Abstract Objectives SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage. Methods In this phase III, double-blind, parallel-group, multicentre study, patients with moderate to severe RA despite MTX were randomized (1:1) to receive 3 mg/kg of either SB2 or INF at 0, 2, 6 and every 8 weeks thereafter. Dose escalation by 1.5 mg/kg up to a maximum dose of 7.5 mg/kg was allowed after week 30. Efficacy, safety and immunogenicity were measured at each visit up to week 54. Radiographic damage evaluated by modified total Sharp score was measured at baseline and week 54. Results A total of 584 patients were randomized to receive SB2 (n = 291) or INF (n = 293). The rate of radiographic progression was comparable between SB2 and INF (mean modified total Sharp score difference: SB2, 0.38; INF, 0.37) at 1 year. ACR responses, 28-joint DAS, Clinical Disease Activity Index and Simplified Disease Activity Index were comparable between SB2 and INF up to week 54. The incidence of treatment-emergent adverse events and anti-drug antibodies were comparable between treatment groups. Such comparable trends of efficacy, safety and immunogenicity were consistent from baseline up to 54 weeks. The pattern of dose increment was also comparable between SB2 and INF. Conclusion SB2 maintained similar efficacy, safety and immunogenicity with INF up to 54 weeks in patients with moderate to severe RA. Radiographic progression was comparable at 1 year. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov; NCT01936181) and EudraCT (https://www.clinicaltrialsregister.eu; 2012-005733-37)

Introduction: Many epidemiological studies have shown that there are numerous risk factors for acute coronary disease. The aim is to determine the effect of risk factors on the echocardiographic changes and quality of life in patients treated with different methods 1 year after myocardial infarction. Methods: The research was a prospective–retrospective, clinical, epidemiological study and was conducted at the Clinic of Cardiology, University Clinical Center Sarajevo. Patients were divided into four groups based on the therapy treatment they got. The patients were divided into four groups based on the therapy treatment they received. The first group consisted of 40 patients who had had myocardial infarction and were treated with medications. The patients in the groups II and III were treated with percutaneous coronary intervention (PCI) [who immediately after incident underwent primary PCI or delayed PCI], and each group consisted of 40 patients. The group IV consisted of 40 patients, who underwent surgical revascularization (coronary artery bypass surgery). After the treatments have finished, an echocardiogram was performed on every patient. The Short Form (SF)-36 health survey was used for testing the life quality. Echocardiogram and the quality of life (QoL) testing were repeated a year after the treatment. Results: The study included 160 patients with a history of myocardial infarction, of which 130 (81.3%) were men, and 30 (18.8%) were women. The average age in the total sample was 54.9 ± 8.8 years. The review of risk factors’ presence showed that in the total sample, most present was hypertension with 134 (83.8%), smoking with 120 (75.0%), and hypercholesterolemia with 110 or 68.8% of patients. Hypertension showed a statistically significant negative effect on the SF-scales only in the group III according to the mental health (P = 0.020), social functioning (P = 0.013), and pain (P = 0.011). A statistically significant effect of smoking was observed in the group III according to left ventricular internal dimension in end-diastole (P = 0.000) and left ventricular internal dimension in end-systole (P = 0.001) in the sense that smokers have the higher values of these parameters, and negative to ejection fraction (EF) (P = 0.001) in the sense that smokers have lower EF. In the group IV, positive correlation was observed to EF (P = 0.038), and negative toward the mitral regurgitation (P = 0.032). Conclusion: High blood pressure negatively affected the QoL. Smoking is negatively associated with all observed echocardiographic parameters in all the groups except with the size of the left atrium.

