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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, 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

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 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.

We investigated early systemic sclerosis (SSc) (that is, Raynaud's phenomenon with SSc marker autoantibodies and/or typical capillaroscopic findings and no manifestations other than puffy fingers or arthritis) versus undifferentiated connective tissue disease (UCTD) to identify predictors of short-term disease evolution. Thirty-nine early SSc and 37 UCTD patients were investigated. At baseline, all patients underwent clinical evaluation, B-mode echocardiography, lung function tests and esophageal manometry to detect preclinical alterations of internal organs, and were re-assessed every year. Twenty-one early SSc and 24 UCTD patients, and 25 controls were also investigated for serum endothelial, T-cell and fibroblast activation markers. At baseline, 48.7% of early SSc and 37.8% of UCTD patients had at least one preclinical functional alteration (P > 0.05). Ninety-two percent of early SSc patients developed manifestations consistent with definite SSc (that is, skin sclerosis, digital ulcers/scars, two or more teleangectasias, clinically visible nailfold capillaries, cutaneous calcinosis, X-ray bibasilar lung fibrosis, X-ray esophageal dysmotility, ECG signs of myocardial fibrosis and laboratory signs of renal crisis) within five years versus 17.1% of UCTD patients (X 2 = 12.26; P = 0.0005). Avascular areas (HR = 4.39 95% CI 1.18 to 16.3; P = 0.02), increased levels of soluble IL-2 receptor alpha (HR = 4.39; 95% CI 1.03 to 18.6; P = 0.03), and of procollagen III aminopropeptide predicted disease evolution (HR = 4.55; 95% CI 1.18 to 17; P = 0.04). Most early SSc but only a few UCTD patients progress to definite SSc within a short-term follow-up. Measurement of circulating markers of T-cell and fibroblast activation might serve to identify early SSc patients who are more likely to develop features of definite SSc.

A 39-year-old woman with a 2-year history of Raynaud’s phenomenon, a previous diagnosis of systemic sclerosis sine scleroderma, and the recent onset of symmetric polyarthritis is reported. Clinical, laboratory, and imaging (radiographs, ultrasonography, and magnetic resonance) features are presented. Treatment and disease course are underlined. Systemic sclerosis articular involvement and its pathologic, clinical, laboratory, imaging, and therapeutic aspects are discussed. The peculiarities of the case are addressed.

Background Systemic sclerosis (SSc) is a chronic autoimmune disease associated with an impaired quality of life, as assessed by SF-36. There are no studies investigating quality of life in early SSc patients (eSSc), as defined by Koenig et al (1). Objectives To assess HRQOL of eSSc patients compared to that of definite SSc patients (defSSc) fulfilling ACR criteria (2). Methods 81 patients consecutively admitted to the Rheumatology Unit of the Second University of Naples from January 1st, 2007 to December 31st 2010 were enrolled in the study. Demographics, disease duration, disease activity and severity and SF-36 were assessed at admission. Patients were classified into 2 groups: eSSc patients according to Koenig et al. (i.e. patients with Raynaud’s phenomenon plus either SSc auto-antibody or an SSc pattern on nailfold capillaroscopy or both) and defSSc patients fulfilling the ACR criteria. Results Out of the 81 patients, 31 were classified as eSSc and 50 as defSSc patients. ESSc patients showed a Physical Component summary score (PCS) ranging from 22 to 56 (median 45) and a Mental Component summary score (MCS) ranging from 25 to 67 (median 43); defSSc patients showed a PCS ranging from 23 to 59 (median 39) and a MCS from 20 to 62 (median 41). Fifty is defined the lower normal limit of both PCS and MCS in general population (3). A PCS score lower than 50 was recorded in 17 out of 31 eSSc patients and in 32 out of 50 defSSc patients (p=0.711); a MCS score lower than 50 was recorded in 22 out of 31 eSSc patients and 34 out of 50 defSSc patients (p=0.988). Among the domains that contribute to PCS, a score lower than normal was found for general health (48%), bodily pain (32%), physical role (29%) domains in eSSc patients and for physical function (54%), general health (50%) and physical role (26%) domains for defSSc patients. Concerning mental component, limitations in daily activities due to emotional role were the most frequent finding in both groups. Conclusions HRQOL is reduced in a significant percentage of both eSSc and defSSc patients. Despite the absence of any clinical manifestation other than Raynaud’s phenomenon, eSSc patients, therefore, display an impairment in quality of life, that should be considered by the clinician attending such patients. References Koenig M et al. Autoantibodiesand microvascular damage are independent predictive factors for the progression of Raynaud’s phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum. 2008;58:3902-12. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Arthritis Rheum. 1980;23:581-90. Ware JE Jr et al. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30:473-83. Disclosure of Interest None Declared