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Objectives:To compare drug survival, effectiveness and safety of anti-IL17A compared to anti-TNF drugs as first line biologic therapy in patients with PsA using real life data from the Czech biologics registry ATTRA. The ATTRA registry is a prospective observational cohort study that captures more than 90% of PSA patients treated with bDMARDs and tsDMARDs in the Czech Republic (CZ). Anti-IL17A bDMARDs have been reimbursed in CZ since Jan 2016.Methods:PsA patients who initiated their first bDMARD in Jan 2016–Mar 2022 with at least one year of follow-up were included. By the type of first bDMARD exposure patients were dichotomized to anti-IL17A and anti-TNF cohorts. Effectiveness was assessed every 3-6 months by composite joint indexes (DAS28-ESR and DAPSA), physician global assessment of psoriasis (PGApso) using numerical rating scale (1-5), and EQ-5D utility. Achievement of modified version of minimal disease activity (MDA) was assessed at each time point. Incidence of reported AEs and SAEs per 1000 patient-years was calculated. Propensity score (PS) matching was used to account for differences in baseline characteristics. Drug survival was visualized using Kaplan-Meier curves, and Cox proportional hazards models were used to calculate adjusted Hazard Ratios (HRs) with 95% confidence intervals (CIs) for risk of discontinuing therapy.Results:994 PsA patients started first-line anti-IL-17A (n=192) or anti-TNF (n= 802) therapy within period Jan 2016–Mar 2022, and 178 and 719 resp. had non-missing values for the efficacy outcomes of interest. Important baseline characteristics were similar between anti-IL17A and anti-TNF cohorts save for swollen joint counts, and after PS matching (using logistic model with 1 covariate: 68 swollen joint count, matching ratio 1:4, caliper 0.1) 177 patients on anti-IL17A and 577 on anti-TNF were PS-matched and further analyzed. Baseline characteristics of PS matched cohorts are shown in Table 1. The drug retention on anti-IL7A was statistically significantly better than on anti-TNF drugs with HR (95% CI) 0.57 (0.41; 0.78), see Figure 1. More pts on anti-IL7A discontinued therapy because of primary failure (31% vs 16%), but less of them because of adverse events (9% vs 17%) or other unspecified reasons (13% vs 21%). In patients remaining on first line therapy, values of composite joint indexes (DAS28-ESR and DAPSA) were significantly lower and of utility EQ-5D significantly higher at each time point since month (M)3 until M18 after start of anti-TNF compared with anti-IL-17A therapy (see Figure 2). On the other hand, skin involvement assessed by PGApso was significantly better in anti-IL17A treated pts at M3 and M12. Rates of achievement of MDA were numerically higher in anti-TNF treated pts, but the difference was not statistically significant. Incidence of both AE and SAE was numerically lower in anti-17A than in anti-TNF treated group (93 vs 168 and 7 vs 18/1000 patient-years resp.).Conclusion:We have observed better drug retention on anti-IL17A compared to anti-TNF therapy despite its inferior effect on composite joint indexes and quality of life in patients with PsA. This discrepancy may be explained either by superior safety, tolerability, and effectiveness of anti-IL17A on skin involvement, limited possibility to switch between anti-L17A drugs, or lower confidence of physicians to switch from anti-IL17A to anti-TNF than vice versa.REFERENCES:NIL.Table 1. Baseline characteristicsFigure 1.Kaplan-Meier curves of drug survival on first-line treatment – anti-IL-17A vs TNFiAcknowledgements:Supported by project 00023728 of Ministry of Health, CZ.Disclosure of Interests:Jakub Zavada Abbvie, Astra Zeneca, Eli-Lilly, Novartis, Pfizer, Sobi, Jana Baranová: None declared, Karel Pavelka AbbVie, UCB, Pfizer, Eli Lilly, Celltrion, MSD, and Novartis, AbbVie, UCB, Pfizer, Eli Lilly, Celltrion, MSD, and Novartis, Jiří Vencovský Abbvie, Biogen, Boehringer, Eli Lilly, Gilead, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Werfen, Abbvie, Argenx, Boehringer, Eli Lilly, Gilead, Octapharma, Pfizer, UCB, Pavel Horak ELI-Lilly, Novartis, Abbvie, Sobi, AstraZeneca, Boehringer, UCB, Sandoz, Zentiva, ELI-Lilly, Novartis, Abbvie, Sobi, AstraZeneca, Boehringer, UCB, Ladislav Šenolt Abbvie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Swedish Orphan Biovitrum, UCB, Abbvie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck Sharp and Dohme, Novartis, Pfizer, Sandoz, Sanofi-Aventis, Swedish Orphan Biovitrum, UCB.