Introduction: Cardiovascular diseases are the leading cause of death in most countries. The aim was to examine the quality of life and to determine the differences in the quality of life in patients one year after myocardial infarction and the relationship between quality of life and echocardiographic parameters in these patients. Material and Methods: The research was a prospective, clinical, epidemiological study and was conducted at the Clinic of Cardiology, University Clinical Center Sarajevo (UCCS). The research was conducted on a sample of 160 patients who had acute myocardial infarction, which are based on the therapeutic procedures divided into four groups. The average age in the total sample was 54.9±8.8 years (range 37-76 years). The research was conducted one year after myocardial infarction (I group of subjects) or 12 months after PCI therapeutic procedures (II and III group of respondents) or coronary artery bypass surgery (IV group of respondents). Results: Comparison of the mean scores of scales in SF-36 questionnaire showed that the highest total score had patients in the group II 67.3±15.2, and the lowest in the group I 57.8±21.4. The increase in ejection fraction leads to a statistically significant increase in quality of life scores at all subscales, in all groups, so that EF has the greatest impact on the quality of life in all respondents. Statistically significant differences in the effects of mitral regurgitation in particular groups have been recorded only in the case of the mental health scale. Conclusions: Ejection fraction has the greatest impact on the quality of life in all patients, regardless of the type of medical treatment.

Background SB2 is developed as a biosimilar of the infliximab reference product (INF). The 30-week and 54-week results of Phase III study have been reported1,2. Objectives To evaluate the safety, immunogenicity, and efficacy in patients with RA who transitioned from INF to SB2 vs maintained INF and who continued to receive SB2 after Week 54 up to Week 78. Methods This study is a randomised, double-blind phase III transition study. Patients with moderate to severe RA were randomised in a 1:1 ratio to receive either SB2 or INF at Weeks 0, 2, 6, and then every 8 weeks thereafter until week 46. At Week 54, patients previously receiving INF were re-randomised in a 1:1 ratio to either receive SB2 (INF/SB2) or continue INF (INF/INF) up to week 70; patients receiving SB2 continued to receive SB2 (SB2/SB2) up to Week 70. Safety, immunogenicity and efficacy were assessed up to week 78. Results At Week 54, 94 patients from INF were transitioned to SB2 (INF/SB2), 101 patients from INF continued to receive INF (INF/INF), and 201 patients from SB2 continued to receive SB2 (SB2/SB2). The safety profile during the transition period was comparable between INF/SB2, INF/INF, and SB2/SB2. The incidence of adverse events during the transition period was 36.2% in INF/SB2, 35.6% in INF/INF, and 40.3% in SB2/SB2. The incidence of infusion related reaction during the transition period was 3.2%, 2.0%, and 3.5%, respectively. Among the patients with overall negative anti-drug antibodies (ADA) results up to Week 54, ADAs were newly developed in 14.6% (6/41) in INF/SB2, 14.9% (7/47) in INF/INF, and 14.1% (11/78) in SB2/SB2. The efficacy was sustained and comparable between the treatment groups.Table 1. Safety Profile During the Transition Period (From Week 54 to Week 78) Number of patients with INF/SB2 INF/INF SB2/SB2 (N=94) (N=101) (N=201) n (%) n (%) n (%) At least 1 treatment-emergent adverse event 34 (36.2) 36 (35.6) 81 (40.3) At least 1 serious adverse event 6 (6.4) 3 (3.0) 7 (3.5) Serious infections 2 (2.1) 1 (1.0) 1 (0.5) Active tuberculosis 0 (0.0) 0 (0.0) 0 (0.0) Infusion-related reaction 3 (3.2) 2 (2.0) 7 (3.5) Malignancy 0 (0.0) 0 (0.0) 0 (0.0) Death 0 (0.0) 0 (0.0) 0 (0.0) Overall ADA positive 43 (45.7) 51 (50.5) 104 (53.6)a Newly ADA positiveb 6 7 11 aPercentage is based on 194 patients with available ADA results. bNewly developed ADA in patients with negative overall ADA up to Week 54. Conclusions The safety, immunogenicity, and efficacy profiles remained comparable between the INF/SB2, INF/INF, and SB2/SB2 up to Week 78, revealing that there were no treatment emergent issues or clinically relevant immunogenicity after switching from INF to SB2. References Choe JY et al. Ann Rheum Dis. 2015–207764 [Epub ahead of print] Choe JY et al. Arthritis Rheumatol. 2015; 67 (suppl 10), 2056 Disclosure of Interest J. S. Smolen Consultant for: Abbvie, Amgen, Astra-Zeneca, Astro, Celgene, Glazo, Janssen, Lilly, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung Bioepis, Sanofi, UCB, J.-Y. Choe Grant/research support from: Samsung Bioepis, Consultant for: Samsung Bioepis, N. Prodanovic Grant/research support from: Samsung Bioepis, J. Niebrzydowski Grant/research support from: Samsung Bioepis, I. Staykov Grant/research support from: Samsung Bioepis, E. Dokoupilova Grant/research support from: Samsung Bioepis, A. Baranauskaite Grant/research support from: AbbVie, Samsung Bioepis, R. Yatsyshyn Grant/research support from: Samsung Bioepis, M. Mekic Grant/research support from: Samsung Bioepis, W. Porawska Grant/research support from: Samsung Bioepis, H. Ciferska Grant/research support from: Samsung Bioepis, K. Jedrychowicz-Rosiak Grant/research support from: Samsung Bioepis, A. Zielinska Grant/research support from: Samsung Bioepis, J. Choi Employee of: Samsung Bioepis, Y. H. Rho Employee of: Samsung Bioepis

