Daniela Iacono

Adult-onset Still’s disease: evaluation of prognostic tools and validation of the systemic score by analysis of 100 cases from three centers

BackgroundAdult-onset Still’s disease (AOSD) is rare inflammatory disease of unknown etiology that usually affects young adults. The more common clinical manifestations are spiking fevers, arthritis, evanescent rash, elevated liver enzymes, lymphadenopathy, hepatosplenomegaly, and serositis. The multi-visceral involvement of the disease and the different complications, such as macrophage activation syndrome, may strongly decrease the life expectancy of AOSD patients.MethodsThis study aimed to identify the positive and negative features correlated with the outcome of patients. A retrospective analysis of AOSD patients prospectively admitted to three rheumatologic centers was performed to identify the clinical features present at the time of diagnosis and to predict the possible outcome. Furthermore, we investigated the as yet to be validated prognostic value of the systemic score previously proposed.ResultsOne hundred consecutive AOSD patients were enrolled. The mean systemic score showed that the majority of patients had a multi-organ involvement. Sixteen patients showed different complications, mainly the macrophage activation syndrome. A strong increase of inflammatory markers was observed. All patients received steroids at different dosages, 55 patients in association with immunosuppressive drugs and 32 in association with biologic agents. Sixteen patients died during the follow-up. Regression analysis showed that the higher values of the systemic score and the presence of AOSD-related complications, assessed at the time of diagnosis, were significantly correlated with patient mortality. A prognostic impact of the systemic score of ≥ 7.0 was reported.ConclusionsOur study showed that a higher systemic score and the presence of AOSD-related complications at the time of diagnosis were significantly associated with mortality. Of note, a cut-off at 7.0 of the systemic score showed a strong prognostic impact in identifying patients at risk of AOSD-related death.

Macrophage Activation Syndrome in Patients Affected by Adult-onset Still Disease: Analysis of Survival Rates and Predictive Factors in the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale Cohort

Objective. Macrophage activation syndrome (MAS) is a reactive form of hemophagocytic lymphohistiocytosis, which can complicate adult-onset Still disease (AOSD). We investigated AOSD clinical features at the time of diagnosis, to assess predictors of MAS occurrence. Further, we analyzed the outcomes of patients with AOSD who experience MAS. Methods. Patients with AOSD admitted to any Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale center were retrospectively analyzed for features typical of AOSD, MAS occurrence, and their survival rate. Results. Of 119 patients with AOSD, 17 experienced MAS (12 at admission and 5 during followup). Twelve patients with MAS at first admission differed from the remaining 107 in prevalence of lymphadenopathy and liver involvement at the time of diagnosis. In addition, serum ferritin levels and systemic score values were significantly higher in the patients presenting with MAS. At the time of diagnosis, the 5 patients who developed MAS differed from the remaining 102 in the prevalence of abdominal pain, and they showed increased systemic score values. In the multivariate analysis, lymphadenopathy (OR 7.22, 95% CI 1.49–34.97, p = 0.014) and abdominal pain (OR 4.36, 95% CI 1.24–15.39, p = 0.022) were predictive of MAS occurrence. Finally, MAS occurrence significantly reduced the survival rate of patients with AOSD (p < 0.0001). Conclusion. MAS occurrence significantly reduced the survival rate in patients with AOSD. Patients with MAS at baseline presented an increased prevalence of lymphadenopathy and liver involvement, as well as high serum ferritin levels and systemic score values. The presence of lymphadenopathy and abdominal pain was associated with MAS occurrence.

Subclinical atherosclerosis and history of cardiovascular events in Italian patients with rheumatoid arthritis: Results from a cross-sectional, multicenter GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study