BackgroundEtanercept is an agent of specific molecular structure and its efficacy in extraarticular disease differs from monoclonal antibodies. This could affect drug survival in some rheumatic diseases with a larger presence of extraarticular involvement.ObjectivesTo compare the drug survival of etanercept to monoclonal anti-TNF antibodies in psoriatic arthritis and describe the response of skin disease to treatment in the two groups.MethodsPatients with PsA starting first-line biological treatment from 01/01/2012 to 30/06/2020 were enrolled from the Czech ATTRA registry and split into two groups as either being treated with etanercept (ETA) or any other anti-TNF. Propensity scores were calculated using covariates based on statistically significant differences in the baseline characteristics and clinical relevance (Table 1). PS was then used to match 81 etanercept to 160 other TNFi patients. We performed a Kaplan-Meier survival analysis and checked for statistical significance using the log-rank test. We calculated survival rates at set time points, median survival time in each group and the hazard ratio of etanercept for drug discontinuation.The Physician global assessment of psoriasis variable (measured on a numerical rating scale 0-5) was sorted in categories of mild (0-1), intermediate (2-3) and severe (4-5) and respective percentages were calculated in the propensity-matched groups at 3, 6, 12 and 24 months. Pearson’s chi-squared test or Fisher’s exact test were used to check the differences for statistical significance.ResultsWe found significantly worse drug survival on ETA compared to other TNFi at each time point (Figure 1). The median survival time on ETA was 35.8 (95% CI 25.1 – 46.6) months compared to 65.7 (95% CI 51.9 – 79.6) months on other TNFi. The HR of ETA for treatment termination was 1.61 (95% CI 1.11 - 2.34), p=0.011.At baseline, there were no differences in skin disease severity. The percentages of mild, intermediate and severe skin disease were 22.2%, 59.3% and 18.5% on etanercept and 25.0%, 55.6% and 19.4% on other TNFi, p=0.853. At 3 months, skin disease was significantly more severe in ETA with 50.0%, 44.8% and 5.2% compared to 76.2%, 23.8% and 0% on other TNFi, p<0.001. At 12 months, the respective percentages were 66.6%, 31.9% and 2.1% on ETA and 84.7%, 15.3% and 0% on other TNFi, p=0.015; at 24 months 62.9%, 37.1% and 0% compared to 84.9%, 15.1% and 0%, p=0.010.ConclusionEtanercept had worse drug retention than monoclonal antibodies in PsA. Patients treated with ETA had more severe skin disease during follow-up compared to those treated with other TNFi, which could lead to earlier switching to another drug.Figure 1.Drug survival of etanercept vs. other TNF inhibitors in patients with PsA.Table 1.Selected baseline characteristics after propensity score matching.Etanercept (n=81)Other TNFi (n=160)pFemales42 (51.9%)78 (48.8%)0.649Age at diagnosis40.0 (34.0–50.0)42.0 (34.0–49.0)0.847Age at 1st line treatment51.0 (42.0–59.0)52.0 (44.0–59.0)0.835Disease duration (yrs)7.1 (2.3–14.4)7.8 (2.9–15.2)0.587DAPSA36.3 (28.1–43.6)36.2 (26.7–45.8)0.946CRP (mg/dl)12.0 (4.8–25.0)15.4 (6.3–28.0)0.227ESR (mm/h)26.0 (16.0–37.0)30.0 (15.0–40.0)0.728Tender joint count (68)12.0 (9.0–19.0)12.0 (7.0–19.0)0.602Swollen joint count (66)8.0 (5.0–11.0)8.0 (4.0–12.0)0.759Patient global assess. (0-100)68.0 (50.0–80.0)70.0 (50.0–80.0)0.832Physician global assess. (0-100)60.0 (45.0–70.0)60.0 (38.5–72.5)0.942Yr of administration 2012-20137 (8.6%)15 (9.4%)0.9732014-201516 (19.8%)35 (21.9%)2016-201721 (25.9%)41 (25.6%)2018-202037 (45.7%)69 (43.1%)Concomitant csDMARD66 (81.5%)126 (78.8%)0.619Concomitant MTX53 (65.4%)97 (60.6%)0.467Concomitant glucocorticoids25 (30.9%)54 (33.8%)0.652Median (IQR) in continuous variables, n (percentage) in categorical variables.AcknowledgementsThis work was supported by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00023728 (Institute of Rheumatology).Disclosure of InterestsNone Declared.

