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Interleukin 6 (IL-6) plays a key role in the inflammatory cascade in rheumatoid arthritis. BMS945429 is a humanised, monoclonal antibody that potently binds IL-6.To conduct aphase II study to determine the efficacy and safety of BMS945429 in patients with active rheumatoid arthritis and an inadequate response to methotrexate.Patients were randomised 1:1:1:1 to BMS945429 (80, 160 or 320 mg; administered intravenously) or placebo plus methotrexate during this 16-week, double-blind trial. The primary efficacy end point was the proportion of patients with a 20% improvement in American College of Rheumatology responses (ACR20) at week 12. Additional end points included ACR50 and ACR70 responses and 28-joint Disease Activity Scores (DAS28).Of 127 randomised and treated patients, 116 completed the trial. ACR20 responders at week 12 were 81% (80 mg; p0.0001 vs placebo), 71% (160 mg; p=0.0005 vs placebo), 82% (320 mg; p0.0001 vs placebo) and 27% (placebo), respectively. By week 16, 14% (80 mg), 28% (160 mg) and 44% (320 mg) of BMS945429 patients were in DAS28 remission (DAS28 score2.6). Statistically significant and clinically meaningful improvements in health-related quality of life (HRQoL) were reported in all active treatment groups. Administration of BMS945429 was associated with increases in liver enzymes and in serum cholesterol. There were no serious infections, infusion reactions or apparent immunogenicity.In this phase II study, BMS945429 was associated with rapid and significant improvements in disease activity and HRQoL in patients with active rheumatoid arthritis and an inadequate response to methotrexate.

Background Osteoporosis is generalized bone disease characterized by disturbed bone strength, consequently fracture predisposition increases. One of the risk factors for osteoporotic fractures is the Body Mass Index (BMI) and it is evaluated according to the following criteria: malnutrition- to 18 kg/m 2 , normal body weight - 20-25 kg/m 2 , overweight - 25-30 kg/m 2 and obesity - over 30 kg/m 2 . Objectives To determine the significance of Body Mass Index for the effect of bisphosphonate therapy in women with newly diagnosed postmenopausal osteoporosis Methods 92 women, with newly diagnosed postmenopausal osteoporosis, were included in this research. According to BMI values, the patients were divided into groups of under 18, 18 to 25, 25 to 30 and over 30 kg/m 2 . The groups were homogenous in relation to other risk factors for the appearance of osteoporosis. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry (DXA) on the Hologic Discovery machine before the therapy, as well as, 12 months after the bisphosphonate therapy. Results T-score values and BMD during 12 month therapy with bisphosphonate the most increased in examinees whose BMI values were in the range of 25 to 30 kg/m 2 (0,330±0,275), and the least in women with BMI below 18 (0,190±0,223), but ANOVA and Dante’s test did not confirm the existence of significant differences between all compared groups. Conclusions Statistically significant difference in the effect of the bisphosphonate therapy was not found in postmenopausal women with newly diagnosed osteoporosis nor with different body mass index. References Kanis JA. Diagnosis of osteoporosis and assessmentof fracture risk. Lancet 2002;359:1929-1936 Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Oden A. Assessment of fracture risk. Osteoporosis Int 2005;16(6):581-589 S. Ilic. Poremecaji ishrane. Interna medicina 2004;2:386-389 Epstein S. Update of current therapeutic options for the treatment of postmenopausal osteoporosis. Clin Ther. 2006; 28(2):151-173 Delmas PD. The use of bisphosphonates in the treatment of osteoporosis. Curr Opin Rheumatolog 2005;17(4):462-466 Asche S, Nelson R, McAdam-Marx C, Jhaveri M and Ye X. Predictors of oral bisphosphonate prescriptions in post-menopausal women with osteoporosis in a real-world setting in the USA. Osteoporosis international 2009; 1427-1436, 2009 Asomaning K, Bertone-Johnson E, Nasca P, Hooven F, Pekow P. Women with low BMI are at increased risk of osteoporosis. Journal of Women’s Health 2006; 15(9): 1028-1034 De Laet C, Kanis JA, Oden E, Johanson E. Body mass index as a predictor of fracture risk: A meta-analysis. International Osteoporosis Foundation and National Osteoporosis Foundation 2005 Ravn P, Cizza G, Bjarnason NH. Low Body Mass Index Is an Important Risk Factor for Low Bone Mass and Increased Bone Loss in Early Postmenopausal Women. Journal of Bone and Mineral Research 1999;14(9):1622–1627 Disclosure of Interest None Declared