Abstract Several studies have pointed out a significant association between rheumatoid arthritis (RA) and accelerated atherosclerosis. At the best of our knowledge, no such study has been carried out in a large Italian series and, in this study, we aimed to investigate the prevalence of both subclinical atherosclerosis and history of cardiovascular events (CVEs), in patients consecutively admitted from January 1, 2015 to December 31, 2015 to Rheumatology Units throughout the whole Italy. Centers members of GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) were invited to enrol patients consecutively admitted from January 1, 2015 to December 31, 2015 and satisfying American College of Rheumatology/ European League Against Rheumatism criteria for RA and to investigate each of them for: traditional cardiovascular risk factors: sex, age, smoking habit, total cholesterol, triglycerides, glycaemia, high blood pressure, metabolic syndrome (MS), type 2 diabetes (T2D); RA features: disease duration as assessed from the first symptom, disease activity as evaluated by DAS28, radiographic damage as assessed by hands and feet x-ray, and previous joint surgery; prevalence of both subclinical atherosclerosis and history of CVEs. Eight centers participated to the study. From January 1, 2015 to December 31, 2015, the 1176 patients, who had been investigated for all the items, were enrolled in the study. They were mostly women (80.52%), with a median age of 60 years (range, 18–91 years), a median disease duration of 12 years (range, 0.8–25 years), seropositive in 69.21%. Nineteen percent were in remission; 17.51% presented low disease activity; 39.45% moderate disease activity; 22.61% high disease activity. Eighty-two patients (6.9%) had a history for CVEs (58 myocardial infarction, 38 heart failure, 10 ischemic transitory attack, and 7 stroke). This figure appears to be lower than that reported worldwide (8.5%). After excluding the 82 patients with a history of CV events, subclinical atherosclerosis was detected in 16% of our patients, (176 patients), a figure lower than that reported worldwide (32.7%) and in previous Italian studies. This is the first Italian multicenter study on subclinical and clinical atherosclerosis in patients with RA. We pointed out a low prevalence of both subclinical atherosclerosis and history of CV events.

The incidence of cardiovascular events in Italian patients with systemic lupus erythematosus is lower than in North European and American cohorts: implication of disease-associated and traditional risk factors as emerged by a 16-year retrospective GIRRCS study: GIRRCS=Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale.

Abstract Previous study from our group has pointed out a lower number of cardiovascular (CV) events in Italian patients with systemic lupus erythematosus (SLE) than in North European and American ones. This study aims to assess the incidence of the first CV event in a large, multicenter, Italian cohort of patients with SLE and search for differences in disease and traditional risk factors among distinct cohorts. Clinical charts of SLE patients consecutively admitted to 5 Italian rheumatologic centers from November 1st 2000 to December 31st 2015 and free of CV events at baseline were retrospectively studied. CV cumulative incidence (ie, the proportion of patients who experienced a new CV event over the follow-up period) and CV incidence rate (ie, the number of events in the cohort divided by the total number of years at risk) were evaluated. The detected incidences were compared with those reported in SLE cohorts from other countries. The median duration of follow-up was 6 years (IQR = 3–11). During the observational period, 37 (cumulative incidence = 7.2%) patients had a first episode of CV event with an incidence rate of 10.1/1000 person-years. The CV cumulative incidence and incidence rate detected in our Italian cohort were lower than those from most North European and American cohorts, characterized by a high impact of traditional risk factors. Nevertheless, the cumulative incidence was similar to that reported in a Spanish cohort with a high frequency of traditional risk factors (geographic impact), while the incidence rate was only slightly higher than that in the Baltimore cohort, which is characterized by a strict follow-up of patients (medical impact). Our results confirmed that Italian lupus patients have a low incidence of CV events. Moreover, the geographic origin, traditional risk factors, and medical approach appear to have an impact on CV disease in SLE.

Low mortality rate in Italian rheumatoid arthritis patients from a tertiary center: putative implication of a low anti-carbamylated protein antibodies prevalence

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.

AB0216 Low mortality rate in italian rheumatoid arthritispatients from a tertiary centre. putative implication of a low anticarbamylated protein antibodies prevalence

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.Abstract AB0216 – Table 1 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

FRI0014 Low-dose aspirin may have a role as primary prophylaxis of cardiovascular events in rheumatoid arthritis: evidence from an italian multicentric retrospective study

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 Rincón 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

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

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.

SAT0057 Low Mortality Rate in A Cohort of Rheumatoid Arthritis Patients from South Italy