Background:Significant progress has been achieved over the course of recent time in elucidating the complex underlying pathophysiological mechanisms of ANCA associated vasculitis (AAV). Despite these breakthroughs in research, the range of laboratory parameters available for evaluation in everyday clinical practice to guide the diagnostic process and management of patients with AAV remains very limited. Much effort is nowadays being expended on identifying such prospective biomarkers and assessing their potential for clinical application.Objectives:To evaluate immune cell (sub)populations of patients with AAV and identify significant differences between patient group and healthy controls, and subsequently to also identify differences between cytometric profiles between subgroups of patients based on overall disease severity, specific organ involvement and presence of disease relapse.Methods:A panel of immune cell (sub)populations was investigated in peripheral blood samples from patients with newly confirmed diagnosis of AAV (n=52) and healthy controls (n=16). Patients with AAV were evaluated based on their initial clinical presentation using the validated Birmingham Vasculitis Activity Index version 3 (BVAS v3). For further analysis, patients were divided into subgroups based on overall disease severity (two groups defined as less severe and more severe by group median BVAS v3 score of 15), presence of particular organ domain involvement, and presence of identified disease relapse later on in the course of the condition requiring treatment reevaluation. Smaller subgroups significant by their clinical severity, namely patients requiring long-term hemodialysis due to AAV-conditioned organ damage (n=6) and patients with lethal course of disease (n=5), were also evaluated. Statistical analysis tools (Mann-Whitney, Spearman correlation, regression analysis) were used to evaluate data obtained.Results:Preliminary analysis reveals significant differences between immune cell populations between studied groups and subgroups – among them non-specific upregulation of peripheral neutrophil granulocytes (p=9.28 ×10-8) and suppression of peripheral lymphocytes (p=2.6×10-8) and monocytes (p=2.06×10-6) in AAV patients compared to healthy controls. Similarly, particular immune cell subpopulations of CD 69+ NK cells (p=3.99 ×10-5) and CD 69+ CD 8+ T-lymphocytes (p=0.008) were highly expressed in AAV patients, whereas subpopulation of nonclassical monocytes was significantly reduced in AAV patients in comparison to healthy controls (p=2.81 ×10-7). These trends were also consistently observed in the comparison between subgroups defined by disease severity as described above, with patients presenting with more severe form of disease having further significantly elevated both CD 69+ NK cells and CD 69+ CD8 + T-lymphocytes (p=0.025, p=0.029) compared to patients with less severe AAV.Conclusion:Significant flow cytometry immune cell profile differences can be observed between groups of patients with diagnosed AAV in comparison to healthy controls, as well as between subgroups of patients based on disease severity and organ involvement. Further inquiry into these differences is warranted, as they may offer potential for clinical application in precising diagnosis, assessing disease severity and possibly guiding treatment choices or even present possible therapeutic targets.REFERENCES:NIL.Figure 1.Figure 2.Acknowledgements:Supported by MH CZ – DRO (FNOL, 00098892) and by IGA_LF_2023_002.Disclosure of Interests:Jakub Videman: None declared, Adela Skoumalova: None declared, Marketa Dudkova: None declared, Martina Skacelova Eli Lilly, Novartis, AbbVie, Sobi, UCB, Anna Petrackova: None declared, Zuzana Mikulkova: None declared, Eva Kriegova: None declared, Pavel Horak Eli Lilly, Novartis, AbbVie, Sobi, AstraZeneca, Boehringer, UCB, Sandoz, Zentiva.

