Angela Rinaldi

Lipid profile of rheumatoid arthritis patients treated with anti-tumor necrosis factor-alpha drugs changes according to disease activity and predicts clinical response.

Postmarketing Phase IV

Erasmus syndrome in a marble worker

Erasmus syndrome is defined as the association of silica exposure and subsequent development of systemic sclerosis. The limited number of cases reported in the literature mainly involves miners and only sporadically other professionals. We describe a case of Erasmus syndrome in a marble worker. A 68 year old man came to our observation complaining pelvic and scapular girdle pain, evening fever, intense weakness and emaciation for about 1 month. He also reported to have had Raynauds phenomenon in his hands for the last 13 years. Also, his occupational history revealed a chronic exposure to silica dust. The patient presented pain in his shoulders and hips, moderate skin thickening and sclerosis in his hands and fingers extending proximally to his wrists. The diagnosis of systemic sclerosis was determined according to his clinical and medical history, the positivity of anti-Scl 70 antibodies, the nailfold capillaroscopy suggestive of an active scleroderma pattern and the detection of a mild restrictive pulmonary syndrome. The evaluation of the organbased complications excluded a gastroenterological and cardiovascular involvement, while the chest computed tomography (CT) detected multiple small nodules with a mantle distribution and enlarged lymph nodes with no signs of interstitial lung disease and fibrosis. Additional tests (positron emission tomography-CT, flexible bronchoscopy and broncho-alveolar lavage) excluded infectious diseases and cancer. However, given the pulmonary involvement, we performed a histological examination of the parenchyma and lymph nodes, which revealed a picture of pneumoconiosis. In the end, the occupational history and the findings from the diagnostic procedures led to the diagnosis of pulmonary silicosis. The precise definition of the pulmonary involvement was essential to the therapeutic approach to this patient.

Orofacial Manifestations and Temporomandibular Disorders of Sjögren Syndrome: An Observational Study

AIMS: Sjӧgren Syndrome is a disorder involving oral tissues, with xerostomia, dysgeusia, dysphagia, tooth decay, gingivitis, angular cheilitis and glossitis. Temporomandibular disorders are a generic term referred to clinical conditions involving the jaw muscles and temporomandibular joint. The aim of this study was to investigate the prevalence of oral manifestations and temporomandibular disorders (TMD) in Sjӧgren Syndrome (SS) patients compared with healthy people. METHODS: The study group included 72 SS patients (2 men, 70 women) diagnosed according to the American-European Consensus Group (AECG) Criteria. A randomly selected group of 72 patients, matched by sex and age, served as control group. The examination for TMD signs and symptoms was based on the standardized Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) through a questionnaire and clinical examination. RESULTS: SS patients complained more frequently (95.8%) of oral symptoms (xerostomia, dysgeusia, dysphagia) than controls (22.2%) (χ2= 80.66 p< 0.001). TMD symptoms (muscle pain on chewing, difficulty in mouth opening, arthralgia, headaches, tinnitus) were complained by 91.7% of SS patients and by 84.7% of controls (χ2= 1,667 p= 0,196). At the clinical examination, 91,7% of SS had at least one oral sign respect to 75 % of controls. The salivary flow measurements showed high statistical significance between the two groups (Unpaired test, p< 0,0001). Myofascial pain (caused by muscular contracture) was significantly higher in the study group than in the control one (p≤ 0,05). Furthermore 18,05% of SS patients showed deflection versus 5,5% of controls (χ2=5,402 p=0,020). CONCLUSIONS: Sjӧgrens Syndrome seems to play a role in temporomandibular joint disorders.

AB0452 Changes in Lipoproteins Associated with Tocilizumab Treatment Do not Influence the Atherogenic Index of Plasma of Rheumatoid Arthritis Patients