Background Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder associated with increased mortality (1), (standardized mortality ratio for all causes–SMR, being 1.47 in the last 50 years) (2). Objectives To investigate the mortality rate and predictive factors as assessed at admission in a cohort of RA patients followed at a South Italy tertiary centre. Methods RA patients admitted to the outpatient Clinic of a tertiary centre from 01/01/2008 to 31/12/2015 were investigated. Table 1 shows patients features (age, sex, disease duration, Simplified Disease Activity Index-SDAI index, Health Assessment Questionnaire-Disability Index-HAQ-DI, Rheumatoid Factor-RF and/or Anti-Citrullinated Cyclic Peptides Antibody-ACPA, concomitant comorbidity) as detected at baseline, and treatment during follow-up. RA patients mortality incidence rate (event/100person year) was calculated, baseline predictors of mortality were analyzed by univariate and multivariate cox-regression analysis. Results A total of 608 RA patients were included (497 women), median age 56.8 years, range 15–89.5. On December 31 2015, 589 out of patient were alive, 19 were known to have died and 7,3% had been lost to follow up. Mortality Incidence rate (MIR) in our cohort was 0.79 deaths/100 person-year, SMR with respect to Italian population was 0.79 (MIR in Italy 1/100 person-year). This feature might depend on the low prevalence of RF/ACPA positivity (69.13%) in our series. Cox regression analysis (univariate analysis) pointed out age at first visit (HR 1.14; p≤0.0001), diabetes (HR 4.395; p=0.004) and a HAQ value>1 (HR 6.02; p=0.02) as independent predictors of mortality. On the contrary, female sex resulted to have a protective role (HR 0.349, p=0.027). At multivariate analysis, the only baseline independent predictor of mortality was age at admission (HR 1.17, 95% CI 1.01–1.35, p=0.026). Conclusions The present study points out a South Italian RA SMR lower than that in general Italian population and significantly lower than that reported in RA patients from other countries (2). This result can depend on the lower percentage of RF/ACPA positive patients in our cohort in respect to general population. Epidemiological studies on the sierological profile of South Italian RA patients are needed. References Sokka T et al. ClinExpRheumatol. 2008;26(Suppl):S35–61. Dadoun S et al. Joint Bone Spine. 2013;80:29–33. Disclosure of Interest None declared

SAT0181 CXCL4 Is Not A Biomarker in Rheumatoid Arthritis Patients Treated with Abatacept and Tocilizumab

Background CXCL4 (platelet factor4, PF4) is a pleiotropic α-granules chemokine, produced by platelets, dendritic cells, macrophages and neutrophils. Recently, CXCL4 levels have been found to increase under treatment with infliximab, in unresponsive Rheumatoid Arthritis (RA) patients [1]. At present, the influence of non TNFalfa blockers biological DMARDs (Abatacept and Tocilizumab) on CXCL4 serum levels not have been investigated in RA. Objectives To investigate CXCL4 serum levels in RA patients naïve for biological disease-modifying anti-rheumatic drugs (bDMARDs) at baseline and after 1-year treatment and look for associations with disease features at baseline and distinct biological therapy overtime. Methods Fifty-six RA were enrolled in the study at the time of initiating a treatment with a biological DMARD. CXCL4 serum levels were investigated by a multiplex suspension immunoassay at baseline and after 1 year and compared with those detected in 30 healthy controls. Epidemiological, clinical and serological features of RA patients at baseline are showed in table 1. Results Out 56 RA patients, 39 (70%) were assigned to an anti-TNF-α treatment (3 patients to Infliximab, 12 to Etanercept, 24 to Adalimumab); 10 to Abatacept and 7 to Tocilizumab. At baseline, CXCL4 serum levels were found to be increased in RA patients as compared to controls but the difference was not significant (1,538 ng/ml vs 1.26 ng/ml, p=0.082). Moreover, CXCL4 levels were not found to be related to any disease feature. At baseline, 6 (10%) RA patients presented serum CXCL4 levels exceeding the 95th percentile of the values detected in controls (4.569 ng/ml). These patients did not differed from the remaining RA patients in any feature. After 1 year of treatment, CXCL4 levels increased with respect to basal values in the whole series (3.280 ng/ml vs 1.538 ng/ml, p<0.0001). However, a different trend was detected in patients undergoing distinct treatments: CXCL4 serum levels were found to increase after 1 year in patients treated with anti-TNF agents (3.595 ng/ml, vs 1,241 ng/ml, p<0.0001); on the contrary, CXCL4 levels at 1-year remained unchanged in patients treated with Abatacept (4.160 ng/ml vs 2.030 ng/ml, p=0.21) and with Tocilizumab (3.310 ng/ml, vs 3.290 ng/ml, p=0.6). At 1-year follow-up, 32 patients could be considered responsive to the treatment (R); 24 (43%) were non-responder (NR). No difference was detected in the change of CXCL4 over time, comparing the 32 responsive to treatment with the 24 unresponsive patients. Conclusions Similarly to previous studies (1) we found an increase in CXCL4 serum levels in patients undergoing an antiTNFa agent, but we failed to find differences between responsive and unresponsive patients. Moreover, we found that treatment with Abatacept and Tocilizumab did not modify CXCL4 serum level. Finally, we failed to detect any correlation between CXCL4 levels and any disease feature both at baseline and during follow-up. References Trocmé C., et al. Ann Rheum Dis. Aug 2009; 68(8): 1328–1333 Disclosure of Interest None declared