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300) Lupus (2010) 19, 1281—1289.

Background:A substantial number of patients with rheumatoid arthritis (RA) continue to experience symptoms despite receiving treatment with biologic (b) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs). This specific group of patients has recently been defined by EULAR as “difficult-to-treat (D2T)” RA [1]. However, determining the optimal approach for the treatment of D2T RA remains a challenge [2].Objectives:Therefore, we conducted a comparative analysis, evaluating the clinical efficacy and drug retention of different b/tsDMARDs initiated in patients with D2T RA.Methods:A cohort of patients treated for RA in the Czech ATTRA biological registry was used to evaluated the subsequent disease course following initiation of subsequent b/tsDMARD in patients fulfilling the EULAR defined D2T RA. Simplified Disease Activity Index (SDAI) and state of remission/low disease activity (LDA) attainment were compared. Drug retention was evaluated using the Kaplan–Meier method, with assessments made at three, six, and 12 months. The results were expressed as medians along with their corresponding 95% confidence intervals (CI). Continuous variables were described by the median along with the 5th and 95th percentiles.Results:Out of the 8,493 patients, 939 (11%) met the EULAR definition of D2T RA. From this cohort, 642 individuals, who had complete data and initiated a subsequent b/tsDMARD after October 2007 and before January 2023, were included in the study. The majority of patients were female (84.7%), with a median age of 56 (34; 74) years. 64.8% of patients were receiving concomitant conventional synthetic DMARDs, and 60.4% were on glucocorticoids. A significant proportion of patients initiated non-TNFi therapy (n=406), with 147 patients initiating IL-6Ri, 133 JAKi, 71 rituximab (RTX), and 55 abatacept (ABA). At month six, SDAI remission/LDA rates were 58.9% (JAKi), 57.5% (RTX), 54.9% (IL-6Ri), 54.4% (TNFi), and 32.2% (ABA) (Figure 1a). The 12-month drug retention on the subsequent b/tsDMARD was 90.1 (83.5; 97.3) for RTX, 68.6 (61.5; 76.6) for anti-IL-6Ri, 67.5 (59.9; 76.0) for JAKi, 59.5 (47.8; 74.2) for ABA, and 58.8 (52.8; 65.4) for TNFi (Figure 1b). The highest treatment retention was observed with RTX, while TNFi showed the shortest treatment retention (median (95% CI) was 71.6 (49.8; NA) vs. 18.4 (14.7; 25.2) months; p< 0.001). 41.1% of patients experienced loss of efficacy, 23.9% had primary failure, and 14.1% discontinued the subsequent treatment due to adverse events.Conclusion:More than half of the patients who initiated subsequent treatment with JAKi, RTX, IL-6Ri, or TNFi after meeting the D2T RA definition, but approximately one-third with ABA, achieved either remission or low disease activity within six months and maintained consistent drug retention for two years. The longest retention on treatment was observed with RTX. In this descriptive analysis, adjustments were not made for baseline parameters that could potentially impact the observed effectiveness outcomes.REFERENCES:[1] Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-35.[2] Nagy G, et al. EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2022 Jan;81(1):20-33.Figure 1.Efficacy (A) and Kaplan-Meier drug retention curves (B) of subsequent treatment with b/tsDMARDs in D2T RA patients.Acknowledgements:Supported by projects NU23-10-00434 and 00023728 of Ministry of Health, CZ.Disclosure of Interests:None declared.

