williams K, Stern MP, Freeman GL, Escalante A. BMC Musculoskelet Disord. 2014 Apr 29;15:142. Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective analysis of a current low disease activity rheumatoid arthritis cohort and review of the literature. Meek IL, Vonkeman HE, van de Laar MA. Diabetes Res Clin Pract. 2016 Oct;120:31–9. Aspirin for primary prevention of cardiovascular disease in patients with diabetes: A meta-analysis. Kokoska LA, Wilhelm SM, Garwood CL, Berlie HD. Rheumatology (Oxford). 2016 Sep;55(9):1623–30. Low-dose aspirin as primary prophylaxis for cardiovascular events in systemic lupus erythematosus: a long-term retrospective cohort study. Iudici M, Fasano S, Gabriele Falcone L, Pantano I, La Montagna G, Migliaresi S, Valentini G. Disclosure of Interest None declared

Background/objective The objectives of this paper are to assess the extent of and the factors associated with hydroxychloroquine (HCQ) non-adherence in systemic lupus erythematosus (SLE) patients with prolonged inactive disease and to investigate relationships between blood HCQ concentration and quality of life (QoL). Methods Consecutive SLE patients, in remission for at least one year and taking a stable dose of HCQ were investigated. At study entry (T0) and six months later (T6) a blood venous sample was taken to measure whole blood concentration of [HCQ] and desethylchloroquine ([DCQ]). Moreover, at T0 each patient completed validated questionnaires assessing QoL, disability, anxiety, depression and visual analogue scales for fatigue, pain, general health (GH), and self-assessment of disease activity. Results Eighty-three patients with a median [HCQ] of 327 ng/ml were enrolled. At T0, 24 (29%) were defined as non-adherent ([HCQ] 100 ng/ml). At multiple logistic regression analysis the physical summary of SF-36 ( p = 0.038), and the concomitant use of immunosuppressants ( p = 0.010) were independently associated with non-adherence. A significant increase of HCQ adherence was observed at T6 ( p 0.05). Conclusions A better health status and the concomitant prescription of immunosuppressants represent risk factors for HCQ non-adherence in SLE patients in remission. Monitoring HCQ levels might represent an important opportunity to improve adherence.

Background The inflammatory contribution to type 2 diabetes (T2D) has suggested new therapeutic targets using biologic drugs designed for rheumatoid arthritis (RA). On this basis, we aimed at investigating whether interleukin-1 (IL-1) inhibition with anakinra, a recombinant human IL-1 receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis). Methods and findings This study, designed as a multicentre, open-label, randomised controlled trial, enrolled participants, followed up for 6 months, with RA and T2D in 12 Italian rheumatologic units between 2013 and 2016. Participants were randomised to anakinra or to a TNFi (i.e., adalimumab, certolizumab pegol, etanercept, infliximab, or golimumab), and the primary end point was the change in percentage of glycated haemoglobin (HbA1c%) (EudraCT: 2012-005370-62 ClinicalTrial.gov: NCT02236481). In total, 41 participants with RA and T2D were randomised, and 39 eligible participants were treated (age 62.72 ± 9.97 years, 74.4% female sex). The majority of participants had seropositive RA disease (rheumatoid factor and/or anticyclic citrullinated peptide antibody [ACPA] 70.2%) with active disease (Disease Activity Score-28 [DAS28]: 5.54 ± 1.03; C-reactive protein 11.84 ± 9.67 mg/L, respectively). All participants had T2D (HbA1c%: 7.77 ± 0.70, fasting plasma glucose: 139.13 ± 42.17 mg). When all the enrolled participants reached 6 months of follow-up, the important crude difference in the main end point, confirmed by an unplanned ad interim analysis showing the significant effects of anakinra, which were not observed in the other group, led to the study being stopped for early benefit. Participants in the anakinra group had a significant reduction of HbA1c%, in an unadjusted linear mixed model, after 3 months (β: −0.85, p < 0.001, 95% CI −1.28 to −0.42) and 6 months (β: −1.05, p < 0.001, 95% CI −1.50 to −0.59). Similar results were observed adjusting the model for relevant RA and T2D clinical confounders (male sex, age, ACPA positivity, use of corticosteroids, RA duration, T2D duration, use of oral antidiabetic drug, body mass index [BMI]) after 3 months (β: −1.04, p < 0.001, 95% CI −1.52 to −0.55) and 6 months (β: −1.24, p < 0.001, 95% CI −1.75 to −0.72). Participants in the TNFi group had a nonsignificant slight decrease of HbA1c%. Assuming the success threshold to be HbA1c% ≤ 7, we considered an absolute risk reduction (ARR) = 0.42 (experimental event rate = 0.54, control event rate = 0.12); thus, we estimated, rounding up, a number needed to treat (NNT) = 3. Concerning RA, a progressive reduction of disease activity was observed in both groups. No severe adverse events, hypoglycaemic episodes, or deaths were observed. Urticarial lesions at the injection site led to discontinuation in 4 (18%) anakinra-treated participants. Additionally, we observed nonsevere infections, including influenza, nasopharyngitis, upper respiratory tract infection, urinary tract infection, and diarrhoea in both groups. Our study has some limitations, including open-label design and previously unplanned ad interim analysis, small size, lack of some laboratory evaluations, and ongoing use of other drugs. Conclusions In this study, we observed an apparent benefit of IL-1 inhibition in participants with RA and T2D, reaching the therapeutic targets of both diseases. Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D. Trial registration The trial is registered with EU Clinical Trials Register, EudraCT Number: 2012-005370-62 and with ClinicalTrial.gov, number NCT02236481., Roberto Giacomelli and co-authors study treatment of comorbid rheumatoid arthritis and type 2 diabetes via interleukin-1 blockade., Author summary Why was this study done? A growing body of evidence suggests the inflammatory contribution to type 2 diabetes (T2D) as observed in rheumatoid arthritis (RA). Interleukin-1 (IL-1) would be a common pathogenic mediator in T2D and RA, suggesting a possible common therapeutic target. We investigated whether IL-1 inhibition with anakinra, a human IL-1-receptor antagonist, could improve both glycaemic and inflammatory parameters in participants with RA and T2D compared with tumour necrosis factor (TNF) inhibitors (TNFis). What did the researchers do and find? In a multicentre, open-label, randomised controlled trial, 39 participants with RA and T2D (age 62.72 ± 9.97 years, 74.4% female sex) were randomised to anakinra or to TNFi in order to evaluate the efficacy of these drugs in controlling the metabolic alterations of T2D. Anakinra showed a significant improvement of metabolic alteration (reduction of percentage of glycated haemoglobin [HbA1c%]) after both 3 months and 6 months of therapy (crude difference of 0.93 HbA1c% between groups), whereas TNFi did not show any significant improvement on these features. No severe adverse events, hypoglycaemic episodes, or deaths were observed. What do these findings mean? Our results suggest the concept that IL-1 inhibition may be considered a targeted treatment for RA and T2D. Managing the inflammatory disease and the metabolic comorbidity by an agent inhibiting IL-1 may lead to a consequent beneficial impact on participants’ compliance, their overall cardiovascular (CV) risk, and the burden of healthcare costs. Our study has some limitations, mainly due to open-label design, and future studies are necessary to fully clarify this topic.

Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory to the initiation of biological therapy in patients with rheumatic diseases. To determine the prevalence of LTBI in patients with rheumatoid arthritis before treatment with biological therapy (anti-TNF, abatacept, and tocilizumab) and the rate of TB conversion during treatment in rheumatoid arthritis (RA) patients, we evaluated the file of 275 patients with RA treated with biological agents. We considered patients with negative baseline TB screening (tuberculin skin test (TST); quantiferon TB gold in tube (QFT-GIT); chest x-ray) and with rescreening for a TB assay every year. Twenty-six patients (10.6%) resulted positive to TB screening at baseline. Two hundred and forty-nine patients (mean age 55.3 ± 11.9; median 55.8 years, range 16–81.9; 210 female) with TB screening negative at baseline were enrolled. One hundred and sixty-eight (67.5%) patients were treated with anti-TNF, 37 (14.9%) patients with abatacept, and 44 (17.7%) patients with tocilizumab. After a period of 12–120 months (median 24), 34 (13.6%) patients displayed conversion of at least one screening assay. Out of the 34 patients with conversion, 6 (16.2%) were treated with abatacept, 7 (15.9%) with tocilizumab, and 21 (12.5%) with anti-TNF. During the follow-up period, no patients developed active TB. Our study shows that a proportion of patients (13.6%) converts at least one TB screening assay during biological therapy. This study underscores the American College of Rheumatology advice for annual screening in some or all biologically treated patients.

Introduction Vascular injury and endothelial cell (EC) apoptosis are the earliest events in systemic sclerosis (SSc), before the onset of fibrosis, and stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGFA), endothelin-1 (ET-1) and platelet-derived growth factors (PDGF-BB) represent the key molecules to study the link between vascular injury and fibrosis during SSc. The University of California at Davis line 200 (UCD-200) chickens display the same hallmarks of human SSc: vascular occlusion, perivascular lymphocytic infiltration and fibrosis of skin and internal organs. In this study we assessed both cytokines and growth factors involved in the early phases of the UCD-200 chickens’ skin lesions, to determine whether these animals might represent an appropriate experimental model to study the pathogenesis of SSc. Material and methods Immunofluorescence analysis was performed on human SSc skin, human healthy control (hHC) skin, UCD-200 combs and HC H.B15 chicken (cHC) combs, using anti-SDF-1, CXCR4, VEGFA, VEGF receptor 1 (VEGFR1), VEGF receptor 2 (VEGFR2), ET-1, ET receptor A (ETAR), ET receptor B (ETBR), PDGF-BB, and PDGF receptor (PDGFR) antibodies. The plasma concentrations of SDF-1, VEGFA, ET-1 and PDGF-BB were determined by ELISA. Results All the molecules analyzed showed higher levels in SSc patients and UCD-200 chickens than in hHC and cHC. Furthermore, the levels of the assessed molecules paralleled the severity of comb involvement. Conclusions The molecular similarities between avian and human SSc, observed in this study, suggest that the UCD-200 chickens are an interesting model for translational approaches to SSc.