Background In the past decade, it is well recognized that patients with rheumatoid arthritis (RA) have increased morbidity and mortality from premature atherosclerosis. There is 1.5 fold increase in mortality due to cardiovascular events compared to general population. Both, traditional and nontraditional factors, such as systemic inflammation and immune dysregulation contribute to this. There are considerable variations between different studies regarding lipid profile and its role in patients with RA. Objectives Objective of our study was to investigate relationship between systemic inflammation and lipid profile in RA patients. Methods 90 RA patients (84,33% female, mean age 53,92±12,83 years) who fulfilled 1987. ACR criteria for RA and 40 age-matched controls with osteoarthritis were enrolled in the study. Group of RA patients consisted from 50 patients treated with Methotrexate (MTX group), mean disease duration 9,27±4,78 years and from 40 patients with early RA (less than 1 year duration) not treated with DMARDs (ERA group). Patients with known cardiovascular, cerebrovascular and peripheral vascular diseases were excluded as well as patients with diabetes, familiar dyslipidemia and those on hypolipemic therapy. Erythrocyte sedimentation rate (ESR), CRP, total cholesterol, LDL, HDL and triglyceride were determined to all subjects. Results Patients in ERA and MTX groups had, as expected, increased markers of inflammation : ESR (64,36±28,91 mm and 41,44±18,68 mm respectively) and CRP (48,48±63,16 mg/L and 11,44±21,77 mg/L respectively) which was significantly higher than in control group (ESR 12,79±6,7 mm and CRP 1,81±0,35 mg/L, p Conclusions Patients with active untreated RA have tendency to have reduced total cholesterol, LDL and HDL. Low levels of HDL are most prominent aterogenic factor in these patients mostly influenced by systemic inflammation. Disclosure of Interest None Declared

Background Rituximab (RTX) is monoclonal antibody that selectively targets CD20+ B cells. The combination of RTX with MTX significantly improves disease symptoms in rheumathodi arthritis (RA) patients who have had an inadequate response to conventional DMARD therapy, and has been shown to improve quality of life in those patients. This is the only study that assessed efficacy and safety of RTX in daily practice in Serbia Objectives To determine the safety and efficacy of additional courses of RTX in patients with RA. Methods This is interim analysis of prospective noninterventional trial that enrolled 130 RA patients with inadequate response to previous biologic and/or synthetic DMARDs treated with RTX (age 50.37±11.59 years; 85.3% females and 14.7% males; disease duration 8.4±6.5 years). Patients were eligible for additional RTX courses (2 infusions of 1,000 mg given 2 weeks apart) if they exhibited disease reactivation measeured by DAS28. Efficacy was assessed by DAS28 (number of tender and swollen joints, VAS-GH, sedimentation) and the disability index of the Health Assessment Questionnaire at baseline and 24 weeks after first, second and third course. Safety was assessed by the number and severity of registered adverse events (AE). Results 114 patients received >1 course of RTX (58 received 2 courses and 10 received 3 courses). Mean DAS28 scores decreased significantly from 6.41±0.97 at baseline to 4.91±1.65/4.33±1.23 and 3.86±1.43, 24 weeks after first/second/third RTX courses; p Conclusions During 3 courses of treatment, rituximab showed significant decrease of DAS28 and and increased quality of life measured by HAQ-DI questionnaire after each following rituximab course. Disclosure of Interest None Declared

Background Treatment of osteoporosis may be expected to affect the remodelling phase of bone repair and therefore promote fracture healing. Ibandronat significantly increase bone mineral density (BMD) and reduce the risk of vertebral, hip and non vertebral fractures in women with postmenopausal osteoporosis Objectives To confirm the efficacy and safety of 1 year ibandronate in OP pts: 150mg oral monthly or quarterly intravenously; to analyze the impact of risk factors and fractures on the efficacy of ibandronate treatment Methods 190 pts with primary OP,average 62.1y, average menopause 16.8y, treated 1 year with oral monthly or quarterly iv injection of ibandronate were included. BMD was measured by DXA Hologic at lumbar spine and proximal femur; OP is defined as the mean BMD expressed as a T-score = -5.0. The profil RTG of TH-LS spine was done before and after the therapy. Substitution of the optimal dose of vitamin D and calcium was applied. Results Previous fracture (37.6%)and smoking (33.5%) were the most common risk factors;75.1% pts had OP and more than one risk factor. Total number of vertebral and nonvertebral fractures at baseline was 71; 25 vertebral, 46 nonvertebral.After therapy, the number of new fractures was 18; 8 vertebral, 10 nonvertebral. After 1 year of oral monthly ibandronate BMD was increased at the spine for 3.0%,hip 3.5%,after ibandronate injection spine BMD was increased for 4.6%, hip 3.6%. Spine and hip BMD increase was higher in pts with OP and multiple risk factors (spine, p=0.000, hip, p=0.01)than those with one risk factor (spine, p=0.04; hip, p=0.02). Pts with multiple fractures and OP had a greater increase in spine and hipBMD(spine, p=0.000; hip, p=0.001) compared to those with 1 or without fracture (spine, p=0.04; hip, p=0.05). Pts with OP and previous BF treatment had no sign. BMD increase at the spine (p=0.334), nor on the hip (p=0.2)opposed to those not previously treated, with statistically sign. BMD increasing(spine, p=0.000, hip, p=0.006). Adverse events were rare,did not lead to stopped the treatment:7.8%pts had a flu like sy,1.1% LS pain,1.1% SVPT, stopped after medical therapy Conclusions Ibandronate is effective,safe drug, orally applied monthly or quarterly iv. in OP pts, especially those with multiple risk factors and multiple fractures Disclosure of Interest None Declared