Objectives To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. Methods This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. Results 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was −1.88% (95% CI −10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. Conclusions SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. Trial registration number NCT01936181.

ABSTRACT Introduction: Non-alcoholic (NAFLD) encompasses a spectrum of disease states, from steatosis (fatty liver) to non-alcoholic steatohepatitis (also called NASH steatosis with inflammatory changes) followed by progression to fibrosis and cirrhosis and hepatocellular carcinoma Excess liver fat is believed to be a manifestation of the metabolic syndrome and not surprisingly NASH is associated with obesity, insulin resistance, dyslipidemia and type 2 diabetes in humans. Aim of the study: is to establish anthropometric and biochemical specificities in patients with non-alcoholic steatohepatitis diagnosed with non-invasive diagnostic methods Material and methods: Study enrolled 170 participants, 130 with NASH steatosis. The non-alcoholic group (control), consisted of 40 normal weight patients without metabolic syndrome. Alcohol intake was estimated with established protocol. Routine biochemistry analysis were performed by standard laboratory procedures; serum levels of serum levels of fasting cholesterol and triglycerides, fasting glucose and insulin, insulin resistance estimated by HOMA index (Homeostasis model assessment), biochemistry tests and a liver ultrasound examination. Results: In study participants group, patients were more obese comparing with controls p < 0, 01, waist line extent also was of greater statistical significance in the non-alcoholic group fatty liver (p < 0, 01). Comparing biochemical parameter values, significant statistical deference has been noted in glaucosis and insulin levels, total cholesterol and gama-glutamil transferase levels, between groups (p<0, 01). Fasting glucose and insulin levels, HOMA-IR were significantly greater in study cohort group patients, as was significantly positive correlation between BMI and waist line extent. Conclusion: Patients with non-alcoholic fatty liver are excessively obese, have greater waist line extent, consequently insulin resistance and impaired glucose metabolism, insulin resistance, dyslipidemia, risk factors known to be associated with the development of cardiovascular disease.

OBJECTIVE Our objective was the comparison of combined utility of two-dimensional (2D) transthoracic echocardiography (TTE) and three-dimensional (3D) TTE versus 2D and 3D transesophageal echocardiography (TEE) in evaluation of anatomy of the left atrium appendage (LAA) and for clot formation in LAA. BACKGROUND 2DTEE as semi-invasive method has been for a long time used to visualize the LAA. Improved echocardiography technology has increasingly improved visualization of LAA by 2DTTE and 3DTTE in many patients and decreased the need for TEE performance. METHODS We compared combined 2DTTE and 3DTTE with 2DTEE and 3DTEE in evaluating the LAA for anatomical features and thrombus. Eighty-six patients underwent 2DTTE, 3DTTE, 2DTEE and 3DTEE. RESULTS LAA could be visualized in all patients. 31 % of patients had one lobe, 43% had 2 lobes and 26% had > 2 lobes. Of 86 patients studied, 79 had no thrombus and 7 had thrombus in the LAA by all modalities. Six patients, 3 with atrial fibrillation (AF), and 4 in sinus rhythm (SR) had a suspected thrombus by 2DTEE. Only in one patient 3DTEE cropping has been needed to clearly show thrombus which was suspected in short axis view on 2DTEE as rounded echo dense mass. CONCLUSIONS Our preliminary study suggests that combined 2DTTE and 3DTTE has comparable accuracy to TEE in evaluating the LAA anatomy and pathology in terms of thrombus. Only in inappropriate (obese) patients 2TTE, but not 3DTTE, may misdiagnose pectinate musculature as thrombus.