Background:The role of innate immunity in systemic lupus erythematosus (SLE) development is already known, but the expression of TLRs might vary in different clinical manifestations of the disease. Only little is known about the expression of TLRs in lupus nephritis (LN). Our study investigated the expression of the m-RNA of Toll-like receptor (TLRs) family as part of the innate gene signature in the clinically defined group of SLE patients with and without the lupus nephritis and assessed their potential for diagnosing organ involvement or damage.Objectives:To determine the differences in the TLRs gene expression signature in systemic lupus erythematosus (SLE) patients with/ without LN and in healthy controls.Methods:The TLR1-10 m-RNA expression was investigated in peripheral blood mononuclear cells from SLE patients (n=74) and healthy controls (n=34). We compared the subgroup of patients with histologically confirmed active lupus nephritis, defined as renal SLEDAI ≥4 (n=13), with non-LN patients. The expression of TLRs m-RNA was performed by RT-qPCR using high-throughput SmartChip Real-Time-qPCR system (WaferGen). Disease activity was evaluated by SLEDAI and damage by SLICC scores. Statistical analysis (Mann-Whitney, U test, regression analysis) were used to evaluate the obtained results.Results:Analysis revealed an upregulation of TLR4 and TLR10 in SLE patients compared to healthy controls (p=0.01, p=0.0007). The active LN group differed from the non-LN group by higher expression of TLR1 (p=0.03), TLR2 (p=0.07), TLR6 (p=0.05) and TLR8 (p=0.03). The expression of TLR2 ant TLR4 correlated with SLE disease activity assessed by SLEDAI (p≤0.05) in lupus group as a whole.. On the other site, no correlation was found with the SLICC index. Multiple correlations were present between the expression of individual TLRs in the whole lupus cohort: TLR1 correlated with TLR2, TLR4, TLR7, TLR8, and TLR10; TLR2 in addition correlated with TLR 3, TLR5 and TLR8; TLR3 to TLR5; TLR 4 to TLR6, TLR7, TLR8; TLR6 to TLR8 and TLR9, TLLR 7 to TLR8 and TLR10 and TLR8 to TLR10.Conclusion:Signature of lupus with LN is characteristic by upregulated TLR1, TLR2, TLR6 and TLR8. The multiple mutual relations of TLRs and their correlation with disease activity demonstrate the activation of innate immunity in SLE and promising targets for future therapies.REFERENCES:NIL.Acknowledgements:Supported by MH CZ – DRO (FNOl, 00098892) and by IGA_LF_2023_002.Disclosure of Interests:Marketa Dudkova: None declared, Anna Petrackova: None declared, Martina Skacelova ELI-Lilly, Novartis, Abbvie, Sobi, UCB, Jakub Videman: None declared, Veronika Smotkova Kraiczova: None declared, Romana Nesnadna: None declared, Milos Kudelka: None declared, Andrea Smrzova: None declared, Adela Skoumalova: None declared, Eva Kriegova: None declared, Pavel Horak ELI-Lilly, Novartis, Abbvie, Sobi, AstraZeneca, Boehringer, UCB, Sandoz, Zentiva, ELI-Lilly, Novartis, Abbvie, Sobi, AstraZeneca, Boehringer, UCB.

Background:Ixekizumab (IXE) and secukinumab (SECU), both interleukin-17A inhibitors (IL-17i), are available for the treatment of active axial spondyloarthritis (axSpA). IL-17i are commonly used following the failure of tumour necrosis factor inhibitors (TNFi) or as the first line biologic. However, limited evidence exists on the efficacy of IXE in axSpA patients previously exposed to SECU.Objectives:This study aims to stratify axSpA patients initiating IXE based on prior exposure to SECU or TNFi. The objective was to compare baseline demographic and clinical disease characteristics, treatment response and drug survival.Methods:Patients with axSpA who experienced treatment failure with SECU or TNFi and promptly initiated IXE as their subsequent biologic therapy between Jan 2021 and Oct 2023 were enrolled from the Czech Republic biologics registry ATTRA. Disease activity was evaluated using the Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), along with CRP at baseline, 3 and 6 months. Comparisons of disease activity scores between SECU-exposed and TNFi-exposed patients were analysed using the Mann-Whitney test. Drug survival was analysed using the Kaplan–Meier method and Cox proportional-hazards model.Results:Among the 5,435 patients treated for axSpA, 101 initiated IXE, with 73 switching directly from prior treatment with TNFi (n=45) or SECU (n=28). A few more patients were female (57.5%) and