Background Rituximab is the only currently available B-cell depleting agent, licensed for use in treatment of rheumatoid arthritis (RA).The optimal therapeutic strategy that would give an answer to the question when is the best moment to repeat a course of rituximab, has not yet been clearly defined. In addition to strictly controlled randomized studies, registers show the effectiveness of different therapeutic strategies applied in daily clinical practice. Objectives To assess the efficacy of rituximab in RA when administered every six months in comparison to a longer period between two courses, according to data from the Serbian registry of RA patients (NARASS). Methods 161 RA patients, treated with rituximab are followed to date in NARRAS. Forty of them (33 women and 7 men, mean age 52 years), who received at least three courses of the drug were selected and analyzed. They were divided into two subgroups: subgroup I (SG 1 ) - 26 (65%) patients who received rituximab every six months, and subgroup II (SG 2 ) - 14 (35%) patients with a time period of seven months or more between two courses. Disease activity score (DAS 28 ) was assessed before each course and six months after the third course of rituximab, and compared between two subgroups of patients. The analysis of variance (ANOVA) and Student’s T-test were used for statistical analyses of data. Results Mean disease duration before diagnosis of RA in two subgroups of patients did not differ significantly (SG 1 : SG 2 =12.6: 17.5 months, p=0.85), as well as disease duration from diagnosis to beginning of treatment with rituximab (SG 1 : SG 2 =133.1: 123.6 months, p=0.71). The mean time period between two courses of rituximab for patients in SG 1 was 6.2 months and for patients in SG 2 8.9 months. Analyzing the data for the whole group of 40 patients we have noticed a statistically significant decrease in disease activity six months after the third course of rituximab, compared to the period before treatment (DAS 28 index decreased from 5.87 to 4.47, p 1 compared to SG 2 - mean DAS 28 decreased significantly (p=0.002) from 6.30 (before treatment) to 4.31 (six months after the third course) in SG 1 , and from 5.12 to 4.80 in SG 2 (p=0.057). Conclusions The efficacy of rituximab is better when patients are retreated regularly at six-month intervals, compared to patients who receive the drug with a longer time period between the courses Disclosure of Interest None Declared

Background Magnetic resonance imaging (MRI) is useful method for detection and quantification of subclinical synovial inflammation and joint damage with better precision than radiography in systemic sclerosis (SSc). Early aggressive treatment of inflammation may prevent joint damage and improve the outcomes Objectives To determine and quantify synovial inflammation by MRI in SSc; to examine the relationship of MRI findings with clinical and radiography features Methods 82 scleroderma patients (77 women and 5 male, mean age 54y,) underwent low field MR imaging with gadolinium at the dominant (clinically most active) hand including wrist and MCP joints 2-5. Assessment of bone marrow edema, synovitis, bone erosions and tenosynovitis was performed by the OMERACT RA MRI scoring system. Clinically features of musculoskeletal manifestations- articular or periarticular pain, joint contractures, swelling were recorded. Standard AP radiographs of the hand and wrist were obtained in 2 planes. Radiologically, we recorded articular (joint space narrowing-JSN, erosions, synovitis), soft tissue (calcification, tenosynovitis) and bone (osteopenia, bone resorption) changes Results 14/82 (17,1%) pts had clinically arthritis; 66/82 pts (80,5%) had arthralgias. Of 82% with scleroderma, 65/82 (79,3%) had inflammatory MR findings with synovitis in 64/82 (78%), erosions in 52 (63,4%) or tenosynovitis in 11 pts (14,1%) Synovitis was more frequently detected on MRI (78%) than clinically (17,1%), p Conclusions MRI is more sensitive method than clinical examination and radiological finding of inflammation in scleroderma. Our study demonstrate the presence of persistant inflammatory, erosive arthropathy of the hand in SSc patients. RAMRIS scoring system, used in RA, also can be used to quantify the inflammatory arthritis in SSc Disclosure of Interest None Declared