GOAL The goal of this study is to determine the effect of the hemodialysis durations on the concentration of inflammatory agents C-reactive protein concentration, fibrinogen and ferritin in hemodialysis patients. There is not enough reliable research data about the primary causes of the increase of these agents levels in the serum. The role of inflammatory agents in the development of primary renal disease, pathogenesis and morphogenesis and in particular the development of complications and comorbidities is unclear. PATIENTS AND METHODS The study included 114 chronic hemodialysis patients who were on dialysis three times a week for 4 hours, according to the regular protocol of hemodialysis at the Cantonal Hospital Zenica, Department for hemodialysis. RESULTS AND DISCUSSION Patients were analyzed according to the hemodialysis duration (years) and on the basis of duration of hemodialysis are divided into 3 groups: According to the average values of fibrinogen in all three groups was p < 0.05 which is not statistically significant difference according to the hemodialysis duration. Average values of ferritin in group 1 (patients less than 1 year on hemodialysis) was 612 +/- 543 in group 2 (patients with hemodialysis duration between 1-10 years) was 1056 +/- 852, and in group 3 (patients with hemodialysis duration over 10 years) was 610 +/- 700. According to the average values of ferritin in all three groups we see that p < 0.05. In the second group ferritin concentrations were highest. In the third group of patients the results were the same as in the first group. CONCLUSION It was found that the duration and type of hemodialysis does not affect the concentration of inflammatory agents in the blood.

UNLABELLED The aim of this study was to determine the influence of inflammatory markers, predictive values of CRP and target hemoglobin (Hb) in patients on chronic hemodialysis. MATERIAL AND METHODS Made is a cross-sectional study of inflammatory agents serum levels-CRP, fibrinogen and ferritin before hemodialysis in 114 patients divided into two groups according to the achieved or unachieved target hemoglobin level in the Cantonal Hospital in Zenica. RESULTS The 57 patients (test group) did not reached the target hemoglobin in the range from 10-12 g/dl and CRP values were significantly higher compared to the control group (57 patients) who had reached targeted hemoglobin values. Levels of fibrinogen and ferritin were not significantly different between the control and the test group. CRP values are in negative correlation with the Hb concentration, while fibrinogen and ferritin values had a positive correlation. Significant negative correlation was only found in case of CRP, respectively, higher CRP was at lower levels of blood Hb. It was found that the predictive value of CRP is 6.5 mg/L to achieve target Hb level. If the CRP increases by 1 mg/L, possibilities to achieve the target Hb level in dialysis patients is reduced by 7.5%, with a sensitivity of 51% and specificity of 77%. Ferritin was elevated due to iatrogenic iron saturation, because all patients received intravenous iron and was treated with erythropoietin. By identification and analysis of inflammatory agents and duration ofhemodialysis, are explored the primary influence on hematopoiesis, of course, with the primary application of erythropoietin and adjuvant agents. It has been shown that CRP alone has an impact on the target Hb level, depending on the hemodialysis duration. CONCLUSION The research results show how what looks as routine findings may be helpful in the timely detection of threatening complications and their treatment, and provide extended and improved quality of life for patients on hemodialysis.