Background Interleukin-6 inhibition by tocilizumab (TCZ) has been associated with changes in the lipoprotein profile [1], which could adversely impact cardiovascular (CV) risk in patients with rheumatoid arthritis (RA) [2]. Objectives The aim of this observational study is to evaluate the effect of TCZ on lipoproteins and on the atherogenic index of plasma (AIP), a useful predictor of cardiovascular risk [3]. Methods Forty patients (36 female; age 55±11 yrs) with active RA and an inadequate response to DMARDs treated with 8 mg/kg TCZ every 4 weeks intravenously, were consecutively enrolled with a 1 year follow-up. Patients on hypolipidemic therapy were excluded. Before and on week 12, 24 and 52, DAS28 and CDAI were evaluated, and blood samples were taken to assess plasmatic levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), and to calculate the AIP (LogTG/HDL). Results During the first 24 weeks of TCZ treatment we observed a progressive increase of about 10% for TC and TG, and of about 30% for LDL-C and HDL-C compared to baseline. In the subsequent 6 months there was a reduction of TC and TG, whereas HDL-C and LDL-C continued to increase to about 40% compared to baseline (see Table). Lipid changes were inversely correlated with both the disease activity scores DAS28 and CDAI. Contextually the AIP was stable around 1, with no statistically significant changes. During the observational period no CV events have been observed.Table 1 N=40 Baseline 12 weeks 24 weeks 52 weeks TC (mmol/L) 5.23±1 5.76±1* 5.85±0.9* 5.48±1.2 HDL-C (mmol/L) 1.26±0.6 1.68±0.4* 1.72±0.6* 1.83±0.3* LDL-C (mmol/L) 2.79±1.5 3.53±0.8* 3.61±0.9* 3.73±1.1* TG (mmol/L) 1.32±0.6 1.57±0.8* 1.61±0.7* 1.46±0.7 DAS28 5.3±1.2 2.9±1.1* 2.7±1.4* 2.5±1.2* CDAI 24±14 13±10* 11±9* 9±8** P<0.05: paired t-student test vs Baseline. Conclusions TCZ acts on the lipid profile increasing all the lipoprotein fraction, especially during the first 6 months of treatment, probably by a direct hepatic effect [4]. On the contrary the net effect of TCZ on AIP, and consequently on CV risk, would seem to be irrelevant. References Kawashiri SY et al. Rheumatol Int. 2011 Souto A et al. Arthr Rheumatol 2015 Gasevic D et al. Lipids Health Dis. 2014 Strang AC et al. Atherosclerosis 2013 Disclosure of Interest None declared

AB0448 Drug Survival of A Patients Cohort with Chronic Inflammatory RHEUMATISM Treated with Abatacept

Objectives The persistence in therapy is an important assessment tool of therapy efficacy in patient with chronic disease. The aim of this study was to evaluate drug survival (DS) of a patients cohort suffering from chronic inflammatory rheumatism treated with abatacept. Methods From September 2008 to March 2013, we retrospectively observed a total of 107 patients starting therapy with abatacept, in a single center of southern Italy. They were 88 females and 19 males, aged between 21 and 85 years (54.65) and with disease duration between 2 and 45 years (11,71). 60 patients were suffering from rheumatoid arthritis (RA; 56.07%), 6 from chronic undifferentiated polyarthritis (5.60%), 2 from juvenile idiopathic arthritis (1.86%), 1 from Stills disease (0,93%) and 38 (35.51%) from seronegative spondyloarthritis (SpA). 91.58% (98 patients) had also comorbidities. 18.69% of the patients (20 patients) were naive to the treatment with biological drugs. 77.00% of patients took DMARDs and 69,39% were receiving steroid. Results DS resulted averaging 15.40 months, retention rate after 1 year (RR1) was 49.53% and after 2 years (RR2) was 25.23%. Half of the patients (53 patients, 49.53%) interrupted the therapy during the observation period, mostly due to inefficacy or loss of efficacy (64.15%) and only 3.77% due to side effects. DS, RR1 and RR2 were clearly higher in patients taking DMARDs compared to patients taking abatacept in monotherapy (14.58 vs 11.26 months, p= ns; 50.64% vs 30.43%, p=0.038 and 24.67% vs 8.69%, p=0.042, respectively). The RA patients showed higher values of the examined parameters compared to the patients with SpA (DS: 17.31 vs 11.36 months, p=0.029; RR1: 53.33% vs 44.73%, p= ns; RR2: 33.33% vs 7.89%, p=0.0001). Considering patients in first-line vs patients in subsequent lines of biological therapy DS resulted 12.50 vs 16.06 months, RR1 45.60% vs 50.57% and RR2 20.00% vs 26.43%; this result could be justified by the shorter period of observation of patients in first-line of biological therapy, due to the more recent use of abatacept in patients naive to biological therapy. 80.00% of these patients resulted in fact still in therapy at the end of the observation vs 43.67% of the patients in subsequent lines of biological therapy (p=0.0001).The average value of DAS 28 and good or moderate EULAR response achievement appeared better in patients in first line of biological treatment (3.59 vs 4.04, p=ns and 63.16% vs. 46.57%, p=0.0228, respectively). Conclusions Into a cohort of patients with chronic inflammatory rheumatism and treated with abatacept DS was in line with the results reported in few studies on the subject. The persistence in therapy was better in patients with RA compared to patients with SpA and in patients treated with DMARDs compared with patients taking abatacept in monotherapy. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2669