HLA-B27 positivity was observed in 83.6% The median age of patients was 48 (32; 69) years (median (5.; 95. percentile)), and the duration of the disease from diagnosis was 9 (2; 26) years. At baseline, axSpA patients with previous SECU exposure, in comparison to those with TNFi exposure, were more likely to receive IXE as a 3rd or 4th line (75.0% vs. 44.4%) and exhibited significantly higher BASDAI (5.8 (2.3; 9.3) vs. 5.0 (0.9; 8.8); p=0.043), but not ASDAS (3.5 (2.1; 5.2) vs. 3.2 (1.4; 4.8); p=0.117) or CRP levels (12.9 (2.2; 41.5) vs. 7.6 (1.0; 46.3) mg/l; p=0.242). In axSpA patients with prior exposure to both TNFi as well as to SECU, substantial reductions in BASDAI and ASDAS were demonstrated at 3 and 6 months (Figure 1A). Probably due to higher previous biologic drug use at baseline, patients with prior SECU exposure exhibited lower rates of ASDAS remission or low disease activity at 3 and 6 months compared to those with prior TNFi exposure (37.6% and 33.3% vs. 50.0% and 45.5%). Overall 12-month drug survival on IXE was 86.3% (72.9; 100.0) for axSpA patients with prior exposure to SECU and 79.7% (67.2; 94.6) for those with prior exposure to TNFi (Figure 1B).Conclusion:IXE demonstrates effectiveness and favourable drug survival in axSpA patients, even among those with prior exposure to SECU, despite a history of multiple biologic treatments. However, a larger patient cohort is required to confirm these findings.Figure 1.Efficacy (A) and Kaplan-Meier curves of drug survival (B) for ixekizumab (IXE) therapy in axial spondyloarthritis patients stratified by prior exposure to secukinumab (SECU) or tumour necrosis factor inhibitors (TNFi).REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Ladislav Šenolt AbbVie, Bristol-Myers Squibb, Celltrion, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi-Aventis, Sobi, UCB, Karel Pavelka: None declared, Kateřina Kusalová: None declared, Jana Baranová: None declared, Pavel Horak: None declared, Leona Procházková: None declared, Sarka Forejtova: None declared, Heřman Mann: None declared, Kristyna Bubova: None declared, Jiří Vencovský: None declared, Jakub Zavada: None declared.

Metal-oxide-based sensors (MOS) can be used for several technological applications in microelectronics, due to their low cost and sensitive capabilities to different chemical species. On the perspective to develop CuO–TiO 2 MOS, our goal was to obtain a homogeneous intermixing of Cu and Ti in the bulk structure of the detectors, exploring the most promising combination between such elements and avoiding the presence of Cu–Ti–O compounds. To do that, several Cu and Ti thin layers were alternatively deposited by Ar + sputtering on silicon wafers and, subsequently, oxidized by thermal annealing. The obtained samples were characterized in terms of %at. Cu–Ti ratios (by RBS and SIMS analyses) and morphology (by AFM and SEM investigations), showing the abundance ratios of such elements in the whole structure. In particular, SIMS maps allowed to study the spatial distribution and thickness of each phase of the Cu–Ti multilayers and further to observe the Cu diffusion and the mixing with Ti, as well as phase separation of CuO and TiO 2 in the samples. This unwanted effect represents an open issue that has to be investigated, in order to improve the MOS fabrication.

Present design of buildings and the way of building assessment focus primary on decreasing of energy consumption, efficient energy management and reduction of greenhouse gas emissions having significant impact on climate change. This emphasis stems from European Union 2020 targets. However, in the issue of comprehensive building assessment are missing headline targets or limits to achieve type-stable level of indoor environment quality. Under the scope of sustainable building assessment can be considered aspect of acoustics, natural and artificial lighting, air quality or thermal behaviour. By means of sustainable development are applied wider targets directly and indirectly influencing overall building performance. This contribution describes connection between application of specific aims of sustainability applied by BREEAM with final influence on energy efficiency and indoor environment in terms of evaluation of thermal comfort using predicted mean vote and predicted percentage dissatisfied indices. The subject of analysis is office building in Brno.