Background Depression increases the burden of RA to the patients and to the society. Objectives To estimate the presence and severity of depression in patients with RA. To determine the interaction of depression with disease activity, the functional disability and the radiographic findings. To analyze the quality of social relatioships in patients with RA. Methods 124 patients (76.78% female, mean age 53.83±10.13 years, mean disease duration 64.4±30.3 month) who fulfilled the ACR 1987 criteria for RA and 115 age-matched healthy controls (CG) were included in this study. Patients with RA were subdivided in 2 groups: patients with mono therapy with Methotrexate (MTX) and patients on combined therapy with MTX and biological therapy. Out of the total number of examinees, 46% received combined therapy (MTX + biological therapy) and 54% of patients were treated using mono therapy (MTX). Disease activity was determined using DAS 28 SE. The functional status was determined on the basis of the HAQ questionnaire, while the radiographic state was scored with the Larsen method. The intensity of the pain was evaluated by completing of VAS scale (0-100 mm). The degree of depression was determined through application of the Beck scale for depression (Beck Depression Inventory). Assessment of the quality social relationships was performed using questionnaire which contained questions concerning demographical characteristics and social relationships. The statistical analyzes was performed by the data SPSS package, version 15.0. Results The symptoms of depression were registered in 73.33% of pts, significantly more than in CG (21.34%), p Conclusions Depression is a frequently present manifestation of RA patients which is most prominently influenced by the degree of functional disability of RA patients. Apart from the medication therapy, the treatment of RA requires an individual psychosocial approach and wider social support. Disclosure of Interest None Declared

Background SBI-087 is a humanized CD20-directed SMIP™ (mono-specific protein therapeutic) that has been shown to deplete B cells in a dose dependent manner in Phase 1 studies in subjects with stable rheumatoid arthritis (RA). Objectives The objective of this study was to evaluate the safety and efficacy of four 200 mg subcutaneous (SC) dosing regimens versus placebo in seropositive subjects with active RA on a stable background of methotrexate (MTX). Methods Subjects with active RA (≥5 tender joints, ≥5 swollen joints, and either C-reactive protein ≥7 mg/L or erythrocyte sedimentation rate ≥28 mm/h) were randomized to either placebo or 1 of 4 active treatment arms receiving 200 mg SBI-087 as follows: (1) Day 1; (2) Day 1, 15; (3) Day 1, Week 12; (4) Day 1, 15, and Week 12. SBI-087 was administered as two 100 mg SC injections in combination with 40 mg oral prednisone or equivalent, acetaminophen, and an antihistamine prior to dosing and 20 mg oral prednisone or equivalent 4 hours post dose. The study consisted of 2 parts: a 24 week initial phase evaluating safety and efficacy and a follow-up phase after week 24 to monitor for safety and B cell recovery. The primary outcome measure was ACR20 at week 16. Secondary outcome measures included ACR50/70 and DAS28 at week 16 and also ACR20/50/70 and DAS28 at week 24. Improvements in individual parameters such as the HAQ-DI and acute phase reactants were also assessed. All subjects were evaluated for safety. Results 209 subjects were randomized into the study. 40 (19.1%) subjects discontinued during the initial phase of the study primarily due to adverse events (15, 7.2%) or lack of efficacy (13, 6.2%). Improvement in the ACR20 primary endpoint was seen in the Day 1, 15, and Week 12 treatment arm (relative to placebo) at week 16 (p Conclusions SBI-087 administered subcutaneously was generally well tolerated. The 200 mg SBI-087 Day 1, 15, and Week 12 treatment arm achieved significant improvement in RA disease activity by week 16 compared to placebo. Disclosure of Interest N. Damjanov: None Declared, M. Tlustochowicz: None Declared, J. Aelion Grant/Research support from: Abbott, BMS, Celgene, Eli Lilly, Novartis, Pfizer, Takeda, Vertex, and UCB, Consultant for: Abbott, Amgen, Takeda, and UCB, A. Dimic: None Declared, M. Greenwald: None Declared, A. Diehl Employee of: Pfizer Inc., I. Bhattacharya Employee of: Pfizer Inc., S. Menon Employee of: Pfizer Inc., I. Gourley Employee of: Pfizer Inc.