The highly specific biomarkers for monitoring of SLE disease activity are not yet defined up to date, due to existing of different clinical SLE phenotypes caused by individual genetic variation. Basically, numerous clinical complications follow SLE patients such as nephritis, atherosclerosis and cardial, CNS, gastrointestinal and ophthalmological complications, as well. Their monitoring in clinical SLE management can be evaluated by analysing of specific biochemical parameters and require permanent clinical observation. The presence of ANAs and anti-ds-DNAs are usual diagnostic SLE autoimmunity parameters, while SLE disease activity biomarkers are C3 and C4 level, anticardiolipin antibodies, anti-Sm/RNPs and, recently level of CD4 and CD8 lymphocytes. However, the number of TCR molecules on the T-cells surface at SLE patients is lower then in normal condition, and otherwise for these receptors CD molecules make specific connection. On the other hand, the T lymphocytes can be also, therapeutical targets at SLE patients, because of their clear direct involving in SLE pathogenesis. The SLE phenotypes are characterized by double CD negativity ( CD3 +/-, CD4-) caused by abnormal level of IL-2 and IL-17. T-lymphocytes have usually alpha-beta and gamma-delta TCR receptors, but for SLE patients is characteristic lower number gama-delta TCR molecules, detected in the peripheral blood specimens. Taking into account all of the facts, we investigated the level of specific usual SLE activity biomarkers (anti-ds-DNAs, C3, C4, anticardiolipin antibodies (beta-2-IgG, beta-2-IgM, ACA-G, ACA-M, CD4 and CD8 level) in serum specimens of SLE patients who underwent to the corresponding chemotherapy in combination with other biochemical and clinical parameters. Once again proved to be, that SLE biomarker monitoring, could be useful aproach for SLE activity disease and prediction organ damage, as well. In our investigation we used the following methods: immunofluorescence microscopy (IFA-ANA), and nephelometry, Hycor ELISA system and Flow cytometry, for precisely quantitative measurements. We determined correlation between C3 and C4 complement components level, CD3 (T-Ly), CD3+/HLA-DR and total HLA-DR with regard to SLE disease activity. Also, CD4 (Th), CD4:CD8 ratio, beta-2-G, beta-2-M not proved to be useful biomarkers in this sense, despite some results specific for some special SLE phenotypes. Anti-Sm/ RNPs proved to be better in SLE diagnostic process.

Thyroid gland is the largest endocrine gland in the body. The thyroid gland produces hormones that regulate the metabolism rate, affect the growth and many functions of various organ systems. Nuclear medicine technique is very useful diagnostic tool in detecting thyroid disease. Thyroid scintigraphy can reveal functional and anatomic information of thyroid gland. A variety of radiopharmaceuticals and methodologies have been used over the years in nuclear medicine. Iodine-131 has been used to image the thyroid several decades. Radioactive Iodine I-131 is useful for the treatment of hyperthyroidism and thyroid cancer. There were 100 participants included in the study who were treated with I-131. The participants were checked 6 months and 12 months after the beginning of the treatment. The results show normalization of the laboratory parameters and hormonal status at the control examinations after 6 months and 12 months therapy with I-131. The side effects did not appear in any of the patients, which demonstrates safe application.

The polyvascular disease is the disease that includes the simultaneous existence of atherosclerotic process on coronary, carotid and lower extremities peripheral arteries. It is very difficult, if not impossible to determine the prevalence of atherosclerosis, because it is one predominant asymptomatic illness. There is no correct information related to atherosclerosis clinical readings, that is to it's most important consequences: coronary heart disease, cerebrovascular disease and peripheral blood vessels obstruction. Atherosclerosis is a complex disease with numerous predisposing factors that we call the risk factors. We divide all atherosclerotic risk factors on changeable and unchangeable (age, sex and heredity). The risk factors can further be divided on classical (conventional) and non-traditional (raised oxidative stress, endothelium disfunction and inflammation). Tobacco smoking can result by the sevenfold risk increase of peripheral arteries disease and at least the double risk increase of coronary arteries disease beginning. These two main forms of cardiovascular diseases, related with tobacco smoking, are the main atherothrombosis consequences. Obesity has overcome the global epidemical proportions with more than one million people with excessively body mass and, at least, 300 millions of clinical obese people. Obesity is considered as chronic inflammation disease that leads towards the chronic mass non-inflammation diseases as atherosclerosis, Diabetes type 2, non-alcohol stetosis of liver, cancer (of prostate, of breast) and osteoarthrosis.

Immunotherapy was introduced as a method into the respiratory system allergies therapy as early as 1911 by Freeman and Noon, who applied it with the patients suffering from pollen rhinitis. Immunity effects of the therapy are basically, suppression of the allergen-specific IgE antibodies synthesis, stimulation of allergen-specific IgG antibodies synthesis, as well as suppression of antigen specific T cell response. Objective of the work was to show efficiency of the immunotherapy in allergic rhinitis treatment through leukocyte formula, total amount of IgE and skin allergy tests. Research results show decrease in eosinophile count in the leukocyte formula, decrease of the total amount of IgE, and decrease of papule and erythema in allergy testing. Immunotherapy is of great importance in the allergic rhinitis therapy and it should be applied wisely.