AB0380 The Inhibition of Tumor Necrosis Factor-Alpha (TNFA) Reduce Plasmatic Reactive Oxygen Metabolites (ROM) of Rheumatoid Arthritis (RA) Patients

Background Accumulating evidences indicate that chronic inflammation and oxidative stress play a key role in the early and accelerated atherosclerosis seen in patients with RA (1). Tumor necrosis factor-alpha (TNFa) overproduction is thought to be the main contributor to increased ROS release in patients with RA (2). TNFa inhibitors are effective treatments in the management of RA but the effects of these drugs on the heart and vessels is under investigation (3,4). Objectives The aim of this study was to assess the circulating levels of reactive oxygen metabolites (ROMs) during anti-TNFa treatment in RA. Methods Forty patients with RA (36 female; age 53±13yrs) treated with different TNFa inhibitors were analyzed for 52 weeks. The oxidant status was determined from plasmatic samples taken before, 24 and 52 weeks after anti-TNFa treatment, by assessing hydroperoxides levels using a Diacron automated method (d-ROMs test), which has proved to be clinically useful as an oxidative stress marker (5). Results Mean ROMs levels before TNFa-inhibitors were 33.2±10 mg H2O2/dL while after 24 and 52 weeks of treatment they were 29.5±7 and 29.3±9 mg H2O2/dL, respectively (P<0.05). Twenty-two (55%) RA patients with active disease had high d-ROM level (>32 mg H2O2/dL). After 24 and 52 weeks of anti-TNFa treatment 50% of patients reached remission/low disease status (DAS-28CRP<3.2) and all these patients had low d-ROM levels (<27 mg H2O2/dL). Conclusions Our result demonstrate that good disease control with anti-TNFa agents is able to reduce oxidative stress in RA patients. References Shoenfeld Y. et al. Circulation 2005;112:3337-47. Szekanecz Z. et al. Ann N Y Acad Sci 2007;1108:349-58. Cacciapaglia F. et al. Autoimmun Rev 2011;10(10):631-5. Kageyama Y. et al. Clin Exp Rheumatol. 2008;26(1):73-80. Vassalle C. et al. J Atheroscler Thromb 2012;19(8):712-7. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2556

THU0194 Lipid Profile of Rheumatoid Arthritis Patients Treated with Anti-TNF-Alpha Drugs Changes According to Disease Activity Response

Background Rheumatoid arthritis (RA) patients present increased mortality due to cardiovascular (CV) events, particularly by inflammation in addition to traditional CV risk factors (mainly changes in lipid profile). Although anti-TNF agents have been proven effective in controlling joint damage and systemic inflammation, nowadays there is still controversy about the real effect of anti-TNF treatment on the lipid profile. Objectives The aim of this study is to evaluate the evolution of the lipid profile after the onset of anti-TNF therapy. Methods Eighty RA patients (65 female, age 53±13 years, disease duration 7±5 years), who failed treatment with DMARDs, have been enrolled in this study, and evaluated, before and at 24 and 52 weeks from the start of anti-TNF treatment, for the following lipid profile: Total-cholesterol (Tot-C), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides (TG), and cholesterol risk ratio (CRR) [Tot-C/HDL-C] was also calculated. At the same time the disease activity scores CDAI, SDAI, DAS44 and DAS28, four variables, were assessed. Twenty-nine patients were treated with etanercept, 19 with adalimumab, 18 with infliximab, 7 with certolizumab-pegol and 7 with golimumab. Results The levels of Tot-C, HDL-C, LDL-C and TG, as well as CRR, didn’t significantly changed during the follow-up period of treatment. Considering the disease activity according to CDAI, SDAI, DAS44 and DAS28, about 50% of patients achieved low disease activity/remission state after 24weeks and about 60% achieved this state after 52 weeks of treatment. In this latter group of patients we observed significantly lower levels of Tot-C, LDL-C, and TG, and a lower CRR compared to those observed in patients with moderate/high disease (see Table). No significant differences were found between the anti-TNF evaluated. Conclusions Our study suggest that anti-TNFα treatment per se do not interfere with the lipid profile of RA patients. While according to response to TNFα treatment, assessed by CDAI, SDAI, DAS44 or DAS28, patients that achieved low disease activity/remission seems to have a protective lipid profile for CV events, so a better control of the disease can also affect the lipid metabolism. Disclosure of Interest None Declared